Archive for the ‘Hypogonadism’ Category

Hypogonadism is a common condition in the male population, with a higher prevalence in older men, obese men, and men with type 2 diabetes. It is estimated that approximately 35% of men older than 45 years of age and 30-50% of men with obesity or type 2 diabetes have hypogonadism.

Testosterone is an important sex hormone in men. It is secreted by the testes and is responsible for the typical male characteristics, such as facial, pubic, and body hair as well as muscle. This hormone also helps maintain sex drive, sperm production, and bone health. The brain and pituitary gland (a small gland at the base of the brain) control the production of testosterone by the testes.

Be open with your doctor about your medical history, all prescription and nonprescription drugs you are now taking, sexual problems, and any major changes in your life. Your doctor will take a thorough history of your symptoms and then complete a physical exam, including your body hair, breast tissue, and the size and consistency of the testes and scrotum.

Your doctor will also use blood tests to see if your total testosterone level is low. The normal range depends on the lab that conducts the test. To get a diagnosis of hypogonadism, you need at least two early morning (710 AM) blood tests that reveal low testosterone in addition to signs and symptoms typical of low testosterone. The cause of hypogonadism can be investigated further by your doctor. This might include additional blood tests, and sometimes imaging such as a pituitary MRI.

Male hypogonadism is a combination of low testosterone levels and the presence of any of these symptoms:

Over time, low testosterone may cause a man to lose body hair, muscle bulk, cause weak bones (osteoporosis), low red blood cells and smaller testes. Signs and symptoms (what you see and feel) vary from person to person.

There are many causes of hypogonadism. They may involve a problem with the testes or with the signal from the brain that controls testosterone secretion. Low testosterone can result from:

Improvement of testosterone levels can improve sexual concerns, bone health, muscle and anemia (low red cells in the blood). Hypogonadism can be treated with the use of doctor-prescribed testosterone replacement therapy. This treatment is safe and can be effective for men who are diagnosed with consistently abnormal low testosterone production and symptoms that are associated with this type of androgen (hormone) deficiency.

Although testosterone replacement therapy is the primary treatment option, some conditions that cause hypogonadism, such as obesity, can be reversible without testosterone therapy. These should be addressed before testosterone therapy is contemplated. If testosterone therapy is needed, goals of treatment are to improve symptoms associated with testosterone deficiency and maintain sex characteristics.

There are many different types of testosterone therapy. Method of treatment depends on the cause of low testosterone, the patients preferences, cost, tolerance, and concern about fertility. You should discuss the different options with your physician "your partner in care" to find out which therapy is right for you.

Injections: Self or doctor administered in a muscle every 12 weeks; administered at a clinic every 10 weeks for longer-acting. Side effects: uncomfortable, fluctuating symptoms.

Gels/Solutions: Applied to upper arm, shoulder, inner thigh, armpit. Side effects: may transfer to others via skin contact must wait to absorb completely into skin.

Patches: Adhere to skin every day to back, abdomen, upper arm, thigh; rotate locations to lessen skin reaction. Side effects: skin redness and rashes.

Buccal Tablets: Sticky pill applied to gums twice a day, absorbs quickly into bloodstream through gums. Side effects: gum irritation.

Pellets: Implanted under skin surgically every 36 months for consistent and long-term dosages. Side effects: pellet coming out through skin, site infection/ bleeding (rare), dose decreasing over time and hypogonadism symptoms possibly returning towards the end of dose period.

Nasal Gel: Applied by pump into each nostril 3x a day. Side effects: nasal irritation or congestion.

Sometimes a medication called clomiphene citrate is used to treat hypogonadism, but this is not FDA approved for this indication. A thorough discussion is needed with your doctor.

You should discuss with your physician how to monitor for prostate cancer and other risks to your prostate. Men with known or suspected prostate or breast cancer should not receive testosterone therapy. You should also talk to your doctor about the risks of testosterone therapy if you have, or are at risk for, heart disease or stroke. In addition, if you are planning fertility, you should not use testosterone therapy.

You should not receive testosterone therapy if you have:

Possible risks of testosterone treatment include:

If you are treated with testosterone, your doctor will need to see you regularly, along with blood tests.Testosterone therapy is only recommended for hypogonadism patients. Boosting testosterone is NOT approved by the US Food and Drug Administration (FDA) to help improve your strength, athletic performance, physical appearance, or to treat or prevent problems associated with aging. Using testosterone for these purposes may be harmful to your health.

There is no firm scientific evidence that long-term testosterone replacement is associated with either prostate cancer or cardiovascular events. The FDA requires that you are made aware that the possibility of cardiovascular events may exist during treatment. Prostate cells are stimulated by testosterone, so be extra vigilant about cancer screenings. African American men over age 45 especially those with family history of cancer are already at risk for prostate cancer.

Continue reading here:
Hypogonadism in Men | Endocrine Society

Background

Clinical hyposmia and anosmia are commonly seen, most frequently with either post-inflammatory, age-related, or idiopathic causes being most frequent. Actual anatomical abnormalities of the olfactory groove or olfactory bulb are far less common. A recent case report showing a possible link between congenital olfactory bulb agenesis and Wolff-Parkinson-White syndrome suggested that there may be a relationship between cardiac arrhythmia and olfactory bulb development. While Kallmann syndrome (KS) is the classic syndrome involving olfactory bulb agenesis and hypogonadotropic hypogonadism, this case report and a prior report noting isolated hypogonadotropic hypogonadism and the Wolff-Parkinson-White syndrome suggest there may be more rare associations between cardiac arrhythmia and olfactory groove abnormalities.

A retrospective study was conducted to attempt to elucidate whether there may be a link between cardiac arrhythmias and olfactory anatomical abnormalities. The olfactory bulb volume (OBV) and olfactory sulcus depth (OSD) of 44 patients with cardiac arrhythmias were compared to 43 healthy control patients. Additionally, 11 patients with acute COVID-19 were also compared in those groups. Patients were seen between September and December 2020. Available MRI images were utilized.

The average right and left olfactory bulb volume was 29.4218.17 mm3 and 25.6715.29 mm3 for patients with cardiac arrhythmia, 40.7930.65 mm3 and 38.9521.87mm3 for healthy controls, and 21.3015.23 mm3 and 17.759.63 mm3 for COVID-19 patients. The average right and left olfactory sulcus depth was 7.681.31 mm and 7.471.56 mm for patients with cardiac arrhythmia, 10.671.53 mm and 10.621.67 mm for controls, and 7.910.99 mm and 8.020.88 mm for COVID-19 patients. The right and left olfactory bulb volume difference versus controls was significant for cardiac arrhythmia patients (p=0.028 and p=0.0038) and for COVID-19 patients (p=0.047 and p=0.0029), and the right and left olfactory sulcus depth difference versus controls was significant for cardiac arrhythmia patients (p<0.0001 and p<0.0001) and for COVID-19 patients (p<0.0001 and p<0.0001). Both COVID-19 and cardiac arrhythmia patients were, on average, significantly older than controls. On multivariate analysis, cardiac arrhythmia or COVID-19 diagnosis did not significantly correlate with smaller olfactory bulb volume, but older age, cardiac arrhythmia diagnosis, and COVID-19 diagnosis did significantly correlate with smaller olfactory sulcus depth. On multivariate analysis, older age was significantly correlated with cardiac arrhythmia diagnosis and COVID-19 diagnosis.

Olfactory bulb volume and olfactory sulcus depth in both cardiac arrhythmia and COVID-19 patients appeared significantly smaller than in controls. Cardiac arrhythmia and COVID-19 patients were significantly older than controls. Age, as well as genetic predisposition, may contribute to a difference in the radiographic olfactory anatomical findings in patients with cardiac arrhythmias and COVID-19.

A recent case report [1] noted an adult patient with previously undiagnosed congenital anosmia as well as the radiographic absence of the olfactory groove/bulbs as well as Wolff-Parkinson-White syndrome. Further investigation revealed a prior case report [2] involving a patient with isolated hypogonadotropic hypogonadism, pronounced hypodontia, and the Wolff-Parkinson-White syndrome. The classic Kallmann syndrome (KS) involves hypogonadotropic hypogonadism and olfactory bulb aplasia. The presence of one of the two classic signs of Kallmann syndrome in the aforementioned case reports but not both, while both involved Wolff-Parkinson-White syndrome, prompted an investigation into whether there may be an association between cardiac arrhythmia in general and olfactory nerve abnormalities [3-7]. The gonadotropinreleasing hormone1 (GnRH) system is involved in the development of both the reproductive and olfactory systems, which may contribute to the concomitant reproductive and olfactory dysfunction seen in Kallmann syndrome patients [4,5]. Human cardiac tissue and cardiac-associated immune cells have been shown to contain GnRH receptors, and studies in cephalopods have suggested that GnRH may have receptor targets in the cardiovascular system, which may explain the possible link between cardiac arrhythmias and olfactory nerve abnormalities. Additionally, a recent study [8] on MRI and CT findings in patients with COVID-19-related anosmia noted that radiographic olfactory changes included olfactory cleft opacification, decreased olfactory bulb volumes (OBVs), and olfactory bulb signal abnormalities such as increased signal intensity, hyperintense foci, and microhemorrhages. Olfactory bulb volume and olfactory sulcus depth (OSD) have been shown to be altered in myriad conditions, from septo-optic dysplasia to depression, post-infectious anosmia/hyposmia, and many others [9-17]. This retrospective study aimed to determine whether patients with cardiac arrhythmias and patients with acute COVID-19 had decreased olfactory bulb volume and olfactory sulcus depth relative to healthy controls.

The patient data were collected through a retrospective review of the records of patients who presented to a university hospital between September 2020 and December 2020, underwent head/brain MRI, and fit the study inclusion and exclusion criteria. Between September and December 2020, the head/brain or maxillofacial MRI of 44 patients with cardiac arrhythmias, 43 healthy control patients, and 11 patients with acute COVID-19 were analyzed. Patients aged 18 years or older were included in the three groups. Cardiac arrhythmia patients were analyzed if they had a current diagnosis of any cardiac arrhythmia and had an available head/brain or maxillofacial MRI completed between September and December 2020. COVID-19 patients were analyzed if they had a current diagnosis of acute COVID-19 and had an available head/brain or maxillofacial MRI completed between September and December 2020. Healthy control patients were analyzed if they had an available head/brain or maxillofacial MRI completed between September and December 2020 and did not carry a current diagnosis of any cardiac arrhythmia, COVID-19, disorders of smell/taste, anosmia, hyposmia, or head trauma. Patient medications were analyzed to exclude patients taking medications that could cause anosmia/hyposmia such as intranasal zinc medications, topical decongestant intranasal sprays, and oral medications such as phenothiazines or nifedipine. Figure 1 shows a coronal MRI image illustrating the olfactory bulb and the olfactory sulcus. OBVs were calculated using volumetric analysis of the olfactory bulb on T2 MRI sequences as previously described [12] using the 3D Slicer software ver. 4.10.2 (http://www.slicer.org/). The 3D slicer software is a free, open-source software package for the analysis of medical imaging developed by Harvard University and facilitated volumetric analysis of the olfactory bulb data. The olfactory bulbs were segmented by tracing their outlines manually, and the software ran a quantification process that rendered the volume of the olfactory bulb. OSD was measured as described previously [8] on coronal T2 images by measuring the depth to the deepest point of the olfactory sulcus along a line tangent to the inferior borders of the gyrus rectus. In addition to patient diagnosis and olfactory bulb volume and sulcus depth, data on patient age and gender were compared. Patient data were de-identified and retrospective, and this study was approved by the SUNY-Upstate Institutional Review Board (1427574-1).

Patient data were compiled in Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA) and the data were analyzed using XLSTAT (Addinsoft, Paris, France). Continuous variables were analyzed using the Students t-test and one-way analysis of variance (ANOVA) for comparison between groups. The Pearson Correlation/Association test was also utilized to determine the correlation between the observed data variables. Multivariate analysis was conducted via logistical regression using XLSTAT, utilizing a Newton-Raphson algorithm. The level of statistical significance was set at p < 0.05.

Table 1 shows the patient characteristics for each group. Of the 44 cardiac arrhythmia patients, 38 had atrial fibrillation only, one had atrial fibrillation and supraventricular tachycardia, three had atrial flutter, one had sick sinus syndrome, and one had prolonged Q-T syndrome. Table 2 shows the olfactory bulb volume and olfactory sulcus depth, patient age, and patient sex data and univariate analysis data for the three patient groups. The average right and left olfactory bulb volume was 29.4218.17 mm3 and 25.6715.29 mm3 for patients with cardiac arrhythmia, 40.7930.65 mm3 and 38.9521.87mm3 for healthy controls, and 21.3015.23 mm3 and 17.759.63 mm3 for COVID-19 patients. The average right and left olfactory sulcus depth was 7.681.31 mm and 7.471.56 mm for patients with cardiac arrhythmia, 10.671.53 mm and 10.621.67 mm for healthy controls, and 7.910.99 mm and 8.020.88 mm for COVID-19 patients. The right and left olfactory bulb volume difference versus controls was significant for cardiac arrhythmia patients (p=0.028 and p=0.0038) and for COVID-19 patients (p=0.047 and p=0.0029), and the right and left olfactory sulcus depth difference versus controls was significant for cardiac arrhythmia patients (p<0.0001 and p<0.0001) and for COVID-19 patients (p<0.0001 and p<0.0001). Multivariate analysis via XLSTAT utilizing logistical regression of the data using an iterative algorithm using the Newton-Raphson algorithm was performed. The multivariate analysis data are shown in Table 3. On multivariate analysis, age (p=0.001) and cardiac arrhythmia diagnosis (p=0.0001) or COVID-19 diagnosis (p=0.0001) remained significant predictors of smaller olfactory sulcus depth but not of smaller olfactory bulb volume. Patient sex was not a significant predictor of olfactory sulcus depth or olfactory bulb volume on multivariate analysis. The average age for the cardiac arrhythmia group was 76.1113.13 years (p<0.0001 vs control group), 51.8617.66 years for the control group, and 69.2717.64 years for the COVID-19 group (p=0.0005 vs. control group). Of the 44 cardiac arrhythmia patients, 28 were male and 16 were female. Of the 43 control patients, 21 were male and 22 were female. Of the 11 COVID-19 patients, six were male and five were female.

The volume of the olfactory bulbs and the depth of the olfactory sulcus are readily obtained from MRI imaging and can be used as a neuroanatomical comparative tool to assess the structure of the olfactory system in patients [18,19]. Olfactory bulb volumes and olfactory sulcus depth values [8,20] vary by patient population, MRI protocol, and measurement/calculation method but are typically on the order of 30-90 mm3 for olfactory bulb volumes and 5-10 mm for olfactory sulcus depth, similar to the average values noted in the patient population in this study. Isolated olfactory nerve agenesis is rare, as in a case report in a 12-year-old girl by Carswell et al. [21], noting a patient with congenital complete absence of the olfactory nerves. Coimbra et al. [3] also reported a similarly rare case of isolated olfactory bulb agenesis. The human olfactory apparatus develops during the fetal stage, and the developing fetus can detect odors as early as 28 weeks, and the developing olfactory bulbs can be seen on MRI at this point. Olfactory axons project from the nasal epithelium prior to the formation of the olfactory bulbs and lack a peripheral ganglion, but the synaptic structures of the future olfactory bulb have this functionality. The olfactory bulb begins to laminate at 14 weeks, but complete myelination occurs postnatally. The olfactory system does not contain direct thalamic projections, but the olfactory bulb and anterior olfactory nucleus essentially serve as thalamic surrogates. Olfactory abnormalities can be seen in children with brain malformations, endocrine disorders, chromosome anomalies, and craniofacial abnormalities [4-6]. Kallmann syndrome is a classically described syndrome presenting with congenital olfactory bulb agenesis. Kallmann syndrome is a subtype of the broader group of isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) syndromes [7]. KSconsists of hypogonadotropic hypogonadism with anosmia and a congenital absence of the olfactory bulbs. There are also less severe and somewhat more common pathologies seen in IGD, including hypothalamic amenorrhea (HA), constitutional delay of puberty (CDP), and adult-onset hypogonadotropic hypogonadism (AHH). The association between hypothalamic hypogonadism and olfactory bulb agenesis in Kallmann syndrome is thought to be related to the association between the GnRH neurons and the olfactory placode. IGD can also be related to non-reproductive features such as midline facial defects, renal agenesis, limb abnormalities, hearing loss, and eye movement and balance disorders.

Acquired olfactory dysfunction can be commonly seen in post-upper respiratory infection (URI) anosmia or hyposmia [10]. Studies have shown that olfactory bulb volume and olfactory sulcus depth decreased in patients with olfactory loss after URI compared to normal controls. Studies have also shown that there may be significant gray matter volume loss in the right orbitofrontal cortex (OFC) in patients with post-infectious olfactory disfunction and that there may be a significant negative correlation between the volume of gray matter in the right OFC as well as olfactory bulb volume with the duration of olfactory loss in these post-infectious olfactory loss patients versus normal controls. Kandemirli et al. [8] examined olfactory function and CT and MRI findings in patients with persistent COVID-19 olfactory dysfunction. They evaluated olfactory function with the Sniffin' Sticks test and collected quantitative measurements of olfactory bulb volumes, olfactory sulcus depths, and olfactory radiographic characteristics. They noted frequent olfactory cleft opacification (~73.9% of cases), subnormal olfactory bulb volumes in ~43.5% of cases, and shallow olfactory sulci in ~60.9% of cases. They also noted frequent abnormalities in olfactory bulb shape, olfactory bulb signal intensity, and frequent microhemorrhages and abnormalities in the clumping of or scarcity of olfactory filia. Studies have also shown that olfactory bulb volume can be decreased in patients with depression, after transsphenoidal pituitary surgery, in patients with Parkinsons disease, and that olfactory bulb volume can be decreased in women and with increasing age [11-17].

In this study, olfactory bulb volume and olfactory sulcus depth in patients with cardiac arrhythmia, acute COVID-19, and healthy controls were measured. Patients with cardiac arrhythmia and COVID-19 had significantly smaller right and left olfactory bulb volumes and olfactory sulcus depths than controls on univariate analysis and were significantly older than controls. On multivariate analysis, olfactory bulb volume did not correlate significantly with cardiac arrhythmia diagnosis or COVID-19 diagnosis. On multivariate analysis, smaller right and left olfactory sulcus depth did significantly correlate with cardiac arrhythmia and COVID-19 diagnosis. On multivariate analysis, older age was also significantly correlated with cardiac arrhythmia and COVID-19 diagnosis. This may indicate that there may be a correlation between the propensity to develop cardiac arrhythmia and the propensity for olfactory dysfunction or atrophy of the olfactory bulb and/or olfactory sulcus over time. This study's limitations include its retrospective nature, which introduces the possibility of recall and selection bias. Given the retrospective nature of this study, there was some heterogeneity in the MRI studies/sequences available for patients in this study. A prospective study in which all patients had a uniform fine-cut MRI protocol standardized for the study protocol and specifically targeted at the olfactory anatomy would be helpful. Additionally, the relatively low patient numbers are a limitationand may limit power in the statistical analysis. Patient medication lists were screened to exclude patients on intranasal or oral medications that may affect olfaction, but the use of medications not reported by patients and not present in the medical record or use of other patient medications that might unknowingly affect olfaction is another possible limitation. The mild diversity in the arrhythmia types in the cardiac arrhythmia group (although the vast majority were atrial fibrillation patients) and the mild heterogeneity in the diagnoses of the control group may also limit the statistical analysis. Future prospective studies with larger patient numbers and a greater diversity of other cardiac arrhythmia types with distinct statistical analyses for each arrhythmia type (e.g., a large number of purely Wolff-Parkinson-White patients) would be of use. The significantly older age of the cardiac arrhythmia and COVID-19 patients may also act as a confounder, and indeed, on multivariate analysis, older age did significantly correlate with smaller olfactory sulcus depth, as did cardiac arrhythmia diagnosis and COVID-19 diagnosis. This may indicate that cardiac arrhythmia, COVID-19 diagnosis or susceptibility, and older age may all correlate significantly with small olfactory sulcus depth, and that older age is also independently correlated with a propensity for cardiac arrhythmia. Additionally, the collection and availability of a formal, standardized olfactory function measurement in all patients, such as Sniffin sticks or the Pittsburgh Smell Identification test, would also allow useful correlation between functional/clinical olfactory data (quantitative olfactory measurements) and radiographic olfactory bulb volume and olfactory sulcus depth data.

This retrospective radiographic study demonstrated smaller olfactory bulb volumes and olfactory sulcus depths on MRI in patients with a history of cardiac arrhythmia and patients with COVID-19 compared to healthy control patients. Cardiac arrhythmia and COVID-19 patients were significantly older than controls. Multivariate analysis demonstrated that cardiac arrhythmia diagnosis and COVID-19 diagnosis, as well as older age, were all significantly associated with smaller olfactory sulcus depth but not with smaller olfactory bulb volume. Future prospective studies with standardized MRI protocols and larger groups of patients with cardiac arrhythmias and larger numbers of healthy controls may help elucidate whether there is a correlation between a predisposition to cardiac arrhythmia and radiographic abnormalities in the olfactory bulb/olfactory sulcus.

See original here:
Olfactory Radioanatomical Findings in Patients With Cardiac Arrhythmias, COVID-19, and Healthy Controls - Cureus

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Report Overview

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1 Hormone Replacement Therapy Market Overview

1.1 Product Overview and Scope of Hormone Replacement Therapy1.2 Hormone Replacement Therapy Segment by Type1.2.1 Global Hormone Replacement Therapy Market Size Growth Rate Analysis by Type 2022 VS 20281.3 Hormone Replacement Therapy Segment by Application1.3.1 Global Hormone Replacement Therapy Consumption Comparison by Application: 2022 VS 20281.4 Global Market Growth Prospects1.4.1 Global Hormone Replacement Therapy Revenue Estimates and Forecasts (2017-2028)1.4.2 Global Hormone Replacement Therapy Production Capacity Estimates and Forecasts (2017-2028)1.4.3 Global Hormone Replacement Therapy Production Estimates and Forecasts (2017-2028)1.5 Global Market Size by Region1.5.1 Global Hormone Replacement Therapy Market Size Estimates and Forecasts by Region: 2017 VS 2021 VS 20281.5.2 North America Hormone Replacement Therapy Estimates and Forecasts (2017-2028)1.5.3 Europe Hormone Replacement Therapy Estimates and Forecasts (2017-2028)1.5.4 China Hormone Replacement Therapy Estimates and Forecasts (2017-2028)1.5.5 Japan Hormone Replacement Therapy Estimates and Forecasts (2017-2028)

2 Market Competition by Manufacturers2.1 Global Hormone Replacement Therapy Production Capacity Market Share by Manufacturers (2017-2022)2.2 Global Hormone Replacement Therapy Revenue Market Share by Manufacturers (2017-2022)2.3 Hormone Replacement Therapy Market Share by Company Type (Tier 1, Tier 2 and Tier 3)2.4 Global Hormone Replacement Therapy Average Price by Manufacturers (2017-2022)2.5 Manufacturers Hormone Replacement Therapy Production Sites, Area Served, Product Types2.6 Hormone Replacement Therapy Market Competitive Situation and Trends2.6.1 Hormone Replacement Therapy Market Concentration Rate2.6.2 Global 5 and 10 Largest Hormone Replacement Therapy Players Market Share by Revenue2.6.3 Mergers and Acquisitions, Expansion

3 Production Capacity by Region3.1 Global Production Capacity of Hormone Replacement Therapy Market Share by Region (2017-2022)3.2 Global Hormone Replacement Therapy Revenue Market Share by Region (2017-2022)3.3 Global Hormone Replacement Therapy Production Capacity, Revenue, Price and Gross Margin (2017-2022)3.4 North America Hormone Replacement Therapy Production3.4.1 North America Hormone Replacement Therapy Production Growth Rate (2017-2022)3.4.2 North America Hormone Replacement Therapy Production Capacity, Revenue, Price and Gross Margin (2017-2022)3.5 Europe Hormone Replacement Therapy Production3.5.1 Europe Hormone Replacement Therapy Production Growth Rate (2017-2022)3.5.2 Europe Hormone Replacement Therapy Production Capacity, Revenue, Price and Gross Margin (2017-2022)3.6 China Hormone Replacement Therapy Production3.6.1 China Hormone Replacement Therapy Production Growth Rate (2017-2022)3.6.2 China Hormone Replacement Therapy Production Capacity, Revenue, Price and Gross Margin (2017-2022)3.7 Japan Hormone Replacement Therapy Production3.7.1 Japan Hormone Replacement Therapy Production Growth Rate (2017-2022)3.7.2 Japan Hormone Replacement Therapy Production Capacity, Revenue, Price and Gross Margin (2017-2022)

4 Global Hormone Replacement Therapy Consumption by Region4.1 Global Hormone Replacement Therapy Consumption by Region4.1.1 Global Hormone Replacement Therapy Consumption by Region4.1.2 Global Hormone Replacement Therapy Consumption Market Share by Region4.2 North America4.2.1 North America Hormone Replacement Therapy Consumption by Country4.2.2 United States4.2.3 Canada4.3 Europe4.3.1 Europe Hormone Replacement Therapy Consumption by Country4.3.2 Germany4.3.3 France4.3.4 U.K.4.3.5 Italy4.3.6 Russia4.4 Asia Pacific4.4.1 Asia Pacific Hormone Replacement Therapy Consumption by Region4.4.2 China4.4.3 Japan4.4.4 South Korea4.4.5 China Taiwan4.4.6 Southeast Asia4.4.7 India4.4.8 Australia4.5 Latin America4.5.1 Latin America Hormone Replacement Therapy Consumption by Country4.5.2 Mexico4.5.3 Brazil

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5 Segment by Type5.1 Global Hormone Replacement Therapy Production Market Share by Type (2017-2022)5.2 Global Hormone Replacement Therapy Revenue Market Share by Type (2017-2022)5.3 Global Hormone Replacement Therapy Price by Type (2017-2022)6 Segment by Application6.1 Global Hormone Replacement Therapy Production Market Share by Application (2017-2022)6.2 Global Hormone Replacement Therapy Revenue Market Share by Application (2017-2022)6.3 Global Hormone Replacement Therapy Price by Application (2017-2022)

7 Key Companies Profiled7.1 Company7.1.1 Hormone Replacement Therapy Corporation Information7.1.2 Hormone Replacement Therapy Product Portfolio7.1. CHormone Replacement Therapy Production Capacity, Revenue, Price and Gross Margin (2017-2022)7.1.4 Companys Main Business and Markets Served7.1.5 Companys Recent Developments/Updates

8 Hormone Replacement Therapy Manufacturing Cost Analysis8.1 Hormone Replacement Therapy Key Raw Materials Analysis8.1.1 Key Raw Materials8.1.2 Key Suppliers of Raw Materials8.2 Proportion of Manufacturing Cost Structure8.3 Manufacturing Process Analysis of Hormone Replacement Therapy8.4 Hormone Replacement Therapy Industrial Chain Analysis

9 Marketing Channel, Distributors and Customers9.1 Marketing Channel9.2 Hormone Replacement Therapy Distributors List9.3 Hormone Replacement Therapy Customers

10 Market Dynamics10.1 Hormone Replacement Therapy Industry Trends10.2 Hormone Replacement Therapy Market Drivers10.3 Hormone Replacement Therapy Market Challenges10.4 Hormone Replacement Therapy Market Restraints

11 Production and Supply Forecast11.1 Global Forecasted Production of Hormone Replacement Therapy by Region (2022-2028)11.2 North America Hormone Replacement Therapy Production, Revenue Forecast (2022-2028)11.3 Europe Hormone Replacement Therapy Production, Revenue Forecast (2022-2028)11.4 China Hormone Replacement Therapy Production, Revenue Forecast (2022-2028)11.5 Japan Hormone Replacement Therapy Production, Revenue Forecast (2022-2028)

12 Consumption and Demand Forecast12.1 Global Forecasted Demand Analysis of Hormone Replacement Therapy12.2 North America Forecasted Consumption of Hormone Replacement Therapy by Country12.3 Europe Market Forecasted Consumption of Hormone Replacement Therapy by Country12.4 Asia Pacific Market Forecasted Consumption of Hormone Replacement Therapy by Region12.5 Latin America Forecasted Consumption of Hormone Replacement Therapy by Country

13 Forecast by Type and by Application (2022-2028)13.1 Global Production, Revenue and Price Forecast by Type (2022-2028)13.1.1 Global Forecasted Production of Hormone Replacement Therapy by Type (2022-2028)13.1.2 Global Forecasted Revenue of Hormone Replacement Therapy by Type (2022-2028)13.1.3 Global Forecasted Price of Hormone Replacement Therapy by Type (2022-2028)13.2 Global Forecasted Consumption of Hormone Replacement Therapy by Application (2022-2028)13.2.1 Global Forecasted Production of Hormone Replacement Therapy by Application (2022-2028)13.2.2 Global Forecasted Revenue of Hormone Replacement Therapy by Application (2022-2028)13.2.3 Global Forecasted Price of Hormone Replacement Therapy by Application (2022-2028)

14 Research Finding and Conclusion

15 Methodology and Data Source15.1 Methodology/Research Approach15.1.1 Research Programs/Design15.1.2 Market Size Estimation15.1.3 Market Breakdown and Data Triangulation15.2 Data Source15.2.1 Secondary Sources15.2.2 Primary Sources15.3 Author List15.4 Disclaimer

Continued.

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Some men with a deficit of sex hormones who take testosterone replacement therapy may experience a benefit that goes beyond improved sexual function.

When men have both hypogonadism and poorly controlled type 2 diabetes, testosterone replacement therapy may improve both sexual function and cognitive function, according to preliminary results of a small clinical trial presented at the Endocrine Societys annual meeting in Atlanta.

The findings are welcome news to men with diabetes and hypogonadism, since they often have a poor quality of life, said the lead study author, Preethi Mohan Rao, MD, of the University of Sheffield, England, in a statement.

Hypogonadism in men, often called low T, develops when the body doesnt produce enough testosterone. While men can be born with the condition, it can also develop later in life and cause symptoms like reduced sex drive, erectile dysfunction, depression, and difficulty concentrating, according to the Mayo Clinic. Not all men with hypogonadism have symptoms, and testosterone replacement therapy is recommended only when they do, according to the Endocrine Society.

Sexual dysfunction is a common symptom of both hypogonadism and type 2 diabetes. Men with type 2 diabetes have about twice the risk of low testosterone, according to the American Diabetes Association. Men with poorly controlled diabetes or obesity, or both, have an even greater risk of low testosterone.

For the new clinical trial, researchers randomly assigned 65 men with hypogonadism and poorly controlled type 2 diabetes to take either placebo shots or injections of testosterone replacement therapy every 12 weeks for six months. Then researchers extended the trial for an additional six months, continuing treatment for men on testosterone and starting testosterone for men in the placebo group.

Over the first six months of the trial, men who took testosterone experienced significantly bigger improvements in quality of life and a larger reduction in symptoms associated with low testosterone.

When these men continued testosterone for an additional six months, they experienced overall symptom improvements as well as increased sexual function and libido, the trial found. In addition, these men performed significantly better on delayed verbal recall tests, assessments done to detect early signs of dementia.

The trial was small, however, and more research is needed before health practitioners change treatment approaches for men with hypogonadism and type 2 diabetes.

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Testosterone May Aid Memory in Men With Uncontrolled Diabetes - Everyday Health

In developed countries where there are large populations of older men, prostate cancer becomes a serious public health problem as its prevalence increases throughout life. In the United States, following lung cancer, prostate cancer is the second-highest cause of cancer death in males, with one estimate claiming that 1.3 million newly diagnosed cases of prostate cancer were recorded in men in 2018 associated with 359,038 deaths [1].

Since the first observation by Huggins and Hodges in 1941, it has been established that androgens (chiefly testosterone) play a key role in promoting tumor growth in prostate cancer patients [2]. Hence, effective anti-cancer therapy revolves around declining exposure to androgens and is referred to as androgen deprivation therapy (ADT). ADT is frequently used with localized treatments such as external beam radiotherapy or brachytherapy [3]. Even though orchiectomy (surgical castration) is a simple and cheap procedure, it is less common due to its irreversibility [4]. Multiple strategies are employed to reduce exposure to testosterone including surgically removing the testes that produce 90% of the hormone or undergoing hormonal therapy which entails either reducing testosterone secretion or blocking androgen receptors. Figure1depicts the hypothalamic-pituitary-gonadal axis and the sites of action of ADT.

ADThas become more common in prostate cancer patients in recent yearswith approximately 40% of men undergoing ADT within six months of diagnosis [5]. Cooperberg and colleagues documented the significant increase in the use of ADT from 1989 to 2001 in their report. The most dramatic change was the increase in the use of ADT in external beam radiation therapy (RT) from 9.8% to 74.6% of patients [6].

The use of ADT in prostate cancer treatment has expanded beyond symptomatic metastatic diseasetreatment to include asymptomatic metastatic disease, primary treatment in localized disease when men are unable to undergo surgery or radiotherapy, adjunct therapy in high-risk diseases treated with radiotherapy, and salvage therapy after relapse after surgery or radiotherapy for presumed localized disease [7,8]. TheEuropean Association of Urology (EAU) guidelines recommend ADT for patients with metastatic disease (level of evidence: A) or combined with RT for individuals with high-risk cancers (level of evidence: A). Further, ADT can be used as a single treatment for men with advanced prostate cancer who refuse, are incapable to take any other form of local treatment, or are asymptomatic, with a prostate-specific antigen (PSA) higher than 50 ng/mL and a tumor that is not well-differentiated (level of evidence: A) [9].

A profound testosterone deficiency created by ADT can cause various adverse short and long-term health effects, including hot flushes, sexual dysfunction, obesity, sarcopenia, dyslipidemia, hyperinsulinemia, osteoporosis, type 2 diabetes mellitus (DM), and cardiovascular disease (CVD) [5,7,8]. Despite the fact that male sex is a known risk factor for coronary artery disease (CAD), evidence is mounting that testosterone may protect men with prostate cancer and men in general against heart disease [8].ADT has been shown to promote adiposity in males; one study reported that after one year of ADT, body fat increased by 9.4% [10].

Most patients with prostate cancer have CVD as comorbidity [11-13]. In men with prostate cancer, CVD is the leading cause of non-cancer mortality. In the mid-1990s, Surveillance, Epidemiologyand End Result (SEER) Medicare-linked data showed that CVD was responsible for around one-fourth of deaths among men with prostate cancer [14]. This piqued the researchers interest in determining what might be causing CVD in this group, focusing on the role of ADT as a contributory factor. In 2010, the American Heart Association, the American Society for Radiation Oncology, and the American Urological Association issued a joint statement to raise awareness of the ADT-CVD relationship [15].

In males with prostate cancer, significant increases in total blood cholesterol and triglyceride levels have also been related to androgen deficiency [16]. CAD is exacerbated by obesity and hyperlipidemia, both of which are risk factors[16]. ADT also raises hemoglobin A1C levels in men who already have DM [17]. Although more research is needed to demonstrate that the link between CVD and ADT is not due to confounding factors, there are multiple physiologically possible mechanisms through which ADT may contribute to CVD development [17].

Dyslipidemia, DM, and obesity are all well-known possible causes of atherosclerotic CVD [18]. Androgens may influence the local inflammatory response, which plays a critical role in the formation of atherosclerotic plaques, as well as plaque instability and rupture, via androgen receptor (AR)-dependent and AR-independent pathways, according to recent studies [17]. As a result, these consequences of medically induced hypogonadism may provide a mechanism through which ADT may raise the risk of cardiac morbidity and mortality. Hence, a thorough systematic review of published papers was performed to precisely analyze the relationship of ADT with cardiovascular events in prostate cancer patients and to assist healthcare providers in making related clinical decisions [10].

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were used to perform this systemic review [19].

Database and Search Strategy

The research was started on November 20, 2021, using online libraries as our database. We searched PubMed, Scopus, Science Direct, and Google Scholar for data collection. Our keywords and medical subject heading (MeSH) search strategiesused are depicted in Table 1.

Eligibility Criteria

Studies investigating the association of ADT with cardiovascular events in prostate cancer patients were included without geographic location or publication status restrictions. The following selection criteria were included: (1) the study was published as an original article and contained the original data (excluding reviews, editorials, and conference summaries); (2) only included patients diagnosed with prostate cancer; (3) the intervention group included ADT (medical or surgical ADT); (4) studies with cardiovascular outcomes as the endpoint. Studies were excluded if any of the following factors were identified: (1) secondary studies; (2) laboratory studies; (3) animal studies; (4) database duplication and lack of detailed results.

Quality Assessment Tools

The assessment was separately conducted by two independent reviewers using the Cochrane risk bias assessment tool for clinical trials and the modified version of the Newcastle-Ottawa Scale (NOS) for quality assessment of observational studies [19]. With the help of another field expert, all discrepancies regarding the inclusion of the studies were resolved. High-quality studies were defined as those that received 70% or more of the highest number of stars. We excluded studies that were of low quality. In total, 16 studies were included [4,19-33]. Table 2 shows the quality assessment of clinical trials using the Cochrane Risk of Bias Tool.

Table 3 shows the quality assessment ofcohort studies using the modified version of the NOS.

Table 4 shows the quality assessment of cross-sectional studies using the modified version of the NOS.

Selection and Data Extraction

Two reviewersseparately obtained data utilizing a predefined data extraction formfrom the final articles after quality assessment. With the help of a third reviewer, disagreements were addressed via debate or consensus.The following information was obtained: first authors name, sample size, research features (i.e., year, design, and setting), type of ADT intervention used in the study, cardiovascular events described in every paper, and other non-cardiovascular events described in the study. Extracted data are summarized in Table 5.

Literature Search

Our extensive search resulted in 425 studies. Only 287 studies remained after removing 108 duplicates. In total, 264 articles were omittedafter reviewing the abstractsand titles because they did not fit the inclusion criteria forthe following causes: secondary studies, laboratory searches, and non-relevant topics. Finally, the entire paper was carefully read, of which five were further excluded because of non-cardiovascular end-point. Figure 2 shows the PRISMA flowchart demonstrating the search process and study selection.

Study Characteristics

In total, 14 observational studiesand two randomized control trials (RCTs ) were included in the systemic review [4,19-33]. The key characteristics of the investigations (published between 2006 and 2020) that were considered are listed in Table 5. Seven studies were performed in America, one in Japan, two in Sweden, one in China, two in Canada, one in Taiwan, and one in Brazil. One clinical trial was done in the United States, Australia, and Canada. The sample sizes in the reviewed clinical investigations ranged from 79 to 201,797 participants. All studies had ADT as the intervention.

Seven of these studies did not mention the specific ADT type used and compared outcomes between patient groups that used ADT to those that did not.The other studies mention the specific type of ADT used and compared the outcomes between patient groups receiving different types of ADT such as GnRH agonists, combined androgen blockade (CAB), surgical castration, and oral anti-androgenwith each other and with the patient group that did not receive ADT.

ADT Versus Non-ADT Groups on Cardiovascular Events

Myocardial infarction (MI), sudden cardiac death (SCD), and CAD: According to a study by Wallis et al., radiation (adjusted hazard ratios (aHR) = 1.16-1.28, p< 0.0001-0.04) and ADT (aHR = 1.18-1.32, p< 0.0001-0.0008) were both linked with an elevated risk of CAD, SCD, and fracture requiring hospitalization after adjusting for baseline differences [32].Radiotherapy was associated with a greater risk of MI (aHR = 1.20, p = 0.02) but not ADT (p = 0.5) [32].In a study by Nguyen et al., individuals who used ADT had a greater risk of CAD (HR = 1.12, 95% confidenceinterval (CI) = 1.09-1.14) and acute MI(HR = 1.11, 95%CI = 1.08-1.15) than those who did not [33].

Standardized incidence ratio(SIR) of CVD, arrhythmia, and ischemic heart disease (IHD): Van Hemelrijck et al. reported thatregardless of the history of cardiovascular illness, SIRfor CVD was high in all males undergoing ADT, with the greatest values among those on endocrine treatment [31]. In this study, endocrine treatment was grouped into anti-androgens, estrogens, orchiectomy, GnRH agonists, GnRH agonist combined with long-term anti-androgens, and other types of endocrine therapy. SIR MI for men without circulatory disease history: 1.40 (95% CI = 1.31 to 1.49), 1.15 (95% CI = 1.01 to 1.31), and 1.20 (95% CI = 1.11 to 1.30) for men undergoing primary endocrine therapy, radical prostatectomy/radiotherapy, and surveillance endocrine therapy, respectively.

Arterial stiffness: Within six months following ADT, the entire sample exhibited no significant increase in arterial stiffness, according to Oka et al., although 55.2% of patients had an elevated cardio-ankle vascular index (CAVI) [28]. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels in the blood significantly increased one month after starting ADT and remained high thereafter.

Hypertension: Over a five-year follow-up period,Wu et al. found that the incidence of new-onset hypertension was 22.6 per 1,000 person-years in patients who did not receive ADT and 33.0 per 1,000 person-years in those who did receive ADT [4]. There was a 1.78-fold enhanced risk of developing new-onset hypertension in the group that received ADT than in the control group (95% CI = 1.61-1.96; p < 0.001). Furthermore, the CAB group had almost doubled the likelihood of subsequent hypertension (aHR = 1.93; 95% CI = 1.71-2.18; p < 0.001).

Cardiovascular morbidity: According to Saigal et al., patients with prostate cancer who had ADT for at least one year had a 20% greater risk of substantial cardiovascular morbidity than those who did not [29]. The individuals began to encounter this elevated risk after just 12 months of treatment.

Cardiovascular mortality: According to Kim et al., patients with no ADT, six months of ADT, and more than six months of ADT, respectively, had cumulative cardiovascular mortality of 2.6% (95% CI = 1.9-3.5%), 2.1% (95% CI = 1.2-3.5%), and 1.4% (95% CI = 1.0-2.0%) at seven years (Grays p = 0.002) [25]. In this study, compared to the more than six-month ADT group, the non-ADT group had greater cardiovascular disease and risk factors at the start.

GnRH Agonist Versus Surgical Castration Versus CAB Versus Anti-androgenson Cardiovascular Events

General risk of CVD: According to a study by O'Farrell et al., males who used GnRH agonists (HR = 1.21, 95% CI = 1.18-1.25) had a greater risk of CVD than the orchiectomy group (HR = 1.16; 95% CI = 1.08-1.25) and that of the anti-androgen group(HR = 0.87; 95% CI = 0.82-0.91) [27]. CVD risk was higher in males who had two or more cardiovascular incidents before starting ADT, with HR of CVD with GnRH agonist treatment of 1.91 (95%CI = 1.66-2.20), HR of CVD with anti-androgen therapy of 1.60 (95%CI = 1.24-2.06), and HR of CVD with orchiectomy of 1.79 (95%CI = 1.16-2.76) versus comparison cohort. Teoh et al., according to the Kaplan-Meier analysis, determined that the orchiectomy group had a higher incidence of new cardiovascular thromboticevents than the GnRH agonist group (p = 0.014) [30]. Age (HR = 1.072, 95% CI = 1.04-1.11; p = 0.001), hyperlipidemia (HR = 2.455, 95%CI = 1.53-3.93; p = 0.001), and orchiectomy (HR = 1.648, 95%CI = 1.05-2.59; p = 0.031) were all found to be significant risk factors for cardiovascular thrombotic events according to multivariate Cox regression analysis.

CVD prevalence: In a study by Morgia et al., a total of 1,075 people were included, with 285 (26.51%) and 790 (73.49%) being discordant and concordant, respectively, according to the EAU criteria [26].Discordant ADT was linked to a higher incidence of cardiovascular issues (odds ratio (OR) = 2.07; p = 0.01) in a multivariate logistic regression analysis adjusted for confounding factors, with GnRH agonists (HR = 3.95, 95% CI = 1.01-15.34; p = 0.005) and CAB (HR = 3.37, 95% CI = 1.10-10.30; p = 0.005) both contributing to cardiovascular complications.

CAD, MI, and SCD: According to Keating et al., treatment with GnRH agonists was linked to statistically significantly greater risks of incident CAD (aHR = 1.19, 95% CI = 1.10-1.28), MI (aHR = 1.28, 95% CI = 1.08-1.5) [23,24]. Oral anti-androgen monotherapy was not linked to any of the outcomes investigated. According to Gandaglia et al., overall, the rates of CAD, MI, and SCD were 25.9%, 15.6%, and 15.8%, respectively after 10 years [21]. After stratification by ADT status (ADT-naive vs. GnRH agonists vs. bilateral orchidectomy), the CAD rates were 25.1%, 26.9%, and 23.2%, respectively. The acuteMI rates were 14.8%, 16.6%, and 14.8%, while the SCD rates were 14.2%, 17.7%, and 16.4%, respectively. GnRH agonists (all p = 0.001) but not bilateral orchidectomy (all p = 0.7) were linked to a greater risk of CAD, MI, and SCD in competing-risk multivariable regression models. According to Amico et al., males aged 65 and over who got six months of ADT had shorter delays to fatal MIs than men in this age group who did not get ADT (p = 0.017) or men younger than 65 years (p = 0.016) [19]. The time to fatal MIs in males aged 65 and older who got six to eight months of ADT compared to three months of ADT revealed no significant difference (p = 0.97). Here, ADT used was GnRH agonists.

Peripheral arterial disease (PAD) and venous thromboembolism (VTE): GnRH agonist usage was linked to a greater risk of PAD (aHR = 1.16; 95% CI = 1.12-1.21) and VTE (aHR = 1.10;95% = CI 1.04-1.15). Orchiectomy was also linked to an elevated risk of PAD (aHR = 1.13; 95% CI = 1.02-1.26) and VTE (aHR = 1.27; 95% CI = 1.11-1.45), according to Hu and colleagues [22].

Cardiovascular mortality: According to Efstathiou et al., cardiovascular mortality was 5.9% for men getting longer-term adjuvant goserelin versus 4.8% for men receiving short-term goserelin after five years (Grays p = 0.16). In multivariate analyses, the treatment arm was not linked to an enhanced risk of cardiovascular mortality when censoring at the time of salvage goserelin (aHR= 1.02, 95% CI = 0.73-1.43; p = 0.9) [20]. Traditional cardiac risk variables such as age, CVD, and DM were all linked to a greater risk of CVD [20].

Systematic reviews are considered the highest level of evidence and are typically emphasized in evidence-based practice because they reduce the errors and biases that can be introduced by single research. A well-conducted systematic review can assist researchers in objectively establishing the boundaries of what is known and what is unknown by summarizing all of the relevant and reliable evidence to enhance clinical decision-making [34,35]. This review attempted to involve all potentially relevant literature related to the research topic, which was cardiovascular events due to ADT in prostate cancer patients.

ADT may be beneficial to prostate cancer patients as part of curative treatment or as a palliative treatment for advanced disease. As the average life expectancy for males with prostate cancer increases, more people may be exposed to the possible adverse effects of ADT over longer periods. Care for cardiovascular events is an important element of the survivorship phase for a significant number of prostate cancer patients.

The 16articles considered in the review were good quality studies as per the NOS andCochrane risk bias assessment tools,out of which 14 were observational studies and two RCTs. Seven of these studies did not mention the specific ADT type used and compared outcomes between patient groups that use ADT to those that did not. The other studies mentioned the specific type of ADT used and compared the outcomes between patient groups receiving different types of ADT such as GnRH agonists, CAB, surgical castration, and oral anti-androgen with each other and with the patient group that did not receive ADT.

ADT Versus Non-ADT Groups on Cardiovascular Events

According to Wallis et al., there is an increase in CAD and SCD in both the groups individually but there is an increase in MI only in the non-ADT group [32]. When discussing the risks and benefits of treatment for localized prostate cancer for formulating a survivorship plan, the increased use of ADT for males with localized disease undergoing radiotherapy, and the observed higher prevalence of CAD, MI, and SCD in these patients should be considered. Nguyen et al. conducted a study thatfound males who received ADT had a higher incidence of CAD, MI, and SCD who did not receive ADT [33].

According to Van Hemelrijck et al., all prostate cancer patients, especially those treated with ADT, have enhanced relative risks of fatal and non-fatal CVD (SIR of CVD, arrhythmia, IHD) [31].According to Oka et al., while the entire cohort did not show a significant change in arterial stiffness with ADT, some patients with CAVI showed an increase in arterial stiffness [28]. The ratio of LDL-C to HDL-C, or LDL-C/HDL-C may impact the development of arterial stiffness following ADT administration. Thus, doctors may be able to use LDL-C/HDL-C values to monitor prostate cancer patients who are at high risk of developing arterial stiffness following ADT therapy in prostate cancer patients.

According to the findings of Wu et al., males who had ADT for prostate cancer are at risk of having hypertension in the future [4]. According to Saigal et al., ADT is related to a significantly higher cardiovascular morbidity in prostate cancer patients and may reduce overall survival in low-risk men [29]. These findings are especially important for deciding whether or not to use ADT in prostate cancer patients in situations where the benefit has not been proven. According to Kim et al., individuals who received longer durations of ADT had a lower cardiovascular mortality rate than those who did not get ADT [25]. These discrepancies are most likely because of patient selection for ADT rather than the impact of ADT.

GnRH Agonist Versus Surgical Castration Versus CAB Versus Anti-androgenson Cardiovascular Events

According to Morgia et al., almost one-third of prostate cancer patients got inappropriate GnRH agonists who in turn had a higher prevalence of CVD [27]. Cardiovascular risk is significantly increased in males who received ADT in the form of GnRH agonists and surgical castration. However, prostate cancer patients who took anti-androgen had a lower chance of developing CVD risk factors. According to the findings of O'Farrell et al., there should be a strong indication for ADT in males with prostate cancer such that the benefits outweigh the risks; this is especially important in males with a recent history of CVD [28].When compared to GnRH agonists, Teoh et al. claimthat surgical castration is linked to a greater risk of cardiovascular thrombotic events. This is an essential factor to consider when choosing an ADT approach, particularly in older men with a history of hyperlipidemia [30].

GnRH agonist treatment for males with locoregional prostate cancer was linked to an elevated risk of diabetes and cardiovascular disease (CAD, MI, and SCD), according to Keating et al. (2006) [23].ADT with GnRH agonists was linked to an elevated risk of diabetes and CVD (CAD, MI, and SCD), ADT with CAB was linked to an enhanced risk of CAD, ADT with orchiectomy was linked to CAD and MI, and oral anti-androgen monotherapy was not linked to any of the outcomes studied, according to Keating (2010) [24]. In males with non-metastatic prostate cancer, Gandaglia et al. revealed that the administration of GnRH agonists, but not orchidectomy, is still associated with a considerably higher risk of CAD, MI, and, especially SCD. In men with a higher risk of CVD, alternative types of ADT should be evaluated [22]. Amico et al. discovered that GnRH agonist use is linked to an earlier onset of fatal MIs in males 65 and older who are treated for six months versus males who are not treated with GnRH agonist [19].

Hu et al. state that ADT in the forms of GnRH agonists and surgical castration for non-metastatic prostate cancer is linked to an enhanced risk of PAD and VTE. The observational research design has limitations as does the inability to examine the usage of oral anti-androgens [22].According to Efstathiou et al., a longer duration of adjuvant GnRH agonist medication does not improve cardiovascular mortality in males with locally advanced prostate cancer, whereas traditional cardiac risk factors, such as DM, prevalent CVD, and age, were significantly associated with higher cardiovascular mortality [20].

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Cardiovascular Effects of Androgen Deprivation Therapy in Prostate Cancer Patients: A Systematic Review - Cureus

FREIENBACH, Switzerland--(BUSINESS WIRE)--EffRx Pharmaceuticals SA, a commercial-stage company that commercializes niche and orphan medicines in Switzerland and Europe, today announced it has recently entered into an exclusive license agreement with Diurnal Group plc, for the registration and commercialization of Efmody as treatment for congenital adrenal hyperplasia (CAH) in Switzerland. Under the terms of the agreement EffRx has received the exclusive rights to register and commercialize Efmody in Switzerland.

Efmody is a modified-release preparation of hydrocortisone that has been specifically designed for the treatment of patients with CAH, a rare condition caused by a genetic deficiency of adrenal enzymes. According to our estimates, there are approximately 450 patients in Switzerland suffering from CAH.

EffRx intends to submit a Market Authorisation Application (MAA) to Swissmedic as treatment for adolescent and adult patients (12 years and older) with the rare condition congenital adrenal hyperplasia (CAH) in Switzerland during the second half of 2022. The MAA submission to Swissmedic for Efmody will be based on the European regulatory dossier and published clinical trial data, with EffRx expecting potential market launch in Switzerland in 2024.

We are excited to sign this additional agreement with Diurnal, enabling us to build on the momentum we have achieved with Alkindi in Switzerland following approval from Swissmedic in November 2021. We believe the unique release profile of Efmody, that mimics the bodys natural cortisol circadian rhythm, could have a genuine impact on CAH patients symptoms. We are aligned with Diurnals strategy to address the unmet medical need in patients suffering from diseases of cortisol deficiency and look forward to working with the Diurnal team to bring Efmody to patients suffering from CAH in Switzerland, Lorenzo Bosisio, Chief Executive Officer of EffRx, commented.

In May 2021, Efmody was granted marketing authorisation in the European Union and was subsequently launched in Germany, Austria and the UK in September 2021. We are pleased to deepen our relationship with EffRx to include the distribution and marketing of Efmody in Switzerland. We have been impressed by the progress EffRx has made with the regulatory approval and reimbursement of Alkindi and look forward to continuing to work with them as they prepare to submit an MAA to Swissmedic for Efmody, Richard Bungay, Interim Chief Executive Officer of Diurnal, commented.

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About congenital adrenal hyperplasiaCongenital adrenal hyperplasia (CAH) is an orphan condition caused by deficiency of adrenal enzymes, most commonly 21-hydroxylase. This enzyme is required to produce the adrenal steroid hormone, cortisol. The block in the cortisol production pathway causes the over-production of male steroid hormones (androgens), which are precursors to cortisol. The condition is congenital (inherited at birth) and affects both sexes. The cortisol deficiency and over-production of male sex hormones can lead to increased mortality, infertility and issues during sexual development including ambiguous genitalia, premature (precocious) sexual development and short stature. Sufferers, even if treated, remain at risk of death through an adrenal crisis.

Current therapy for CAH uses a variety of generic glucocorticoid (steroid) preparations including hydrocortisone, dexamethasone, prednisolone and prednisone in the US, with no standard treatment regimen. Approximately two-thirds of CAH patients are estimated to have poor disease control, leading to elevated androgen levels. The condition is estimated to affect a total of approximately 16,000 patients in the US, with over 400,000 in the rest of the world.

About Efmody (hydrocortisone modified-release hard capsules)Efmody is a preparation of hydrocortisone that has been specifically designed to mimic the circadian rhythm of cortisol when given in a twice-a-day "toothbrush" regimen (administered last thing at night before sleep and first thing in the morning on waking) to control androgen excess and chronic fatigue in patients with diseases of cortisol deficiency. The first indication for Efmody is congenital adrenal hyperplasia (CAH) in adults and adolescents (children older than 12 years of age). Efmody has been extensively studied in 239 human subjects including 138 CAH patients who have taken part in clinical trials in Europe and the US.

The MHRA and European Commission marketing authorisation approval of Efmody was based on a Phase 3 study conducted in a total of 122 patients enrolled across 11 clinical sites, including sites in Great Britain, the largest ever interventional clinical trial completed in CAH. The Phase 3 data was supported by detailed analysis of data from an open-label safety extension study for patients completing treatment in the Phase 3 study, which is assessing the impact of treatment with Efmody over an extended period, with a number of patients on this trial having been treated for over five years. Summary of Product Characteristics (SmPC) for UK (Northern Ireland) can be found here.

About EffRx PharmaceuticalsEffRx Pharmaceuticals is a commercial-stage pharmaceutical company focused on the late stage development and commercialization of prescription medications for niche and orphan indications. The business model is centered around providing superior clinical and commercial value propositions for physicians, payers and patients.

EffRx pro-actively seeks in-licensing opportunities for Europe in niche therapeutic areas, with a primary interest for rare diseases, where EffRx has received an orphan drug designation (ODD) from the FDA. EffRxs go-to-market competence is proven by the development, launch and lucrative expansion of Binosto in a highly competitive European market. Our lead commercialized product, Binosto for the treatment of osteoporosis, is marketed in the US as well as selected European and Asian countries.

About Diurnal Group plcDiurnal Group plc is a European, UK-headquartered, specialty pharmaceutical company dedicated to developing hormone therapeutics to aid lifelong treatment for rare and chronic endocrine conditions, including congenital adrenal hyperplasia, adrenal insufficiency, hypogonadism and hypothyroidism. Its expertise and innovative research activities focus on circadian-based endocrinology to yield novel product candidates in the rare and chronic endocrine disease arena.

For further information about Diurnal, please visit http://www.diurnal.com

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EffRx Pharmaceuticals Signs Exclusive License Agreement With Diurnal for the Registration and Commercialization of Efmody in Switzerland - Business...

Far-right talking heads like Tucker Carlson love bemoaning the state of masculinity, as measured by their very narrow and stereotypical lens, as though it is in some sort of crisis. To that end, Carlson recently humored the internet (and world?) by offering up a wellness solution for this so-called crisis in his "Tucker Carlson Original" documentary, title "The End of Men." And Carlson's prescription, to stop the death spiral of the American man, was something called "testicle tanning."

"The solutions are actually really simple," fitness professional Andrew McGovern told Carlson. "Red-light therapytesticle tanninghas massive benefits."

Testicle tanning, more formally known as red-light therapy for testosterone, involves exposing one's scrotum to infrared light; this, supposedly, increases testosterone levels. Trailers for Carlson's documentary feature multiple images of a naked white man appearing to plug his testicles into some sort of infrared light device. As his bottom half lights up, the man's arms slowly raise, indicating some sort of victory or enlightenment has been achieved. Presumably with the help of testicle tanning.

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"Half the viewers right now are like, 'What?! Testicle tanning, that's crazy!'" Carlson responded. "But my view is: Okay, testosterone levels have crashed and nobody says anything about it, that's crazy, so why is it crazy to seek solutions?"

This isn't the first time the idea of testicle tanning has entered the public discourse. In 2015, former Major League Baseball player Gabe Kaplermade headlinesfor promoting testicle tanning as a solution to Vitamin D deficiencies in men. "If you want to be your strongest, get some sun on your boys. And by boys, I mean your testicles," Kapler said.

"Half the viewers right now are like, 'What?! Testicle tanning, that's crazy!'" Carlson responded. "But my view is: Okay, testosterone levels have crashed and nobody says anything about it, that's crazy, so why is it crazy to seek solutions?"

In 2017, self-proclaimed "biohacker" Ben Greenfield wrotein Men's Health magazine about his experience trying red-light therapy on his testicles to increase his testosterone levels. After, Greenfield claimed to have "never felt better."

But despite these anecdotes, there has been little written about whether this is actually a therapy that many people are doing or, if there is there any scientific evidence to suggest it works. A related trend, ofperineum sunning, was briefly a wellness trend in 2019 and 2020. Yet in my research, I could find no spas that offered the testicle tanning service. Indeed, in 2020,Inverse reportedthat it is more of an "at-home treatment" rather than something being offered as a service.

In any case, those interested in testicle tanning can purchase in-home devices such as light beds, lamps, lasers, and infrared saunas, which range in price from hundreds to thousands of dollars. In 2019, researchers estimated that the global light therapy market was expected to surpass $1 billion by 2025, though light therapymostly includes non-testicle related treatments for things like eczema and psoriasis.

The greatest irony behind the testicle tanning fad, however, is that it seems to do the opposite of what boosters like Tucker Carlson say that it does. Indeed, urologists do not recommend red-light therapy to boost testosterone, noting exposure of infrared light can negatively affect a male's testicles and may actually lower testosterone levels.

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"Any extreme chronic exposure can prove harmful for the testes leading to decreased testosterone, decreased sperm counts and subsequent infertility," reproductive urologist Dr. Ranjith Ramasamy told Salon via email. "However, the true efficacy of testes-focused light therapy in improving testosterone levels is currently unknown and not backed by the scientific literature."

Ramasamy said that there have been some studies to show that red-light therapy can improve the destruction of cells on a person's skin. Indeed, it is sometimes used to treat wrinkles, redness, acne, scars and other signs of aging. But "the true effectiveness of this therapeutic modality remains unknown," Ramasamy notes.

Advocates of the therapy often point to one study from researchers at the University of Siena in Italy from 2016 who claimed that "bright light increases testosterone levels and leads to greater sexual satisfaction in men with low sexual desire." Professor Andrea Fagiolini recruited 38 men who had been diagnosed with hypoactive sexual desire disorder or sexual arousal disorder, both conditions that are characterized by a lack of interest in sex.

Fagiolini divided the study participants into two groups, one of which received treatment with a specially adapted light box and the other which received a placebo. Both groups received an hour of treatment from a light box for two weeks. The researchers claimed there were significant differences in the groups, with increased testosterone levels in the group exposed to a light box, but they recognized the study was small and thus they couldn't "recommend this as a clinical treatment." Notably, the study wasn't published in a peer-reviewed journal, and participants' testicles were directly exposed to the light.

Ramasamy added that too much sunlight could negatively affect male testicles, too, and lead to decreased sperm count and "intratesticular testosterone levels."

"This study fails to mention that the men in this study were likely suffering from hypogonadism given the low testosterone level and presence of symptoms (in this case low sex drive or libido)," Ramasamy told Salon. "Testosterone levels are very dependent on quantity and quality of sleep and the use of aids to optimize such as light therapy could theoretically increase endogenous testosterone production," Ramasamy said, adding that this study doesn't indicate that light therapy focused on the testicles specifically could increase testosterone.

"Previous studies examining the use of light therapy focused on the testicles have often been done in men suffering from fertility issues such as azoospermia or asthenozoospermia with no indication or studies supporting its use in healthy men," Ramasamy continued. "The few studies demonstrating the use of red-light in increase testosterone levels have been done in animal subjects which are very imperfect models of humans and do not fully represent our own physiology."

Ramasamy added that too much sunlight could negatively affect male testicles, too, and lead to decreased sperm count and "intratesticular testosterone levels."

"The testicles are vital organs responsible for producing the majority of testosterone and source of sperm, both of which are essential for maintaining fertility," Ramasamy said. "Normally the testicles prefer to be in a slightly cooler environment than the core body temperature which is one of the reasons they move in response to local temperature."

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Tucker Carlson hawks testicle tanning to boost testosterone. Experts say it may do the opposite - Salon

Prevalence of hypogonadism

In the Baltimore Longitudinal Study on Ageing, it was found that 19% of men over 60 years had low testosterone. The Hypogonadism in Males (HIM) study estimated the overall prevalence of hypogonadism at approximately 39% in men aged 45 years or older (18). It has been estimated that only 535% of hypogonadal males actually receive treatment for their condition (19,20).

Measuring testosterone levels in populations, while useful, is different from measuring hypogonadal symptoms. A subject can have low testosterone levels, but can also have no clinically significant symptomatology. Likewise, measurement of symptoms alone is not reliable, as hypogonadal symptoms are non-specific. The Massachusetts Male Ageing Study (MMAS) measured a combination of testosterone levels and hypogonadal symptoms and found between 6% and 12% of men had symptomatic androgen deficiency (21). An interesting observation from the MMAS was that half of the men found to have symptomatic androgen deficiency at one stage were found to be eugonadal when retested at a later stage (22). This is probably because there is subject-to-subject variation in testosterone secretion and in the testosterone threshold where symptoms become manifest. As discussed below, a measurement of low testosterone in a patient should be reconfirmed at a later stage before considering treatment.

Older men are more likely to have low testosterone levels: in the HIM study, for example, the prevalence of low testosterone in the 4554 age group was 34%, whereas it was 50% in men over 85 years (18). Likewise, in the Baltimore study the percentage of men with low testosterone increased from 12% in men in their 50s, to 49% in men over 80 years of age (23).

There appears to be no consistent evidence that the prevalence of hypogonadism differs between racial and ethnic groups (2426).

Higher rates of hypogonadism than those in the general population are associated with various common diseases or conditions. The HIM study calculated odds ratios for some common conditions (). It is not yet understood whether the low testosterone levels are a consequence of the disease, are connected with the diseases aetiology, or are one of the causes of the disease. Further studies are needed to determine if treating the associated hypogonadism is likely to improve the patients disease symptoms.

Odds ratios for hypogonadism for various comorbidities from the HIM Study (18)

Vascular tissue (including endothelium and vascular smooth muscle cells) contains androgen receptors, so it is to be expected that testosterone (or its metabolite, oestrogen) is likely to affect the cardiovascular system. In fact, the increased risk of cardiovascular disease in males compared with females has been taken to imply a role for testosterone (or oestrogen) in the disease. Human observational studies, however, have shown no associations between high testosterone levels and coronary artery disease, and testosterone has been shown to dilate the coronary arteries both in vitro and in vivo. Some studies have shown that testosterone can be considered to have a positive effect on reducing the risk factors for cardiovascular disease; for example, inverse relationships have been shown between testosterone levels and body mass index (BMI), waist circumference, waist-hip ratio, serum leptin, low-density lipoprotein (LDL) cholesterol, triglyceride and fibrinogen levels. Low testosterone is associated with dyslipidemia, hypertension, obesity and diabetes, all of which increase the risk of cardiovascular disease and are features of the metabolic syndrome (27,28).

A negative view of testosterones impact on cardiovascular disease comes from the observation that high-density lipoprotein (HDL) cholesterol levels decrease in patients on oral testosterone therapy, or when taken in supraphysiological doses by athletes (29,30). However, when given as a transdermal gel to hypogonadal men, there is either no significant change or only minor changes in HDL levels (28,31,32). Whatever the subtleties of the effects of testosterone on lipids, recent data have demonstrated that low testosterone concentrations are associated with an increased incidence of cardiovascular events, and an increase in acute myocardial infarction and stroke.

The relationship between testosterone and HDL is confounded by the fact that both HDL and testosterone are inversely related to BMI. In fact, epidemiological analyses have found that HDL levels are positively linked to testosterone levels in middle-aged men. Data from the MMAS have demonstrated that there is a strong, positive relationship between HDL and testosterone in men with cardiovascular disease (low total or free testosterone correlates with low HDL cholesterol) (31).

Recent work in the Rancho Bernardo, California population has shown that men with serum total testosterone levels in the lowest quartile (< 241 ng/dl) were associated with a higher risk (38%) of cardiovascular mortality, compared with those who have higher total testosterone levels, independent of age, obesity and lifestyle choices (33). In fact, those with low testosterone were 40% more likely to die (all-cause mortality) than those with higher levels. This is in contrast to what was found in the MMAS study where total testosterone levels were unrelated to all-cause mortality (34,35).

A meta analysis, published in 2007, of randomised trials that assessed the effect of exogenous testosterone on cardiovascular events, however, concluded that the inference that testosterone use in men is not associated with important cardiovascular effects was only weakly supported. Large randomised trials using men with and without cardiovascular disease and with cardiovascular end-points are needed to better assess the consequences of testosterone treatment on cardiovascular risk (36).

A recent study (2009) from Italy demonstrates that testosterone treatment in elderly patients with chronic heart failure improves insulin sensitivity and various cardiorespiratory and muscular outcomes (37).

In 2007, it was estimated that 23.6 million people, or 7.8% of the US population, had diabetes (38). Projections based on data from the National Health and Nutrition Examination Surveys (NHANES) show that by 2021 there are anticipated to be approximately 33 million people with diabetes in the United States, representing 13.5% of the population (39).

Low testosterone concentrations are known to occur in association with type 2 diabetes. However, clinicians have often not related low testosterone concentrations to clinical hypogonadism. The first attempt to measure free testosterone and to establish hypogonadism as a feature of male type 2 diabetes was made by Dhindsa et al. in 2004 (40). This has been confirmed in several other studies including the HIM study (41). In the HIM study, a diabetic man was approximately twice as likely to be hypogonadal compared with a non-diabetic man (18). Prevalence in diabetic men has been estimated at 3350% (18,40,42). With such a high prevalence, hypogonadism is a candidate for the most common complication of male type 2 diabetes. Analysis of gonadotropin levels demonstrates that the hypogonadism in type 2 diabetes is mostly hypogonadotropic (secondary) hypogonadism (40). There is no relation between the degree of hyperglycaemia and testosterone concentration (40,43).

C-reactive protein, a marker for systemic inflammation, has been found to be markedly elevated in patients with secondary hypogonadism and type 2 diabetes. The concentrations of C-reactive protein in these patients are twice as high as those in eugonadal type 2 diabetics, whose C-reactive protein levels are already elevated compared with non-diabetics. Such patients have also been shown to have mild anaemia, low bone mineral density (BMD) in the arms and ribs, and increased adiposity when compared with eugonadal type 2 diabetics (44,45). These features are similar to those of hypogonadal patients without diabetes. Another intriguing observation is that prostate-specific antigen (PSA), a marker for prostate cancer, is significantly lower in type 2 diabetics and this is related to their lower plasma testosterone concentrations (46). The clinical significance of this remains to be elucidated.

Interestingly, low testosterone concentrations predict the development of type 2 diabetes. Utilising data from the NHANES III survey, it was found that men in the lowest free testosterone tertile were four times as likely to have diabetes as those in the highest free testosterone tertile (47).

Type 1 diabetes does not seem to be associated with hypogonadism, suggesting that hypogonadism is specific to type 2 diabetes and not related specifically to hyperglycaemia (43).

Obesity amongst adult men had a prevalence of 33.3% in 20052006 according to the most recent NHANES review (48). An adult who has a BMI between 25 and 29.9 kg/m2 is considered overweight, whereas an adult who has a BMI of 30 kg/m2 or higher is considered obese. This is not a rigid rule as BMI does not directly measure body fat, so athletes, for example, may have high BMIs even though they are not overweight (49).

The health risks associated with obesity are well known, increasing the risk for type 2 diabetes, hypertension, atherosclerotic diseases and coronary heart disease. Obesity is strongly associated with type 2 diabetes: approximately 83% of diabetic patients are overweight or obese (50). Obesity is also associated with low total testosterone and reduced SHBG levels. There is an inverse linear relationship between total testosterone and BMI, and free testosterone concentrations also decrease with increasing BMI. There is an inverse relationship between serum total and free testosterone levels and visceral fat mass. Thus, the degree of hypogonadism is positively correlated to the degree of obesity in obese men (51,52).

A person with metabolic syndrome is defined as having central obesity in addition to any two of these four factors: hypertension ( 130/85 mm Hg), reduced HDL (< 40 mg/dl in males), raised triglycerides ( 150 mg/dl) or raised fasting plasma glucose ( 100 mg/dl)(53). It is considered a high risk for coronary heart disease (19,54). As the constituent elements of metabolic syndrome are themselves correlated with testosterone concentrations, it is perhaps not surprising that hypogonadism is also associated with the metabolic syndrome, as has been shown in a number of epidemiological studies (55,56).

Low testosterone levels are correlated with insulin resistance in both epidemiological and interventional studies, and this may be attributable to the effect of testosterone on adiposity. Low testosterone levels increase fat mass and decrease lean muscle, resulting in increased adipose tissue (52).

Adipose tissue affects testosterone levels by increasing the aromatisation of testosterone to estradiol, because the aromatase enzyme is concentrated in adipocytes. This reduces serum and tissue testosterone levels. The estradiol produced by aromatisation also provides negative feedback on the HPG axis, further reducing testosterone. Thus, adiposity potentially leads to hypogonadism, which itself promotes further adiposity. illustrates the main hypogonadal-obesity-insulin resistance connections and also includes other factors such as TNF- (an adipokine), which is elevated in obese males (42,51,57,58).

The interrelationship between hypogonadism and insulin resistance (after (42,51)). LH, luteinizing hormone. Low testosterone stimulates an increase in adiposity. Adipose tissue contains high concentrations of aromatase, which reduces testosterone concentrations by converting it to estradiol. The estradiol negatively feeds back on the HPG system, reducing testosterone production in the Leydig cells. Increasing adipose tissue increases insulin resistance, which negatively impacts the Leydig cells as well as inhibiting the release of luteinizing hormone (LH) via the release of adipokines (inflammatory cytokines) such as TNF-. Leptin, released in response to increased adiposity, also inhibits the release of LH via its effect on the release of gonadotropin-releasing hormone

However, it seems likely that testosterone may suppress insulin resistance independently of its effects on adiposity. The withdrawal of testosterone therapy in hypogonadal patients that had been stabilised on this therapy leads to an increase in insulin resistance within 2 weeks and prior to significant weight gain (59). A recent study showed that supervised diet and exercise increased testosterone levels in hypogonadal men with metabolic syndrome and newly diagnosed type 2 diabetes. In addition, a small dose (50 mg/day) of testosterone gel improved both glycemic control and insulin sensitivity over and above the improvements because of diet and exercise (60). The mechanism underlying the insulin sensitising effects of testosterone needs to be elucidated.

An important proviso to this discussion is that further research into the role of hypogonadism in obesity, metabolic syndrome and diabetes is required to gain a better understanding of the pathogenic mechanisms involved and that, at present, it is not known whether hypogonadism is the cause or the consequence of these conditions.

Osteoporosis is an under-recognised problem in men. Ten to twenty per cent of individuals with osteoporosis over 50 years old in the United States are men (25). Up to 13 million men are at increased risk because of low BMD and up to 2 million of these have osteoporosis (61,62). Men have almost 30% of all hip fractures and men are twice as likely to die in hospital than women after a hip fracture. Hip fracture incidence is low until after 75 years, when the risk increases exponentially. Vertebral fractures are also common, although they are only about half as common in men compared with women (63).

There are many suspected causes of osteoporosis, and the most frequent are corticosteroid use, Cushings syndrome, hypogonadism and excessive alcohol consumption. In a study of elderly men in a nursing home who have experienced hip fractures, 66% were hypogonadal (64).

Other common secondary causes are smoking, low calcium intake and vitamin D deficiency or insufficiency (61).

Various epidemiological studies in men have examined associations between testosterone and estradiol levels and BMD. Estradiol levels in men have been consistently and positively associated with BMD. Testosterone is also positively associated with BMD, but the relationship is weaker than that of estradiol (65,66).

Interventional studies have shown that testosterone replacement therapy in hypogonadal males increased spine BMD and trabecular connectivity (61,67). However, studies of testosterone therapy in men with osteoporosis are limited and none have used fractures as an end-point; so although there is significant evidence of an association between hypogonadism and osteoporosis, there is no established causal link between the two.

Testosterone levels are lower in men being treated with corticosteroids. Systemic glucocorticoids can reduce testosterone biosynthesis in the testis; in addition, glucocorticoids impact the HPG axis by inhibiting the release of LH (17,68). As a result, patients being treated with glucocorticoids for such chronic conditions as rheumatoid and osteoarthritic inflammation, skin inflammations, asthma, chronic obstructive pulmonary disease (COPD) and inflammatory bowel disease are at an increased risk of hypogonadism.

There have been some studies that suggest that COPD patients have a higher incidence of hypogonadism than the general population and that glucocorticoid treatment is only part of the reason. The pathophysiology of this remains unclear, but suggestions have been made that it might be connected with chronic hypoxia, and a systemic inflammatory response (68). A number of studies have shown that testosterone therapy can improve lean body mass and BMD and strength in hypogonadal men with COPD (17).

Long-acting opioids such as methadone, morphine sulphate, fentanyl and oxycodone for the treatment of chronic pain often result in opioid-induced androgen deficiency (OPIAD). In a casecontrol study of 40 cancer survivors it was found that 90% of those on opioid treatment were hypogonadal compared with only 40% of the control group (69). The mechanism for OPIAD is thought to involve suppression of GnRH release by the hypothalamus, thereby inducing secondary hypogonadism (17,70).

Apart from the effects of testicular cancers, which may have a direct impact on testosterone secretion, the prolonged radiation treatment, chemotherapy using antimitotic drugs or corticosteroids or pain treatment medications characteristic of cancer treatment are likely to induce hypogonadism (17). These drugs may induce Leydig cell dysfunction or germinal epithelial failure (71). The HPG axis may also be affected by androgen-, or ectopic adrenocorticotropin hormone-producing tumours, leading to secondary hypogonadism (17).

Androgen deficiency is strongly associated with AIDS wasting syndrome, and testosterone therapy in HIV-positive hypogonadal men increases lean body and muscle mass and perceived well-being, and decreases depression (7274). Approximately 2050% of HIV-infected men receiving highly active antiretroviral therapy are hypogonadal. While these prevalence levels may superficially appear similar to the background figures in the population, most studies are based on middle-aged populations. HIV patients with AIDS are younger and therefore, comparisons have to be carried out with appropriately age-matched controls.

The cause of this hypogonadism is probably as a result of a number of factors, including lipodystrophy induced by highly active retroviral medications; testicular atrophy caused by opportunistic infection; disruption of the HPG axis resulting from malnutrition; and the results of medications such as the antimycotic ketoconazole, which inhibits steroid biosynthesis (17).

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A practical guide to male hypogonadism in the primary care ...

This article was originally published here

J Diabetes Res. 2021 Dec 20;2021:1347588. doi: 10.1155/2021/1347588. eCollection 2021.

ABSTRACT

INTRODUCTION: To evaluate whether waist circumference (WC) or hyperglycemia is more closely associated with hypogonadism in middle-aged men. Research Design and Methods. This cross-sectional study analyzed male participants under 65 years old from the MJ Health Screening Center in Taiwan from 2007 to 2016. Basic patient characteristics with relevant parameters were obtained. We used the chi-square test to perform a correlation analysis for HbA1c and WC between participants with and without hypogonadism. A one-way ANOVA with post hoc Scheffes method was applied to compare the mean testosterone (T) among the HbAlc and WC groups (normal blood sugar with normal WC (NBSNW), abnormal blood sugar with normal WC (ABSNW), normal blood sugar with abnormal WC (NBSAW), and abnormal blood sugar with abnormal waist circumference (ABSAW)).

RESULTS: The 5,680 participants were divided into two groups based on the presence (n = 599) or absence of hypogonadism (n = 5,081), which was defined as total testosterone (TT) < 300 ng/dL. The mean TT of group NBSAW (443.71 220.59 ng/dl) was significantly lower than that of group ABSNW (506.64 191.08 ng/dl, p < 0.001). Moreover, the mean TT of group ABSAW (398.89 146.24 ng/dl) was significantly lower than that of group ABSNW (506.64 191.08 ng/dl, p < 0.001). The ORs after adjusting for BMI, TG, HDL, SBP, and DBP were statistically significant when comparing NBSAW vs. NBSNW (OR = 2.846; 95%CI = 2.266-3.575; p < 0.001), ABSNW vs. NDNW (OR = 1.693; 95%CI = 1.309-2.189; p < 0.001), and ABSAW vs. NBSNW (OR = 4.613; 95%CI = 3.634-5.856; p < 0.001).

CONCLUSION: The current study showed that WC should be the risk factor that is more closely associated with hypogonadism than hyperglycemia in middle-aged men.

PMID:34966822 | PMC:PMC8712173 | DOI:10.1155/2021/1347588

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Waist Circumference Is More Closely Associated with Hypogonadism than Is Hyperglycemia, Independent of BMI in Middle-Aged Men - DocWire News

This article was originally published here

Urologiia. 2021 Dec;(6):130-135.

ABSTRACT

COVID-19 is a new highly contagious infectious disease caused by the SARS-CoV-2. The World Health Organization (WHO) on March 11, 2020, has declared the novel coronavirus (COVID-19) outbreak a global pandemic. More attention is currently paid to the fact that men are more at risk for worse outcomes. In addition, SARS-CoV-2 can infect the testes, potentially affecting testosterone production, as well as having a negative influence on the reproductive potential. Our aim was to review the current concepts of the possible influence of testosterone levels on the pathogenesis of COVID-19 in men and to present the available data on the impact of COVID-19 on the structure and function of the testis. Based on the analysis of 72 articles using the MEDLINE database (PubMed), it can be concluded that testosterone is involved in the co-regulation of the synthesis of angiotensin-converting enzyme-2 and transmembrane serine protease-2, facilitating the penetration of SARS-CoV-2 into target cells and promoting easier infection in men. On the other hand, low testosterone levels increase the risk of cardiopulmonary complications. Hypogonadism appears to be an important unfavorable prognostic factor for the disease. Orchitis is a reported complication of COVID-19. Damage to testicular tissue is possible due to direct invasion by a virus, a secondary autoimmune reaction, hyperthermia and thrombosis of testicular microvessels. Prophylaxis of possible vertical and sexual transmission of infection is recommended. Despite the available data, further studies are required to assess the definite role of androgens in the course of infection and the influence of SARS-CoV-2 on male reproductive potential.

PMID:34967175

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Andrological aspects of new coronavirus infection Covid-19 - DocWire News

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The ExtenZe is a male enhancement pill and herbal blend of L-arginine, Yohimbe extract, horny goat weed, piper longum, ginger, zinc, pregnenolone, and folate. Unlike other supplements that use substantial doses, ExtenZe contains lower dosages of a large number of ingredients.

If you want to buy penis enhancement pills to increase nitric oxide production for penis enlargement, taking male enhancement supplements offered by Extenze is the best solution. This supplement improves erectile function as well as sexual pleasure.

The company claims that ExtenZe is the first line of defense against the small erect penis and low confidence. It improves the blood flow to your sexual organs and strengthens your erection. It will help if you consume the Extenze supplement once daily to experience its benefits.

ExtenZe Price: $45

Leading Edge Health is the producer of Pro Solution male enhancement supplements. The company considers this formula as the worlds top-rated male enhancement system. Pro Solution uses various ingredients such as Solidilin, Butea Superba, Momordica, Korean ginseng, cordyceps, amla, apigenin, and Arjuna to give you a healthier sex drive, firmer erections, more intense orgasms, reduce stress, and promote ejaculation control.

Also, manufacturers offer a 67-day refund policy and a 100% satisfaction guarantee.

Pro Solution Price: $60

Hyper Male Force claims to increase penis length permanently like Savage Grow Plus and Male Dominator supplements in this list. The manufacturers of this supplement claim that Hyper Male Force can increase the length of the penis within a few days by targeting critical areas in your brain.

The Hyper Male Force supplement is formulated by Dr. Kleimer, who is a well-known penis reconstruction specialist. He used his medical expertise and vast experience in developing hyper male force male enhancement supplements.

He added 19 ingredients, including ashwagandha, Rhodiola Rosea, L-theanine, hawthorn, and skullcap.

Hyper Male Force Price: $59

Male Dominator is a natural male enhancement pill that contains 14 powerful ingredients to increase penis size by 4 inches in just 30 days. Some of the ingredients found in Male Dominator are Saw Palmetto, Cayenne, Epimedium Sagittatum, Damiana Leaf, Muira Puama, Oat Straw, and Inosine.

The makers of the Male Dominator supplement claim that it permanently increases your penis size and supports testosterone production, blood flow, and energy levels.

Male Dominator Price: $69

There are many male enhancement supplements available today, each claiming to improve sexual performance and sex drive. However, not all supplements are effective. To help you pick the best supplement, we have made a list of the 11 best male enhancement pills according to the following ranking factors.

Many male enhancement supplements contain natural ingredients and herbs, while others include dangerous substances that cause side effects. We rank supplements that use science-backed ingredients with proven safety and efficiency.

Along with adding quality ingredients, it is also necessary to add the correct dosages of ingredients. An average adult needs substantial doses of ingredients to gain the required benefits. We have ranked those male enhancement pills that contain clinically significant dosages of effective ingredients.

There is no clinical evidence and trials that prove the efficacy of male enhancement pills; however, some clinical studies indicate the benefits of ingredients added in male enhancement pills. Most supplements in our list contain active ingredients in the exact dosages as used in clinical studies.

You can get male enhancement pills in different price ranges from $10 to $100, but we rank the products that offer good value for the money. In our list, you will find male enhancement pills in your budget whether you want to spend a few dollars or more, and all of these products offer good value for their cost.

Checking a companys reputation is one of the most crucial ranking factors. Some companies have a long-standing record of producing high-quality products, while others make cheap male enhancement pills to earn a few bucks.

We rank those companies that are transparent in disclosing ingredients, dosages, benefits, and side effects of the product. Also, the companies with a long-standing record of producing effective supplements are on our list of best male enhancement pills.

Many companies advertise unrealistic and anatomically impossible benefits. They claim that their male enhancement pill can increase the length of the penis permanently. However, this is not possible. We rank the supplements that advertise actual benefits and are effective in improving your sexual drive.

These are the ranking factors that we used to rank the 11 best male enhancement supplements.

According to science, some natural ingredients can improve male sexual performance, libido, and energy levels. It can also help the body to produce more testosterone and increase blood flow to support erection.

With increasing age, the testosterone levels in the body drop, developing the chance of erectile dysfunction. The blood flow also decreases. About 40% of males above 40 years of age have erectile dysfunction. A 2013 study found that 26 percent of males seeking treatment for erectile dysfunction were above 40 years of age. These studies show that erectile dysfunction is more common in aged males. Therefore, many male enhancement supplements specifically cater to age-related performance issues.

Yohimbe, a natural herb extracted from Pausinystalia Yohimbe, has been used as traditional medicine for sexual issues in areas of west Africa. This herbal extract is added to many male enhancement pills, including ExtenZe. According to the research, Yohimbe blocks alpha-2 adrenergic receptors and increases the production of nitric oxide. Thus, increasing blood flow to the penis and improving erection in males.

Some male enhancement pills contain black ginger extract. A study in 2016 suggests the effects of black ginger extract on improving physical fitness performance and muscular endurance.

Several popular male enhancement pills contain the amino acid L-arginine. A few studies prove the effects of 5000 mg arginine on increasing blood flow. However, other studies suggest L-arginine be ineffective for treating erectile dysfunction. Bodybuilders and athletes consume L-arginine before and after the workout to boost their performance.

Horny Goat Weed, another popular ingredient found in many male enhancement pills, contains icariin. Icariin blocks phosphodiesterase type 5 that stops the widening of arteries in the penis to get an easy erection. Studies on rats also suggest the effects of horny goat weed in improving erectile dysfunction symptoms in rats.

Furthermore, research shows that males deficient in zinc have lower testosterone levels than those who get the recommended daily dose of zinc. A study proves that about 17.3% of the population that suffers from zinc deficiency has low testosterone and hypogonadism. In another study, researchers found that 30mg of zinc intake increases the level of testosterone. However, there are no extra benefits of zinc supplements if you are already taking recommended daily doses.

Vitamin D is the main ingredient of male enhancement supplements. You can get vitamin D from dairy products, multivitamins, and other foods. Only 20 to 30 minutes of sunlight exposure can also raise vitamin D levels in your body. Researchers gave vitamin D supplements to a group of people in a study, and their testosterone levels increased by 20%. Another study conducted in 2011 concluded that vitamin D3 increases bioactive and free testosterone levels by 25%.

Tribulus Terrestris is a plant-based extract used in multiple male enhancement supplements. It has been used as an aphrodisiac for centuries. The research found that three months of Tribulus Terrestris supplement boosted testosterone production by 13%. During these three months, males also experienced fewer symptoms of erectile dysfunction. Another study found an improved sexual drive in women taking Tribulus Terrestris. With 7.5mg of Tribulus Terrestris extract intake per day, women also experienced better desire, lubrication, arousal, and satisfaction.

Some male enhancement supplements claim to improve semen volume, sperm production, and orgasm intensity.

These pills contain zinc, fenugreek, ashwagandha, maca root, and D-aspartic acid. Several studies suggest the benefits of all these ingredients. One study shows that a daily intake of 500mg of fenugreek increases free and total testosterone levels in the body. Another study in 2012 found that D aspartic acid increases sperm concentration and motility.

Many male enhancement pills in our list contain ginseng. Asian Ginseng is an herb native to southern China and Korea. Ginseng raises luteinizing hormone, which signals the body to form more testosterone.

Research states that ginseng increases the nitric acid in the blood and aids in reducing body fatigue, boosts mood, improves memory, and improves the quality of sleep. Another research proves that the ginseng herb increases testosterone, luteinizing hormone, DHT, and adrenocorticotropic hormone.

Science suggests that one of the best male enhancement formulas is the daily workout. Regular exercise for only 20 to 30 minutes raises blood flow to the penis and improves sexual performance. Studies show that slim males have better sexual performance than overweight males.

Overall, no research proves the efficiency of male enhancement pills, and the claims that these supplements can permanently enlarge the size of the penis are invalid. However, scientific evidence proves the effects of herbs, vitamins, and minerals in improving sexual function. Therefore, by picking male enhancement pills containing science-backed ingredients, you can boost your testosterone levels and sexual performance.

FDA does not approve male enhancement supplements. Therefore, most male enhancement pills do not undergo lab testing or clinical trials before being sold to consumers.

Moreover, many male enhancement pills manufacturing companies are also not transparent in showing the ingredients and dosages. Consuming pills with unknown ingredients can be hazardous for you. We recommend you check each supplement you take; if the elements have GRAS status, it is safe to use at standard dosages.

Also, always check for the manufacturers reputation before making any purchase and never exceed the recommended dose of the supplements. On exceeding the amount, you may feel indigestion, stomach discomfort, dizziness, and other symptoms.

Male enhancement supplements contain different types of ingredients, each with different recommended dosages.

As per science, a daily intake of 30 mg zinc is associated with normal testosterone levels. While other studies suggest recommended daily intake of zinc as 11 mg per day.

Similarly, some studies use 1000mg of Tribulus Terrestris, and others use about 5mg of this herb.

We recommend you follow the dosage instructions on the label of the male enhancement supplement you consume to avoid side effects.

Some of the top natural ways to improve male sexual performance are:

Studies suggest growth hormone production is most noteworthy during sleep. If you get enough sleep daily, you will not face hormonal imbalance. Getting 8 to 9 hours of uninterrupted sleep per day helps maintain hormone levels in the body. Also, good and deep sleep reduces stress and anxiety, supporting your sexual performance.

Eating a balanced diet is crucial for health and wellness. You must add vegetables, vitamins, fruits, minerals, protein, zinc, vitamin D, and other essential nutrients to your diet. If your body does not get all the necessary elements for producing testosterone, you cannot enjoy healthy sex. Also, try to add foods rich in omega 3 fatty acids such as avocados, tuna, salmon, and olive oil to your diet.

Smoking impacts badly on your heart and everyday wellbeing. Quitting smoking will raise blood flow in the body, improve cardiovascular health, and support all other body functions.

Weight lifting and strength training are some of the best ways to raise hormones such as testosterone in the body. A study shows, a strength training program for four weeks can increase the testosterone levels in the body. Exercises such as squats, deadlifts, and bench presses that target big muscles significantly influence testosterone levels. It also supports you in reducing weight, thus improving sexual functions.

High-intensity interval training and sprinting are the best workouts for raising testosterone levels and reducing weight. This workout requires an individual to exert maximum energy for a short time. If you can spend 10 to 20 minutes sprinting daily, you can enjoy high testosterone levels and improved sexual performance.

Stress increases cortisol levels, accumulates fats, and reduces testosterone levels in the body. Lowering anxiety and stress levels is vital to boost testosterone levels and increase your sexual performance. You can decrease your anxiety with the help of meditation, brisk walking, reading books, and other methods. Reducing stress will improve your bedroom performance.

Consult your doctor if you are anxious about your sexual function and none of the natural remedies or supplements improve your condition. We also suggest you talk to your doctor before starting any male enhancement pills.

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Reviewing the Top 5 Best Male Enhancement Pills in 2022 to Buy - The Daily World

OverviewWhat is hypogonadism?

Hypogonadism occurs when sex glands called gonads produce little, if any, sex hormones. It affects teenagers and adults of all genders. The condition causes a low sex drive or libido. Hypogonadism is sometimes called gonad deficiency.

Testicles (testes) in the male reproductive system produce testosterone, the main male hormone. Hypogonadism in men is the result of low testosterone.

Ovaries in the female reproductive system produce estrogen, progesterone and testosterone. Women with hypogonadism are often low in estrogen and progesterone.

Two glands in your brain, the hypothalamus and pituitary, send signals to sex glands. These signals tell your body to make sex hormones. When you have hypogonadism, something within the brain or sex glands interferes with hormone production.

Healthcare providers look at the cause to determine if hypogonadism is:

Starting in their late 40s or 50s, everyone has lower amounts of sex hormones. As a result, sex drives decrease. These changes are expected. They arent necessarily a sign of hypogonadism. Younger people who have little to no interest in sex may have hypogonadism.

Conditions and treatments that raise the risk of primary hypogonadism include:

Risk factors for secondary hypogonadism include:

It isnt clear why some people develop hypogonadism. For unknown reasons, a problem with the sex glands or brain affects the bodys production of sex hormones.

Hypogonadism symptoms vary depending on the cause and a persons gender. Teenagers may get a diagnosis of secondary hypogonadism when they dont start puberty on time. For example, teen girls with hypogonadism may not get their periods or develop breasts. Boys might not grow facial hair or have underdeveloped testicles.

Adults may experience a low sex drive (sexual dysfunction), as well as hair loss and hot flashes. Other common complaints include fatigue and difficulty concentrating.

Signs of hypogonadism in females include:

Signs of hypogonadism in males include:

Your healthcare provider will assess your symptoms and perform a physical exam. Women may also have a pelvic exam.

You may get one or more of these tests:

Hypogonadism can cause:

Hypogonadism treatments vary depending on the cause. For primary hypogonadism, hormone replacement therapy can raise hormone levels. Men may have testosterone therapy, while women may have estrogen and progesterone hormone therapy. These treatments come in gels, implants, pills, shots and skin patches. Female hormone therapy may slightly increase a womans risk of uterine (endometrial) cancer, blood clots and strokes.

If a pituitary gland problem like a tumor causes secondary hypogonadism, you may need medication, radiation therapy or surgery.

Primary hypogonadism can be a chronic condition that requires ongoing treatment. If you stop hormone replacement therapy, hormone levels can plummet, causing symptoms to return.

If a treatable condition like a pituitary gland tumor causes hypogonadism, hormone levels should return to normal after your healthcare provider treats the tumor.

You should call your healthcare provider if you experience:

You may want to ask your healthcare provider:

A note from Cleveland Clinic

Low sex hormone levels can negatively affect your physical and mental health. Teenagers may be self-conscious about their underdeveloped appearance. Many adults experience some disinterest in sex as they get older. But a sudden drop or complete halt to any sexual desire may indicate hypogonadism. Dont be embarrassed to tell your healthcare provider whats going on (or not going on) in the bedroom. Treatments can get hormone levels back in the normal range.

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Low Sex Drive (Hypogonadism): Symptoms, Treatment

This article was originally published here

Am J Mens Health. 2021 Nov-Dec;15(6):15579883211058606. doi: 10.1177/15579883211058606.

ABSTRACT

It has been suggested that hypogonadism increases the risk for inguinal hernia (IH). The aim of this study was to investigate any association between androgen deprivation therapy (ADT) for prostate cancer and increased risk for IH. The study population in this population-based nested case-control study was based on data from the Prostate Cancer Database Sweden. The cohort included all men with prostate cancer who had not received curative treatment. Men who had been diagnosed or had undergone IH repair (n = 1,324) were cases and controls, where not diagnosed, nor operated on for IH, matched only on birth year (n = 13,240). Conditional multivariate logistic regression models were used to assess any temporal association between ADT and IH, adjusting for marital status, education level, prostate cancer risk category, Charlson Comorbidity Index, ADT, time since prostate cancer diagnosis, and primary prostate cancer treatment. Odds ratio (OR) for diagnosis/repair of IH 0 to 1 year from start of ADT was 0.5 (95% confidence interval [CI] = [0.38, 0.68]); between 1 and 3 years after, the OR was 0.35 (95% CI = [0.26, 0.47]); between 3 and 5 years after, the OR was 0.39 (95% CI = [0.26, 0.56]); between 5 and 7 years after, the OR was 0.6 (95% CI = [0.41, 0.97]); and >9 years after, the OR was 3.68 (95% CI = [2.45, 5.53]). The marked increase in OR for IH after 9 years of ADT supports the hypothesis that low testosterone levels increase the risk for IH. The low risk for IH during the first 8 years on ADT is likely caused by selection of men with advanced cancer unlikely to be diagnosed or treated for IH.

PMID:34918553 | DOI:10.1177/15579883211058606

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Androgen Deprivation Therapy and the Risk for Inguinal Hernia: An Observational Nested Case Control Study - DocWire News

Having low testosterone levels can prove to be a serious problem. This hormone is well-known because it plays a critical role in sexual desire. It also controls a number of important bodily functions, and not only during puberty. For example, testosterone is involved in muscular development. As a result, it is in charge of your physical growth above anything else.

As a result, regardless of gender, healthy production of the hormone is critical for your well-being. It is natural for testosterone levels to drop as men age, but fortunately, there is a way to break out from such a vicious cycle. You can rely on testosterone boosters to help you when you need them.

These products are being sold on tens of thousands of authority websites. You can easily come across a dozen with a quick web search. However, many of these sites may lead you astray. They have a reputation for relying on sponsorships and the like. As a result, doing your research is the best way to make an informed decision. This is especially true when it comes to testosterone boosters and other such medications.

To come up with this roundup, we looked at a wide variety of options, and our results are based on extensive, non-biased testing. No argument is based on a whim since all evidence is gathered from reliable sources, including customer reviews and clinical test reports.

After that, we were able to compile a roundup of the best testosterone boosters. These are the products that effectively stand out from the crowd and boost your bodys testosterone production naturally. These are also made from ingredients that havent been linked to any adverse effects. In a nutshell, these are the safest and most effective testosterone boosters available on the internet. We present the top five testosterone boosters based on these factors and expectations.

TestoPrime is a creation of Wolfson Brands (UK) Limited. The brand developed this supplement over five years ago. It quickly gained traction on the market, and even today, it stays at the top of our list. Such occurrences arent random, though. The company invests its resources in third-party testing to ensure that they create the best testosterone booster possible.

TestoPrime utilizes a formula that naturally rejuvenates your body. It results in gradual changes without sudden stress. A daily dose of only four TestoPrime capsules will increase the supply of testosterone to the bloodstream. In turn, the conversion of fat to energy will hasten. Also, due to the vitamin content, TestoPrime allows for testosterone retention, improving the blood flow and your sex drive.

The product uses only 12 organic ingredients, including minerals, vitamins, and extracts. It does not contain chemical additives or allergens, and it is also non-GMO. Customers report significant improvements within the first 20 days of use. The benefits include fat loss, increased muscle strength, and a better physique.

Visit the Official Website of TestoPrime

Since TestoPrime is a 100% natural product, you dont need a special prescription for it. You can simply go to their website and buy the booster whenever you want one. As for feedback, TestoPrime boasts an almost perfectly positive review score.

This popular testosterone booster comes from Muscle Club, a U.K.-based company. Testogen can combat the declining testosterone levels even in elderly users. Also, unlike certain artificial treatments or illegal anabolic boosters, its an entirely natural compound. So, it provides a simple and viable alternative to invasive hormonal therapy.

Testogens formula comprises 11 natural ingredients to boost your testosterone levels. In addition, it features a carefully selected mix of vitamins and minerals. Its primary ingredients are D-aspartic acid, fenugreek, and zinc. These elements also act as testosterone-preserving agents, so they postpone their conversion into estrogen.

Visit the Official Website of Testogen

Zinc protects cells against oxidative stress, according to a 1996 study. Oxidative stress, according to another study, is common to the male reproductive system and testicular tissue. Yet, antioxidants can help fight against this imbalance, thus improving sperm production.

Testogen also contains Vitamin D3. This element increases the free testosterone levels. Next, the body will use it to boost your energy levels, sex drive, muscle growth, etc.

The manifestation of these benefits varies from person to person. Some people begin to notice positive changes in the first week. For others, it may take longer. Testogens website recommends a dose of 4 capsules per day for best effect.

According to Crazybulks website, Testo-Max is an effective alternative for artificial testosterone boosters. Plus, it is an entirely safe and legal supplement. Each capsule contains various pure and natural ingredients. Among others, there is vitamin D3, magnesium, d-aspartic acid, etc.

Testo-Maxs blend features potent and effective elements. For instance, d-aspartic acid is vital in restoring hormonal balance in resistance-trained men. Its also proven to increase testosterone production by 45% in just a few weeks.

On the other hand, magnesium boosts testosterone levels by 26%, according to clinical studies. However, this is only one of the ingredients, and they all combine in Testo-Max. Finally, intake of vitamin D is always welcome, even though sunlight is its most consistent source. According to an NCBI study, low vitamin D levels in males reflect low testosterone levels.

Visit the Official Website of Testo-Max

On CrazyBulks website, there is sufficient information about this product, along with frequently asked questions. Hence, visitors can easily find their way and place an order or complaint. Thats why Testo-Max is rated so highly on popular review sites and forums. Its a well-rounded, affordable product thats also easy to find.

As we age, our bodies cease to function with the same efficiency. This slowing down translates into reduced testosterone secretion. In turn, well feel a decline in our energy levels. That is not a good thing in the slightest: it means reduced physical performance and libido. But the negatives wont stop there. Another common symptom is sudden weight gain. Also, according to recent studies, the average man loses 1% of their testosterone store every year, beginning at age 30.

The decline of testosterone levels can bring about a host of problems, even if it is a naturally occurring facet of life. Fortunately, the Prime Male natural testosterone booster offers a way to contradict this body tendency.

Prime Male is a combination of several organic ingredients that help you get back on track. Some of these substances include ashwagandha extract, magnesium, and luteolin (found in citrus fruit). They work in tandem to reinstitute the hormonal balance. Also, they govern the percentage of free (unbound) testosterone in your body.

The body is then free to use free testosterone for many purposes, including fat loss, building lean muscle, and boosting sexual drive. Finally, the Prime Male supplement card breaks down the percentage composition of the ingredients used in the mix. So, each customer will know exactly how it works.

Visit the Official Website of Prime Male

TestRX, made by Leading Edge Marketing Ltd, is a natural testosterone booster formulated to replenish dwindling testosterone levels. Its ingredients include vitamins like K2, B6, and D3, various minerals, and other plant-based ingredients. So, its a perfectly safe mixture suitable for any adult to intake.

If one follows the instructions, TestRX will soon build up in their bloodstream and cause beneficial changes. By steadily increasing the testosterone level, TestRX elicits a notion of youthfulness within the body. So, its a confidence booster that also helps with muscle growth and your sexual stamina.

TestRXs trifecta of zinc, magnesium, and d-aspartic acid (DAA) is indeed famous for its efficacy. This formula is proven time and time again to be completely risk-free, too. Hence, its not an experiment but more of a carefully measured blend.

According to a study, zinc helps in the preservation of testosterone and boosts all muscle-building processes. The supplements official website also points to another aspect: the noticeable increase in energy levels. With that, TestRX may manage to mimic the effects of some popular energy drinks.

Visit the Official Website of TestRX

Another essential element is magnesium. As studies indicate, it can boost athletes performance and improve testosterone levels. Finally, the fenugreek extracts have a similar effect on the immune system, adding even more to the overall effectiveness of TestRX.

Leading Edge Marketing Ltd. recommends a cycle of two capsules of TestRX in the morning and two before dinner. Thats the best way to allow this formula to dissolve into your bloodstream. Also, this supplement is entirely risk-free, so youll be able to order it without a note from your physician.

You can buy TestRX on their official website. However, its prices are constantly changing with current demand. So, you might run into some good discounts, too.

To develop this list, we started by searching for the most popular testosterone boosters available today. Since these products are fairly sought-after, the list had many, many entries at that point. So, we proceeded by digging deeper into their ingredients and effectiveness.

We looked at the history of the brands and how they source their ingredients. Any past reports of foul play or overwhelmingly negative feedback resulted in the elimination of that product. Instead of those, we focused primarily on risk-free products.

This multi-layered process allowed us a detailed insight into this landscape. Finally, after evaluating all that data, we came up with a list of the five best testosterone boosters you can order today.

Some of the criteria we considered when trimming down the list of testosterone boosters include:

Of course, customers may have specific relationships with some elements. As a result, its critical to understand whether a product could cause an allergic reaction. Finally, those substances determine the products overall effectiveness. Stress prevention, fat burning, higher energy levels, endurance, muscle strength all such aspects depend on them.

When suffering from subnormal testosterone levels, one must promptly take action. Hormonal imbalance is a serious condition that will impede your life in a significant way. Worst of all, it is a naturally occurring part of the aging process. So, even if it isnt an after-effect of a disorder, it can cause problems. Either way, it demands your attention.

From a medical standpoint, the usage of testosterone boosters is among the safest remedies for such predicaments. This is because theyre intricately made with heavily researched formulas. Also, they dont pose added stress to the body-rather, theyll elicit a more gradual and beneficial change.

However, given how many similar products you may come across online, a more critical eye is needed. Knowing when to give a brand a hard pass is a type of skill. Plus, its a decision best made early on before anything goes south.

Hence, one should keep in mind some essential pointers while researching for a testosterone booster. Heres what to look out for:

Companies will do their best to draw your attention. Theyll use clever catchphrases that sound familiar or present some miracle effects. Yet, when it comes to testosterone boosters, one should be 110% clear on what to expect. Luckily, the most reputable brandslike the five mentioned abovego far and beyond to remain in the spotlight.

In other words, if a brand is well-known, its earned that status the hard way. In todays world, word of bad results spreads faster than light. Every single negative review tends to stick to a product for years to come. Therefore, trusted brands mustve done a lot of things right and not just in a few months. Theyve climbed there over a much longer span, all while working hard not to drop the ball.

Also, popular products carry multiple efficiency evaluations. The companies go through much scrutiny before the green light. And even afterward, they are held accountable for all cases. Helpful customer support service is only one aspect of this, but one that might indicate a caring company.

Its no secret that companies are ever-evolving when it comes to scientific research. Especially for testosterone boosters, there is a steady stream of inventions that push the industry forward. However, one should keep track of all this. It is advisable always to check what the box states for its primary ingredients.

Naturally, the presence of chemical additives and preservatives should be a definitive no. Artificial steroids have a high chance of causing adverse side effects, and thats only the best-case scenario. As a result, it is prudent to ensure that the product you are about to purchase is entirely pure and natural.

On a related note, consider your medical history at all times. If theres a history of blood-related conditions, please remember to consult with an expert first. Pre-existing disorders might spiral further still if you were to take chances. For example, they can over-increase the red blood cell production, thus escalating the risk of a heart attack. Another consequence is an enlarged prostate, making urination painful and difficult.

Brands with license and approval from government-sanctioned boards are obligated to meet specific standards. Hence, you can rest sure that they adhere to rigorous manufacturing practices.

As a result, those products carry a lower risk factor. So, buying from FDA-approved companies should be a priority. Make sure to develop this instinct before opting for a testosterone booster.

Trusted brands incorporate fair refund policies and money-back guarantees. They back up all of their products, which instills a sense of security within the buyer. By navigating these rules, youll never have to puzzle out what to do next. If a product proves inefficient, you should file a complaint and get refunds. Hence, make sure that such a development is part of the plan right at the start.

Buy products from companies that use clinically-proven ingredients and are

A 2015 FDA study indicates that testosterone boosters may or may not cause a sporadic increase in testosterone levels in men. However, most of these supplements contain zinc and B vitamins which are natural energy boosters. They also improve the biological availability of testosterone in the blood.

Many of these testosterone boosters contain aspartate, magnesium, mono-methionine aspartate, or ZMA. Those ingredients may enhance exercise performance and post-exercise recovery. In short, most testosterone boosters are herbal testosterone supplements.

The best testosterone boosters are natural supplements that enhance testosterone and related hormones in your body. Many of these boosters work by blocking the supply of estrogen (the female sex hormone) and its effects on the male body.

For patients suffering from hypogonadism, testosterone boosters can indeed turn their lives around. These products are built to increase your energy levels and libido.

Some reports indicate positive mood swings and a stronger sex drive. Usually, this goes hand-in-hand with steady muscle growth. In addition, testosterone boosters can quell problems associated with erectile dysfunction too.

Above all else, however, take note if youre suffering from any kind of heart condition. If you doubt whether it would be OK to start taking testosterone boosters, dont hesitate to see your doctor ASAP.

According to studies, resistance exercises such as weight lifting have a tremendous effect on testosterone production in men. Surprisingly, studies have found only a minor increase in the hormone in women who do a similar exercise.

High-intensity interval training also produced good results in men. In comparison, such an approach could significantly increase testosterone levels in far less than 45 minutes.

Some testosterone boosters, especially those bought over the counter (OTC), may be safe when consumed in moderation. They also come with a unique set of beneficial side effects.

However, they cannot permanently guarantee that your testosterone level will always remain high. The best way to stay safe is to sift through the ingredients. Plus, make sure to follow the doctors orders, and focus on the FDA-approved testosterone supplements.

The best testosterone boosters are herbal supplements as they do not contain harmful anabolic steroids, although there is evidence of the contrary. Most notably, athletes who use the best testosterone booster supplements to boost muscle mass and improve performance. However, when things go too far, there come risks related to kidney or liver damage.

Healthy, natural boosters like the ones discussed in this article can help you achieve the desired hormonal balance. Yet, dont think of them as a lifelong therapy solution. Instead, just take things one step at a time and do frequent re-checks.

So, buying testosterone boosters from verified sources is still the best way to go. Such testosterone boosting supplements will most likely provide you with a boost in testosterone production.

Testosterone levels tend to decrease with age. According to American Urological Association studies, about 2 out of 10 men in their 60s suffer from low testosterone. The number increases to 3 out of 10 men in their 70s and 80s.

A blood test is used to determine the testosterone level in your body. In men, a range of symptoms appears when testosterone levels fall below normal. If that happens, it may result in slower sex drive, hair loss, decreased energy levels, weak erections, sudden mood changes, etc.

On average, a mans testosterone peaks at the age of 20. Then, in the next few years, the levels move to a gradual decline. Experts believe that the healthiest men have testosterone levels between 400 to 600 ng/dL. Measures severely outside these limits point to a hormonal disorder.

However, signs of low testosterone become more apparent after the age of 30. A decrease in libido often accompanies it, leading most men to lose confidence in that aspect. While the reasons may simply accompany older age, this pattern may not be universal. In truth, many factors contribute to erectile dysfunction in men.

At first, youll probably notice your skin getting thicker. This is because your pores will become larger, resulting in a more oily appearance. Also, you might start to sweat more often. In tandem with this, the odors of your urine and sweat might change, too.

Following all this, a change in your emotional state is expected. You may start to develop a narrower range of feelings. However, you should generally enjoy a more positive mood. Studies confirm that an increase in testosterone affects your temper.

Finally, increased testosterone may improve your gym performance and age-related erectile dysfunction. Your healthy testosterone levels & energy levels will probably increase as well.

There are several ways to improve testosterone in men naturally. One of the most common and evidence-based methods is resistance training. By including weight lifting and other physical activities in your daily routines, youll experience a significant jump in testosterone levels.

An improved diet of more protein, carbs, and healthy fats can help boost testosterone levels, too. We recommend a diet based solely on whole foods because they contain larger amounts of testosterone-boosting nutrients.

Furthermore, high-stress levels can elevate the hormone cortisol, according to some studies. These unnatural amounts of cortisol in the bloodstream can rapidly deplete your testosterone store.

Also, you can take advantage of the sun to boost your vitamin D supply. Several studies have shown that vitamin D is capable of working as a natural testosterone booster. You can also avoid estrogen-inducing compounds commonly found in junk food. To do so, one might have to change their unhealthy eating habits, though.

Finally, you can opt for any one of the five best testosterone boosters featured on our list. In doing so, youll end up supporting the other methods mentioned here. Either way, they all function even better when combined.

As men age, their testosterone level is expected to decline naturally. It is a fact of life that likely wont be avoided. And when it takes a swing, youll probably notice its benefits. They often include lower overall energy, reduced muscle mass, unstable mood, and difficulty in weight loss.

These changes can occur even if you follow a healthy diet and workout routine. So, even the most disciplined of us suffer as a result of this. Regardless, theres a solution fit for everyone. Testosterone boosters are a smooth path towards hormonal balance, and the right testosterone boosting supplements are entirely natural and clinically tested.

Lastly, if you have any pre-existing conditions, make sure to consult your doctor before choosing a testosterone booster. These products can affect many critical bodily functions, and you wont want to test your luck there.

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5 Best Testosterone Boosters to Increase Testosterone Levels in 2022 - Us Weekly

Alternative names for male hypogonadism

Testosterone deficiency syndrome; testosterone deficiency; primary hypogonadism; secondary hypogonadism; hypergonadotrophic hypogonadism; hypogonadotrophic hypogonadism

Male hypogonadism describes a state of low levels of the male hormone testosterone in men. Testosterone is produced in the testes and is important for the formation of male characteristics such as deepening of the voice, development of facial and pubic hair, and growth of the penis and testes during puberty. Gonadotrophin-releasing hormone, made in the hypothalamus, stimulates the pituitary gland to produce luteinising hormone and follicle stimulating hormone (gonadotrophins). The gonadotrophins then act on the testes causing them to produce testosterone.Low levels of testosterone can occur due to disease of the testes or from conditions affecting the hypothalamus or pituitary gland. Men can be affected at any age and present with different symptoms depending on the timing of the disease in relation to the start of puberty. In some cases, it can be difficult to tell if there is a true deficiency of testosterone, particularly when the levels are in the borderline range.

Male hypogonadism can be divided into two groups.Classical hypogonadism is where the low levels of testosterone are caused by an underlying specific medical condition, for example Klinefelter's syndrome, Kallmanns syndrome or a pituitary tumour.Late-onset hypogonadism is where the decline in testosterone levels is linked to general ageing and/or age-related diseases, particularly obesity and type 2 diabetes.It is estimated that late-onset hypogonadism only affects about 2% of men over the age of 40.

There are two types of classical male hypogonadism primary and secondary.Primary hypogonadism occurs when the low level of testosterone is due to conditions affecting the testes.Primary hypogonadism is also referred to as hypergonadotrophic hypogonadism, whereby the pituitary produces too much luteinising hormone (LH) and follicle stimulating hormone (FSH) (gonadotrophins) to try and stimulate the testes to produce more testosterone. However, as the testes are impaired or missing, they are not able to respond to the increased levels of gonadotrophins and little or no testosterone is produced. In some patients with primary hypogonadism, testosterone levels may be within the normal range, but the increased LH and FSH indicates that the pituitary gland is trying to compensate for a deficiency and treatment may still be needed.

Examples of conditions affecting the testes, which lead to primary gonadal failure, include:

Secondary hypogonadism results from conditions affecting the function of the hypothalamus and/or pituitary gland.It is also known as hypogonadotrophic hypogonadism due to low levels of LH and FSH resulting in decreased testosterone production.Secondary hypogonadism often occurs as part of a wider syndrome of hypopituitarism.Examples of causes can include:

The signs and symptoms depend on the stage at which the patient presents with hypogonadism in relation to sexual maturity.If testosterone deficiency occurs before or during puberty, signs and symptoms are likely to include:

Around the time of puberty, boys with too little testosterone may also have less than normal strength and endurance, and their arms and legs may continue to grow out of proportion with the rest of their body.

In men who have already reached sexual maturity, symptoms are likely to include:

As some of these symptoms (e.g. tiredness, mood changes) can have multiple causes, diagnosis of male hypogonadism may sometimes get missed initially.

Male hypogonadism is more common in ageing men. The levels of testosterone in men start to fall after the age of 40. It has been estimated that 8.4% of men aged 5079 years have testosterone deficiency.Male hypogonadism is also linked with type 2 diabetes: approximately 17% of men with type 2 diabetes are estimated to have low testosterone levels.

Male hypogonadism does not run in families.There are genetic causes of hypogonadism, which include Klinefelters syndrome and Kallmanns syndrome; however, these conditions occur sporadically, they are not inherited from the parents.

A detailed medical history should be taken.In particular, it is important to find out if virilisation (development of normal male characteristics) was complete at birth, whether the testes descended and to see if the patient went through puberty at the same time as his peers. The patient should be thoroughly examined and the presence and size of the testes recorded, and whether they are correctly positioned in the scrotum.

Many of the symptoms of male hypogonadism are non-specific and can be caused by a range of conditions. Therefore, when diagnosing hypogonadism, it is important that biochemical tests are performed to assess the levels of testosterone in the blood to confirm diagnosis. Blood tests will be carried out to measure testosterone levels.The blood sample should be collected preferably at 9 a.m. (this is because levels of testosterone change throughout the day) and in the fasting state (because eating can lower testosterone leves). The blood test can can be carried out as an outpatient appointment. If the result of the first test shows a low level of testosterone, the test should be repeated after two or three weeks to confirm the result. Other hormones are also tested along with the second blood sample. These hormones include luteinising hormone, follicle stimulating hormone and prolactin (produced by the pituitary gland).The results of these blood tests will help distinguish between primary (low testosterone and high gonadotrophins) and secondary (low testosterone and normal or low gonadotrophins) hypogonadism.Testosterone is carried around the blood stream by a protein called Sex Hormone Binding Globulin (SHBG). SHBG is often checked at the same time as testosterone as it makes it easier to interpret whether there is a true deficiency. In patients with obesity and type 2 diabetes, SHBG is often low which can make the testosterone level appear lower than it really is.

Depending on the findings of the above tests, other investigations may be carried out. These include: a bone densitometry test to assess the impact of testosterone deficiency on bone; semen analysis; genetic studies; and an ultrasound of the testes to check for nodules or growths.

Treatment of classical hypogonadism involves replacement of testosterone with the aim of raising the level of testosterone in the blood to normal levels.Exact treatment will vary between patients and be tailored to their individual needs.Different preparations of testosterone are available:

All these are outpatient treatments. All of these options should be discussed with a medical professional and the most appropriate treatment option chosen.During treatment with testosterone replacement, regular blood tests should be carried out to monitor testosterone levels and if necessary, the dose adjusted to ensure levels return to the normal range.Tablet forms of testosterone taken by mouth are not recommended due to a link with liver damage, and because it is more difficult to monitor replacement.

Testosterone should not be given if the patient has prostate cancer, because it might make the tumour grow quicker. Before starting treatment with testosterone, a blood test to measure a hormone produced by the prostate called PSA (prostate-specific antigen) is carried out (PSA levels are elevated in prostate cancer).The prostate may also be examined (via the back passage) to rule out prostate cancer.

For patients who have been diagnosed with late-onset hypogonadism, there is currently not enough evidence for us to know whether treatment with testosterone is safe and effective over the long term.While there are some short-term studies that indicate it may benefit these patients over a short period of time, there is a need for longer-term clinical trials in this area, following a large number of patients, to assess the long-term impact of testosterone treatment on patients with late-onset hypogonadism. Areas that particularly require focus are assessing the effects of treatment on the likelihood of developing cardiovascular disease, prostate cancer and secondary polycythaemia (a condition in which there are increased numbers of red blood cells in the blood, which may predispose to increased blood clots).

If patients have any concerns about their health, they should contact their GP in the first instance.

There can be mild side-effects of testosterone replacement depending on the form used: injectable forms can cause pain and bruising at site of injection; the gel form can cause skin irritation.

Treatment with testosterone can cause an increase in red blood cells (known as polycythaemia), which increases the risk of thrombosis.Regular blood tests should be carried out during treatment to check for an increase in red blood cells.Enlargement of the prostate is another serious side-effect that should be monitored.Prostate examination and a blood test for PSA should be performed every three months for the first year and then annually in men over the age of 40 years after starting treatment.If patients have any concerns about these possible side-effects, they should discuss them with their doctor.

Symptoms of male hypogonadism, such as lack of sex drive, inadequate erections (erectile dysfunction) and infertility, can lead to low self-esteem and cause depression. Professional counselling is available to help deal with these side-effects; patients should talk to their doctor for more information.Patients generally see an improvement in their sex drive and self-esteem following testosterone replacement therapy. Erectile dusfunction is a common symptom in patients without hypogonadism and may need treatment in addition to testosterone.

Male hypogonadism has been linked with an increased risk of developing heart disease (low testosterone can cause an increase in cholesterol levels). Studies have shown that testosterone levels can be lower in men with type 2 diabetes and in men with excess body weight. However, it is not clear whether this is an association or a direct cause and effect. Lifestyle changes to reduce weight and increase exercise can raise testosterone levels in men with diabetes.

Testosterone levels in men decline naturally as they age.In the media, this is sometimes referred to as the male menopause (andropause) although this is not a generally accepted medical term.Low testosterone levels can also cause difficulty with concentration, memory loss and sleep difficulties.Current research suggests that this effect occurs in only a small group of ageing men.However, there is a lot of research in progress to find out more about the effects of testosterone in older men and also whether the use of testosterone replacement therapy would have any benefits.

Last reviewed: Mar 2018

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Male hypogonadism | You and Your Hormones from the Society ...

This article was originally published here

J Endocrinol Invest. 2021 Nov 18. doi: 10.1007/s40618-021-01700-7. Online ahead of print.

ABSTRACT

PURPOSE: Hypogonadism was described in high number of male subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we investigated whether low testosterone (T) values may influence the clinical presentation and outcome of SARS-CoV-2-related pneumonia in a large population of adult males with coronavirus disease 19 (COVID-19).

METHODS: Two hundred twenty one adult males hospitalized for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano-Milan (Italy) were consecutively evaluated for arterial partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, serum T and inflammatory parameters at study entry, need of ventilation during hospital stay and in-hospital mortality.

RESULTS: Subjects low T values (< 8 nmol/L; 176 cases) were significantly older (P = 0.001) and had higher serum interleukin-6 (P = 0.001), C-reactive protein (P < 0.001), lactate dehydrogenase (P < 0.001), ferritin (P = 0.012), lower P/F ratio (P = 0.001), increased prevalence of low T3 syndrome (P = 0.041), acute respiratory insufficiency (P < 0.001), more frequently need of ventilation (P < 0.001) and higher mortality rate (P = 0.009) compared to subjects with higher T values. In the multivariable regression analyses, T values maintained significant associations with acute respiratory insufficiency (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.79-0.94; P < 0.001 and in-hospital mortality (OR 0.80, 95% CI 0.69-0.95; P = 0.009), independently of age, comorbidities, thyroid function and inflammation.

CONCLUSION: Low T levels values are associated with unfavorable outcome of COVID-19. Prospective studies are needed to evaluate the long-term outcomes of hypogonadism related to COVID-19 and the clinical impact of T replacement during and after acute illness.

PMID:34792796 | DOI:10.1007/s40618-021-01700-7

Originally posted here:
Low testosterone predicts hypoxemic respiratory insufficiency and mortality in patients with COVID-19 disease: another piece in the COVID puzzle -...

The following discussion and analysis of our financial condition and results ofoperations should be read in conjunction with our unaudited condensedconsolidated financial statements and notes thereto appearing elsewhere in thisQuarterly Report on Form10-Qand Old Clarus's audited financial statements and notes thereto for the yearended December 31, 2020 included in the Prospectus as filed with the Securitiesand Exchange Commission pursuant to Rule 424(b)(3) on October 7, 2021. Some ofthe information contained in this discussion and analysis or set forth elsewherein this Quarterly Report on Form10-Q,including information with respect to our plans and strategy for our businessand related financing, includes forward-looking statements that involve risksand uncertainties. As a result of many factors, our actual results could differmaterially from the results described in or implied by the forward-lookingstatements contained in the following discussion and analysis.Unless otherwise indicated or the context otherwise requires, references in thisManagement's Discussion & Analysis of Financial Condition and Results ofOperations section to "Clarus," "we," "us," "our" and other similar terms referto Old Clarus (as defined below) prior to the Business Combination (as definedbelow) and to the Company and its consolidated subsidiary after giving effect tothe Business Combination.OverviewWe are a pharmaceutical company focused on the commercialization of JATENZO, thefirst and only oralT-replacement,orT-replacementtherapy ("TRT") of its kind that has received final approval by the U.S. Foodand Drug Administration ("FDA"). We believe that current users of TRT are not satisfied with their currentoptions and desire a therapeutic that is safe, effective and more convenient.Our primary goal for JATENZO is for it to become the preferred choice for TRTamong men with hypogonadism - T deficiency accompanied by an associated medicalcondition. In parallel, our broader vision is for Clarus to become a profitablepharmaceutical company dedicated to providing solutions to unmet medical needsby advancing androgen and metabolic therapies for men and women.Our corporate objectives include maximizing the commercial success of JATENZO inthe United States and internationally by making it the preferred choice for TRTfor men with hypogonadism, expanding its research and development portfolio withadditional metabolic therapies for men and women and sourcing new technologiesthrough its business development efforts.We believe JATENZO offers hypogonadal men and prescribing physicians a safe andeffective oral replacement option and has a number of advantages over thecurrently approved replacement therapies, including:CONVENIENT Easy-to-swallow softgel taken BID with food (twice daily) Dose adjustableEFFECTIVE 87% of men achieved T levels in normal range Restored T levels to mid-normal rangeSAFE Safety profile consistent with TRT class

No liver toxicity - JATENZO bypasses first-pass hepatic metabolism; liver

toxicity not observed in clinical studies of up to 2 years duration.

continue to commercialize JATENZO in the United States for the treatment

--------------------------------------------------------------------------------

Table of Contents

incur sales and marketing costs to support the commercialization of JATENZO;

or acquire additional product candidates for other medical conditions;

adapt our regulatory compliance efforts to incorporate requirements

experience delays or encounters issues with additional outbreaks of the

pandemic in addition to any of the above.

salaries, benefits and other related costs, including stock-based

compensation expense, for personnel engaged in research and development

post-marketing requirements of the FDA for JATENZO and pharmaceutical

A $1.7 million decrease in outsourced advertising and promotion costs due

a $0.4 million increase in commercial analytic and market research costs,

A $1.0 million increase in personnel costs, including stock-based

a $0.6 million decrease in consulting and professional fees, primarily

A $1.0 million decrease in costs related to research and development

A $0.9 million increase in license fees related to the License Agreements

with HavaH and McGill.

A $2.6 million increase in marketing costs, primarily related to the

a $0.2 million increase in patient assistance costs and other sales and

a $1.3 million decrease in commercial analytics and market research costs.

A $2.6 million increase in personnel costs, including stock-based

compensation expense, primarily due to an increase headcount and external

a $0.8 million increase in consulting and professional fees, primarily

a $0.5 million increase in insurance fees, related to directors' and

a $0.2 million increase in other general and administrative expenses.

A $0.9 million increase in license fees related to the HavaH Agreement

a $1.0 million increase in clinical costs related to Phase 4 studies

related to the development of JATENZO, our lead commercial product;

a $1.6 million decrease in costs related to research and development

consulting services.

Net cash used in operating activities (34,452 ) (35,661 )Net cash used in investing activities

Net cash provided by financing activities 49,192 47,220

Net increase in cash and cash equivalents $ 14,720 $ 11,497

the costs of future activities, including product sales, marketing,

the costs of manufacturing commercial-grade product and necessary

the costs of preparing, filing and prosecuting patent applications,

obtaining, maintaining, expanding and enforcing its intellectual property

our ability to establish and maintain collaborations on favorable terms,

if at all.

(1) We have $43.1 million outstanding aggregate principal on our senior secured

notes that bear interest at 12.5% and mature on March 1, 2025.

(2) We have an operating lease agreement for our office space.

--------------------------------------------------------------------------------

Edgar Online, source Glimpses

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CLARUS THERAPEUTICS HOLDINGS, INC. Management's Discussion and Analysis of Financial Condition and Results of Operations. (form 10-Q) -...

New York, United States: The newly published business Bio-Identical Hormone Replacement Therapy Market research report by the team of industrial researchers and market analysts at DECISIVE MARKETS INSIGHTS contains qualitative data on market items like the top leading market corporations, their implemented methods and methodologies, recent developments, market strategies, financials, and many more. Partnerships, successful company methodologies, profit production procedures, construction initiatives, and other procedures are some of the primary strategies and approaches used by top corporations to increase their profits percentages. This market research report also encourages and assists clients in gaining a better understanding of crucial market features that are projected to increase at a faster rate in the near future.

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Bio-Identical Hormone Replacement Therapy Market Segmentation-By Type : Estrogen Hormone Growth Hormone Thyroid Hormone Testosterone HormoneBy Application : Menopause Hypothyroidism Growth Hormone Deficiency Male Hypogonadism Other Diseases By Key Players : Eli Lilly Teva Novo Nordisk Pfizer Bayer

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Bio-Identical Hormone Replacement Therapy Market to Rise Due to the Increasing Applications and Wider Reach, Players Pfizer Bayer. Energy Siren -...

An extensive research report on the Hormone Replacement Therapy Market envisaged diligently by MarketResearch.Biz comprises a 360-degree view of the present market situation as well as its future growth survey. This report will offer you all the accurate data related to the different market bifurcations covering a crystal-clear idea on the Hormone Replacement Therapy market. In addition, we are literally promising you to give the perfect information on the distinct marketing angles and status over the upcoming duration of 2021-2030. There are some of the most important marketing aspects that are adequately boosting the growth of the worldwide market. They are gross margins, market penetrations, CAGR study, Porters 5 Force Model, descriptive and well-defined graphical representations, business strategies, etc.

A report comprising market current and future trends, market analyst opinions and perspectives, competitive scenario, and key regions from both regional and global aspects. This Global Hormone Replacement Therapy Market report offers an overview of the ongoing state of the market and forecasts of future progress. SWOT study is used to calculate strong market players performance and calculating their strengths and weaknesses. The report studied different factors, covering driving factors and challenges. Among its other features is the recognition of key players in the market and split study and forecasting. In addition to Hormone Replacement Therapy market new entrants, the study report helps them to estimates the market opportunity. Furthermore, the study focuses on the current issues, technical progress, and future opportunities that will influence the market. According to a study of upcoming trends, the global Hormone Replacement Therapy Market is projected to grow in the upcoming years.

Competitive Landscape with Key players:

Abbott Laboratories, Novartis, Pfizer Inc, Mylan Laboratories, Merck and Co, Novo Nordisk, Bayer Healthcare, Eli Lilly, Genentech

Hormone Replacement Therapy Market Taxonomy

Segmentation by Product: Estrogen Hormone Replacement Therapy, Human Growth Hormone Replacement Therapy, Thyroid Hormone Replacement Therapy, Testosterone Hormone Replacement Therapy.

Segmentation by Route of Administration: Oral, Parenteral, Transdermal, Others.

Segmentation by Type of Disease: Menopause, Hypothyroidism, Male Hypogonadism, Growth Hormone Deficiency, Others.

Regional Outlook: The Hormone Replacement Therapy Market

The current study analyzes the Hormone Replacement Therapy Market thoroughly. Research is also conducted for Russia, China, the United States, Taiwan, Germany, the United Kingdom, Italy, Japan, South Korea, Canada, France, Mexico, and Southeast Asia. It is expected that North America, Europe, Asia-Pacific, Latin America, and the rest of the world have the largest prudence in the Hormone Replacement Therapy market world.

Among other things, this report calculates factors that contribute to regional growth, such as the environment, Hormone Replacement Therapy market economic progress, and social factors. In the analysis, regional production records, revenue information, and manufacturer data were studied globally. Revenue and volume projection consider regional differences.

This report offers understanding into the accompanying variables:

Understanding Business Sector Development: This research provides a far-reaching outlook of the items provided by the top influencing players in the global Hormone Replacement Therapy market.

Advancement of new items: Reports anatomize the most latest innovative turns of events, innovative business strategies, and item dispatches.

Evaluating the cutthroat scene: Comprehensive investigation of market systems, geographic introduction, and item fragments of the markets prominent players.

Advancement of new business sectors: An cumulative manual for developing business sectors. Various areas are inspected across topographies in this report.

Market Expansion: The complete overview of progress and interests in the worldwide Hormone Replacement Therapy market, like new items, undiscovered topographies, and current patterns.

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Significant incorporation in the Hormone Replacement Therapy market report:

Impacts of the Covid 19 on progress status, temporarily and long haul.

A portion of the business crucial patterns.

Income, volume, and deals insights are included in this report.

Mentioned development possibilities.

Market and submarket development estimations.

Roundabout and direct deals channels: positives and negatives.

Hormone Replacement Therapy market sellers, dealers, and merchants are on the top of the list.

The labor force size and rebuild spaces of each organization are crucial subtleties.

Items and administrations are provided by the important players on the lookout.

Data from each organization in regard to its calculating model, deals volumes, net income, working interest, and a portion of the complete industry.

Itemized information on showcasing strategies, highlight the market, commercialization rates, just as other business-related information.

Table of Content

Section 1: Global Hormone Replacement Therapy Industry Outlook

Section 2: Global Economic Effect on Hormone Replacement Therapy Industry

Section 3: Global Market Competition by Industry Key Players

Section 4: Global Productions, Revenue (Value), with respect to the Regions

Section 5: Global Supplies (Production), Consumption, Export, Import, globally

Section 6: Global Productions, Revenue (Value), Current Trend, Price, Product Type

Section 7: Global Market Study, on the basis of Application

Section 8: Hormone Replacement Therapy Market Pricing Study

Section 9: Market Chain Analysis, Sourcing Strategy, and Downstream Buyers

Section 10: Business strategies and vital policies by Distributors/Suppliers/Traders

Section 11: Key Marketing Strategy Study, by Key Vendors

Section 12: Market Growth Driver Analysis and Their Impact Study

Section 13: Global Hormone Replacement Therapy Market Forecast

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Hormone Replacement Therapy Market Rise in Sustainability Around The World 2021 2030 - Taiwan News

Choosing The Right Supplement Will Help You Boost Your Testosterone With No Side Effects

The hormone which is called testosterone is produced naturally in the testicles of men and ovaries of women. For men, it plays an important role in the development of make male growth and bringing in masculine characters. As for women, it is produced in smaller amounts. During the adolescent years, this hormone is produced at its best level all the way until early adulthood. Once you reach the age of 30 and above, this natural hormone starts to drop slightly each year.

While in the younger years, these hormones help to develop facial hair, deeper voice, and overall all growth development, in the years after 30, the drop in this hormone can inhibit the quality of life. To stabilize the natural growth of this hormone, people often choose supplements that are the closest thing to steroids and are naturally safe as well. This helps them to regain muscle mass and improve bone density. It allows them to enjoy a healthy sex drive and also helps to alleviate their mood. The verbal memory and thinking ability are also enhanced with the balance of this hormone.

Before you start looking for a booster, your first step should be to get examined properly by a doctor. The natural effects of low testosterone are generally decreased muscle mass, weight gain, and other conditions. However, sometimes there can be other underlying medical conditions that could be having the same symptoms. If your doctor does indeed state after the tests that you have low levels of t-hormones or hypogonadism, then you can proceed towards purchasing a supplement for the same.

A t-hormone or testosterone hormone booster can help you to benefit in many ways. However, the most crucial part of it is to buy the right one that does not cause any negative side effects. Most people prefer to buy it online as it saves them both time and money. To make sure you buy the right one you must do your due research. This will ensure that you have bought the right supplement and the ingredients are of good quality. Below are 6 things to look for when buying the testosterone booster.

When it comes to buying such supplements, there are a galore of products to choose from. This can be confusing. When you want to have the best over-the-counter testosterone booster, start by ensuring that the seller and manufacturer are indeed legitimate. This ensures that the product that you receive is of superior quality and will benefit you from its use. Research a bit on the company to see if they have been long enough in the market so that their brand is well known. Most of these drugs have a shelf life of 5 years, so if the company has been around that long as well, then it is legit. Another way to see if the company is genuine, check if they have a money-back guarantee. This claim can only be made by companies that are confident about their product so that they will not sell any low-quality ingredients. Furthermore, if the supplement does not work for you, you will get a refund.

When you are looking to buy supplements, you will need to give a closer look at all the ingredients present in them. These should be more on the natural side and of high quality. With the right ingredients and quality, you will be able to get faster and better muscle recovery. There are many ingredients that you can cross-check to see if they are scientifically proven to boost testosterone levels. These ingredients generally are fenugreek, ginseng, zinc, Vitamin D3, and so on.

When buying a booster online or from a shop, you need to ensure that the dosage is right for you. Sometimes taking a higher dosage can have more effective results but at the same time can bring in higher risks of getting the side effects. So make sure the dosage is right before investing in a supplement. You can take medical advice or that of your gym instructor to help you understand what dosage is right for you.

Reviews are helpful for all sorts of purchases of goods or services. It allows you to understand how other people with similar problems like yours, felt about their experience with a particular product or service. The same principle can be used when buying supplements. You can check other consumer reviews to see what the experience of other people has been and then make a decision if they will be effective for you as well. Of course, boosters with more positive reviews are the ones that you should go for.

While reading the positive reviews is a good idea, if there are any negative testimonials, then you should read that too. If there are quite a few negative testimonies then it will be better to refrain from the supplement. This way you will not spend your hard-earned money on something that does not seem to work.

Firstly, you should look for supplements that have no side effects but there are chances that while buying one, you will end up taking one that has some potential side effects. This could be because there would be some harmful ingredients that can have negative side effects so check it properly before use. Also, check with your doctor what are the expected side effects that you can expect so that you are more prepared.

The above points must be kept in mind when you want to find the right product. A reputable seller who is offering the products at competitive prices and has good reviews to show should be your first choice. Compare a few supplements against each other and look for something that has the best potency. Simultaneously, you can also try some natural ways by eating the right food vitamins, and herbs to help you improve your testosterone level. After all, when it comes to your health, you want to put your best foot forward.

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6 Things To Look for In a Good Testosterone Booster Supplement - The Portugal News

This article was originally published here

Curr Oncol. 2021 Aug 28;28(5):3331-3346. doi: 10.3390/curroncol28050289.

ABSTRACT

Androgen deprivation therapy (ADT) is successfully used in patients with advanced prostatic cancer, but there are many concerns about its systemic side effects, especially due to advanced age and frequent comorbidities in most patients. In patients treated with ADT there are metabolic changes involving the glycaemic control and lipid metabolism, increased thrombotic risk, an increased risk of myocardial infarction, severe arrhythmia and sudden cardiac death. Still, these adverse effects can be also due to the subsequent hypogonadism. Men with heart failure or coronary artery disease have a lower level of serum testosterone than normal men of the same age, and hypogonadism is related to higher cardiovascular mortality. Many clinical studies compared the cardiovascular effects of hypogonadism post orchiectomy or radiotherapy with those of ADT but their results are controversial. However, current data suggest that more intensive treatment of cardiovascular risk factors and closer cardiological follow-up of older patients under ADT might be beneficial. Our paper is a narrative review of the literature data in this field.

PMID:34590590 | DOI:10.3390/curroncol28050289

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Androgen Deprivation Therapy, Hypogonadism and Cardiovascular Toxicity in Men with Advanced Prostate Cancer - DocWire News

One of the key factors fueling the growth of the global hormone replacement therapy market is increasing acquisitions. Pfizer Inc., a pharmaceutical firm headquartered in the United States, combined with OPKO Health Inc., a business based in the U.S., in 2014 to create a long-acting growth hormone (hGH-CTP) and novel therapies for growth hormone deficient individuals. hGH-CTP is more convenient since patients just require one injection each week instead of daily dosages. In the U.S. and Europe, hGH-CTP has been designated as an orphan medication for children and adults with growth hormone deficiencies.

The expansion of the global hormone replacement therapy market is projected to be aided by a strong pipeline. In 2017, Novo Nordisk A/S, a Danish firm, completed phase 3 clinical studies for Somapacitan. This medication is used to treat adult testosterone deficiency.

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Major Company Profiles Covered in This Report:Novartis AG, Abbott Laboratories, Mylan N.V., Merck KgaA, Bayer AG, Pfizer Inc., Novo Nordisk A/S, QuatRx Pharmaceuticals, Teva Pharmaceutical Industries Ltd., Amgen, Inc., and Eli Lilly and Company.

The market for hormone replacement treatment is projected to expand due to the rising prevalence of various chronic diseases.

The market for hormone replacement treatment is projected to expand due to the rising prevalence of hypogonadism in adult males throughout the world. Hypogonadism affects 2.1 percent to 12.8 percent of middle-aged men, according to the European Association of Urologys 2016 study. In Europe, the prevalence of low testosterone and hypogonadism symptoms in males aged 40 to 79 ranges from 2.1 percent to 5.7 percent.

The expansion of the global hormone replacement therapy market is projected to be aided by easier access and government assistance for research and development efforts. NGOs such as the National Gaucher Society provide financial assistance to patients who require expensive insulin replacement treatment.

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Companies are concentrating their efforts on creating generic versions of numerous medications for the treatment of diseases that are more common in women, such as hypothyroidism. On July 24, 2017, Teva Pharmaceutical Industries Ltd. introduced a generic version of Vagifem, 10 mcg, in the United States. Estradiol vaginal inserts are a kind of oestrogen used to treat atrophic vaginitis caused by menopause.

Furthermore, Mylan N.V. received FDA clearance for its Abbreviated New Medication Application (ANDA) for Estradiol Vaginal Cream USP, 0.01 percent on December 29, 2017, and therefore marketed the drug in the U.S. This cream is the first generic alternative to Allergans Estrace Cream, which is used to treat vulvar and vaginal atrophy.

Mylan is one of the few firms that sells Estradiol in cream, gel, transdermal patch, and tablet form. This will benefit both healthcare personnel and patients, as well as ensuring the businesss long-term viability.

Major companies contributing in the global hormone replacement therapy market are Pfizer Inc., QuatRx Pharmaceuticals, Mylan N.V., Abbott Laboratories, Amgen, Inc., Novartis AG, Eli Lilly and Company, Bayer AG, Merck KgaA, Teva Pharmaceutical Industries Ltd., and Novo Nordisk A/S.

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Testosterone is an essential hormone for male growth and masculine characteristics. In males, testosterone is primarily produced in testicles, and in females, it is produced in ovaries and adrenaline glands. In women, testosterone is produced in a very small amount. At adolescence, testosterone level may increase up to 30 times and after adulthood, the level decreases by a certain amount each year. In this article, we will discuss how testosterone therapy can help you by increasing your testosterone levels.

Healthy Heart and Blood Circulation

Low testosterone levels are associated with many cardiovascular risks. Testosterone helps in producing red blood cells from bone marrow. It also helps in keeping your heart healthy, ensuring a healthy blood flow to all organs and muscles of the body helping to keep the body at its peak level. A 2000s study report says that men having heart diseases after undergoing hormone therapy showed improvements in their heath. According to the U.S. Department of Veterans Affairs,in 2015 more than 83K men who underwent hormone therapy, showed a significantly lower risk of heart attack and stroke compared to untreated men.

Reduces Fat

Testosterone helps in reducing body fat and increasing muscle mass. A proper muscle mass helps in controlling the weight and increases the energy production inside the body. After getting testosterone therapy, men who had low testosterone levels previously reported a significant change in body mass and increase in strength. For better results, one must try strength enhancement exercise after therapy.

For testosterone therapy and hormone replacementvisit NovaGenix.

Strengthens Your Bones

Strong bones play an important role in supporting your bodys muscles and organs. As age increases, testosterone decreases as a result of which bone density also decreases significantly. Weak bones and osteoporosis are some common problems that men develop with age. High doses increase bone density but there is no medical evidence yet to show that an increase in testosterone levels can reduce the risks of bone fractures.

Improves Verbal Memory and Reasoning Ability

There is a strong connection between testosterone levels and thinking and verbal ability. Testosterone therapy in men of age group between 34 and 70 years showed a significant improvement in spatial memory. Men with increased testosterone levels also have a lower risk of having Alzheimers disease.

Improves Libido

Testosterone level rises naturally in response to sexual activity and arousal. Men with improved testosterone levels have higher sexual activity. It should also be noted that erectile dysfunctions are not always related to low testosterone levels, it may happen due to other conditions also.

Better Mood

Low testosterone level is often responsible for the low quality of life. Low testosterone levels cause depression, irritability, fatigue, etc. These symptoms are more common in men suffering from hypogonadism. But for men whose testosterone level decreases normally with age do not show all such mood-related symptoms.

These are the 6 benefits you can have by increasing testosterone level with testosterone therapy. Besides all these benefits, there are also some risks that you should not ignore, like increased urination, low sperm count, decrease in size of testicles, increased aggressiveness, etc.

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Top 6 Benefits of Testosterone Therapy Times Square Chronicles - Times Square Chronicles

Hormone Replacement Therapy Market Outlook 2021

Hormone Replacement Therapy market report is the major research for those who look for an entire analysis of markets. The report covers all information on the Global and regional markets, including old and future trends for market demand, size, trading, supply, competitors, prices, and globalpredominant vendors information. We have provided CAGR, value, volume, sales, production, revenue, and other estimations for the global as well as regional markets.

The market is designed to serve as a ready-to-use guide for developing accurate pandemic management programs allowing market players to successfully emerge from the crisis and retract numerous gains and profits. The SMI analyzes recent strategic activities, such as partnerships, acquisitions, mergers, collaborations, and joint ventures. The report analyzes the demographics, growth potential, and capability of the market through the forecast period 2021 to 2027. The players included in this report are chosen in terms of their product portfolio, market share, brand value, and the well-being of the organizations. Our report is based on current situations across the globe.

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Top players listed in Hormone Replacement Therapy report:

Novartis AG, Abbott Laboratories, Mylan NV, Merck KgaA, Bayer AG, Pfizer Inc., Novo Nordisk A/S, QuatRx Pharmaceuticals, Teva Pharmaceutical Industries Ltd., Amgen Inc., Eli Lilly and Company

Hormone Replacement Therapy Market Segmentation

Global Hormone Replacement Therapy Market,By Type

Oral, Parenteral, Others

Global Hormone Replacement Therapy Market,By Applications:

Hypothyroidism, Male Hypogonadism, Growth Hormone Deficiency, Menopause, Others

If you are part of the Hormone Replacement Therapy industry or intend to be, then study would provide you comprehensive outlook. It is vital to keep your market knowledge up to date analysed by major players and high growth emerging players. If a different set of players need to be analysed as per geography or regional target then enquire us with your customized requirements.

The report forecasts revenue growth at all geographic levels and provides an in-depth analysis of the latest industry trends and development patterns from 2020 to 2027 in each of the segments and sub-segments.

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TheHormone Replacement Therapy market research follows a four-step methodology: primary research, secondary research, market estimation, and final presentations. Data is collected through self-conducted research methods in the primary research, whereas in secondary research, data is collected from previously conducted studies.The market estimation involves data processed in primary and secondary research. The final step is a holistic representation of the data and analysis made to make the report highly comprehensible for the reader.

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Hormone Replacement Therapy Market by 2027 Worldwide Growth Opportunities Recent Trends Forecast by Types and Application to 2027 The Manomet Current...

What makes a man? This question has been a subject of great argument for many centuries. However, the thing that leaps to the mind first is, undeniably, testosterone. Testosterone is the most vital male sex hormone that is a critical factor in mens adolescence.

An optimal proportion of testosterone maintains high energy levels as well as enhances body strength and masculinity. Besides, it is a crucial aspect regarding physical changes in boys.

But, what course of action should you adopt if you have lower testosterone levels? You will find a vast chain of treatments and procedures in this regard, but it is hard to access an authentic one.

In that sense, you have landed on the right platform. With enough research on this significant health affair, we will introduce you to the precious nine ways that will help you increase testosterone naturally. And, the good news is these will bring beneficial changes to your overall health and well-being.

So, keep scrolling down.

Your diet has a significant impact on your testosterone levels. Recent studies have found that men who consume a low-fat diet face testosterone deficiency. Therefore, always be mindful of your diet routine and stay away from prolonged dieting strategies.

Eating bulked-up ingredients fuels your masculinity. Therefore, following a rich diet plan and the intake of the best testosterone booster supplements might boost up your testosterone levels effectively.

You might be missing some essential nutrients in your daily diet that may boost your T levels.

We have discussed their importance and how you can have all of them at once below in detail:

D-Aspartic acid is a natural amino acid that can increase your testosterone levels effectively. Colossal research has been done on D-Aspartic acid, which shows it is bound to many fruitful outcomes regarding the whole male reproductive system.

Recent studies have revealed D-Aspartic acid works on some critical testosterone-stimulating hormones like follicle-stimulating hormones and luteinizing hormones, which increases your testosterone levels.

Adding D-Aspartic acid into your diet for 12 days may help enhance testosterone levels and other hormones. Additionally, it may also elevate their production and transportation around the body.

Many studies have also shown that such amino acids may be helpful in sperm production and quality. So, overall, it can be a significant step towards better testosterone levels.

Magnesium is a critical mineral deeply associated with the vital processes in our body, like cellular processes, bone formation, and muscle functions.

A couple of researches revealed magnesium supplementation for four weeks increases testosterone levels in athletic and sedentary individuals.

A magnesium-rich diet can, directly and indirectly, translate it into an increased T level (since magnesium is also responsible for converting Vitamin D into an active form).

Although magnesium deficiency is more common in old age, many younger people, like athletes, may also suffer from it, as many minerals like Zinc, magnesium, etc., may be lost in sweat. Therefore, make sure you consume a proper intake of magnesium.

Though many competitive supplements include magnesium as an ingredient, dietary magnesium always comes first, so try to reach out to the magnesium-rich foods that are abundant, such as greens, nuts, seeds, dry beans, whole grains, and wheat and oat bran.

Try to stay away from magnesium oxide, as it may cause some significant health issues like intestinal discomfort or diarrhea.

Zinc is found to be the second most abundant element in humans. Apart from having countless benefits in other health regards, researchers have found Zinc may play a tremendous role in mens masculinity, fertilization, sperm quality, and hormonal secretion.

Some researchers have also witnessed that an average Zinc concentration in the body is required for the normal functioning of the pituitary gland, which is highlighted in male reproductive potential.

Zinc is found to affect mens fertility in numerous ways. In addition, low zinc levels in the body have a highlighted negative effect on testosterone concentrations.

So, keeping all of this in mind, try to incorporate zinc supplements in your diet, which include oysters, beef, nuts, chicken, beans, and many more.

TestoPrime is the answer, as it is an effective testosterone-boosting supplement. With TestoPrime, you can get all of the essential nutrients in a single package.

You can get all of these benefits by using this natural testosterone booster. The influential testosterone support can help you maintain your pubescent liveliness with new and fresh testosterone.

TestoPrime is a cost-friendly and 100% dependent combination of natural ingredients, like vitamins and fruit extracts, mainly created to give the best results and promote your overall health.

Men who have entered their 40s or are near to it are advised to purchase it. It may not only bring a flood of testosterone into your body, but it may also help you get rid of tiredness, low energy levels, loss of focus, decreased sexual desires, and a bad memory.

So, if you want all these in a short time, grab this fantastic T-boosting supplement.

Modern studies have shown testosterone makes you manly, and vitamin D supports your bones and muscles. However, recently, it has been concluded these two biomarkers are associated with many other body functions and may affect each others levels.

Vitamin D is an essential nutrient that is achieved via sun exposure and many diet supplements. The essential vitamin crucially influences the proper growth and functioning of bones, muscles, nerves, and numerous body organs.

Various researches have been performed on discovering the role of vitamin D in testosterone boosting. It has been found that low vitamin D levels can drop your testosterone levels theoretically. Additionally, it can lead to improper working of the testes.

A few years ago, it was concluded that men with lower Vitamin D and T levels might have more cardiovascular diseases. In addition, people with low T levels may experience some other sexual problems like erectile dysfunction and lower sexual drives. These can be treated with Vitamin D.

Always make sure to have enough Vitamin D included in your diet. There are various supplements available in the market. Another option is to go out in the sunshine, as it is the most reliable and productive way of consuming vitamin D.

Therefore, the sun is the best way to get vitamin D. When you take some Vitamin D-rich supplements or expose your skin to sun rays, your body absorbs it. Your liver will then translate it into its active form called 25(OH) D, which your doctor looks for when he suggests a Vitamin D blood test.

The active form of Vitamin D is then transported throughout your body for different functions. It is now proven the male reproductive system is one of its receivers.

Apart from that, there are some other ways to consume vitamin D like:

Exercises tend to be the most crucial factor in preventing many health diseases. Surprisingly, this can also be the best alternative to increase your testosterone levels. You can increase your testosterone levels on your own by adopting some essential pieces of training and workouts.

Low testosterone levels are nearly bound to lowered energy levels, decreased muscle mass, and inadequate mental health. Exercises can be the best in this regard.

Exercises increase testosterone in two ways:

Research has found that heavy training like weight lifting may be the best way to boost testosterone. Lifting heavy weights may help gain muscle mass and, likewise, higher T levels. If you are new to this, opt for a trainer to get basic knowhow of it.

High-intensity interval exercises, if done along with weight lifting, may be the best combination that will not only elevate your T levels but may also help promote heart health.

High-intensity training is also found to have positive effects on testosterone levels. Research revealed that resting for a couple of minutes between intervals is more advantageous.

Moderate cardio exercises also contribute to some extent, as they protect your heart and inhibit extra cortisol productions, which can negatively impact your muscle mass and T levels.

Make sure to stay away from chronic and prolonged exercises like cycling, running, and swimming for a long time, as these may cause problems regarding your testosterone production.

Follow a reliable diet plan that includes the intake of all of the necessary nutrients in the proper proportions. A balanced diet is a crucial factor in elevating T levels. Hundreds of researches show that low testosterone levels and poor diet patterns are strongly interrelated.

A balanced diet not only enhances your T levels, but it has countless health benefits. Many studies show that alterations in dietary plans may lead to hypogonadism. Consuming a balanced diet enriched in proteins, carbs, and healthy fats can go longer toward normal T levels as you age.

Many essential nutrients like proteins, carbs, and healthy fats may bring noticeable benefits to your health and hormonal secretions.

According to recent health researchers, a diet rich in proteins may aid a lot in testosterone boosting. However, another study has revealed low protein levels may damage the Leyden cells assigned to testosterone production.

Therefore, try to increase your protein intake. This will help you in fat loss which, likewise, is linked with your testosterone. Moreover, it will support your muscle development, which may be essential in testosterone boosting.

Carbs may bring out a rapid increase in your T levels. According to the latest research, eating a carbohydrate-rich diet may be harmful to diabetic people, but it is associated with a high testosterone level in the average person. Instead, try to consume carbs from starchy tubers such as potatoes, yams, pumpkins, etc.

When it comes to fats, many of you may think it has nothing to do with testosterone levels, but it is essential to take a sufficient amount of healthy fats to produce testosterone effectively. In this regard, saturated fats are beneficial.

It would be best if you add the following foods to your daily routine:

In short, we would say a healthier diet will result in a healthier weight that may boost your T levels even if you age.

The pressures you are dealing with in your life may reveal several ways. Lower T levels are one of these. Stress may affect some essential hormones like testosterone responsible for pubescence in boys. However, the clear physiological linkage between stress and low testosterone is not known.

Many researchers and physicians have shown some brain chemicals released in response to stress and anxiety, and then they might be transferred to the testosterone-controlling sites in the brain.

Other research shows stress elevates the cortisol levels in the body. Cortisol is a stress hormone released by adrenal glands in the kidneys when you are under stress. It is assigned with the management of numerous processes in the body like metabolism and immune system. Therefore, increased cortisol impacts testosterone productions negatively.

In this regard, meditation may be the best option to get rid of stress. Researchers have found that at least 20-30 minutes of meditation per day will indirectly lower cortisol and increase your testosterone and growth hormone levels.

Always try to manage yourself in stressful situations. This will preserve your sanity and promote your health in many ways.

Lack of sleep can adversely affect the secretions and levels of many essential hormones and chemicals in the body, including testosterone. Simply speaking, your testosterone levels are directly linked with your sleep. So, the longer you sleep, the higher your T levels will be.

Recent studies have disclosed that testosterone production is at its peak during the REM stage of your sleep. Many physicians also suggest that for a healthy testosterone level, around seven to nine hours of sleep are required.

People who have problems regarding their sleep should consult a doctor, as they unconsciously face a significant problem.

Your T levels are also affected by many other factors. For example, healthier life is based upon the regulation of your sex hormones like testosterone.

Always try to stay away from some chemicals like endocrine disruptors, as they can spoil your hormones badly. Some of them are estrogens compounds that can adversely affect your T levels. So, try to maintain a distance from BPA, Parabens, and other chemicals.

They act as estrogen-rich elements, and your body may make mistakes in recognizing them due to their similar composition. They create disturbances in normal body functions. So, choose the products which do not have them.

It is a common fact that excessive alcohol and drug consumption may have several adverse effects on your health and, particularly, on your liver. But, does alcohol affect your T levels?

The answer is yes. When you consume alcohol and other similar drugs, your body requires a lot of time to break and process the alcohol. In this way, your system focuses mainly on this task ,which in turn, causes your liver to work more.

During this process, your liver does not get time to perform its other functions, like breaking down some hormones, including estrogen and testosterone. In other words, when you consume alcohol regularly, your testosterone levels are not the same as they are when you avoid alcohol.

Some men are still having a proper T level while consuming alcohol, but that is rare. If you want a normal and healthy T level, it should be your top concern to avoid alcohol and other drug supplements.

Even in just 30 days, you can get an average level of testosterone after quitting your alcohol and drug consumption. Proper T levels are an essential part of your health and well-being. Therefore, staying away from alcohol and drug consumption can be the easiest step to achieve such goals.

Mental health is something that should never be ignored. Talking about how it affects testosterone levels in the body, you might not believe us. But, if you are stressed out and mentally upset, your T-levels drop significantly low.

Do not hesitate to consult a psychiatrist whenever you feel like there is something troubling you and making you depressed. Always talk about your mental health with professionals, as it is not a thing to be ignored.

More to keep in mind is to constantly check the medications you are taking for other health problems. This is because they might contain any ingredient that promotes low T levels. This might not happen, but you should be careful and talk to your online therapist if you feel anything like that.

Testosterone is an important male sex hormone that promotes masculinity. It also facilitates many other body functions.

A lot of options are available in the market to boost your T levels, including many therapies, treatments, artificial supplements, and pills. But, the best way to do so is to follow or implement something natural.

In addition to following the simple tips we mentioned above, TestoPrime might help you a lot with getting your testosterone levels boosted up. It is associated with many extra health benefits regarding your heart, brain, and weight balance in addition to boosting T-levels.

However, if you are already on some kind of medication, or have a particular medical condition, make sure to consult your doctor before opting for any supplement.

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9 Ways to Increase Testosterone Naturally in 2021 - Men's Journal