Male Hypogonadism – Causes, Symptoms, Diagnosis, Treatment

Posted: January 2, 2019 at 2:42 pm

Male hypogonadism is a condition in which your body does not produce enough of the testosterone hormone; the hormone that plays a key role in masculine growth and development during puberty, mental cognition or has an impaired ability to produce sperm or both. Clinically low testosterone levels can lead to the absence of secondary sex characteristics, infertility, muscle wasting, and other abnormalities.

You may be born with male hypogonadism, or it can develop later in life, often from injury or infection. Low testosterone levels may be due to testicular, hypothalamic, or pituitary abnormalities. The effects of male hypogonadism and what you can do about them depend on the cause and at what point in your life male hypogonadism occurs. Some types of male hypogonadism can be treated with testosterone replacement therapy.

Male hypogonadism can significantly reduce the quality of your life and has resulted in the loss of livelihood and separation of couples, leading to divorce. It is also important for you to recognize that testosterone is not just a sex hormone. There is an important research being published to demonstrate that testosterone may have key actions on metabolism, on the vasculature, and on brain function, in addition to its well-known effects on bone and body composition.

Male hypogonadism is a common condition in the male population, with a higher prevalence in older men, obese men, and men with type 2 diabetes. If you are concerned about your testosterone levels It is important to talk to doctor about ways to manage.

The pituitary gland is a tiny organ, the size of a pea, found at the base of the brain and is often referred to as the master gland. As the master gland of the body, thepituitary gland produces and stores manydifferent hormones that travel throughout your body, directing certain processes or stimulating other glands to produce other hormones.

The following hormones are made in the anterior (front part) of the pituitary gland:

The back part of the pituitary gland is called the posterior pituitary. It produces the following two hormones:

When the pituitary gland doesnt operate in a healthy manner, this can lead to pituitary disorders.

Hormones are essential to reproductive health in all aspects of a mans sexual life. The hypothalamus and pituitary gland are located at the base of the brain, and they work together to release hormones luteinizing hormone (LH) and follicle stimulating hormone (FSH) that stimulate the testes to produce testosterone and sperm. Testosterone, the main male hormone, helps maintain sex drive; vitality; sperm production; facial, pubic, and body hair; muscle; and bone.

In men, important health issues related to hormonal imbalances or deficiencies include:

These conditions are often, but not always, related to each other.

Testosterone is the most important sex hormone that men have. Throughout mens lifespan, testosterone plays a critical role in sexual, cognitive, and body development. During fetal development, testosterone aids in the determination of sex. The most visible effects of rising testosterone levels begin in the prepubertal stage. During this time, body odor develops, oiliness of the skin and hair increase, acne develops, accelerated growth spurts occur, and pubic, early facial, and axillary hair grows. In men, the pubertal effects include enlargement of the sebaceous glands, penis enlargement, increased libido, increased frequency of erections, increased muscle mass, deepening of voice, increased height, bone maturations, loss of scalp hair, and growth of facial, chest, leg, and axillary hair. Even as adults, the effects of testosterone are visible as libido, penile erections, aggression, and mental and physical energy.

Testosterone 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.

In the short term, low testosterone (also called hypogonadism) can cause:

Over time, low testosterone may cause a man to lose body hair, muscle bulk, and strength and to gain body fat. Chronic (long-term) low testosterone may also cause weak bones (osteoporosis), mood changes, less energy, and smaller testes. Signs and symptoms (what you see and feel) vary from person to person.

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.

You should NOT receive testosterone therapy if you have:

Low testosterone can result from:

Low testosterone is common in older men. In many cases, the cause is not known.

During a physical exam, your doctor will examine your body hair, size of your breasts and penis, and the size and consistency of the testes and scrotum. Your doctor may check for loss of side vision, which could indicate a pituitary tumor, a rare cause of low testosterone.

Your doctor will also use blood tests to see if your total testosterone level is low. The normal range is generally 300 to 1,000 ng/dL, but this depends on the lab that conducts the test. To get a diagnosis of low testosterone, you may need more than one early morning (710 AM) blood test and, sometimes, tests of pituitary gland hormones.

If you have symptoms of low testosterone, your doctor may suggest that you talk with an endocrinologist. This expert in hormones can help find the cause. 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.

Testosterone replacement therapy can improve sexual interest, erections, mood and energy, body hair growth, bone density, and muscle mass. There are several ways to replace testosterone:

The best method will depend on your preference and tolerance, and the cost.

There are risks with long-term use of testosterone. The most serious possible risk is prostate cancer. African American men, men over 40 years of age who have close relatives with prostate cancer, and all men over 50 years of age need monitoring for prostate cancer during testosterone treatment. Men with known or suspected prostate cancer, or with breast cancer, should not receive testosterone treatment.

Other possible risks of testosterone treatment include:

Figure 1. The pituitary gland location

Figure 2. The hypothalamus and pituitary gland (anterior and posterior) endocrine pathways and target organs

Figure 3. Male reproductive system

Figure 4. Testicle anatomy (normal)

The cerebral cortex the layer of the brain often referred to as the gray matter is the most highly developed portion of the human brain. This portion of the brain, encompassing about two-thirds of the brain mass, is responsible for the information processing in the brain. It is within this portion of the brain that testosterone production begins. The cerebral cortex signals the hypothalamus to stimulate production of testosterone. To do this, the hypothalamus releases the gonadotropin-releasing hormone (GnRH) in a pulsatile fashion, which stimulates the pituitary gland the portion of the brain responsible for hormones involved in the regulation of growth, thyroid function, blood pressure, and other essential body functions. Once stimulated by the gonadotropin-releasing hormone (GnRH), the pituitary gland produces the follicle-stimulating hormone (FSH) and the luteinizing hormone (LH). Once released into the bloodstream, the luteinizing hormone (LH) triggers activity in the Leydig cells in the testes. In the Leydig cells, cholesterol is converted to testosterone. When the testosterone levels are sufficient, the pituitary gland slows the release of the luteinizing hormone via a negative feedback mechanism, thereby, slowing testosterone production. With such a complex process, many potential problems can lead to low testosterone levels. Any changes in the testicles, hypothalamus or pituitary gland can result in hypogonadism. Such changes can be congenital or acquired, temporary, or permanent.

Recent studies have found that testosterone production slowly decreases as a result of aging, although the rate of decline varies. Unlike women who experience a rapid decline in hormone levels during menopause, men experience a slow, continuous decline over time. The Baltimore Longitudinal Study of Aging reported that approximately 20% of men in their 60s and 50% of men in their 80s are hypogonadal 1). The New Mexico Aging Process Study showed a decrease in serum testosterone of 110 ng/dL every 10 years 2). As testosterone hormone levels decline slowly, this type of hypogonadism is sometimes referred to as the partial androgen deficiency of the aging male (PADAM). With the growing elderly population, the incidence of partial androgen deficiency of the aging male may increase over the next few decades.

Regardless of the age or comorbid conditions, obesity is associated with hypogonadism 3). The Baltimore Longitudinal Study of Aging found that testosterone decreased by 10 ng/dL per 1-kg/m2 increase in body mass index 4). Another study also showed reduced testosterone levels in men with increased total abdominal adiposity 5). The proposed causes for the effects of obesity on testosterone level include increased clearance or aromatization of testosterone in the adipose tissue and increased formation of inflammatory cytokines, which hinder the secretion of the gonadotropin-releasing hormone 6). Similar to the projections for an aging population, the increasing incidence of obesity may lead to an increased incidence of secondary male hypogonadism. When the risk factors of obesity and age are removed, diabetes mellitus still remains an independent risk factor for male hypogonadism. Although diabetes mellitusrelated hypogonadism was previously thought to be associated with testicular failure, study results show one-third of diabetic men had low testosterone levels, but also had low pituitary hormone levels 7). Population projections expect the number of cases of diabetes mellitus to rise from 171 million in 2000 to 366 million in 2030 8). This drastic increase in cases will impact the prevalence of male hypogonadism as well. Certain medications are shown to reduce testosterone production. Among the medications known to alter the hypothalamic-pituitary-gonadal axis are spironolactone, corticosteroids, ketoconazole, ethanol, anticonvulsants, immunosuppressants, opiates, psychotropic medications, and hormones 9).

The complications of untreated hypogonadism differ depending on what age it first develops during fetal development, puberty or adulthood.

A baby may be born with:

Pubertal development can be delayed or incomplete, resulting in:

Complications may include:

Male hypogonadism means the testicles dont produce enough of the male sex hormone testosterone.

There are two basic types of male hypogonadism that exist:

Common causes of primary hypogonadism include:

This condition results from a congenital abnormality of the sex chromosomes, X and Y. A male normally has one X and one Y chromosome. In Klinefelters syndrome, two or more X chromosomes are present in addition to one Y chromosome (46,XXY). The Y chromosome contains the genetic material that determines the sex of a child and the related development. The extra X chromosome that occurs in Klinefelters syndrome causes abnormal development of the testicles, which in turn results in the underproduction of testosterone.

Before birth, the testicles develop inside the abdomen and normally move down into their permanent place in the scrotum. Sometimes, one or both of the testicles may not descend at birth. This condition often corrects itself within the first few years of life without treatment. If not corrected in early childhood, it may lead to malfunction of the testicles and reduced production of testosterone.

If a mumps infection involving the testicles in addition to the salivary glands (mumps orchitis) occurs during adolescence or adulthood, long-term testicular damage may occur. This may affect normal testicular function and testosterone production.

Too much iron in the blood can cause testicular failure or pituitary gland dysfunction, affecting testosterone production.

Because of their location outside the abdomen, the testicles are prone to injury. Damage to normally developed testicles can cause male hypogonadism. Damage to one testicle may not impair testosterone production.

Chemotherapy or radiation therapy for the treatment of cancer can interfere with testosterone and sperm production. The effects of both treatments are often temporary, but permanent infertility may occur. Although many men regain their fertility within a few months after the treatment ends, preserving sperm before starting cancer therapy is an option that many men consider. Howell et al. 10) reported that hypogonadism was seen in 30% of the men with cancer and 90% of these gentlemen had germinal epithelial failure.

Older men generally have lower testosterone levels than younger men do. As men age, theres a slow and continuous decrease in testosterone production. The rate that testosterone declines varies greatly among men. As many as 30% of men older than 75 have a testosterone level that is below normal, according to the American Association of Clinical Endocrinologists. Whether or not treatment is necessary remains a matter of debate 11).

In secondary hypogonadism, the testicles are normal, but function improperly due to a problem with the pituitary or hypothalamus. A number of conditions can cause secondary hypogonadism, including:

Abnormal development of the hypothalamus the area of the brain that controls the secretion of pituitary hormones can cause hypogonadism. This abnormality is also associated with the impaired development of the ability to smell (anosmia) and red-green color blindness.

An abnormality in the pituitary gland can impair the release of hormones from the pituitary gland to the testicles, affecting normal testosterone production. A pituitary tumor or other type of brain tumor located near the pituitary gland may cause testosterone or other hormone deficiencies. Also, the treatment for a brain tumor such as surgery or radiation therapy may impair pituitary function and cause hypogonadism.

Certain inflammatory diseases such as sarcoidosis, histiocytosis, and tuberculosis involve the hypothalmus and pituitary gland and can affect testosterone production, causing hypogonadism.

This virus can cause low levels of testosterone by affecting the hypothalamus, the pituitary, and the testes.

The use of certain drugs, such as, opiate pain medications and some hormones, can affect testosterone production 12).

Being significantly overweight at any age may be linked to hypogonadism.

Stress, excessive physical activity, and weight loss have all been associated with hypogonadism. Some have attributed this to stress-induced hypercortisolism, which would suppress hypothalamic function 13).

Risk factors for hypogonadism include:

Hypogonadism can be inherited. If any of these risk factors are in your family health history, tell your doctor.

Male hypogonadism is characterized by serum testosterone levels

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

Hypogonadism can also cause mental and emotional changes. As testosterone decreases, some men may experience symptoms similar to those of menopause in women. These may include:

Hypogonadism can also begin during fetal development or before puberty. Signs and symptoms depend on when the condition develops.

Fetal development

If the body doesnt produce enough testosterone during fetal development, the result may be impaired growth of the external sex organs. Depending on when hypogonadism develops and how much testosterone is present, a child who is genetically male may be born with:

Puberty

Male hypogonadism may delay puberty or cause incomplete or lack of normal development. It can cause:

Your doctor will conduct a physical exam during which he or she will note whether your sexual development, such as your pubic hair, muscle mass and size of your testes, is consistent with your age. Your doctor may test your blood level of testosterone if you have any of the signs or symptoms of male hypogonadism.

Early detection in boys can help prevent problems from delayed puberty. Early diagnosis and treatment in men offer better protection against osteoporosis and other related conditions.

Doctors base a diagnosis of male hypogonadism on symptoms and results of blood tests that measure testosterone levels. Because testosterone levels vary and are generally highest in the morning, blood testing is usually done early in the day, before 10 a.m.

If tests confirm you have low testosterone, further testing can determine if a testicular disorder or a pituitary abnormality is the cause. Based on specific signs and symptoms, additional studies can pinpoint the cause. These studies may include:

Testosterone testing also plays an important role in managing male hypogonadism. This helps your doctor determine the right dosage of medication, both initially and over time.

Treatment for male hypogonadism depends on the cause and whether youre concerned about fertility.

Hormone replacement. For hypogonadism caused by testicular failure, doctors use male hormone replacement therapy (testosterone replacement therapy). Testosterone replacement therapy can restore muscle strength and prevent bone loss. In addition, men receiving testosterone replacement therapy may experience an increase in energy, sex drive, erectile function and sense of well-being. Testosterone replacement therapy 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.

While testosterone replacement therapy is the primary treatment option some conditions that cause hypogonadism are reversible without testosterone therapy. These should be addressed before testosterone therapy is contemplated. If testosterone therapy is needed, goal of treatment is to improve symptoms associated with testosterone deficiency and maintain sex characteristics. There are many different types of testosterone therapy. You should discuss the different options with your physician your partner in care to find out which therapy is right for you.

If a pituitary problem is the cause, pituitary hormones may stimulate sperm production and restore fertility. Testosterone replacement therapy can be used if fertility isnt an issue. A pituitary tumor may require surgical removal, medication, radiation or the replacement of other hormones.Assisted reproduction. Although theres often no effective treatment to restore fertility in a man with primary hypogonadism, assisted reproductive technology may be helpful. This technology covers a variety of techniques designed to help couples who have been unsuccessful in achieving conception.

In boys, testosterone replacement therapy can stimulate puberty and the development of secondary sex characteristics, such as increased muscle mass, beard and pubic hair growth, and growth of the penis. Pituitary hormones may be used to stimulate testicle growth. An initial low dose of testosterone with gradual increases may help to avoid adverse effects and more closely mimic the slow increase in testosterone that occurs during puberty.

Testosterone replacement therapy is the primary treatment option for hypogonadism. Ideally, the therapy should provide physiological testosterone levels, typically in the range of 300 to 800 ng/dL. According to the guidelines from the American Association of Clinical Endocrinologists 15), the goals of therapy are to:

To achieve these goals, several testosterone delivery systems are currently available in the market. Clinical guidelines published in 2006, by the Endocrine Society 17), recommend reserving treatment for those patients with clinical symptoms, rather than for those with just low testosterone levels.

Method of treatment depends on the cause of low testosterone, the patients preferences, cost, tolerance, and concern about fertility.

Oral Tablets

Oral testosterone tablets, under the brand name Andriol, are available in other countries. Android and Testroid both methyl testosterone products are FDA approved oral formulations.

Although relatively inexpensive, oral products undergo extensive first-pass metabolism and therefore require multiple daily doses. Oral products are associated with elevated liver enzymes, GI intolerance, acne, and gynecomastia. Regardless of the treatment option, patients should be aware of the risks associated with testosterone therapy, including:

Patients should be educated on the signs and symptoms of these adverse effects and instructed to notify their doctor if any of these occur.

There is no firm scientific evidence that long-term testosterone replacement is associated with either prostate cancer or cardiovascular events. Recent research also suggests testosterone therapy might increase your risk of a heart attack. 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.

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Male Hypogonadism - Causes, Symptoms, Diagnosis, Treatment

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