Male Hypogonadism

Testosterone is one of the most important hormones for men. If your testosterone levels drop too low, it can cause many changes to your body, such as trouble building muscle, sexual dysfunction, and fatigue.

The medical term for testosterone deficiency that causes symptoms is male hypogonadism. Male hypogonadism can develop if your testicles don’t produce enough testosterone or if other glands in your body don’t produce enough of the hormones that tell your testicles to produce testosterone.

Hypogonadism is particularly common among older men since testosterone levels tend to decline throughout your life, but it can affect men of all ages.

Stay with us as we look at some of the causes of hypogonadism, including why it develops, potential symptoms, and how it can be treated.

Male Hypogonadism

Testosterone is the primary sex hormone, or gonadal hormone, in men. It gives males the ability to produce sperm and gives them their secondary sex characteristics, such as:

• broad shoulders

• facial hair

• deep voices

Male hypogonadism is when you have symptoms because your testosterone levels drop below a normal range.

About 95 percent of testosterone produced in men is created inside the testicles. The other five percent is produced in the adrenal glands above your kidneys. In females, the ovaries produce some testosterone. Testosterone also plays an important role in female health, but the primary female sex hormone is estrogen.

Male hypogonadism may develop if you experience a problem with your testicles or a problem with the glands that stimulate the production of testosterone in your testicles.

Male Hypogonadism: Testosterone Levels 

The normal range for testosterone measured by a morning blood test varies depending on the lab where you have your blood test, but generally is between 300 ng/dL and 1000 ng/dL for males. Normal levels also vary by age, with normal levels in younger men being higher than in older men. Some experts like me  recommend using age-specific thresholds to diagnose testosterone deficiency in men ages 20 to 44.

Your doctor may diagnose you with hypogonadism if your morning serum testosterone levels are low on at least two separate tests and you have symptoms consistent with low testosterone. 

Testosterone levels generally decrease with age in adult men, starting around age 30. They decline by about 100 ng/dL every 10 years.

In ideal circumstances, testosterone levels in males over 65 are between 500 and 800 ng/dL. Young adults are usually between 600 and 900 ng/dL. 

The prevalence of hypogonadism is difficult to quantify but has been reported to be as high as 40 percent in men over 45 and about 50 percent in men over 80.

Testosterone and other male sex hormones are collectively known as androgen hormones. Androgen hormones help maintain many aspects of your health.

If androgen levels drop too low, you can experience symptoms like fatigue, trouble building muscle, and sexual dysfunction.

Symptoms of Male Hypogonadism 

Symptoms and signs associated with hypogonadism include:

• reduction in erection frequency

• infrequent morning erections

• chronic and unexplained fatigue

• low libido

• smaller testicular size

• erectile dysfunction

• loss of body hair and pubic hair

• trouble building muscle mass or loss of muscle mass

• hot flashes

• infertility, maybe with a low sperm count

Other potential male hypogonadism symptoms include:

• depression

• irritability

• poor concentration

• increased body fat

• decreased physical performance

• reduced muscle strength

• reduced endurance

• weight loss

• reduced energy and appetite

• gynecomastia (male breasts)

• anemia (low red blood cell count)

Signs of hypogonadism in children before puberty can include:

• genitals that don’t appear clearly male or female

• micropenis (an atypically small penis )

• undescended testicles on both sides

• delayed puberty

Chronic hypogonadism can lead to complications such as cardiovascular disease or osteoporosis.

Osteoporosis is the loss of bone density. It often doesn’t cause symptoms but can raise your risk of developing a bone fracture.

Researchers think that low testosterone could increase the development of cardiovascular disease by contributing to:

• increased inflammation

• insulin resistance

• high blood lipid levels

• atherosclerosis, the build-up of plaque along the walls of your blood vessels

Male hypogonadism can be caused by genetic factors, conditions that you develop throughout your life, or as a side effect of treatments for some conditions such as cancer.

Causes of Male Hypogonadism 

Male hypogonadism develops when your body doesn’t produce enough testosterone. 

The production of testosterone usually requires the secretion of hormones from glands in your brain called your hypothalamus and pituitary gland. Problems with your testicles or either of these glands can lead to hypogonadism. Here’s how the process works:

• Your hypothalamus produces a hormone called gonadotropin-releasing hormone (GnRH).

• GnRH tells your pituitary gland to produce two hormones: follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

• FSH tells your testicles to increase sperm production. LH stimulates your testicles to make testosterone.

Doctors characterize hypogonadism as either primary or secondary hypogonadism:

• Primary hypogonadism is when low testosterone production is caused by problems with your testicles.

• Secondary hypogonadism is when low testosterone production develops due to problems with your hypothalamus or pituitary gland

Some of the causes of male hypogonadism are genetic, meaning they’re inherited from your parents or caused by genetic abnormalities that occurred spontaneously when you were conceived. Other causes are acquired, meaning you develop them throughout your life.

Causes of Primary Hypogonadism

Causes of primary hypogonadism include:

• Klinefelter syndrome. Klinefelter syndrome is a genetic condition when you're born with one or more extra X chromosomes. Most men assigned male sex at birth have one X and one Y chromosome. People with this syndrome have two or more X and one Y chromosomes.

• Undescended testicles. Cryptorochidism, also known as undescended testicles, is a condition in which one or both of your testicles do not drop into normal position in the scrotum before birth. It affects about 1.8 to 8.4 percent of children at birth and 1.0–1.5 percent by age one.

• Mumps orchitis. Mumps orchitis is swelling in the testicles that develops in about 1 in 3 males who develop mumps after puberty. Mumps is a viral infection that’s usually preventable with vaccination.

• Cancer treatment. Men who receive hormone therapy to treat prostate cancer or chemotherapy for other forms of cancer may develop low testosterone levels. Hormone therapy blocks or lowers testosterone levels in your body, and chemotherapy can cause problems with testicular function.

• Aging. Hypogonadism may develop as part of the natural aging process.

• Hemochromatosis. Hemochromatosis is a medical condition where excessive iron builds up in your body. It can lead to low testosterone and other complications like liver disease.

Causes of Secondary Hypogonadism

Causes of secondary hypogonadism include:

• Congenital abnormalities. Conditions present from birth that cause problems with the release of GnRH from your hypothalamus or LH from your pituitary gland can lead to secondary hypogonadism. 

• Kallmann syndrome. Kallmann syndrome is characterized by a lack of sexual maturation during puberty. It’s caused by genetic mutations that impair GnRH release.

• Stress-related hypogonadotropic hypogonadism. Prolonged strenuous physical exercise and extreme weight loss can cause elevated corticotropin-releasing hormone. High levels of this hormone can decrease the release of GnRH.

• Pituitary tumors. Most pituitary tumors are non-cancerous, but even non-cancerous tumors can impair the release of hormones from your pituitary gland.

• Sheehan syndrome. Sheehan syndrome is caused by bleeding in the brain during childbirth. It leads to damage to the pituitary gland.

• Infections. Infections of your pituitary gland can lead to damage that impairs its release of LH and other hormones. 

• Anabolic steroids. Anabolic steroids are synthetic versions of testosterone often abused for muscle gain. When you take anabolic steroids, your hypothalamus and pituitary can sense that the level of testosterone in your blood is high, which causes these glands to stop producing FSH and LH. Without FSH and LH, your testicles stop making sperm and testosterone. Basically, your body is stopping natural testosterone production to compensate for the high levels of androgens in your blood from abusing anabolic steroids.  The problem is that when you stop taking anabolic steroids, your testicles may not recover their own testosterone production for up to 2 years. During this time levels remain very low and affected people may have profound symptoms of low testosterone. 

•  Traumatic head injury. Traumatic head injuries can lead to pituitary damage that impairs LH release.

Male hypogonadism can develop in any person who is biologically male. Older adults and some people with particular diseases or genetic conditions are at an elevated risk.

Risk Factors for Male Hypogonadism 

Having a genetic condition that impairs your testosterone production can put you at a high risk of developing hypogonadism. The same is true for genetic conditions impairing your GnRH or pituitary hormone production.

Male hypogonadism also seems to be more common in people with obesity or diabetes. Large studies suggest that hypogonadism could occur in as many as 45-57.5 percent of obese males.

Obesity is considered the most significant risk factor for testosterone deficiency. The link between these two conditions goes both ways. Lower testosterone levels can promote fat gain, while increased body fat can impair your body’s ability to produce testosterone by impairing the release of GnRH.

About a third of men with type 2 diabetes have low testosterone levels, with some studies estimating that it could be up to two-thirds.

Other risk factors that have been linked to hypogonadism include:

• increased age

• some infections, such as HIV

• malnutrition

• previous chemotherapy or radiation therapy

• chronic opioid abuse

• infertility

• chronic anabolic steroid use

The diagnostic process for hypogonadism often starts by talking with your primary healthcare provider. If they suspect that you may have a problem with your hormone levels, you may be referred to a doctor who specializes in endocrinology or to a urologist who specializes in men’s health.

Diagnosing Male Hypogonadism

Your healthcare provider will start by:

• reviewing your personal and family medical history

• performing a physical exam

• considering your symptoms

They may ask you questions from the Androgen Deficiency in Aging Males test, a 10-item questionnaire that can guide doctors toward diagnosing hypogonadism. Examples of some of the questions on this questionnaire include:

• Do you have a decreased libido (sex drive)?

• Do you have a decrease in strength and/or endurance?

• Are your erections less strong?

The primary test for diagnosing male hypogonadism is a blood test to measure your total testosterone levels. Doctors usually perform this test in the morning because this is when your testosterone levels are generally highest.

You’ll usually receive an 8 a.m. and 10 a.m. test. The results of two tests are often sufficient to make a diagnosis if they both show you have a low total testosterone level.

Your doctor may also want to measure levels of other substances in your blood. You may receive blood tests for:

• FSH and LH hormone levels

• free testosterone levels

• thyroid hormone levels

• vitamin D

• iron

• transferrin

• estradiol

• cortisol

• prostate-specific antigen (PSA) levels

You may also receive other test such as:

• imaging of your pituitary gland

• genetic studies

• semen analysis

Karyotype testing may be performed in young adults to rule out Klinefelter syndrome, or other genetic syndromes. This type of testing uses a blood sample or other fluid sample to look for abnormal chromosomes that contain your genetic information.

Not all men with low testosterone require treatment. If treatment is needed, it usually involves taking a synthetic version of the hormone testosterone to increase your levels. In some cases, though, a doctor may recommend taking medication that promotes your body’s own production of testosterone instead of giving you synthetic testosterone. This is especially important for men interested in preserving their fertility because taking testosterone can cause male infertility.

Along with testosterone treatment, you may also receive treatment for the underlying cause of your condition.

For example, if you have an undescended testicle you may require surgery. Pituitary tumors may be removed surgically or shrunk with medications.

Male Hypogonadism Treatment

Your healthcare provider can help you determine whether you may benefit from testosterone replacement or other treatment for hypogonadism.

Some males may have low testosterone levels but don’t develop any symptoms. If you fall into this category, you likely won’t need treatment, but your doctor may want to follow up to make sure you don’t develop symptoms in the future.

The most common treatments for hypogonadism include:

• testosterone replacement therapy (TRT)

• clomiphene citrate (generic for Clomid®)

• enclomiphene citrate

• anastrozole

• human chorionic gonadotropin (hCG)

Testosterone Replacement Therapy (TRT)

The primary treatment for male hypogonadism is testosterone replacement therapy. TRT can be delivered in several different ways, such as:

• oral capsules

• gels that you apply to your body, arms or legs

• a patch applied to your thigh or torso

• an intramuscular injection

• a gel-like substance applied to your gums and cheeks

• a nasal spray

• implantable pellets under your skin

Until recently, TRT was not typically delivered orally because of the risk of liver damage and poor absorption, but several safe and effective oral forms of testosterone were approved starting in 2019. 

Nonetheless, TRT may not be suitable for everyone, especially those who hope to have kids someday. The most common side effects include low sperm count, an increase in red blood cells (erythrocytosis), and breast growth. While earlier studies on TRT suggested an increase in cardiovascular events like stroke and heart attack, these risks have been debunked.  

Clomiphene Citrate

Clomiphene belongs to a class of medications called selective estrogen receptor modulators (SERMs). These drugs boost luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to trigger testosterone and sperm production. 

Though clomiphene is FDA-approved to treat infertility in women, it is often prescribed off-label for men with hypogonadism. Unlike TRT, clomiphene does not cause infertility, though it can cause side effects like mood swings, hot flashes, and headaches.

Enclomiphene Citrate

Like clomiphene, enclomiphene is also a SERM prescribed off-label for male hypogonadism. It works similarly by boosting LH and FSH levels to increase testosterone without harming sperm production.

Some men prefer taking enclomiphene to clomiphene because the drug is better tolerated with fewer adverse effects.      

Anastrozole

Anastrozole is an aromatase inhibitor. It blocks the conversion of testosterone to estradiol, which raises serum testosterone concentrations and intratesticular testosterone. 

Studies have shown that anastrozole doesn't just raise testosterone levels.  Similar to TRT, anastrozole can improve sexual desire, muscle mass, and strength. Unlike TRT, anastrozole does not lower sperm parameters. 

Human Chorionic Gonadotropin (hCG)

Like TRT, hCG is typically administered through injections to increase testosterone concentrations. It acts as an analog of LH by stimulating the Leydig cells to produce and release intratesticular testosterone. Unlike TRT, hCG preserves sperm production and does not alter testicle size.  

Low testosterone levels are common among people with type 2 diabetes and obesity. Taking steps to prevent these conditions may help reduce your chances of developing hypogonadism.

Male Hypogonadism Prevention Tips

You may be able to reduce male hypogonadism by taking steps to reduce type 2 diabetes and obesity. These might include:

• eating plenty of whole foods like fruits, vegetables

• exercising regularly

• eating plenty of protein

• minimizing your intake of added sugar

• getting plenty of sleep

• reducing stress from your life

• make small changes to your lifestyle to get in more exercise such as taking the stairs instead of the elevator

Think you may be struggling with hypogonadism? Reach out to a healthcare provider to find out if your symptoms are the result of abnormally low testosterone levels. They’ll offer guidance on how to get diagnosed and what treatments can help. 

If hypogonadism is impacting your ability to get or maintain an erection, find out what ED treatments are available.