Testosterone Deficiency Syndrome

Testosterone deficiency syndrome is a condition that occurs when the body does not produce enough testosterone, the main male hormone that plays a key role in sex drive, muscle mass, and physical and mental energy.

Table of contents

• What is testosterone deficiency syndrome?
• Other names for this condition
• The role of testosterone in the body
• Symptoms and signs
• Causes and risk factors
• Who is affected?
• What is considered a low testosterone level?
• How is it diagnosed?
• Treatment options
• Monitoring during treatment
• Potential risks of treatment

What is testosterone deficiency syndrome?

Testosterone deficiency syndrome, also known as male hypogonadism, occurs when the body does not produce enough testosterone, the main male hormone^[1]. Testosterone plays a key role in an individual’s sex drive, muscle mass, and mental and physical energy^[1].

male hypogonadism, testosterone deficiency, low testosterone, low-T, andropause, primary hypogonadism, secondary hypogonadism, hypergonadotropic hypogonadism, hypogonadotropic hypogonadism

This condition generally affects older individuals, but younger patients can also be affected^[1]. The condition can affect people with testicles at any age from birth through adulthood^[2].

While the term “andropause” is sometimes used for this condition, it is inaccurate. Unlike menopause (when a woman’s body stops producing eggs and menstrual periods end), testosterone deficiency syndrome is not an inevitable result of aging^[1]. Men’s testosterone levels decline gradually, about 1% to 2% each year beginning in their 40s, while women’s estrogen levels fall more quickly during menopause^[6].

Other names for this condition

Healthcare providers may use several different names when referring to testosterone deficiency syndrome. These include male hypogonadism, testosterone deficiency, low testosterone (often abbreviated as “low-T”), primary hypogonadism, secondary hypogonadism, hypergonadotropic hypogonadism, and hypogonadotropic hypogonadism^[2].

The role of testosterone in the body

Testosterone is the main androgen, a hormone responsible for masculine traits. Produced by the testicles, specifically by Leydig cells, testosterone is what gives men their manliness^[2]. It is responsible for male characteristics like a deep voice, muscular build, and facial hair^[6].

Testosterone is essential for sperm production (called spermatogenesis). Levels of testosterone are naturally much higher in men than women^[2].

In men, testosterone helps maintain and develop sex organs and genitalia, muscle mass, adequate levels of red blood cells, bone density, sense of well-being, and sexual and reproductive function^[2]. Testosterone also fosters the production of red blood cells, boosts mood, keeps bones strong, and aids thinking ability^[6].

Your body usually tightly controls the levels of testosterone in your blood. Levels are typically highest in the morning and decline through the day^[2]. Your hypothalamus and pituitary gland (both located in the brain) normally control the amount of testosterone your testicles produce and release. The hypothalamus releases gonadotropin-releasing hormone (GnRH), which triggers the pituitary gland to release luteinizing hormone (LH). LH then travels to the testicles and stimulates the production and release of testosterone. The pituitary also releases follicle-stimulating hormone (FSH) to cause sperm production^[2].

Symptoms and signs

Symptoms of low testosterone can vary considerably, particularly by age and how severe the condition is^[2]. The clinical picture is usually typical in young men whereas it is usually less clear in older men, because of their slow decline in testosterone levels^[7].

Symptoms that highly suggest low testosterone in men include reduced sex drive (also called libido), difficulty obtaining or keeping an erection (erectile dysfunction), loss of armpit and pubic hair, shrinking testicles, hot flashes, and low or zero sperm count, which causes male infertility^[1][2].

Other symptoms of low testosterone in men include difficulty concentrating or making decisions, poor results from exercise programs, increase in body fat, loss of lean body (muscle) mass, loss of bone density, depression, poor work performance, unfavorable changes in cholesterol profile, depressed mood, and difficulties with concentration and memory^[1][2].

Some men with low testosterone do not have any symptoms^[6]. Symptoms may also be caused by other conditions, such as high blood pressure or diabetes. If any of these symptoms are bothering you, talk with your provider^[6].

How testosterone deficiency affects different age groups

When testosterone deficiency occurs in the womb before birth, it can affect the development of outer sex organs. Depending on when it starts and how much testosterone there is, a baby whose genes are male may be born with female genitals, genitals that are neither clearly male nor clearly female (called ambiguous genitals), or male genitals that don’t develop fully^[3].

Male hypogonadism that occurs in the first 10 years of life can delay puberty or cause incomplete or lack of usual development. It can get in the way of muscle mass growth, the voice getting deeper, growth of body and facial hair, and growth of the penis and testicles. It can cause the arms and legs to grow more than the trunk of the body, and growth of breast tissue (called gynecomastia)^[3].

In adults, hypogonadism can change certain physical traits and affect the ability to have children. Early symptoms might include less sex drive, less energy, and depression. Over time, men with hypogonadism can have difficulty getting and keeping an erection (called erectile dysfunction), problems having children (called infertility), and less hair growth on the face and body^[3].

Associated health conditions

Testosterone deficiency syndrome can contribute to the start or worsening of various diseases. This can include increased risk of cardiovascular disease, increased risk of death from a cardiovascular event, increased risk of metabolic syndrome (high blood pressure, elevated insulin levels, excess belly fat and abnormal cholesterol levels), strong association with diabetes, strong association with atherosclerotic disease of the aorta (the main artery carrying blood from the heart), higher incidence of prostate cancer, and association with more aggressive variants of cancer^[1].

• testicles
• hypothalamus
• pituitary gland
• aorta

Causes and risk factors

Any issue with your testicles, hypothalamus or pituitary gland can cause low testosterone^[2]. The most common cause of low testosterone is age. Beginning around age 30 to 40, testosterone levels may start to slowly decrease. This occurs naturally^[6].

Other causes of low testosterone include medicine side effects, such as from chemotherapy or corticosteroid drugs; testicle injury or cancer; problems with glands in the brain (hypothalamus and pituitary) that control hormone production; low thyroid function; too much body fat (obesity); other disorders, chronic diseases, treatments, or infection; chronic illness; stress; and alcoholism^[1][6].

Children can be born with male hypogonadism due to congenital conditions (medical conditions that you’re born with). One example is Klinefelter syndrome, when a genetically male child is born with an extra X chromosome. Children with Klinefelter syndrome may have smaller testicles that produce less testosterone. Children with intersex conditions (development of both male and female reproductive organs) may also have trouble with testosterone production^[9].

If there is a problem with the pituitary gland, the testicles might not get the “message” to produce testosterone. Testicles that have been injured in an accident or through pelvic trauma may not function properly. If a man has one or both testicles surgically removed due to cancer, his body will produce less testosterone. Chemotherapy and radiation can affect testosterone production too^[9].

Who is affected?

It’s difficult for researchers to estimate how common low testosterone is since different studies have different definitions for low testosterone. Data suggest that about 2% of men may have low testosterone. Other studies have estimated that more than 8% of men aged 50 to 79 years have low testosterone^[2].

The overall prevalence of testosterone deficiency syndrome varies from 6% to 9.5% in community-dwelling men aged 40 to 70 years, and rises to 15% to 30% in diabetic or obese men^[7].

Low testosterone is more likely to affect people who are older, have obesity, have poorly managed type 2 diabetes, have obstructive sleep apnea (a condition where breathing stops and starts during sleep), have chronic medical conditions such as kidney dysfunction or cirrhosis of the liver (severe scarring of the liver), or have HIV/AIDS^[2].

Men with sexual dysfunction, low physical activity, abdominal obesity, loss of muscle mass and strength, diabetes or metabolic syndrome should be screened for testosterone deficiency syndrome^[7].

Testosterone deficiency syndrome is underdiagnosed and undertreated; less than 10% of men with this condition receive treatment^[7].

What is considered a low testosterone level?

The American Urology Association (AUA) considers low blood testosterone to be less than 300 nanograms per deciliter (ng/dL) for adults. However, some researchers and healthcare providers disagree with this and feel that levels below 250 ng/dL are low^[2].

One recent study helped define testosterone ranges in young men by measuring sample testosterone levels obtained during the conduction of several large studies in a central Centers for Disease Control and Prevention (CDC) lab. This study revealed that 303 ng/dL was the fifth percentile value among healthy non-obese patients between 19 and 39 years of age. Therefore, a cutoff of 300 ng/dL is not unreasonable to use^[8].

Providers also take symptoms into consideration when diagnosing low testosterone. It’s important to remember that a lab result alone cannot diagnose testosterone deficiency syndrome. Symptoms must also be present to confirm the condition^[2][8].

How is it diagnosed?

Physicians should not measure testosterone levels unless a patient has signs and symptoms of hypogonadism, such as loss of body hair, sexual dysfunction, hot flashes, or gynecomastia. Depressed mood, fatigue, decreased strength, and a decreased sense of vitality are less specific to male hypogonadism^[4].

Testosterone deficiency is typically diagnosed with a simple blood test^[1]. Doctors diagnose low testosterone based on a physical exam, a review of symptoms, and the results of multiple blood tests since levels can fluctuate daily^[6].

A member of your healthcare team does a physical exam and looks at your sexual maturing. This is to see if your pubic hair, your muscle mass and the size of your testes are typical for your age^[12].

Blood tests can show testosterone levels. Testosterone levels are most often highest in the morning. So blood testing is usually done between 8 and 10 a.m. It might be done on more than one day^[12]. Low testosterone levels must be demonstrated in at least two morning serum samples taken at an interval of 1 to 2 weeks^[7].

Testosterone therapy should be initiated only after two morning total serum testosterone measurements show decreased levels, and all patients should be counseled on the potential risks and benefits before starting therapy^[4].

If tests show low testosterone, further testing can help find the cause. These studies might include pituitary hormone testing (measurement of serum follicle-stimulating hormone and luteinizing hormone levels to distinguish between primary (testicular) and secondary (hypothalamic-pituitary) hypogonadism), semen analysis, pituitary imaging, and gene studies^[7][12].

Comorbid diseases (other diseases occurring at the same time) and drug interactions must be excluded before considering a diagnosis of testosterone deficiency syndrome^[7].

Treatment options

When a specific cause for testosterone deficiency is identified, treatment can be focused on that cause. In the case of excess pituitary secretion of hormones, for example, medicine or surgery may be used to correct the underlying problem^[1].

If your doctor can identify the source for declining levels, for instance, weight gain or a particular medication, he or she may first address that problem^[6].

When no specific cause can be identified, testosterone replacement therapy is the most common treatment. Testosterone replacement therapy raises the body’s testosterone levels through regular administration of testosterone^[1]. It can raise testosterone levels and help ease the symptoms of male hypogonadism, including less desire for sex, less energy, less facial and body hair, and loss of muscle mass and bone mass^[12].

When synthesizing what has been written about testosterone replacement in medical journals, it’s safe to say that most men will have improvement in sex drive and libido. Improvement in other areas such as mood, vitality, energy and strength is not as well defined or predictable. Erections may improve in some patients, but there is rarely a drastic improvement. Some studies do suggest that testosterone replacement may help medications like Viagra and Cialis work better^[8].

Potential benefits of therapy include increased libido, improved sexual function, improved mood and well-being, and increased muscle mass and bone density; however, there is little or mixed evidence confirming clinically significant benefits^[4].

Methods of testosterone replacement

Various methods can be used to deliver testosterone replacement therapy. These include patches, gels, intramuscular testosterone supplementation (delivered through periodic injections), or “pellets” implanted beneath the skin^[1].

A patch is applied once every 24 hours, in the evening, and releases small amounts of the hormone into the skin. Gels and creams can be applied to the skin. Intranasal sprays are another option. Intramuscular injections of testosterone enanthate or cypionate can be given periodically. Pellet implants, such as TESTOPEL, can be placed under the skin^[8][12].

There are several treatment options available. Healthcare providers typically start by checking your insurance coverage. If your preferred treatment isn’t covered, they can help you explore affordable alternatives, such as generic or compounded options, when available^[8].

Testosterone taken by mouth (oral) isn’t often used for treatment of hypogonadism. Oral testosterone can cause serious liver problems and doesn’t keep testosterone levels even. The U.S. Food and Drug Administration has approved one oral testosterone replacement, testosterone undecanoate (Jatenzo, Tlando, Kyzatrex). The lymph system absorbs it, so it might not cause the liver problems seen with other oral forms^[12].

Monitoring during treatment

Anyone taking testosterone replacement should have a medical checkup and blood tests several times during the first year of treatment and yearly after that. This is to see how well the treatment works and to watch for side effects^[12].

Testosterone, blood count and estrogen levels along with studies such as PSA (prostate-specific antigen) levels, and other hormone levels (as needed) will be monitored with periodic blood tests^[8].

Men receiving testosterone therapy should be monitored regularly for adverse effects and treatment effectiveness, including testosterone measurements, complete blood count to measure hematocrit (the percentage of red blood cells in the blood), and prostate-specific antigen testing^[4].

Potential risks of treatment

Before starting treatment, men should be counseled about the uncertainty of the long-term safety of testosterone, including possible cardiovascular harms, and patients and physicians should engage in shared decision making, weighing the risks and benefits of therapy^[4].

The U.S. Food and Drug Administration warns that testosterone therapy may increase the risk of cardiovascular complications^[4].

Testosterone replacement therapy has risks. These may include infertility, enlarged prostate leading to difficulty urinating, blood clots, worsening cardiovascular disease, sleep problems, cholesterol problems, and at this time, it is unclear whether testosterone replacement therapy increases the risk of prostate cancer or symptoms of benign prostatic hyperplasia (non-cancerous enlargement of the prostate). However, testosterone replacement therapy is avoided in men with prostate or breast cancer as it may worsen their condition. There is an increased risk of high blood pressure with testosterone replacement therapy^[6].

The Endocrine Society recommends against testosterone supplementation for men in certain situations, including those who have prostate or breast cancer, have an elevated blood level of prostate-specific antigen (a blood test used to screen for prostate cancer), or have a prostate nodule that can be felt during a rectal exam^[6].

Other circumstances in which testosterone supplementation is not recommended include a plan to become a father in the near-term, an elevated red blood cell count, severe untreated sleep apnea, severe lower urinary tract symptoms, poorly controlled heart failure, heart attack or stroke within the last 6 months, and a tendency to form blood clots (a condition called thrombophilia)^[6].

If you do not notice any change in symptoms after treatment for 3 months, it is less likely that testosterone replacement therapy treatment will benefit you^[6].