Low Testosterone

Testosterone is the best-known androgen (i.e., male sex hormone). It is secreted by the testicles and is responsible for the development and maintenance of secondary male characteristics (e.g., increased body and facial hair, enlarged larynx, deep voice, muscularity). Low testosterone (i.e., hypogonadism) results from the failure of the testicles to produce normal levels of testosterone due to a problem within the hypothalamic-pituitary-testicular (HPT) axis.^[1]

• Low sex drive
• Erectile dysfunction (i.e., the inability to get or keep an erection)
• Low sperm count
• Reduced muscle mass and strength and increased fat mass
• Low bone density (i.e., osteoporosis)
• Loss of body hair
• Gynaecomastia (i.e., enlargement of breast tissue)
• Sleep disturbances
• Reduced energy, depressed mood, and trouble concentrating

Testosterone levels are assessed using a blood test. The cutoff for low testosterone differs between organizations, but most define it as a total testosterone level of <231–275 ng/dL.^[2] Testosterone levels should be assessed early in the morning (between 7–11 a.m.) when peak levels occur, and in a fasted state. Two separate low testosterone measurements (preferably four weeks apart) along with clinical signs and symptoms of low testosterone are needed to be diagnosed with low testosterone.

Testosterone replacement therapy (TRT) is the primary treatment option for low testosterone and can be given as an oral pill, buccal tablet (which dissolves in the mouth), injection, nasal gel, topical gel, transdermal patch (worn on the skin), or implant.^[1] TRT appears to be safe,^[3] although there is limited data on long-term safety.

Each form of administration can cause unique adverse effects, but in general, TRT may cause erythrocytosis (as indicated by a hematocrit level > 54%), acne, oily skin, reduced sperm production, and/or growth of metastatic prostate cancer.^[1] Additionally, TRT is contraindicated for certain populations such as people with a recent history of heart attack or stroke, heart failure, or prostate cancer.^[1]

A long list of supplements are marketed as testosterone boosters, but there is scant evidence to suggest that any of them affect testosterone levels.^[4][5] Some of the more popular options include saw-palmetto, ashwagandha, tribulus-terrestris, fenugreek, d-aspartic-acid, maca, horny-goat-weed, and boron.

Supplementing with certain nutrients such as vitamin D, zinc, and magnesium can slightly increase testosterone levels if dietary intake and serum levels are inadequate.^[6]

In many men low testosterone is caused by reversible conditions, such as excess body fat and chronic disease (e.g., type-2-diabetes, metabolic-syndrome). Consequently, a hypocaloric diet is very effective for increasing testosterone levels in this population,^[7] whereas a hypocaloric diet seems to reduce testosterone levels in lean men.^[8][9]

In addition, dietary fat is a potential nutrient of concern because limited evidence suggests that low-fat diets (≤25% of energy intake) decrease testosterone levels compared to higher-fat diets (about 40% of energy intake).^[10]

Exercise — whether it’s aerobic exercise, high-intensity interval training, or resistance training — increases testosterone levels,^[11] especially when it’s included as part of a lifestyle intervention to reduce body weight.^[12] Exercise may also improve the effectiveness of TRT.^[13] Bariatric surgery is another effective method for increasing testosterone levels in men with obesity.^[14]

The cause of low testosterone is classified as either primary or secondary and further categorized as functional or organic. Primary hypogonadism originates from a problem in the testicles, while secondary hypogonadism indicates a problem in the hypothalamus or the pituitary gland, which are the parts of the brain that signal the testicles to produce testosterone.^[1]

Functional hypogonadism is caused by factors that suppress testosterone levels (e.g., medications, obesity, type 2 diabetes, aging, excessive exercise, malnutrition) but are potentially reversible, while organic hypogonadism is caused by a congenital, structural, or destructive condition (e.g., Klinefelter syndrome, Kallmann syndrome, hemochromatosis, inflammatory disease, injury to the testicles, traumatic brain injury, chemotherapy or radiation) that results in largely irreversible hypothalamic, pituitary, or testicular dysfunction.^[1]