This medication is used in men who do not make enough of a natural substance called testosterone. Testosterone belongs to a class of drugs known as androgens. Testosterone helps the body to develop and maintain male sexual characteristics (masculinity), such as a deep voice and body hair. It also helps to maintain muscle and prevent bone loss, and is necessary for natural sexual ability/desire.Testosterone may also be used in certain adolescent boys to cause puberty in those with delayed puberty.This product should not be used in women.
Testosterone undecanoate is a long-acting man-made version of testosterone, the natural male sexual hormone. Testosterone is responsible for the normal growth and development of male sex organs and characteristics. It includes growth and development of male organs of penis, testicles, prostate, body hair, vocal cord thickening, and muscle and fat distribution. The FDA approved testosterone undecanoate in March 2014.
Testosterone therapy is increasingly common in the United States, and many of these prescriptions are written by primary care physicians. There is conflicting evidence on the benefit of male testosterone therapy for age-related declines in testosterone. 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. 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. 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. The U.S. Food and Drug Administration warns that testosterone therapy may increase the risk of cardiovascular complications. Other possible risks include rising prostate-specific antigen levels, worsening lower urinary tract symptoms, polycythemia, and increased risk of venous thromboembolism. Patients receiving testosterone therapy should be monitored to ensure testosterone levels rise appropriately, clinical improvement occurs, and no complications develop. Testosterone therapy may also be used to treat hypoactive sexual desire disorder in postmenopausal women and to produce physical male sex characteristics in female-to-male transgender patients.
Benefits of Testosterone Replacement Therapy
LIBIDO AND ERECTILE FUNCTION
A common indication for testosterone therapy is treatment of decreased sexual desire or erectile dysfunction. A systematic review found 23 randomized trials of testosterone therapy’s effects on libido; 13 trials showed some benefit, eight showed no benefit, and two had mixed results.
Although evidence regarding erectile dysfunction is mixed, young men with hypogonadism and erectile dysfunction appear to benefit from testosterone therapy. Some studies have shown improvement in erectile dysfunction in older men and men with comorbid conditions, whereas others have not. Moreover, even in positive studies, the effect of testosterone has been smaller than the effect traditionally reported with phosphodiesterase-5 inhibitors, suggesting that testosterone should not be first-line treatment for erectile dysfunction. There is some evidence supporting the use of testosterone therapy as second-line therapy in men with low testosterone when phosphodiesterase-5 inhibitors are ineffective. There is no evidence that testosterone improves erectile function in men with normal testosterone levels. As part of the Choosing Wisely campaign, the American Urological Association says physicians should not prescribe testosterone therapy for men with erectile dysfunction and normal testosterone levels.
BONE DENSITY, BODY COMPOSITION, AND MUSCLE STRENGTH
Low testosterone levels (less than 200 ng per dL [7.0 nmol per L]) are associated with decreased bone density and unfavorable body composition changes. Testosterone therapy increases bone density at the lumbar spine but not at the hip in middle-aged men with testosterone deficiency. In older men, testosterone therapy increases bone density in the spine and hip. There is no evidence that testosterone therapy leads to decreased fractures or falls. Testosterone therapy consistently increases lean mass and decreases fat mass, but the effect sizes are small and studies have generally failed to demonstrate improvement in strength or physical function.
DEPRESSION, MOOD, COGNITION, WELL-BEING, VITALITY
The few studies of testosterone therapy for depressed mood had mixed results. Testosterone therapy does not improve cognitive function in men with or without preexisting cognitive impairment. There is also mixed evidence for prescribing testosterone to improve vitality, general quality of life, and male “symptoms of aging,” with some studies demonstrating improvement with therapy, and other studies finding no change.
Testosterone and Cardiovascular Health
In a 2015 advisory, the U.S. Food and Drug Administration (FDA) warned that testosterone use is possibly associated with increased cardiovascular risk and advised physicians to discuss this risk with patients before initiating testosterone therapy. This warning came after two observational studies and a meta-analysis of randomized controlled trials showed an increased cardiovascular risk, and the Testosterone in Older Men with Mobility Limitation (TOM) randomized controlled trial was stopped early because of concerns about a higher incidence of cardiovascular adverse events in the testosterone treatment group. However, other meta-analyses did not find an increased cardiovascular risk, and several other observational studies have appeared to demonstrate decreased cardiovascular risk with testosterone therapy. Additionally, one of the observational studies that showed increased risk was criticized for its statistical analyses, and many of the adverse events leading to the early stoppage of the TOM trial were of questionable clinical significance. Although the findings of the TOM trial are concerning, this study enrolled a high-risk population, and its findings may not be generalizable to most men being considered for testosterone therapy.
Proponents of testosterone therapy point to a large number of observational studies consistently finding higher cardiovascular morbidity and mortality in men with low baseline testosterone levels and suggest that treating low testosterone should lead to decreased risk, although it is unclear whether low testosterone was a cause of the increased cardiovascular risk or merely a marker of poor overall health. No randomized controlled trial has demonstrated decreased cardiovascular events or mortality with testosterone therapy.
A recent systematic review found some evidence of benefit in congestive heart failure and increased time to ST segment depression in exercise testing. The review found inconsistent effects of testosterone therapy on lipids and no beneficial effect on reported angina.
The effects of testosterone therapy on cardiovascular health remain unclear. The FDA has mandated that testosterone product manufacturers conduct a large-scale randomized controlled trial specifically to determine cardiovascular risk, but results of any such trial would not be available for years. In the meantime, physicians must counsel patients that the cardiovascular risks and benefits of testosterone therapy are uncertain and should engage in shared decision making.