Testosterone Replacement Therapy in Men With Sexual Dysfunction

Is testosterone replacement therapy (TRT) safe and effective for the management of sexual dysfunction in men whose testosterone levels are unknown?

TRT provides little to no benefit in men with sexual dysfunction in whom testosterone levels are unknown.¹ (Strength of Recommendation: A, consistent, good-quality, patient-oriented evidence.)

Erectile dysfunction (ED) and low libido may result in an inability to experience pleasure during sexual activity. The overall prevalence rates of ED and low libido in men are 22% and 15% to 25%, respectively, and both increase with age.² Sexual dysfunction can negatively impact work productivity, health-related quality of life, self-esteem, and mood.^3,4 The US Food and Drug Administration has approved TRT only for men with testosterone deficiency, a stance supported by the American Urological Association (AUA).^5,6 However, TRT has been widely used in practice to treat sexual dysfunction, regardless of serum testosterone level.⁷

This Cochrane review included 43 randomized controlled trials and 11,419 adult men with sexual dysfunction (average age 40 years or older in each study), regardless of testosterone level. It also included trials that used validated questionnaires to define sexual dysfunction, such as the Aging Males' Symptoms (AMS) scale and the International Index of Erectile Function (IIEF).¹ AMS scale consists of 17 items, categorized into three domains (ie, psychological, somatic, sexual sub-scale) on a scale of severity from 1 (none) to 5 (extremely severe) points per question, with higher scores indicating more severe symptoms of testosterone deficiency. IIEF consists of 15 items, categorized into five domains (ie, erectile function, orgasmic function, sexual desire, intercourse satisfaction, overall satisfaction) on a scale from 0 (severe impairment) to 5 (no impairment) for each question; lower scores indicate more severe symptoms of ED.

More than 90% of the studies were conducted in Europe and the United States.¹ Most trials examined testosterone (ie, 12 studies with oral form, 12 studies with intramuscular injection, 16 studies with gel, two studies with patches) in various doses compared with a matched placebo. Study duration ranged from 6 weeks to 24 months. This review excluded men with polycythemia, a history of cancer, severe obstructive sleep apnea, elevated prostate-specific antigen, or severe chronic medical or psychiatric conditions (eg, diabetes, hypertension, depression, schizophrenia). The study outcomes were erectile function, sexual quality of life, cardiovascular mortality, treatment withdrawal due to adverse events, prostate-related events, and lower urinary tract symptoms.

In adult men with sexual dysfunction, TRT provided little to no benefit over 12 months for symptoms of erectile function, compared with placebo, in trials using either of the validated questionnaires (nine trials; 2,808 participants; moderate-certainty evidence).

TRT also resulted in little to no difference in sexual quality of life in trials that used the AMS scale (five trials; 1,030 participants; moderate-certainty evidence) or the IIEF (two trials; 786 participants).¹ Compared with placebo, TRT was associated with little to no difference in cardiovascular mortality, withdrawal due to adverse events, prostate-related events, and lower urinary tract symptoms over 12 months (moderate-certainty evidence).

Because of the short duration of studies, the long-term effects of TRT on erectile function and the risk of withdrawal due to adverse effects remain uncertain.¹ Notably, many of these studies (19 of the 21 studies that received supported funding) were supported by pharmaceutical companies. Many trials excluded patients with chronic medical and psychiatric conditions, which are common among individuals with sexual dys-function, limiting the generalizability of these conclusions. This review investigated TRT in men regardless of testosterone level, highlighting the need for further research specifically in men with testosterone deficiency.