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Touchet BJ, Williams VL. Testosterone replacement in men with sexual dysfunction in the absence of hypogonadism. afp. 2025;111(4):311-312. Accessed April 28, 2026. https://www.aafp.org/pubs/afp/issues/2025/0400/mbtn-testosterone-replacement-men-sexual-dysfunction.html

Study Population: 43 randomized controlled trials that included 11,419 men 40 years and older with sexual dysfunction; sexual dysfunction was defined as acquired symptoms of decreased libido or erectile dysfunction

Efficacy Endpoints

Erectile function, sexual quality of life

Harm Endpoints

Cardiovascular mortality, prostate-related events, lower urinary tract symptoms, and treatment withdrawal due to adverse events

Narrative

Male sexual dysfunction includes erectile dysfunction, ejaculatory disorders, premature ejaculation, and low sexual desire or libido.2^, 3 Erectile dysfunction is the most common symptom of male sexual dysfunction, with a prevalence of 24% in the United States that increases with age.2 Sexual dysfunction can lead to anxiety and depression, relationship difficulties, lack of sexual confidence, reduced quality of life, and poor self-esteem.4^, 5

Testosterone replacement therapy is approved by the US Food and Drug Administration for men with low total testosterone levels in association with certain medical conditions.6 The Endocrine Society recommends testosterone replacement therapy for symptomatic men with consistently low testosterone levels (300 ng/dL [10.41 nmol/L] or less).7 The American Urological Association recommends that testosterone replacement therapy be used only in men who have documented low testosterone and symptoms consistent with sexual dysfunction.8 However, studies have shown that testosterone replacement therapy is used regularly in men with reported symptoms of sexual dysfunction without testosterone measurements.9 Testosterone replacement therapy seems to improve symptoms of sexual dysfunction in symptomatic men with unequivocally low testosterone levels.7

In this Cochrane review, 43 randomized controlled trials included men 40 years and older with sexual dysfunction.1 Men with primary or secondary hypogonadism, elevated prostate-specific antigen, prostate cancer history, untreated obstructive sleep apnea, polycythemia, severe chronic medical or psychiatric conditions, or fragile health status were excluded. Follow-up ranged from 6 weeks to 24 months.

Erectile function and sexual quality of life were evaluated using validated tools such as the Aging Males’ Symptoms scale or the International Index of Erectile Function questionnaires, and reviewers defined a minimal clinically important difference. Results were examined in the two periods of less than 12 months (short term) and more than 12 months but less than 24 months (long term). Comparisons included testosterone vs placebo, testosterone vs a phosphodiesterase type 5 inhibitor (PDE5I), and testosterone plus a PDE5I vs a PDE5I alone.

Moderate-certainty evidence demonstrated no likely difference between testosterone and placebo in the short term for each of the considered outcomes. That is, none of the outcomes met or exceeded the minimal clinically important difference.

Very low-certainty evidence demonstrated unclear results when comparing testosterone with placebo in the long term for erectile function and withdrawal due to adverse events, with all other outcomes not reported. Very low-certainty evidence also demonstrated unclear results when comparing testosterone and a PDE5I in the short term for erectile function, sexual quality of life, and prostate-related events, with all other outcomes not reported.

Low-certainty evidence demonstrated no apparent difference between testosterone plus a PDE5I compared with a PDE5I alone for erectile function, sexual quality of life, and treatment withdrawal due to adverse events. Evidence was uncertain regarding prostate-related events, and cardiovascular mortality was not reported.

Caveats

Almost one-half of the studies had pharmaceutical company funding (19 of 42). Exclusion criteria included common chronic medical and psychiatric conditions, which limits generalizability. Additionally, studies focused on symptoms of sexual dysfunction and did not include total testosterone measurements. This limits the applicability of the study in relation to current guideline recommendations. Finally, robust long-term evidence is lacking, which limits the ability to provide adequate premedication counseling.

Conclusion: In men with symptoms of sexual dysfunction but no known testosterone deficiency, testosterone replacement therapy does not appear to be different from placebo in the short term. In the long term, it is uncertain whether testosterone replacement therapy is helpful because data were low quality. Current testosterone replacement therapy guidelines recommend confirming unequivocally and consistently low testosterone levels in men with sexual dysfunction before initiating testosterone therapy.

Given these limitations, especially that the studies did not measure total testosterone levels at baseline, we have assigned a color recommendation of yellow (unclear benefits). It is difficult to know whether testosterone replacement therapy would have helped men with known low testosterone levels and symptoms of sexual dysfunction. High-quality studies that include more common medical and psychiatric conditions, as well as actual testosterone values in men with reported sexual dysfunction, are needed.

The original manuscript was published in Medicine by the Numbers, American Family Physician as part of the partnership between TheNNT.com and AFP.

Author

Bradley J. Touchet, MD; Verneeta L. Williams, MD
Supervising Editors: Shahriar Zehtabchi, MD

Published/Updated

April 30, 2026