Clinician Article

Efficacy and Safety of Testosterone Treatment in Men: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

  • Diem SJ
  • Greer NL
  • MacDonald R
  • McKenzie LG
  • Dahm P
  • Ercan-Fang N, et al.
Ann Intern Med. 2020 Jan 21;172(2):105-118. doi: 10.7326/M19-0830. Epub 2020 Jan 7. (Review)
PMID: 31905375
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  • Endocrine
    Relevance - 6/7
    Newsworthiness - 5/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 6/7
    Newsworthiness - 5/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 6/7
    Newsworthiness - 5/7
  • Geriatrics
    Relevance - 5/7
    Newsworthiness - 4/7
  • Internal Medicine
    Relevance - 5/7
    Newsworthiness - 4/7


BACKGROUND: Testosterone treatment rates in adult men have increased in the United States over the past 2 decades.

PURPOSE: To assess the benefits and harms of testosterone treatment for men without underlying organic causes of hypogonadism.

DATA SOURCES: English-language searches of multiple electronic databases (January 1980 to May 2019) and reference lists from systematic reviews.

STUDY SELECTION: 38 randomized controlled trials (RCTs) of at least 6 months' duration that evaluated transdermal or intramuscular testosterone therapies versus placebo or no treatment and reported prespecified patient-centered outcomes, as well as 20 long-term observational studies, U.S. Food and Drug Administration review data, and product labels that reported harms information.

DATA EXTRACTION: Data extraction by a single investigator was confirmed by a second, 2 investigators assessed risk of bias, and evidence certainty was determined by consensus.

DATA SYNTHESIS: Studies enrolled mostly older men who varied in age, symptoms, and testosterone eligibility criteria. Testosterone therapy improved sexual functioning and quality of life in men with low testosterone levels, although effect sizes were small (low- to moderate-certainty evidence). Testosterone therapy had little to no effect on physical functioning, depressive symptoms, energy and vitality, or cognition. Harms evidence reported in trials was judged to be insufficient or of low certainty for most harm outcomes. No trials were powered to assess cardiovascular events or prostate cancer, and trials often excluded men at increased risk for these conditions. Observational studies were limited by confounding by indication and contraindication.

LIMITATION: Few trials exceeded a 1-year duration, minimum important outcome differences were often not established or reported, RCTs were not powered to assess important harms, few data were available in men aged 18 to 50 years, definitions of low testosterone varied, and study entry criteria varied.

CONCLUSION: In older men with low testosterone levels without well-established medical conditions known to cause hypogonadism, testosterone therapy may provide small improvements in sexual functioning and quality of life but little to no benefit for other common symptoms of aging. Long-term efficacy and safety are unknown.

PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42018096585).

Clinical Comments

Family Medicine (FM)/General Practice (GP)

This is an important article for UK General Practice as I have noticed increasing numbers of male patients asking about treatment with testosterone. We will soon follow the US unless evidence is widely available to GPs.

Family Medicine (FM)/General Practice (GP)

This is a methodologically very well developed evidence report. As so often, it leaves us practicing doctors a little perplexed: Based on methodologically not very valuable studies, it is shown that sexual function and quality of life improve a little. The review cannot make any statements on the assessment of relevant undesirable effects such as prostate cancer and heart attack. The bottom line is we don't know if testosterone does more harm than good. However, that is the problem of the included literature and not that of the very good review.


This Clinical Guidelines based on a systematic review of 38 RCTs found no effects on physical function, depression or cognitive function. We must be aware of disease mongering (a practice of widening the diagnostic boundaries of illnesses prompted by drug companies) to expand the markets for treatment. Hypogonadism is more prevalent in male old people because testosterone plasma levels decrease with age. The FDA recommends testosterone supplementation only for classic hypogonadism.

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