Susan J. Diem, MD, MPH; Nancy L. Greer, PhD; Roderick MacDonald, MS; Lauren G. McKenzie, MPH; Philipp Dahm, MD, MHSc; Nacide Ercan-Fang, MD; Allison Estrada, MD; Laura S. Hemmy, PhD; Christina E. Rosebush, MPH; Howard A. Fink, MD, MPH; Timothy J. Wilt, MD, MPH
Acknowledgment: The authors thank Eric Linskens, who assisted with the statistical analysis.
Financial Support: The American College of Physicians.
Disclosures: Dr. Diem reports grants from the National Institute on Aging outside the submitted work. Drs. Diem, Greer, Hemmy, and Wilt and Mr. MacDonald report that this review was funded by a contract with the American College of Physicians. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-0830.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Corresponding Author: Susan J. Diem, MD, MPH, One Veterans Drive (111-0), Minneapolis, MN 55417; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Diem, Greer, Dahm, Ercan-Fang, Estrada, Hemmy, Fink, and Wilt; Mr. MacDonald; Ms. McKenzie; and Ms. Rosebush: One Veterans Drive (111-0), Minneapolis, MN 55417.
Author Contributions: Conception and design: S.J. Diem, N.L. Greer, P. Dahm, N. Ercan-Fang, L.S. Hemmy, T.J. Wilt.
Analysis and interpretation of the data: S.J. Diem, N.L. Greer, R. MacDonald, P. Dahm, L.G. McKenzie, L.S. Hemmy, C.E. Rosebush, H.A. Fink, T.J. Wilt.
Drafting of the article: S.J. Diem, R. MacDonald, L.G. McKenzie, P. Dahm, T.J. Wilt.
Critical revision of the article for important intellectual content: N.L. Greer, P. Dahm, N. Ercan-Fang, H.A. Fink, T.J. Wilt.
Final approval of the article: S.J. Diem, N.L. Greer, R. MacDonald, L.G. McKenzie, P. Dahm, N. Ercan-Fang, A. Estrada, L.S. Hemmy, C.E. Rosebush, H.A. Fink, T.J. Wilt.
Statistical expertise: R. MacDonald, P. Dahm, T.J. Wilt.
Obtaining of funding: T.J. Wilt.
Administrative, technical, or logistic support: N.L. Greer, A. Estrada, T.J. Wilt.
Collection and assembly of data: S.J. Diem, N.L. Greer, R. MacDonald, L.G. McKenzie, A. Estrada, L.S. Hemmy, C.E. Rosebush.
Testosterone treatment rates in adult men have increased in the United States over the past 2 decades.
To assess the benefits and harms of testosterone treatment for men without underlying organic causes of hypogonadism.
English-language searches of multiple electronic databases (January 1980 to May 2019) and reference lists from systematic reviews.
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 by a single investigator was confirmed by a second, 2 investigators assessed risk of bias, and evidence certainty was determined by consensus.
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.
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.
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.
American College of Physicians. (PROSPERO: CRD42018096585)
Diem SJ, Greer NL, MacDonald R, et al. Efficacy and Safety of Testosterone Treatment in Men: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians. Ann Intern Med. 2020;172:105–118. [Epub ahead of print 7 January 2020]. doi: https://doi.org/10.7326/M19-0830
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Published: Ann Intern Med. 2020;172(2):105-118.
Published at www.annals.org on 7 January 2020
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