Controversies in Testosterone Therapy

Sex Med Rev. 2021 Jan;9(1):149-159. doi: 10.1016/j.sxmr.2020.09.004. Epub 2020 Dec 9.


Introduction: Testosterone prescriptions have increased dramatically in recent years, largely because of changes in expert guidelines. Concerns have been raised that testosterone therapy (TTh) may be associated with an increased incidence of conditions such as cardiovascular (CV) disease, thromboembolic events, obstructive sleep apnea (OSA), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) and also may be a beneficial therapy in the management of prediabetes. As such, considerable debate remains regarding which hypogonadal populations are appropriate candidates for TTh.

Objectives: This systematic review aims to affirm or refute, using the most current evidence, the published concerns surrounding TTh and its potential increased risk of conditions such as CV disease, thromboembolic events, OSA, urolithiasis, BPH, and PCa, as well as its role as a potential tool for managing prediabetes.

Methods: A systematic review of literature surrounding TTh and its impact on increasing risk for the adverse conditions mentioned previously was performed. 62 publications were selected for inclusion based on their relevance to the effects and risks of TTh. Evidence is current through December 2019.

Results: Evidence demonstrates that positive associations exist between TTh and OSA, erythrocytosis, as well as urolithiasis. TTh may potentially be used to treat hypogonadal men with prediabetes. While low testosterone is positively correlated with adverse CV events, TTh in hypogonadal men either has no effect or decreases such risk. TTh is likely not associated with increased risk of PCa incidence or recurrence.

Conclusions: Despite historical beliefs that TTh increases the risk of CV disease, thromboembolic events, BPH, and PCa, recent evidence suggests that TTh conveys less risk than previously perceived. While caution should continue to be exercised, evidence suggests that TTh is a reasonable treatment option in many hypogonadal men who were previously excluded from TTh based on risk factors and prior health histories. Twitchell DK, Pastuszak AW, Khera M. Controversies in Testosterone Therapy. Sex Med Rev 2021;9:149-159.

Keywords: Cardiovascular; Diabetes; Hypogonadism; Prostate cancer; Testosterone; Testosterone therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Hormone Replacement Therapy
  • Humans
  • Hypogonadism* / drug therapy
  • Male
  • Polycythemia*
  • Prostatic Neoplasms*
  • Testosterone / therapeutic use


  • Testosterone