Assessing safety in hormonal male contraception: a critical appraisal of adverse events reported in a male contraceptive trial

BMJ Sex Reprod Health. 2020 Apr;46(2):139-146. doi: 10.1136/bmjsrh-2018-200206. Epub 2019 Nov 21.


Introduction: There is unmet need for male contraceptive options, but a recent injectable combination male contraceptive trial was terminated early due to adverse events (AEs).

Methods: We examined the frequency of reported AEs by male research participants compared with AEs reported in prescribing information of approved female hormonal contraceptive methods. Published data from trials of the top five most-used female hormonal contraceptives, supplemented by contemporary contraceptive research, were compared with the frequency of AEs reported in a male injectable hormonal contraceptive trial.

Results: We observed similar frequencies of AEs reported by users of male contraceptives compared with those reported by female users. Among quantitatively comparable AEs, compared with men, women reported experiencing higher frequencies of headaches, pelvic pain, and weight gain and similar frequencies of decreased libido. Compared with women, men reported experiencing higher frequencies of acne and mood changes. Men discontinued participation due to AEs at a lower frequency than women.

Conclusions: Female hormonal methods generally have similar frequencies of AEs to those reported in a recent male hormonal contraceptive trial, and male users had lower rates of discontinuation due to AEs. There were fewer serious AEs of the male contraceptive than reported in contemporary female trials which resulted in FDA licensure. This suggests there may be implicit bias in the scientific community regarding the level of acceptable risk for users of male contraceptive methods.

Keywords: hormonal contraception; male contraception.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acne Vulgaris / epidemiology
  • Acne Vulgaris / etiology
  • Adult
  • Contraceptive Agents, Male / standards
  • Contraceptive Agents, Male / therapeutic use
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Headache / epidemiology
  • Headache / etiology
  • Hormonal Contraception / methods
  • Hormonal Contraception / standards*
  • Humans
  • Levonorgestrel / adverse effects
  • Levonorgestrel / therapeutic use
  • Libido / drug effects
  • Male
  • Mood Disorders / epidemiology
  • Mood Disorders / etiology
  • Patient Safety / standards*
  • Patient Safety / statistics & numerical data
  • Pelvic Pain / epidemiology
  • Pelvic Pain / etiology
  • Progestins / adverse effects
  • Progestins / therapeutic use
  • Weight Gain / drug effects


  • Contraceptive Agents, Male
  • Progestins
  • Levonorgestrel