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

Abstract

IntroductionThere is unmet need for male contraceptive options, but a recent injectable combination male contraceptive trial was terminated early due to adverse events (AEs).MethodsWe 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.ResultsWe 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.ConclusionsFemale 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.

Emerging approaches to male contraception

“…Male hormonal contraceptive trials have reported a number of adverse side effects, including signs such as acne and weight gain and symptoms such as depression and reduced libido (22), although the rates of these symptoms are similar to those reported by women using female hormonal methods of contraception (23). Women using hormonal contraception experienced more headaches and weight gain than men did, but the decrease in libido was comparable across genders.…”

“…Women using hormonal contraception experienced more headaches and weight gain than men did, but the decrease in libido was comparable across genders. In contrast, men in hormonal contraceptive trials experience more acne, increases in libido, and depression (23). Women were more likely to discontinue the use of the contraceptive agent than men (23), but this may be because of the fact that the data from women came from real-world use (24), whereas the male data come from a contraceptive efficacy trial (21) in which the men were self-selected volunteers.…”

“…In contrast, men in hormonal contraceptive trials experience more acne, increases in libido, and depression (23). Women were more likely to discontinue the use of the contraceptive agent than men (23), but this may be because of the fact that the data from women came from real-world use (24), whereas the male data come from a contraceptive efficacy trial (21) in which the men were self-selected volunteers. The issue of depression in men in male contraceptive studies is particularly worrisome.…”

Epistemic risk and nonepistemic values in end‐of‐life care

“…In both cases, our decision depends heavily on various social attitudes and values: for example, upon how the disease and its treatment are viewed. Abbe and Roxby describe how a clinical trial of an injectable male contraceptive was terminated early due to adverse events like acne or mood changes, even though contraceptives used frequently and widely by women had similar frequencies of adverse events to those reported in the male contraceptive trials 18 . Moreover, trials of female contraceptives which were used to justify their licensing reported more serious adverse events than trials of male contraceptives which were abandoned 18 .…”

“…Abbe and Roxby describe how a clinical trial of an injectable male contraceptive was terminated early due to adverse events like acne or mood changes, even though contraceptives used frequently and widely by women had similar frequencies of adverse events to those reported in the male contraceptive trials 18 . Moreover, trials of female contraceptives which were used to justify their licensing reported more serious adverse events than trials of male contraceptives which were abandoned 18 . This suggests that we evaluate the risks of medications based not only upon their adverse effects, but upon who is experiencing them.…”