Safety & Side Effects
Side effects of hormonal male contraception have been well documented in clinical trials. Early trials of progestins found evidence of weight gain, transient loss of libido in some men and some regimens tested caused gynecomastia and liver function impairment. Certain nonhormonal methods, such as adjudin, show a narrow-dosing margin between efficacy and safety, raising concerns about long-term use.
Participants in clinical trials of current formulations have reported frequent side effects, including night sweats, frequent changes in mood and libido and changes in body composition (weight or fat gain). A 2011 Phase II trial of injectable testosterone undecanoate and injectable norethindrone enanthate was terminated owing to reports of depression in participants. Longer-term safety concerns related to cardiovascular, hematological and prostate effects persist, although there is evidence that the effects on the prostate are not significant. Long-term systemic effects on vital organs may be significant and have not yet been well documented. However, there is no evidence of long-term risks and similar safety concerns apply to all hormonal female methods.
Assurance that infertility is reversible will be vital for any method to be successful. There is variability in both patterns of spermatogenesis suppression, from 6–12 weeks and recovery, from 6 weeks to 6 months. However, return to fertility has been found to be complete. In 30 trials including 1549 men, no participant failed to recover concentrations of 20 million sperm/ml and the median recovery time was 3.4 months. While these lag times are perhaps not ideal, similar lag times apply to vasectomy and a lag of 1 month generally applies to female oral contraceptives.
As nonhormonal approaches do not usually interfere with androgen-dependent functions or organs, such as the prostate and because of the specificity of many of their targets, it is likely that their side effects would be minimal. Depending on the nature of the target (e.g., sperm maturation or motility), there is evidence that nonhormonal male contraceptives could evoke both faster onset and recovery time than hormonal approaches.
As with any new pharmaceutical agent, a complete understanding of the long-term effects will not be possible until Phase IV postmarketing data can be collected. Despite the questions that remain regarding side effects and safety, there is currently much more information relating to the efficacy and safety of male methods compared with what was known about female methods when they were launched in the 1960s.
Expert Rev Pharmacoeconomics Outcomes Res. 2012;12(5):605-613. © 2012 Expert Reviews Ltd.