Latest advances in oral hormonal male contraception: efficacy, mechanisms of action, and future perspectives

Between 2008 and 2011, the rate of unintended pregnancies decreased by approximately 18% in the USA, largely due to the wider use of effective, long-acting, reversible contraceptives among women, such as intrauterine devices and subdermal implants. Despite advances in female contraception, the development of safe and convenient male contraceptive methods remains a significant clinical challenge. Current clinical research focuses on two oral hormonal agents: dimethandrolone undecanoate (DMAU) and 11β-methylnortestosterone dodecylcarbonate (11β-MNTDC). These synthetic androgenic and progestagenic steroids inhibit gonadotropin secretion and spermatogenesis by suppressing key molecules of the hypothalamic–pituitary–gonadal axis. Phase I and IIa trials have shown that they effectively suppress luteinizing hormone, follicle-stimulating hormone, and testosterone to contraceptive levels and have favorable safety profiles and mild adverse effects (e.g., slight weight gain and minor libido changes), with 11β-MNTDC associated with relatively milder adverse effects. DMAU and 11β-MNTDC differ slightly in their metabolic effects and tolerability. Longer-term phase IIb and III clinical trials are required to confirm their efficacy, reversibility, and safety. Both agents have the potential to become the first reversible oral hormonal male contraceptive.