In the US, unplanned pregnancies represent > 40% of all pregnancies, a number that approaches 50% globally.¹ Unplanned pregnancies adversely impact the physical and economic health of women, children, and their partners.² Restrictions on reproductive agency for women following the June 2022 Dobbs v Jackson Supreme Court decision overturning Roe v Wade, which established women’s federal right to abortion, threatens to increase these rates. Even prior to the Dobbs decision, unplanned birth rates have been significantly higher in states with more restrictive abortion policies,³ numbers which are expected to increase with more restricted access to safe abortion services.

Contraception is our most effective tool in preventing unplanned pregnancy and abortion. Women have a multitude of contraceptive options including birth control pills, intrauterine devices, implants, and vaginal rings. In contrast, male contraception has been limited to condoms and vasectomy, both of which have significant limitations including high failure rates (condoms) and inconsistent and invasive reversal (vasectomy). There is increased urgency to develop and introduce novel male contraceptives; such technologies have the potential to make a significant impact towards strengthening reproductive choices for both men and women and reducing unplanned pregnancies globally.

Emerging Options: Hormonal Male Contraception

Analogous to female hormonal contraceptives, male hormonal contraception employs exogenous sex steroids to interrupt the hypothalamic-pituitary-gonadal axis. Exogenous androgens, alone or in combination with a progestin, suppress secretion of gonadotropins, impairing testosterone production and profoundly suppressing spermatogenesis. Proof-of-concept efficacy studies, sponsored by the WHO in the 1980s, utilized testosterone injections to demonstrate the effectiveness of the hormonal approach, which was further optimized with the addition of progestins in subsequent studies. Further, these fundamental studies elucidated that contraceptive efficacy could be achieved without inducing azoospermia; in fact, a sperm concentration of ≤ 1 million/mL results in a contraceptive failure rate of 1.4/100 person years, comparable to the female birth control pill.⁴

To date, more than 3000 couples have tested the efficacy of combined male hormonal contraceptives, demonstrating both the effectiveness and reversibility of this approach. Currently, a multi-site, international study of over 400 couples is nearing completion. This phase 2b study will evaluate the efficacy of the first ever self-administered, daily male hormonal contraceptive, a combined Nestorone/Testosterone transdermal gel,⁵ and results are expected in early 2025. Concurrently, single agent “combined” male hormonal contraceptives, steroid molecules structurally related to 19-nortestosterone with both progestenic and androgenic action, are also in clinical trials and show promise as once-daily “birth control pills” for men.⁴ These more refined hormonal methods have minimal side effects and have shown high rates of acceptability among both users and their partners in clinical trials.⁴ Thus, there is considerable enthusiasm amongst developers that male hormonal approaches to reversible contraception will be available within a decade.

Emerging Options: Nonhormonal Male Contraception

Nonhormonal male contraceptive options are also in the development pipeline, including contraceptives that target sperm motility, interfere with the process of sperm maturation, or provide a reversible, anatomic barrier to sperm transport. These methods aim to provide effective contraception without altering hormone levels, reducing the risk of hormonal side effects but not eliminating the possibility for other off-target effects. Progress in moving nonhormonal male contraceptives to human trials has been slow, but there has been recent progress towards advancing these methods towards the clinic. Inhibition of sperm motility has shown promise in rodent knock-out models, and new targeted inhibitors appear to have some effectiveness as a reversible, oral contraceptive in mouse models.⁶ Retinoic acid is required for sperm maturation; inhibitors of retinoic acid signaling have recently reached phase 1 human trials.⁷ Strategies to develop a “reversible vasectomy” by administering impermanent barriers within the vas deferens are also in clinical trials in the US and abroad.⁸ Like hormonal male contraceptive development, development of nonhormonal methods will require significant guidance from regulatory agencies for developers to understand the safety and efficacy expectations for approval.

Acceptability and Uptake

While it is impossible to know the true uptake of novel male contraceptives until they reach the market, there is considerable evidence that both men and their female partners have a keen interest in male contraceptive methods.⁹ Across a variety of national and ethnic groups, surveys of men suggest willingness to try novel male methods, including pills, transdermal gels, and periodic injections. Moreover, participants in clinical trials of hormonal methods across an array of modes of delivery are overwhelmingly positive.⁹ Evolving societal norms and attitudes towards reproductive responsibility, gender roles, and perceptions of masculinity suggest men are increasingly interested in sharing the burden of contraception with their partners. An uptick in vasectomy volumes post Dobbs likely reflects these changes.¹⁰

Potential Impact and Conclusion

The landscape of male contraception is evolving, with research exploring new methods to provide men and couples with greater control over their reproductive choices. In the post-Roe era, contraceptive utilization has even greater urgency. Unplanned pregnancies disproportionately impact women of color and women in low resource settings; thus, the introduction of new contraceptive methods has the potential to improve these inequities if these new methods are made accessible. Indeed, a modeling study of reversible male methods which assumed only a 10% uptake among interested men projected a 5% to 40% decline in unintended pregnancies across disparate markets including the US and Nigeria.¹¹

The development of safe, effective, reversible male contraception has the potential to revolutionize reproductive health and empower individuals to take greater control over their fertility. By expanding contraceptive options, male contraception may reshape attitudes towards reproductive health, promote shared responsibility, encourage greater involvement of men in family planning, and improve public health outcomes for all.