While pills, implants, intrauterine devices, and barrier methods have provided women with reproductive autonomy and family planning options for decades, the current contraceptive landscape places a disproportionate amount of physical and mental burden for pregnancy prevention on women. But what about men?
Beyond condoms and vasectomies, both of which come with their own disadvantages – condoms for their relatively high failure rate with typical use, and vasectomies for their semi-permanency – male contraception remains limited, and progress has been slow.
Unfortunately, the solution isn’t as simple as making a male version of the female birth control pill. While female birth control pills work by suppressing ovulation, thickening the cervical mucus and/or altering the uterine lining, the challenge with developing a male pill is that it would have to suppress sperm production and/or viability or inhibit ejaculation in a way that avoids adverse mood and sexual side effects. Preliminary studies of hormonal male birth control pills have attempted to modify testosterone, which is necessary for sperm production, to slow down the rate of metabolization. However, the modified methyltestosterone has been linked with liver toxicity among other undesirable side effects.
Research is being conducted for various hormonal, non-hormonal and medical devices that could provide men with a diversity of options suitable for different lifestyles. Birth control methods need to be dependable and ideally reversible. Aside from these conditions, they should also ideally have minimal side effects, be easy to take or use, and be affordable.
One hormonal method that has been successful as a long-acting, reversible method for men is the NES-T (Nesterone/Testosterone) gel. The gel is applied to each shoulder topically to prevent sperm production while keeping healthy levels of testosterone to minimize side effects and maintain sexual drive and function. This product is currently in Phase 2b clinical trials to evaluate dosage and efficacy, and researchers are hopeful that it will be the first male contraceptive product to reach Phase 3 (confirmation of safety and efficacy in a larger cohort) within the next five to six years.
While hormonal methods are likely to be first to hit the market, non-hormonal options are still needed. In addition to having fewer side effects, non-hormonal contraceptives provide the potential for more diverse drug profiles through target specificity, providing the advantage of targeting different mechanisms of action (i.e., late-stage sperm production) and function compared to its hormonal counterpart that is limited to early-stage sperm inhibition. There are several reversible non-hormonal pills currently in clinical trials that show promise. YCT-529, developed by YourChoice Therapeutics, is a retinoic-acid receptor alpha inhibitor that works by blocking vitamin A access in the testes, thereby inhibiting sperm production. Additionally, a fast-acting, short-term male birth control pill using a soluble adenylyl cyclase (sAc) inhibitor, which has been shown to slow sperm motility and prevent sperm maturation in mice, is currently in preclinical testing, with plans to initiate clinical trials sometime in 2025 for market release by 2031 if shown to be effective in humans. If successful in getting Food and Drug Administration (FDA) approval, this innovative strategy would be particularly appealing for men who have infrequent sexual activity and prefer to not have regular adherence.
The last category of male birth control involves medical devices. In contrast to pharmaceutical methods, which on average have a research and development period of 12 years, medical devices benefit from a shorter timeline of three to seven years to regulatory approval. These devices are typically referred to as vas-occlusive contraception because they involve implanting a device or material (i.e., hydrogel) that blocks the transport of sperm through the vas deferens, the tube that carries sperm to the ejaculatory ducts. Unlike vasectomy, which doesn’t always guarantee reversibility, vas-occlusive methods are easily reversible through the natural degradation of the material, allowing men to restore their fertility if desired. Two companies that currently have occlusion gel contraceptives in the pipeline are Contraline, whose product ADAM is currently in Phase 1 clinical trial testing, while NEXT Life Sciences predicts regulatory approval of its product, Plan A, as early as 2026.
It takes time and continuous treatment to suppress sperm levels to a subfertile threshold.
While the results of the clinical trials are promising and encouraging, most researchers in the field believe it will realistically be another five to 10 years before both hormonal and non-hormonal contraceptives are on the market. Scientifically, there are several fundamental challenges that make male contraceptives more difficult than female contraceptives. Men produce millions of sperm a day while women produce one egg every month, so it takes time and continuous treatment to suppress sperm levels to a subfertile threshold. It is also crucial to consider the pharmacokinetics and timing of drug action, since unlike female contraceptives that act continuously within the body, the method must be designed to target a specific stage in the sperm maturation process.
Once the drugs have been proven effective, there still are several safety requirements to ensure minimal side effects. Currently, aside from condoms and vasectomies, no other male contraceptives have been FDA approved. Part of the drug approval process requires assessing the risk and benefits to the individual taking the drug. For male contraceptives, the risk-benefit criteria are set higher than female contraceptives since there are no tangible health benefits; thus, these medications require a perfect assessment of no risks or side effects. In contrast, female birth control typically results in a range of side effects including irregular bleeding, mood changes, weight gain, headaches and nausea. However, these risks are deemed acceptable by the FDA given the much higher risk of morbidity and mortality associated with pregnancy and childbirth.
Stephanie Page, endocrinologist and Professor of Medicine at University of Washington, says regulatory approval criteria for male contraceptives will evolve because “we should be thinking about the risk as a [couple], not just the man, since both of them are responsible for the pregnancy, and both of them should be responsible for the outcome of the pregnancy […] because we’re trying to prevent a health consequence in the partnership.”
Bringing these products to market requires substantial investments beyond grants and funding from the National Institute of Health and the Male Contraceptive Initiative (MCI). Unfortunately, pharmaceutical companies that could provide ample funding for male contraceptives do not perceive a demand for these products. Moreover, recent federal funding cuts to reproductive health research terminated many studies previously funded by the United States Agency for International Development (USAID), including a female sAc-based contraceptive. Funding losses strain university infrastructure and operations, and threaten to disrupt the research pipeline, leaving many studies unfinished and slowing progress in male contraceptive research.
Another key challenge lies in cultural barriers to male contraceptive uptake. Despite the growing interest in male contraceptives, many couples may still rely on female contraceptives due to the lack of awareness of, and education about, the alternative options for men. That doesn’t mean couples are satisfied with female contraceptives, especially since these existing methods have been associated with several adverse side effects.
Experts believe that a shift in mindset would promote the uptake of male contraceptives. In our conversation with Logan Nickels, Chief Research Officer at MCI, he emphasized that “the conversation has to shift away from thinking about male contraceptives and female contraceptives as mutually exclusive landscapes with two separate populations demanding them … male contraception [is] women’s health.”
Aside from preventing unintended pregnancies, the advancement of male contraceptives will more equitably distribute the benefits and burdens of pregnancy prevention, promoting a sense of shared responsibility for all involved.
To learn more about the current science behind male contraception, we invite you to listen to episode #128 of Raw Talk Podcast, “Male Contraceptives: A Shared Responsibility”. We would like to acknowledge the efforts and ideas of the episode #128 team: Braeden and Hannah were Show Hosts; Mariam and Kristina were our Content Creator and Promo respectively; Angela was our Audio Engineer; and Atefeh was our Executive Producer.
Hi John,
Thank you for taking the time to read this article and for your comment.
I do agree that the way it was phrased can cause confusion and misinformation and for that, I do apologize. I wanted to clarify that what I meant was vasectomies can be reversed but it is not always successful nor does the surgery guarantee a return to fertility–it depends on various factors such as time since vasectomy, so it is generally considered a permanent procedure.
The author unfortunately gets it wrong in the second paragraph:
“Beyond condoms and vasectomies, both of which come with their own disadvantages – condoms for their relatively high failure rate with typical use, and vasectomies for their semi-permanency – male contraception remains limited, and progress has been slow.”
The author’s own reference regarding “semi permanence” of vasectomies says otherwise: “Vasectomy, like other sterilization procedures, is considered a permanent form of birth control”.