More than six decades after the introduction of the female birth control pill, women’s contraceptive options have expanded dramatically. Today, women can choose from multiple hormonal pills and patches, implants, and hormonal and non-hormonal intrauterine devices (IUDs), providing a range of reversible, reliable ways to prevent pregnancy.
Men, by contrast, remain largely limited. Their only options are the barrier condom, which has a typical failure rate of 18 percent in the first year of use, or the essentially irreversible vasectomy. This imbalance contributes to a striking public health reality: Globally, there are approximately 121 million unintended pregnancies annually, with significant health, economic, and social consequences for women and families.
There is growing demand among men for new contraceptive choices. In one US and Canada survey of over 2,000 men, 75 percent reported a willingness to try novel male contraceptives.
Excitingly, new options may be on the horizon with several contraceptives recently entering human clinical trials, and at least a dozen others approaching preclinical development. For the first time in decades, men may soon have a suite of reliable, reversible contraceptive options comparable to those long available to women.
Why haven’t more male birth control methods been developed?
Over the last 50 years, many male contraceptives have been tested, but most have stalled due to side effects or impracticality. One of the earliest approaches was exogenous testosterone, which suppresses the hormones needed for endogenous steroid production and spermatogenesis.
However, testosterone can’t be administered orally because it is rapidly broken down by the liver, rendering it ineffective. Because of this, the first hormonal contraceptives for males were weekly intramuscular injections.
Two clinical trials by the World Health Organization in the 1990s demonstrated that 60 percent and 96.6 percent of men reached contraceptive-level suppression (≤1 million sperm per mL) after weekly injections of testosterone. However, the approach ultimately proved impractical. Sperm suppression typically required three to four months, while recovery after discontinuation could take as long as seven months. Moreover, a small subset of men never achieved sufficient suppression, and 12 percent of participants discontinued due to the demanding nature of the weekly injections.
Testosterone treatment has been associated with a range of side effects, including serious risks such as cardiac toxicity and liver damage. The most common adverse effect is erythrocytosis, which has been linked to cerebrovascular disease. Other less severe side effects include weight gain, acne, injection-site pain, and mood changes such as aggression or decreased libido. In addition, approximately 2.2 percent of men fail to achieve sufficient sperm suppression, suggesting that certain men are “nonresponders” to testosterone treatment.
These risk factors are particularly important in the development of male contraception because regulatory agencies maintain a very low tolerance for adverse effects in healthy individuals. Unlike most drugs, which are prescribed to treat illness and are tolerated despite side effects because the benefits outweigh the risks, male contraceptives would be taken by healthy men who face no personal health risks from pregnancy or childbirth. For women, contraceptives mitigate the significant medical risks of unintended pregnancy, making some adverse effects an acceptable trade-off. In contrast, even mild side effects in men can limit adoption, forcing developers and regulators to demand an almost zero-risk profile. As a result, safety remains the critical hurdle in male contraceptive development.
What is changing now?
The limitations of earlier testosterone-only regimens have driven interest in alternative hormonal approaches and non-hormonal methods that avoid these issues. The most advanced of these is NES/T, a once-daily transdermal gel that combines nestorone, a progestin, with testosterone to suppress sperm production while maintaining normal hormone levels. Developed by the Population Council’s Center for Biomedical Research in collaboration with the National Institute of Child Health and Human Development (NICHD), NES/T could soon become the first FDA-approved hormonal contraceptive for men.
In a recently completed global Phase 2b clinical trial involving 222 men, 86 percent of participants reached contraceptive-level suppression by week 12, with a median time to suppression of less than 8 weeks. This is significantly faster than prior testosterone-only regimens, which often required 9–15 weeks. The addition of nestorone reduces the testosterone dose needed and accelerates suppression, while maintaining physiologic testosterone levels to preserve sexual function, bone and muscle mass, and libido.
NES/T has shown promising potential for efficacy, safety, reversibility, and patient acceptability. Contraline, a biotech company specializing in next-generation contraceptives, has since exercised its exclusive option agreement to license NES/T and advance it into Phase 3 trials. “The enthusiasm and demand we have seen from the patients and investigators involved in the NES/T trials have been unmistakable: the world is ready for male birth control,” said Kevin Eisenfrats, co-founder & CEO of Contraline.
However, its effectiveness outside of controlled settings remains to be determined. NES/T requires consistent daily application, and contraceptive protection is compromised if doses are missed. Moreover, NES/T requires two months of daily use before reaching full effectiveness, compared with two to seven days for female oral contraceptives. The upcoming Phase 3 trial will be critical in assessing safety, efficacy, and adherence in a broader and more diverse population, providing the evidence needed for regulatory review.
Towards a male contraceptive pill
Earlier this year, the first clinical trial of a nonhormonal oral male contraceptive published results in Communications Medicine, demonstrating safety and tolerance. The daily pill, YCT-529, developed by YourChoice Therapeutics, works by blocking the RAR-α receptor (retinoic acid receptor-α) in the testes, disrupting the vitamin A-dependent signaling pathway that initiates sperm production.
In the Phase 1a study, 16 healthy men received single ascending doses up to 180 mg. The drug was well tolerated at all dose levels, with only mild, transient side effects such as headache and no significant changes in testosterone, libido, or mood. Pharmacokinetic data showed good oral bioavailability and a long half-life of 2–3 days, suggesting the potential for convenient dosing. While this trial did not measure effects on sperm counts, it established a crucial safety milestone, and longer studies are now underway to test sustained dosing and contraceptive efficacy.
A set-and-forget approach
For men who prefer not to take drugs that interfere with hormones or sperm production, physical barriers offer an alternative approach. Occlusion gels are injectable hydrogels placed directly into the vas deferens, the tube that transports sperm from the testes to the ejaculatory ducts. Once injected, the hydrogel solidifies into a semisolid barrier that blocks sperm, working much like a vasectomy but without cutting the vas deferens.
Two companies are developing occlusion gels for men. Contraline is advancing ADAM, a set-it-and-forget-it method, designed to provide up to two years of contraception. The hydrogel naturally degrades over time, similar to IUDs in women. Contraline has also developed a minimally invasive reversal procedure, tested in preclinical models, to restore fertility on demand.
In April 2025, the first-in-human trial reached a key milestone, demonstrating both safety and efficacy at 24 months. Two participants achieved an absence of sperm at the 24-month mark, highlighting ADAM’s long-term contraceptive potential. Additional participants continue to show efficacy at 12, 15, 18, and 21 months, assessed through lab-based semen analysis and at-home sperm testing.
NEXT Life Sciences is also developing a hydrogel, Vasalgel, designed to block sperm for up to 10 years. Using a proprietary, minimally invasive delivery system tested in Australia, the gel can be administered quickly in a variety of clinical settings. In June 2025, NEXT Life Sciences announced the successful completion of its North American trial with a 100 percent success rate, building on previous successful studies in Australia and Canada.
“Knowing that many women do not tolerate hormone-based pills or contraception devices, the addition of Plan A [Vasalgel] to the market gives everyone a wider array of contraception options,” said Darlene Walley, CEO of NEXT Life Sciences, in a company statement.
The ideal goal of male contraception
The long-term vision is to develop on-demand, temporary fertility blockers. Such a pill could be taken shortly before sexual activity to temporarily suppress sperm, preventing fertilization, with normal sperm function restored within hours.
Recent advances in understanding the molecular machinery of male reproduction have identified several promising targets. For example, in a 2024 study published in PNAS, researchers targeted a protein called SMRT (silencing mediator of retinoid and thyroid hormone receptors) in mice. SMRT normally helps regulate gene expression by turning off certain genes in reproductive tissues. By using an existing cancer drug, MS-275, to inhibit SMRT, the researchers were able to temporarily disrupt sperm production, leading to reversible infertility.
Another target is sAC (soluble adenylyl cyclase), an enzyme critical for sperm motility and maturation. In 2023, researchers demonstrated that inhibiting sAC rendered male mice infertile within 30 minutes of a single dose, and fertility was fully restored the next day. Efforts are ongoing to identify compounds suitable for human testing.
Looking ahead, continued advances in understanding male reproductive biology and innovative delivery methods suggest a future in which men will have a full suite of safe, effective, and reversible contraceptives, offering a more balanced and equitable approach to reproductive responsibility.
Frequently Asked Questions:
Why haven’t men had more contraceptive options until now?
Most male contraceptives tested over the last 50 years faced obstacles such as undesirable side effects, slow onset of action, variable efficacy, or impractical delivery methods. For example, testosterone-only regimens require injections and carry risks such as cardiac toxicity, liver damage, and erythrocytosis. Importantly, regulatory agencies also require extremely low-risk profiles since these drugs would be taken by healthy men who do not personally face the medical risks of pregnancy or childbirth.
What male contraceptives are currently in development?
A diverse range of options are in the pipeline, including hormonal gels, nonhormonal oral pills, long-acting occlusion gels, and experimental on-demand approaches. Together, these could finally offer men safe, reversible, and practical choices beyond condoms and vasectomy.
What hormonal male contraceptives are currently in development?
The most advanced hormonal option is NES/T, a once-daily transdermal gel combining testosterone and nestorone (a progestin). NES/T suppresses sperm production while maintaining normal hormone levels. In a Phase 2b trial, 86% of men reached contraceptive-level sperm suppression in less than 8 weeks. Phase 3 trials will assess efficacy and safety in real-world conditions.
Are there nonhormonal male contraceptive pills?
Yes. YCT-529 is a nonhormonal oral pill that blocks the RAR-α receptor in the testes, halting sperm production. A Phase 1 trial showed it is safe and well tolerated. Other research, including targeting SMRT and sAC proteins, has shown temporary infertility in mice without affecting testosterone or sex drive. These approaches could lead to reversible, on-demand male contraceptives.
What are occlusion gels?
Occlusion gels are injectable hydrogels placed into the vas deferens, forming a barrier that blocks sperm from entering semen. Unlike a vasectomy, this method is reversible. Examples include ADAM, which provides up to two years of contraception, and Vasalgel, designed for up to 10 years. Both are in clinical trials with promising safety and efficacy results.
