Female oral contraceptive pills have been in use since the 1960s, but why are there still no oral contraceptives for males? Despite years of promising research and trial results, we appear to be no nearer to a commercially available, on-demand male contraceptive pill. What gives?
In most countries around the world, women and other people who menstruate have access to an array of contraceptive measures, should they want or need them.
In addition to barrier methods, such as female condoms, people with a female reproductive system can undergo tubal ligation — a form of female sterilization — or get a contraceptive implant, birth control shot, contraceptive patch, an intrauterine device (IUD), a vaginal ring, or contraceptive pills.
According to the latest available data from the Centers for Disease Control and Prevention (CDC), 14%Trusted Source of women aged 15–49 in the United States use oral birth control.
Indeed, the burden of contraceptive careTrusted Source in heterosexual relationships falls predominantly on female partners, research shows. This may not be so surprising if we look at the contraceptive methods currently available for men or people with male reproductive systems.
Condoms and vasectomies are not enough
In most countries around the world, there are only two available male contraceptive methods: condoms, the most common barrier method of contraception, and vasectomy, which is a minimally invasive surgical procedure and permanent contraceptive method.
Vasectomies are presented as reversible, but the results of a reversal procedure are not guaranteed. Some medical sources suggest that while the reversal procedure itself has up to a 95% success rate, pregnancy rates following a vasectomy reversal range between 30–70%.
So while vasectomies are quick, easy, and very safe procedures, they may not leave much space for a change of heart regarding reproductive choices.
When it comes to 100% reversible male contraception, the only option is condoms, but many men — and indeed, in many cases, their partners — dislike this method for various reasons. Research has shown that a top reason for men rejecting condoms is that the ones that are commercially available, by and large, are not the right fit, size-wise.
Furthermore, both penis-havers and their partners can have allergies to latex, the material that many condoms are made of, or to some substances in the lubricants or spermicides coating some condoms.
This indicates that there is a stringent need for new male contraceptive methods. Indeed, men around the world have overwhelmingly attested that they would be open and even keen to try out new birth-control methods, according to a large survey conducted by Steve Kretschmer, founder and executive director of DesireLine, a consultancy firm serving the health development sector.
‘Very high’ demand for new contraceptive methods
Kretschmer’s survey addressed 15,678 men and 9,122 female partners from eight countries: the United States, Côte d’Ivoire, the Democratic Republic of Congo, Kenya, Nigeria, Bangladesh, India, and Vietnam.
The research — whose findings Kretschmer presented at a World Health Organization (WHO) webinar series in September 2022 — was co-funded by The Bill & Melinda Gates Foundation and the Male Contraceptive Initiative.
Kretschmer told Medical News Today that “[t]he research included samples of [approximately] 2,000 men in the [low- and middle-income country] markets and 3,000 men in the U.S., sampled to be representative of men aged 18–60, who have had sex with a woman within the past year.”
The survey also included female partners to assess their level of trust in their male partners’ contraceptive use, as well as their willingness to shift the burden of contraceptive care to their partners.
According to Kretschmer, this survey found that the “[d]emand for [novel] male [contraceptive technologies] is very high, with [the] form of administration, e.g., pill versus gel on shoulder, etc. dominating what drives preference.”
Respondents in some low- and middle-income countries said they would prefer a contraceptive in gel form. “Do note that the ‘gel on shoulder’ preference seen in the African countries […] is for the ‘administrative form’ of a gel only, not for the specific current hormonal product in development (Nestorone/Testosterone Transdermal GelTrusted Source) which is a gel on shoulder application,” noted Kretschmer.
In the U.S., men seemed to be a lot keener on a potential male contraceptive pill. MNT also conducted brief social media surveys asking male MNT and Healthline readers whether they would be open to taking a contraceptive pill in the future.
Of 44 MNT respondents engaging on Twitter, 59.1% said that yes, they would consider taking male contraceptive pills. Of 376 HL respondents engaging on Instagram, 54% responded in the affirmative.
So if the demand is there, why is a male contraceptive pill yet to make its appearance on the market?
The first male contraceptive clinical trials
The first clinical trials for male hormonal contraceptives hail back to the 1970sTrusted Source. Male hormonal contraceptives have the aim of interfering with testosterone production and ultimately stopping the production of sperm.
Without sperm in the semenTrusted Source, or seminal fluid, the fluid that typically comes out of the penis at ejaculation, and which acts as a carrier vehicle for the sperm, there is no danger of fertilizing ovules, or eggs, produced by the ovariesTrusted Source, which results in pregnancy.
The first male hormonal contraceptives to be tested were injection-based, they appeared to be ultimately safe and effective, and the trial participants were able to produce sperm again once they stopped receiving the injections.
Yet several participants discontinued their involvement in these early trials due to the fact that it took a long time for the injections to take full effect and stop the production of sperm, and because they had a “dislike of the injection schedule.”
Later trials — in the early 2000s — tested the efficacy of hormonal contraceptive implants, though often they still required an additional injection protocol.
Studies showed that the participants did not experience any serious side effects, and the contraceptive method appeared effective, yet many of the male participants dropped out, reportedly due to study “protocol-related reasons” and “altered personal circumstances.”
While all this research provided key information about what might be effective and what not, none of them got very far, as the frequency of the required injections put off many of the study participants.
What happened to more recent studies?
Data from one of the more recent studies that promised an effective contraceptive for males were reported in The Journal of Clinical Endocrinology & Metabolism in 2016. This phase 2 clinical trial tested an injectable combination hormonal contraceptive in a group of 320 healthy volunteers aged 18–45 years.
An injection with too frequent side effects
The injection — administered once every 8 weeks — contained norethisterone enanthate and testosterone undecanoate, and its aim was to suppress sperm production.
The study concluded that the contraceptive was effective in reducing sperm production almost to nil, and confirmed that this effect was reversible — all of which was good news. However, it also issued an important caution: Among the participants, there was a high “frequency of reported moderate and severe mood disorders including depression” linked to the use of the injectable contraceptive.
Despite the promising results on efficacy and overall safety, this male contraceptive candidate never made it to the market. Why? The obvious answer seems to be that the participants were uncomfortable and unwilling to put up with the reported side effects — indeed, 20 of the original 320 participants dropped out of the trial for this reason.
Yet the answer may not be as simple: Reportedly, around 75% of the volunteers said they would be happy to continue on the contraceptive at the end of the trial. So if the participants themselves were willing to continue, why did the researchers put an end to the trials? The answer is in the study paper itself.
The WHO Department of Reproductive Health and Research had established an independent Data Safety and Monitoring Committee to assess the trial results, as the WHO was one of the co-sponsors of the study.
In the study paper, the authors note that, in 2011, the external monitoring committee determined that “for safety reasons, recruitment [of further participants for the clinical trials] should be stopped and enrolled participants should discontinue receiving injections and be transitioned to the recovery phase” because, in their estimation, “the risks to the study participants outweighed the potential benefits.”
Since then, several studies on both hormonal and nonhormonal contraceptive candidates have made the headlines, all promising the imminent advent of a commercially available male contraceptive.
Oral hormonal contraceptive candidates
In June 2022, researchers from New York University presented the results of preliminary animal studies and a phase 1 clinical trial testing two oral hormonal contraceptives at the Endocrine Society annual conference in Atlanta, GA.
The drug candidates — dimethandrolone undecanoate (DMAU) and 11 beta-methyl-19-nortestosterone-17 beta-dodecylcarbonate (MNTDC) — are progestogenic androgens that have the potential to suppress sperm production. They also have another benefit, according to the researchers: They could help maintain healthy muscle, bone, and sexual function.
The phase 1 study results suggested that the candidates had potential, and that they were overall well tolerated by the participants. However, it remained unclear what the best dosage would be, and further studies are due.
MNT contacted one of the study authors for more information on the current study development, but as of the date of this article’s publication, we have not had a response.
Nonhormonal contraceptive candidates
Also in 2022, researchers from the University of Minnesota presented the results of a preliminary animal study testing a nonhormonal oral contraceptive candidate at the American Chemical Society spring meeting. Their drug candidate, YCT529, works by targeting the retinoic acid receptor alpha, which plays a role in sperm formation.
In theory, by not using hormones, the drug should also have fewer and less serious cases of the side effects associated with hormonal contraceptives.
The same research team also investigated another potential nonhormonal candidate, EF-4-177, which targets a cyclin-dependent kinaseTrusted Source (CDK), a type of protein involved in regulating the cell cycle.
In a study in mice — whose findings appeared in The Journal of Medicinal Chemistry in January 2023 — the researchers found that EF-4-177 was able to bind well to a CDK called CDK2, which is implicated in sperm production.
This approach seemed effective in the rodent model — the researchers reported that after 28 days on the contraceptive candidate, the sperm count of the mice decreased by approximately 45%.
MNT reached out to the senior author of these studies, Prof. Gunda Georg, who is a professor of medicinal chemistry at the University of Minnesota, to find out more about her and her research team’s progress on the contraceptive candidates.
Prof. Georg told us that, while she and her team are working on several potential candidates, “the project that is the furthest along” involves the selective retinoic acid receptor alpha inhibitor YCT525. This compound, she noted, is now licensed to the pharmaceutical company Your Choice Therapeutics (YCT).
“The next step, which is imminent, is the submission of an IND (Investigational New Drug) application by YCT to the Food and Drug Administration (FDA). After submission of the IND, the FDA has 30 days to respond and either allow or not alow the clinical trial to go forward,” the researcher noted.
“We have had the female pill for about 60 years and it is about time a male pill was developed so that men would be able to better participate in preventing pregnancies. It also would provide men with reproductive autonomy that is better than condoms and vasectomy, the only choices for men right now,” said Prof. Georg.
She also noted that one of the main challenges in getting any potential male contraceptive approved for market distribution is making sure that any side effects are negligible.
“It is a very interesting challenge to work on contraception because a contraceptive will not cure a disease and therefore the bar for safety is much higher than if you develop a drug for cancer or Alzheimer’s disease treatment,” she explained.
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