Scientists may be inching closer to developing the first nonhormonal contraceptive pill for men after receiving promising results from animal trials.
The research presented at the American Chemical Society (ACS) spring meeting 2022 lays the ground for clinical trials to see if the contraceptive is effective in human males.
There are many birth control options available to women. However, for some women, these can have side effects. In contrast, there are two forms of birth control for men: the male condom and vasectomy. Both have few notable side effects and serious complications are rare.
Consequently, women tend to bear the burden of responsibility for managing contraception and experience the side effects of using contraceptives.
This burden may be addressed if scientists develop safe and effective male contraceptives.
“Despite advances in reproductive healthcare, women are still forced to spend their fertile years shouldering the responsibility of contraception,” a British Pregnancy Advisory Service (BPAS) spokesperson told Medical News Today.
“Although vasectomies are available, we’ve seen a huge decrease in funding for the procedure across the United Kingdom, with some areas heavily restricting or defunding access for those who want it,” they said.
“For over 100 years now, contraceptive research has focused largely on developing birth control that either stops women from ovulating or makes it difficult for sperm to enter the uterus. Meanwhile, recent studies on male contraception have fallen by the wayside because the side effects are judged to be too burdensome — despite the prevailing expectation of what women are willing to endure to avoid pregnancy.“
– The British Pregnancy Advisory Service (BPAS)
“Coupled with a lack of funding and research interest into methods of contraception for men, the bottom line is that few have seen the benefit — financial or otherwise — in working to provide reliable contraceptives for men,” the spokesperson explained.
Prof. Richard Anderson, Ph.D., Elsie Inglis professor of clinical reproductive science and the deputy director of the Centre for Reproductive Health at the University of Edinburgh Scotland, told MNT that research on nonhormonal male contraceptives had taken place but had not resulted in an effective contraceptive in humans.
“The hormonal approach to male contraception continues to be developed, but men make millions of sperm every moment, and that needs to be completely stopped. There have also been some very promising approaches to a nonhormonal method, but often these haven’t worked or had safety issues when the studies have moved from the lab/animal models to humans,” said Prof. Anderson, who was not involved in the research.
MNT also spoke with Md Abdullah al-Noman, a graduate student at the Institute for Therapeutics Discovery and Development at the University of Minnesota, who presented the research at ACS Spring 2022.
“Most female contraceptives target sex hormones such as estrogen and progesterone. Efforts have been made to develop male birth control pills by targeting the male sex hormone testosterone. But that leads to side effects such as weight gain, depression, increased level of LDL, etc,” he said.
“Since men do not have to suffer the consequences of pregnancy, the threshold for side effects from birth control pills is rather low. This is a big barrier to developing a male contraceptive. That’s why we are trying to develop nonhormonal birth control pills to avoid hormonal side effects.“
– Md Abdullah al-Noman
To go about this, al-Noman and his colleagues conducted an experiment targeting the retinoic acid receptor alpha (RAR-α) protein in male mice.
RAR-α helps bind a type of vitamin A known as retinoic acid that plays a role in sperm formation. By disabling RAR-α, the researchers were able to render the mice sterile.
According to al-Noman, “men produce around 1,500 sperm per heartbeat. This massive production of sperm needs vitamin A in different stages. But we need vitamin A for many essential physiological processes as well.”
Al-Noman and his colleagues synthesized the compound YCT529 to inhibit the RAR-α protein.
“So, we specifically blocked the action of vitamin A in such a way that it reduces sperm production without interfering with other functions of vitamin A to preclude side effects,” he told MNT.
The pill not only reduced sperm count in mice and was able to prevent pregnancy with 99% effectiveness, but it also did so without any observable side effects, he added.
“However, it’s hard to predict how the human clinical trial will go since that’s the most significant barrier for a drug candidate to prove its safety and efficacy. We licensed this candidate to YourChoice Therapeutics, and they are planning to take it to clinical trial by the end of this year,” said al-Noman.
According to the BPAS spokesperson, a safe and effective nonhormonal male contraceptive would ensure that men and women share the responsibility of birth control fairly.
“This isn’t just a question of benefits for men — it’s a matter of working toward ensuring that fertility and contraception are a shared burden and that women are no longer expected to spend the bulk of their fertile years avoiding pregnancy without an active contribution from their partners.“
– The British Pregnancy Advisory Service (BPAS)
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