If the pill passes the clinical trial, the drug could potentially be on the market in five years.

Women have many choices when it comes to birth control. Think of the pill, a contraceptive patch, the IUD and so on. Apart from a condom or a fairly permanent sterilization, men have few options. It means that women bear most of the responsibility for preventing unplanned pregnancies – something that is increasingly perceived as unpleasant by both women and men. And so there has been a call for a real ‘men’s pill’ for years.

male pill

Scientists have been trying to develop an effective oral contraceptive for men for decades. To date, however, there are still no approved pills on the market. But why is the road to the ‘men’s pill’ so bumpy? “Most female contraceptives target sex hormones, such as estrogen and progesterone,” researcher Md Abdullah Al Noman explained in an interview with Scientias.nl from. “Efforts have been made to develop male contraceptive pills that target the male sex hormone; testosterone. However, this leads to unpleasant side effects, such as weight gain, depression, elevated cholesterol, etc.”

little enthusiasm

Because men do not have to experience the consequences of a pregnancy, there are not many men who willingly take a male pill with associated side effects. “This is a major barrier to developing a male contraceptive,” said Al Noman. “That’s why we’re trying to develop non-hormonal birth control pills to prevent hormonal side effects.”

Unplanned Pregnancies
The appearance of a male pill is not only important to expand the number of options available to men. The number of unplanned pregnancies is currently much lower than it was 50 years ago. Yet the female contraceptive methods that have appeared on the market over the past 20 years have not reduced this much further. Globally, half of all pregnancies are unintended. On the one hand, this results in an abortion with major medical, financial and physiological consequences, but it also contributes to overpopulation. This indicates that currently available contraceptives are not adequate. The male pill could therefore also be seen as an extra option to further reduce the number of unplanned pregnancies.

Al Noman and his team have taken an important step. To develop a non-hormonal male pill, they targeted a protein called the retinoic acid receptor alpha (RAR-α) with a difficult word. This protein belongs to a family of three nuclear receptors that bind retinoic acid; a form of vitamin A that plays an important role in cell growth, differentiation (including sperm formation), and embryonic development.

Vitamin A

How it works? “Men produce about 150 sperm cells per heartbeat,” explains Al Noman when asked. “This massive production of sperm is made possible in part by vitamin A at various stages. We also need vitamin A for many essential physiological processes. That’s why we specifically blocked the action of vitamin A in a special way, so that it only reduces sperm production. That way, no other functions are disrupted and we exclude side effects as much as possible.”

Experiment

The researchers designed a compound called YCT529 that has been shown to inhibit RAR-α very potently. When administered orally to male mice for 4 weeks, YCT529 drastically reduced sperm count. Plus, it was a whopping 99% effective in preventing pregnancy. “And all this with no discernible side effects,” emphasizes Al Noman. The mice were able to sire puppies again 4 to 6 weeks after they were no longer given the drug.

A non-hormonal male contraceptive (known as YCT529; structure shown here) prevents pregnancy in mice by blocking a vitamin A receptor, with no apparent side effects. Image: Md Abdullah Al Noman

The findings from the study are promising. Because it really expands the birth control options – and therefore responsibilities – for men. If you gave men more options, they might be more involved in preventing pregnancy than they are now. It can also offer a solution for single men and let them decide for themselves about their fertility. A male pill can then ensure that a man is sure that he does not accidentally get a woman pregnant. That’s a lot more relaxing.

Women

But to what extent are women actually ready for a male pill? Do they dare to hand over that responsibility? “It’s indeed a popular assumption that women don’t trust their partner to take a male pill,” says Al Noman. “But a study has shown that most women from all cultures do trust their partners. Only two percent said they did not trust their partner. In addition, an effective male contraceptive pill does not have to be the only method of contraception for a couple; it can also supplement the women’s pill to prevent the latter from failing.”

clinical trial

Although the researchers have shown that their non-hormonal male pill is effective in preventing pregnancies in mice, we should not celebrate too soon. “So far, YCT529 has shown promising preclinical results,” says Al Noman. “It appears to be able to reduce sperm production without significant side effects. In addition, fertility is restored after stopping the pill. To date we have not had any setbacks. However, it is difficult to predict how the human clinical trial will progress. We still have to demonstrate safety and efficacy there.”

The researchers plan to begin testing in humans in the third or fourth quarter of 2022. If the pill also passes this clinical trial, we may not have to wait long before the drug hits the market. “If all goes well and the drug proves to be safe and effective in clinical trials, the pill could hit the market within this decade, perhaps five years,” concludes Al Noman.