For decades, research has been carried for an effective birth control pill for men without side effects. Recently, researchers at Minnesota University observed in mice that acting on the RAR-α protein involved in sperm formation makes them temporarily sterile without side effects. The researchers identified a compound they called YCT529 that inhibits this protein and is 99% effective in preventing pregnancy when administered in mice. These animals regained fertility after 4-6 weeks. The next step is to start clinical trials in humans and these are expected to start this year.
Currently, women bear most of the responsibility for contraception. There are barrier methods, such as the female condom, the diaphragm and the IUD (Intrauterine Device); and hormonal ones, such as the patch, the vaginal ring, injections, hormone pills and implants. Tubal ligation is the definitive surgical method; it consists of a cutting or blocking the fallopian tubes to prevent eggs from reaching the uterus. Unlike the 9 methods available to women, men only have two options: the male condom and vasectomy. This last method consists of surgery to cut the vas deferens so that no sperm can leave the testicles. Vasectomies can sometimes be reversed, but not always successfully. Research has continued for years looking for effective methods for men, similar to the contraceptive pill for women.
An effective pill has been under investigation for years, but so far research has focused on methods that act on the male sex hormone, testosterone. Its inhibition causes side effects such as weight gain, depression and increased bad cholesterol or LDL. For this reason, the research team in this study identified the protein RAR-α (Retinoic Acid Receptor alpha). This protein is part of a group of three nuclear receptors that bind retinoic acid (a derivative of vitamin A) and is necessary for embryonic development, cell growth and differentiation, for example, by the formation of sperm.
The researchers designed 100 compounds capable of inhibiting RAR-α and found that the compound YCT529 could do so effectively without side effects. Other studies had already been carried out with drugs that inhibited the other two receptors, RAR-β and -γ but less efficiently (with some adverse effects). Oral administration of YCT529 reduced sperm count, preventing pregnancy. One month after administration of the compound was stopped, the mice were fertile again. These are promising results in the search for an effective non-hormonal male contraceptive method. These results will allow the start of clinical trials in humans this year, 2022. However, because it has worked in mice does not necessarily mean it will work in humans; so the search for new compounds continues.