The male contraceptive pill seems safe and effective

The male contraceptive pill seems safe and effective

The so-called pill, which is the male version of the birth control pill, may be closer. A study presented at Endo 2022, the Endocrine Society's annual meeting in Atlanta, Georgia, showed that two experimental male contraceptive pills (DMAU and 11β-MNTDC) appear to reduce testosterone without causing "unacceptable side effects" , so much so that most of the men who took part in the trials said they were in favor of continuing to take the drug even after the end of the trial, and even recommending it to friends and acquaintances.

"So far, the options for male contraception - comments Tanar Jacobsohn, chief researcher at the Contraceptive Development Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the institute that conducted the experiment - consisted essentially in the vasectomy and the use of condoms , and were therefore very limited compared to those for female contraception. The development of a contraceptive mas effective and reversible oral chile will expand reproductive options for men and women, have a major impact on public health by reducing the number of unwanted pregnancies and allow men to play an active role in family planning. "

Drugs DMAU (abbreviation for dimethandrolone undecanoate) and 11β-MNTDC (abbreviation for nortestosterone dodecylcarbonate) have been under study for some time and have a fairly similar mechanism of action. As early as 2018, a study conducted by the University of Washington and presented, once again, at the annual meeting of the Endocrine Society, showed that DMAU is safe in human tests and that it can reduce the levels of the hormones involved in sperm production. Like most female contraceptive pills, it contains a combination of hormones, particularly an androgen and a progestin, and affects the body's production of testosterone. The problem lies in the fact that, if on the one hand the decrease in testosterone in the testicles actually reduces the production of sperm (and therefore has a contraceptive effect), its decrease in the blood causes side effects such as difficulty in ejaculation, decreased desire, sudden changes. mood and changes in muscle mass. For this reason, all pharmacological approaches of this type (still in the experimental phase) usually combine a hormonal contraceptive with the intake of testosterone by injection or via gel, which absorbed by the skin are able to supply testosterone at levels low enough to avoid production. sperm count but high enough to prevent the aforementioned side effects from occurring. DMAU gets around the problem because it contains undecanoate, a long-chain fatty acid that slows down the testosterone breakdown process, allowing it to be taken only once a day. Similar results for 11β-MNTDC: a study presented at Endo 2019 (conducted on a small group of men) had already demonstrated its efficacy and safety.

The most recent trials The latest results are related to two clinical trials phase 1 with 96 healthy male participants, 28 days in duration. Two or four pills containing the active ingredient or a placebo were administered: testosterone levels fell below normal after seven days of taking the pill, while in the placebo group they remained unchanged.

Furthermore, 75% of the men who took the drug said they wished to continue taking it in the future (in the case of placebo the percentage was 46.6%); in men who took the full dose (400 mg, four pills a day) testosterone levels were significantly lower than in those who took the half dose. There were no significant differences between the two groups, however, as regards satisfaction, the willingness to continue the treatment and the possibility of recommending it to others.

"Positive experiences in clinical trials - continues Jacobsohn - and the high acceptance rate for these drugs may be key factors in convincing the public of the safety of a male contraceptive pill that could be available in the coming decades ".

The alternatives: non-hormonal pills The roads for making a male birth control pill are not just hormonal. In March 2022, for example, a team of scientists said at the American Chemical Society annual meeting that they had developed a 99% effective male contraceptive pill (in mice) and would test in humans by the end. of the year. The work was led by experts from the University of Minnesota, and the drug presented targets a protein called "retinoic acid receptor alpha" (RARα). Retinoic acid is a "by-product" of vitamin A, and has a key function in cell growth, sperm formation and embryo development. Retinoic acid, in particular, must interact with RARα in order to perform these functions. : it has in fact been observed that mice lacking the gene responsible for the production of RARα are sterile. The work in question started from this idea, whose authors developed a compound (identifying its cellular structure with the help of a computer model ) to block the action of RARα. The chemical, called YCT529, acts only on RARα and not on the other two receptors (RARβ and RARγ) of retinoic acid, to minimize possible side effects: administered orally to mice for two weeks , the substance significantly decreased sperm counts and was found to be 99% effective in reducing pregnancies, with no side effects. Six months after treatment, the mice are fertile again. If human trials are successful, the drug could be available in five years.

Another possible candidate for the role of "pill" is a compound developed and tested (also on mice) in 2015 by Haruiko Miyata's team, and described on the pages of Science. The drug targets calcineurin, a protein that plays a very important role in sperm formation. Miyata and colleagues, in particular, analyzed two specific variants of the protein in detail, finding that in mice in which these variants had been inhibited by administration of cyclosporine they became sterile, although still able to mate: their spermatozoa in fact were not able to mate. able to fertilize the eggs, not even through in vitro fertilization, as they were less flexible and unable to bend as they should to penetrate the egg membrane. The team found that it took just 5 or 6 days of feeding to make the animals sterile, and more importantly, that a week after stopping treatment, fertility was fully restored.







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