Contraceptive pills for men: another attempt
Researchers from Columbia University Medical Center are working to create the first non-steroidal oral contraceptive for men. In mice, low doses of the test substance, an antagonist of the retinoic acid receptor (one of the forms of vitamin A), caused the cessation of sperm synthesis. No side effects could be detected, and after discontinuation of the drug, spermatogenesis in the experimental subjects was fully restored.
The fact that vitamin deficiency, among other things, leads to infertility, has been known for a long time. And the head of the work, Debra J. Wolgemuth, who studied the consequences of removing the gene of one of the retinoic acid receptors, RARalpha, from the genome of mice (which, as you might guess, leads to male infertility), was lucky to come across an article describing the unsuccessful results of developing a drug for skin and inflammatory diseases. Bristol-Myers stopped working on the drug because of a side effect: it had a toxic effect on the male sex glands - very similar to the result of knockout of the RARalpha gene.
What kind of toxic effect it was, the article did not indicate, but a check in Dr. Vogelmuth's laboratory showed: there is no silver lining. The substance, the rights to which the pharmaceutical concern refused, caused the same changes in the testes in mice as a pronounced deficiency of vitamin A or the absence of a retinoic acid receptor. Checking the effectiveness of different dosages showed that in order to make mice infertile, 1 mg of the drug per kilogram of mouse weight for a month is enough.
Steroid hormones, on the basis of which other male contraceptives have been developed, can reduce sexual desire and increase the risk of cardiovascular diseases and benign prostatic hyperplasia. The RARalpha inhibitor does not affect either the sexual life of mice or other studied indicators of their health, including vision ("chicken blindness" – a violation of twilight vision is one of the first signs of hypovitaminosis A, but other retinoids are involved in the synthesis of photosensitive pigments). And, although real men are not afraid of injections, the drug in tablets is, of course, better than injections of oil solutions of hormones.
Now researchers must finally make sure that their pills are safe and effective even with prolonged use, and most importantly, that the contraceptive effect will remain reversible after many years of use. Then it will be possible to test the drug on human males.
Article by Chung et al. Oral Administration of a Retinoic Acid Receptor Antagonist Reversibly Inhibits Spermatogenesis in Mice is published in the latest issue of the journal Endocrinology.
A. Chubenko
Portal "Eternal youth" http://vechnayamolodost.ru10.06.2011