July 1, 2011

A Male Contraceptive?

Research on mice has found a way to reduce male fertility without reducing libido. Sounds good, right?

Researchers at Columbia University Medical Center may have developed the first practical male contraceptive. Two studies published in June show it to be safe, effective and reversible in mice. Once taken off the contraceptive, male mice were able to reproduce and their male offspring were fertile and appeared normal in all other respects. Better yet, it's an oral contraceptive.

There's no word on when tests in humans might begin.

When mice were no longer given the contraceptive, their ability to produce sperm returned.

The compound stops sperm production by interfering with vitamin A metabolism. It's been known for nearly a century that lack of vitamin A causes male sterility. But most previous studies on male contraceptives have been with steroids. These have been plagued by several problems, including a loss in male libido.

The Columbia researchers report that their mice are mating quite happily.

The contraceptive is a retinoic acid receptor (RAR) antagonist. It acts by binding to cellular receptors that retinoic acid, which is formed in the body from dietary vitamin A, would normally bind to.

The contraceptive was originally being studied by a pharmaceutical company as a treatment for skin and inflammatory diseases, but those studies ceased when it became apparent that the compound lowered fertility. But a compound that lowers fertility is exactly what the Columbia researchers were looking for.

In their first study, the researchers tested the effects of administering the contraceptive for four months. They found no ill effects in treated mice, other than the sterility caused by the contraceptive. When mice were no longer given the contraceptive, their ability to produce sperm returned.

The second study tested the longer term effects of the contraceptive. Mice were given the contraceptive for up to 16 weeks and the dose was lowered to 40% of that used in the first study. Results were similar to those seen in the first study, with the additional observations that two male mice were able to reproduce once the contraceptive was withdrawn and that their male progeny were likewise fertile and appeared normal in all other respects. In fact, mice given the contraceptive for 16 weeks had their fertility return faster than did mice given the contraceptive for a shorter period.

The contraceptive did not affect testosterone production. Neither did it affect vision. Vitamin A plays an essential part in the visual process, but this process does not involve RARs.

An article on the short-term study was published in the June 2011 issue of Endocrinology. The results of the long-term study were presented on June 4 at Endo 2011, the Endocrine Society's 93rd Annual Meeting and Expo, held in Boston from June 4-June 7. An abstract of this presentation is freely available.

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