Washington: Researchers at Columbia University Medical Center are developing a pill what may be the first non-steroidal, oral contraceptive for men.
Tests of low doses of a compound that interferes with retinoic acid receptors (RARs), whose ligands are metabolites of dietary vitamin A, showed that it caused sterility in male mice. The researchers found that low doses of the drug stopped sperm production with no apparent side effects. Normal fertility was restored soon after drug administration was terminated.
Scientists have known for almost 100 years that depriving an animal of dietary vitamin A causes male sterility. While investigating targeted loss of function of the gene encoding one of the RARs, RARalpha, which results in male infertility, senior author Debra J. Wolgemuth, ran across a paper by Bristol-Myers Squibb on a compound that was being tested for the treatment of skin and inflammatory diseases.
The compound seemed to cause changes in the testis similar to the mutation that Wolgemuth and first author Sanny S. W. Chung were studying in her lab. Wolgemuth and her team than tested the drug in mice and noted that the changes it caused were similar to what one sees with vitamin A-deficiency and loss of function of RARalpha.
"We were intrigued. One company`s toxin may be another person`s contraceptive," she said. To investigate whether the compound prevented conception at even lower levels than those cited in the company`s study, Wolgemuth`s team placed the treated male mice with females and found that reversible male sterility occurred with doses as low as 1.0mg/kg of body weight for a 4-week dosing period.
The study was recently presented at the 93rd Annual Meeting and Expo in Boston, Massachusetts.