photoThe invention of the birth control pill unleashed the sexual revolution of the 1960s, but it was up to women to buy the prescription and remember to take the pill every day. Now, a half-century later, could men soon be sharing the responsibility?

Perhaps. Researchers at Columbia University Medical Center say they are close to development of 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. And crucial for a contraceptive, the effects were only temporary. The researchers say normal fertility returns soon after the drug is no longer used.

Long searach

Scientists have been on the trail of a male pill for quite some time. Earlier research led the investigators to the discovery that manipulating the retinoid receptor pathway could interfere with the process of spermatogenesis, which is necessary for sperm production.

Like many new drug discoveries, this one was the by-product of completely different drug research. Columbia's Debra J. Wolgemuth, Ph.D., stumbled 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 she and her team were studying.

Testicular toxin

According to the paper, Bristol-Myers dropped its interest when it found that the compound also was – in the company’s words – “a testicular toxin.” The paper did not elaborate on how the drug caused infertility, so Wolgemuth and her team tested the drug in mice to find out; they noted that the changes it caused were similar to the ones they were seeking.

“We were intrigued,” said Dr. Wolgemuth. “One company’s toxin may be another person’s contraceptive.”

The story is similar to the one involving Viagra, Pfizer's erectile dysfunction drug. It was originally developed to treat angina. It was adapted to its present use when researchers noted the side effects among healthy test subjects included erections.

Experimenting with mice

To investigate whether the Bristol-Myers compound prevented conception at even lower levels than those cited in the company’s study, Wolgemuth and her 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.

One advantage of using a non-steroidal approach, the researchers say, is avoiding the side effects commonly associated with steroidal hormone-based methods. Male steroid-based options have been plagued with adverse effects, including ethnic variability in efficacy, as well as an increased risk of cardiovascular disease and benign prostatic hyperplasia.

Another side effect of hormonal options for men has been diminished libido, which sort of defeats the entire premise of a male contraceptive. But the Columbia researchers say that drawback will also likely be avoided if a method involving manipulation of the retinoid receptor pathway proves successful.

“We have seen no side effects, so far, and our mice have been mating quite happily,” said Wolgemuth.