Will the latest attempt at male contraceptive pills reach the market?

The first female birth control pill was developed in the 1950s by a scientific team led by Gregory Pincus and financed by the suffragist Katharine McCormick. The combination of hormones designed by Pincus altered the menstrual cycle and suppressed ovulation, thus overcoming a difficult technological challenge. Science tried for decades to develop a similar pill for males, but none have reached the market so far.

But at the spring meeting of the American Chemical Society (ACS), a group of researchers from the University of Minnesota recently presented the conclusions of a study on mice that shows promising results.

Many of the chemical compounds tried so far to prevent the production of sperm rely on hormonal mechanisms, much as female contraceptives do, except the target in this case is testosterone, the male sex hormone. But because of the complex hormonal balance in any living being, tinkering with hormones can have frequent side effects, as women on birth control will attest to. In the case of men, clinical trials with hormone-based contraceptives led to weight gain, depression and lack of sexual desire. As a result, condoms remain the most popular kind of male contraceptive.

Abdullah Al Noman, who led the ACS presentation, said his team’s alternative would bypass these side effects. Their lab, headed by Gunda Georg, developed a compound that they called YCT529 and which is designed to block the action of a protein called retinoic acid receptor alpha, or RAR alpha. This protein normally interacts with the retinoic acid that the body produces by converting vitamin A, and which plays a big role in sperm production.

By inhibiting RAR alpha, male mice became sterile without any apparent side effects. After being administered to male mice for four weeks, YCT529 reduced sperm counts and was 99% effective at preventing pregnancy. And when the males were taken off the pill, they regained their reproductive abilities in under 90 days.

José Gutiérrez Ales, president of the Contraceptives Society of Spain, said the results in mice looked promising but warned that “the jump to humans always yields surprises.”

Research leader Gunda Georg, who is also head of the department of medicinal chemistry at the University of Minnesota and a consultant for YourChoice Therapeutics, the company that owns the rights to YCT529, agreed that “only clinical trials [on humans] will show whether this effective, reversible medication without side effects becomes a reality.” Trials could begin in the second half of this year, according to Georg.

Failed attempts

There is a precedent of a non-hormonal male contraceptive that performed well in animal trials but was ultimately abandoned. A few years ago, gamendazole showed promising results in mice but was not further developed because the duration of the patent was not enough to get the drug to market within a reasonable time period, said Georg.

A historical combination of technical difficulties and lack of interest has slowed down the development of male contraceptives other than condoms and vasectomy procedures. The success of female birth control pills has also reduced commercial interest for a male version. It is women who bear most of the consequences of an unwanted pregnancy, and both gynecologists and pharmaceutical companies have argued that women may not trust men to take their pill at the right time. Or that many men may not be willing to accept the inconveniences or their share of responsibility in an issue that medicine has already resolved, even if it means significant side effects for women.