For years, scientists have worked towards formulating a male oral contraceptive, similar to the several oral pills available for women. Now, a group of researchers from the University of Minnesota (MN, USA) has taken an important step towards that goal by making modifications to some promising experimental compounds.
One of the potential candidates for a male contraceptive is testosterone. "At certain doses it causes infertility," explained Jillian Kyzer, one of the researchers. "But at those doses, it doesn't work for up to 20 percent of men, and it can cause side effects, including weight gain and a decrease in 'good' cholesterol."
A male contraceptive would need to satisfy several requirements, added team leader Gunda Georg. It would need to be quick acting, soluble and couldn’t adversely affect libido, and it would need to be safe enough to provide long-term contraception, while still being reversible without damaging sperm or embryos. Georg stated: "That's a very high bar for bringing a male contraceptive to market.”
Drug companies have tackled the problem with come experimental compounds, but these have critical drawbacks. For example, one compound is good at inhibiting fertility but is poorly soluble and so cannot be taken by mouth. Kyzer pointed out: "No one wants to inject themselves with a needle once a day or once a week for most of their lives.”
Another candidate is poorly selective of cellular targets, interacting with both the retinoic acid receptor-α, which is involved in fertility, and two other retinoic acid receptors that have no connection to fertility, potentially causing side effects.
The team is creating substances similar in chemical structure to these compounds, and while the optimal male contraceptive has yet to be discovered, they have made some progress. They have gained a better understanding of how tweaking the chemical structure of test compounds affect their cellular interactions in the body. One such change made the test compound more soluble, while another improved the compounds’ stability, meaning they would last longer in the body. Both changes, however, also reduced the specificity of the compounds for the intended retinoic acid receptor-α target.
The researchers are now investigating the potential of hybrid compounds, which incorporate structural features from other compounds known to interact with the fertility-affecting retinoic acid receptor.