Since 1960, many women have shouldered the daily burden of hormonal birth control, facing side effects ranging from nausea to an increased risk of heart attack. Yet, after more than six decades on the market, little progress has been made to improve these pills or offer a male counterpart to alleviate the burden on the female body and mind. Now, a new study brings hope for a non-hormonal, reversible male birth control pill—potentially reshaping the future of contraception.
Martin Matzuk, a professor at the Baylor College of Medicine, is dedicated to researching more effective and affordable options in reproductive medicine. To achieve this, his lab has helped develop DNA-encoded Chemistry Technology (DEC-Tec), a method for screening small molecules that enables scientists to use just one test tube to analyze more than a billion different compounds with drug-like properties. The lab has created more than seventy digital DNA-encoded chemical libraries that collectively contain more than seven billion molecules. The DEC-Tec library database allows researchers to easily identify, synthesize, and analyze drug-like compounds.
To explore new options for male birth control, Matsuk and his team recently began investigating inhibitors of the gene STK33, which produces a protein essential for sperm development in mice and humans. The protein emerged as a promising target based on prior studies suggesting its crucial role in sperm cell functionality.
Using DEC-Tec, the team investigated a database of more than one hundred forty billion DNA-encoded molecules for properties that may allow them to inhibit STK33. A few compounds emerged as possible inhibitors, but the team quickly found that these compounds were degraded before they could travel to the testis to prevent functional sperm production.
To work around this, Matsuk and his team began modifying these compounds in hopes of improving their longevity in the body. Soon, they discovered a non-hormonal inhibitor within the DEC-Tec library named CDD-2807 which, when modified, could pass the liver and act potently in the testis.
The lab began investigating the abilities of the modified CDD-2807 compound in live male mice through two protocols. In the first protocol, six mice were given a low dosage of the compound twice a day. In the second protocol, seven mice were given a dose more than three times higher once a day. After twenty-one days of treatment, treated mice and untreated control groups were placed in separate habitats with fertile female mice.
In the first month of treatment in protocol one, treated mice produced fewer litters, each with fewer pups, compared to the control group. In the first month in protocol two, only one female mouse among the seven housed with treated male mice produced a litter, and that one litter had only one pup. Even more astonishing is the fact that after the first month, the treated mice in both protocols stopped producing litters of pups entirely, while the untreated mice continued to produce more litters.
To test if the treatment’s effects on male fertility were reversible, the team stopped administering the compound. Within just three weeks, these mice resumed producing offspring at the same rate as untreated mice. Furthermore, no mice died or gained substantial weight upon being administered modified CDD-2807, suggesting that inhibition of STK33 did not lead to noticeable adverse health effects. Therefore, while there are still uncertainties regarding the long-term effects of inhibiting STK33, the early results demonstrate that a male, non-hormonal, reversible birth control pill may be well within reach.In the near future, the team plans to expand their experimental scope by investigating the effect of CDD-2807 on STK33 in primates. Matsuk and his team have opened up new avenues for achieving equity in family planning. For decades, the responsibility of family planning has fallen on female bodies and minds, but with a pill against male fertility on the horizon, that burden may be relieved from women.