Male Contraceptive Drug Shows Promise in Preclinical Study

Few options to prevent unintended pregnancies currently exist for males. However, a contraceptive drug candidate may make this a reality as seen during preclinical trials in mice.

Key takeaways:

The compound developed by Weill Cornell Medicine professors can quickly prevent sperm from advancing to prevent pregnancies.

Jochen Buck, M.D., Ph.D., and Lonny Levin, Ph.D., are co-senior authors of the study published in Nature Communications on February 14. One of the key motives behind their research is the current lack of male contraceptives — which are more prominent for women.

Few options for male contraceptives

The primary options to prevent unintended pregnancies for males are condoms or to receive a vasectomy. According to the CDC, condoms have a 13% typical use failure rate.

A vasectomy, on the other hand, is a permanent surgical procedure to prevent sperm from going into the penis to prevent egg fertilization. The recovery time for a vasectomy is one week, but it may take 12 weeks for the sperm count to drop to zero. The CDC says the typical use failure rate for a vasectomy is .15%.

While condoms prove to be somewhat inefficient and vasectomies are permanent, Buck and Levin were hopeful to create a fast-acting contraceptive to prevent unplanned pregnancies.

Although unintended pregnancies have dropped in recent years, the CDC highlights that 75% of pregnancies for teenagers aged 15 to 19 are unintended. The groups with the rates for highest unintended pregnancies include those who have failed to obtain a high-school diploma, low income, are aged 18 to 24 years old, or are single. Also, Black and Latino minorities are more susceptible to unintended pregnancies.

Children from unintended pregnancies are at increased risk for health concerns if the mother contained an unhealthy lifestyle. The CDC provides recommendations on its website to assist women concerned with their unintended pregnancy.

Contraceptive preclinical trial success

The new contraceptive drug candidate developed by Buck and Levin is a single dose of a soluble adenylyl cyclase (sAC) inhibitor called TDI-11861. Previously, the duo uncovered mice genetically engineered to lack sAC are infertile.

In 2018, one of Buck and Levin’s postdoctoral associates, Melaine Balbach, Ph.D., discovered the contraceptive benefits of sAC while studying it as a treatment for an eye condition. During Balbach’s research, she found mice who consume a drug that inactivates sAC failed to produce sperm. This finding and other reports assured Buck and Levin that sAC inhibition might be a safe and effective contraceptive method.

A single dose of the TDI-11861 sAC inhibitor halts mice sperm for nearly two-and-a-half hours, with effects continuing through the female reproductive tract after mating. After 24 hours of consuming TDI-11861, normal mice sperm levels returned.

All 52 mating attempts were prevented by TDI-11861, with the drug having no effect on the mice’s will to mate. Along with the effectiveness of the preclinical trials, its benefits don’t take too long to kick in. Balbach highlighted the drug’s fast-acting ability in a Weill Cornell Medicine press release.

"Our inhibitor works within 30 minutes to an hour," Balbach said. "Every other experimental hormonal or non hormonal male contraceptive takes weeks to bring sperm count down or render them unable to fertilize eggs."

Researchers believe the success found in the mice trials provides the blueprint for developing an on-demand male contraceptive. Before that happens, researchers must repeat their success in a different preclinical model on rabbits.

The sAC inhibitor discovered by Cornell investigators is not the only male contraceptive option that has garnered attention in recent years. Last year, a new male contraceptive concept from the University of Minnesota was presented to the American Chemical Society (ACS).

To create a non-hormonal contraceptive, researchers targeted a protein called the retinoic acid receptor alpha (RAR-α) — which has a vital role in cell growth, differentiation, and embryonic development. By eliminating the RAR-α gene, mice became sterile. Based on past reports, the drug was destined for clinical trials before the start of 2023.

Despite few options to prevent unintended pregnancies for males currently existing, breakthrough treatments seem to be inching closer.

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