Male birth control pill appears safe and effective in early trial

An experimental birth control pill for men safely lowered reproductive hormones to contraceptive levels in a 1-month trial, researchers reported at ENDO 2018, the Endocrine Society’s 100th annual meeting, held March 17-20, 2018, in Chicago, IL.

The prototype oral contraceptive dimethandrolone undecanoate (DMAU) is a prodrug that converts to dimethandrolone (DMA), which binds to both androgen and progesterone receptors to suppress gonadotropins and yet maintain androgenic effects. In preclinical studies, researchers found that DMAU inhibited spermatogenesis.

“DMAU is a major step forward in the development of a once-daily ‘male pill’,” said senior investigator Stephanie Page, MD, PhD, professor of medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA. “Many men say they would prefer a daily pill as a reversible contraceptive, rather than long-acting injections or topical gels, which are also in development.”

Despite a demand for a “male pill,” developing one has been problematic because oral forms of testosterone may cause liver inflammation, Dr. Page noted. Also, previous oral testosterone formulations required two doses a day to be effective because they clear the body too quickly for once-daily dosing.

To slow this clearance, researchers added undecanoate, a long-chain fatty acid, to produce DMAU, Dr. Page explained.

Marked hormone reductions

This study investigated the safety, pharmacokinetic, and pharmacodynamic effects of DMAU in healthy men aged 18 to 50 years. Researchers randomly assigned men to receive either oral placebo or oral DMAU in one of three dose groups—100 mg, 200 mg, or 400 mg—and one of two formulations in the capsule—castor oil or powder.

For 28 days, the men took the placebo or drug once daily with food, because DMAU must be taken with food to be effective, Dr. Page noted.

A total of 83 men completed the study. On the first and last days of the trial, researchers monitored participants’ hormone levels and vital signs.

All participants who received DMAU showed reductions of serum testosterone into the hypogonadal range. Participants given the highest dose of DMAU, 400 mg (whether in castor oil or powder formulations), demonstrated serum testosterone that had diminished “to near castrate levels.” This dose group also had marked suppression of follicle-stimulating and luteinizing hormones—the lack of which reduces sperm production in men.

“Despite having low levels of circulating testosterone, very few subjects reported symptoms consistent with testosterone deficiency or excess,” Dr. Page said.

No serious adverse events occurred among participants. Those given DMAU demonstrated mild weight gain (median ~3-9 lbs) and decreases in high-density lipoprotein cholesterol (median 7-17 mg/dL). Tests of liver and kidney function showed all participants maintained safe levels.

“These promising results are unprecedented in the development of a prototype male pill,” Dr. Page said. “Longer term studies are currently under way to confirm that DMAU taken every day blocks sperm production.”

This research was supported by funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.