Synthetic androgen shows promise as male birth control pill
The investigational oral synthetic androgen dimethandrolone undecanoate (DMAU) suppresses serum testosterone levels to near castrate levels and appears safe when taken once daily for a month, showing potential as a male contraceptive pill, according to a study.
“DMAU is a major step forward in the development of a once-daily ‘male pill’,” said study senior investigator Professor Stephanie Page of the University of Washington in Seattle, Washington, US. “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.”
The double-blind study involved 100 healthy men (aged 18–50 years) who were randomized to placebo or oral DMAU (100, 200, or 400 mg) formulated in castor oil/benzyl benzoate or powder in capsule and taken once daily with food. [ENDO 2018, OR15-2]
Pharmacokinetic study revealed that serum concentrations of both dimethandrolone (DMA) and DMAU (p<0.001 for both) showed a dose-response relationship at 28 days.
All active treatment groups saw their serum testosterone levels dropped to the hypogonadal range by day 28 (median, 13.4 ng/dL), regardless of doses or formulations.
Also, both hormones required for sperm production—the follicle-stimulating and luteinizing hormones—were suppressed to <1 IU/L in all participants in the 400-mg group (except one receiving 400 mg castor oil formulation).
The low hormones levels, according to Page, were consistent with effective male contraception demonstrated in previous longer-term studies.
“Despite having low levels of circulating testosterone, very few subjects reported symptoms consistent with testosterone deficiency or excess,” she said.
There were no significant changes in vital signs or EKG. Nor were there significant changes in mood (p=0.68) or sexual function monitored prospectively by questionnaires. Nine participants reported decreased libido, of which eight were on DMAU and one received placebo.
No serious adverse events were reported.
However, HDL-C levels decreased by a median range of 7–17 mg/dL, hematocrit increased by a median of 0.2–2 percent, and weight increased by a median of 1.5–3.9 kg with DMAU treatment.
Also, acne occurred in eight participants—five from the DMAU and three from the placebo groups.
Nonetheless, all adverse events resolved by study conclusion.
According to Page, previous developments of male contraceptive pills were hampered by short half-life of the drug and side effect such as liver inflammation. In the current study, all participants passed safety tests for liver and kidney function.
“Daily oral administration with food of DMAU for 28 days in young healthy men is well tolerated … [and] suppresses serum testosterone to near castrate levels,” said Page. “These promising results are unprecedented in the development of a prototype male pill … [and] support further development of DMAU as a single agent oral male contraceptive pill.”
“Longer term studies are currently under way to confirm that DMAU taken every day blocks sperm production,” she added.