Providing men with a practical and reversible contraceptive option is long overdue.1 Sixty years following the development of birth control pill for women, a ‘male pill’ may be on the near horizon, according to an early study conducted by Prof. Stephanie Page of the University of Washington in Seattle, and colleagues, with results presented at ENDO 2018: The Endocrine Society Annual Meeting held in Chicago.1,2
The experimental male oral contraceptive—called dimethandrolone undecanoate (DMAU), is a pro-drug that is converted to dimethandrolone (DMA), which binds to both androgen and progesterone receptors and suppresses gonadotropins.2 This drug, when tested at its highest dose (400mg), was found to markedly suppresses serum testosterone and two other hormones involved in sperm production, without serious side effects when taken once-daily for a month.2
“These promising results are unprecedented in the development of a prototype male pill,” said Prof. Page in a press release.3
Indeed, progress toward a male birth control pill has been stymied because of the need for multiple daily dosing, as well as the potential for adverse events, including hepatotoxicity, and depression. Nonetheless, DMAU managed to jump over these hurdles.3
“Oral forms of testosterone may cause liver inflammation, and they clear the body too quickly for once-daily dosing, thus requiring two doses a day. However, DMAU contains undecanoate, a long-chain fatty acid, which slows this clearance,” said Prof. Page.3
It is noted that the drug’s androgen-like properties were important in preventing side effects typically associated with low testosterone levels.3 “Despite having low levels of circulating testosterone, very few subjects reported symptoms consistent with testosterone deficiency or excess,” said Prof. Page. “The big message for us in the research field is that there really were no adverse events or effects… There weren’t common side effects you’d get from oral medications like nausea and we did not see any liver signals [of damage].”3,4
In this double-blind study, 83 healthy men (age 18-50 years) were randomly assigned to receive either daily oral placebo or DMAU with food in 1 of 3 dose groups (100, 200, or 400mg) and 1 of 2 capsule formulations (castor oil/benzyl benzoate or powder in capsule).2
After 28-days of treatment, all active treatment groups achieved reductions of serum testosterone into the hypogonadal range (median 13.4ng/dL) without significant differences between doses or formulations.2 Meanwhile, all subjects at the 400mg group achieved suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (<1IU/L).2
That level of suppression has been associated with blockage of spermatogenesis in pre-clinical studies, and the research team is currently conducting longer-term studies to test for sperm suppression.2,3
The few side effects observed in treatment arms were weight gain (median +1.5kg to +3.9kg) and decreases in higher-density lipoprotein cholesterol (median -7mg/dL to -17mg/dL), both of which Prof. Page said were mild.2,3 Importantly, DMAU did not seem to cause serious adverse events or hepatotoxicity.2,3
However, she cautioned that a short study period may make it difficult to know whether liver damage could have occurred with long-term use of the drug.5 “We’re confident, but this [current] study was too short. Ultimately, we need to do a study with couples. There’s a lot of work to do.”5
Nevertheless, this study opened the door for future research to test for a more equitable contraceptive option, and it is hoped that the rate of unwanted pregnancies will drop someday soon.
1. Male birth control pill one step closer to reality, researchers say. CNN (Accessed May 4, 2018, at https://edition.cnn.com/2018/03/20/health/male-birth-control-pill-study/index.html).
2. Thirumalai A, Ceponis J, Amory JK, et al. Pharmacokinetic and pharmacodynamic effects of 28 days of oral dimethandrolone undecanoate in healthy men: a prototype male pill. Presented at: ENDO 2018: The Endocrine Society Annual Meeting; Chicago, IL; March 17-20, 2018. Abstract OR15-2.
3. Dimethandrolone undecanoate shows promise as a male birth control pill [press release]. Endocrine Society (Accessed May 4, 2018, at https://www.endocrine.org/news-room/2018/dimethandrolone-undecanoate-shows-promise-as-a-male-birth-control-pill).
4. A Once-a-Day Male Birth Control Pill Shows Promise in Human Trial. Gizmodo (Accessed May 4 2018, at https://gizmodo.com/a-once-a-day-male-birth-control-pill-shows-promise-in-h-1823890390).
5. Once-Daily ‘Male Pill’ Shows Promise in Early Study. Medscape (Accessed May 4 2018, at https://www.medscape.com/viewarticle/894080_print).