NEW ORLEANS — An investigational male birth control pill was generally safe with signs of efficacy in healthy men, according to results of a phase I, placebo-controlled study.
Tested in 40 healthy men, daily doses of 11β-methyl-19-nortestosterone (11β-MNTDC converted to 11β-MNT) effectively suppressed luteinizing hormone (LH) and follicle-stimulating hormone (FSH), reported Fiona Yuen, MD, of Los Angeles Biomedical Research Institute (LA BioMed) at Harbor-UCLA Medical Center in Torrance, California, and colleagues.
11β-MNTDC is an orally bioavailable, modified testosterone combined with a progestin, they explained in a late-breaking poster at ENDO 2019, The Endocrine Society annual meeting.
Due to the suppression of LH and FSH, testosterone was also suppressed leading to a reduction in spermatogenesis after 28 consecutive days of therapy:
- LH: median change 6.0 IU/L for placebo vs 1.9 IU/L for a 200-mg dose vs 0.3 IU/L for a 400-mg dose
- FSH: median 3.1 IU/L vs 1.2 IU/L vs 0.2 IU/L
- Testosterone: median 461.1 ng/dL vs 22.3 ng/dL vs 7.6 ng/dL
Because of the androgenic properties of 11β-MNTDC, sexual functioning and other testosterone-related traits are preserved in these men, explained co-author Christina Wang, MD, also of LA BioMed, during an ENDO 2019 press conference.
“The question that we are always asked — are men willing to use novel contraceptives?” Wang said. She cited responses from a global survey of nearly 10,000 men, over half of whom said they would try a new method of contraception, with a pill being preferred over an injectable option.
This isn’t the first attempt at a novel male oral contraceptive, all of which have ultimately failed, so far. However, another investigational pill — dimethandrolone undecanoate (DMAU) — showed similar safety and efficacy in a presentation at ENDO 2018.
The current double-blind study, which was conducted at two medical centers, included adult men, ages 18 to 50, who were given a single oral dose of 11β-MNTDC with food. Ten men were randomized to the placebo, while 14 men were given a 200-mg dose and 16 were given a 400-mg dose for 28 days.
Blood sampling took place on day 1 and day 28 to assess 24-hour serum concentration of 11β-MNTDC, along with testosterone, LH, and FSH suppression. Questionnaires were also given to the participants to assess side effects, such as mood and sexual functioning.
The agent was also safe and well-tolerated, with no serious adverse events or discontinuations reported, according to the authors. Twice per week, the individuals underwent testing for vital signs, hematocrit, lipids, and liver function tests, and the researchers also looked at EKGs and QTc intervals, all of which were not significantly affected.
Side effects were generally mild, with a few reported of fatigue, headache, acne, and libido reduction. There were two reports of mild erectile dysfunction. In the higher dose group, there was a slight decrease in sexual desire score, although there weren’t any changes in sexual activity.
The most notable side effects seen with the pill were changes in body weight and cholesterol, which were both dose-dependent and significantly higher than placebo in the 400 mg dosage for all outcomes:
- Weight: median change 0.6 kg for placebo vs 1.3 kg for 200 mg vs 1.9 kg for 400 mg
- Hematocrit: 0% vs 1.2% vs 1.0%
- LDL: 3 mg/dL vs 10 mg/dL vs 18 mg/dL
- HDL: -3 mg/dL vs -9 mg/dL vs -11.5 mg/dL
However, Wang told MedPage Today she believes these are the extent of any possible side effects with this drug, and none will likely emerge with a longer duration of exposure.
“We are pursuing another compound. The two compounds are like brother and sister, and that compound has gone into men for around 12 weeks. And because we know the action of androgens, we know the action of a progestin, so I think we are covering our grounds,” she stated. “I don’t think with longer exposure we will see unexpected side effects. Obviously, we are monitoring [participants] very carefully, not only asking them, but using validated questionnaires and so they can [respond] in private.”
However, these side effects may ultimately pose a barrier to this novel contraceptive gaining traction in clinical practice, suggested Stephen Codella, MD, of Temple University Hospital in Philadelphia.
Codella, who was not involved with the study, told MedPage Today that the findings are interesting, but the potential complications of systemic testosterone suppression may lead to “unacceptable side effects for the intended population.”
Also, “there still needs to be further studies about efficacy,” he said.
Additional, longer-term studies are currently underway, Wang told MedPage Today, and her “whole collaborative science team is developing a male hormone contraception that can be administered as an intramuscular, long-acting reversible injection, as well as a transdermal gel.”
“We are pursuing many methods to make the male contraception similar to the woman’s,” she said
Wang disclosed relevant relationships with Spouse, Clarus, Self, Antares, TesoRX, and the Testosterone Replacement Therapy Manufacturers Consortium.
Yuen and Codella disclosed no relevant relationships with industry.