By Rebecca Bowers

EXECUTIVE SUMMARY

Early studies of a potential male contraceptive pill, which contains a modified testosterone that has the combined actions of an androgen and a progesterone, are underway. The experimental male oral contraceptive, known as 11-beta-methyl-19-nortestosterone dodecylcarbonate, or 11-beta-MNTDC, was the subject of a recent study to analyze its safety, tolerability, pharmacokinetics, and pharmacodynamics.

  • Levels of luteinizing hormone and follicle-stimulating hormone, required for sperm production, dropped greatly when the study drug was used, compared to placebo. The drug’s effects were reversible after stopping treatment, analyses indicate.
  • Researchers also are investigating an oral form of dimethandrolone undecanoate. In early research, investigators found that doses of 200 mg or less markedly suppressed serum testosterone, luteinizing hormone, and follicle-stimulating hormone.

Early studies of a potential male contraceptive pill, which contains a modified testosterone that has the combined actions of an androgen and a progesterone, are underway.1 The experimental male oral contraceptive, known as 11-beta-methyl-19-nortestosterone dodecylcarbonate, or 11-beta-MNTDC, was the subject of a recent study to analyze its safety, tolerability, pharmacokinetics, and pharmacodynamics.

To conduct the research, scientists enrolled 40 healthy men at the Los Angeles BioMed Research Institute at Harbor-UCLA Medical Center in Torrance, CA, and the University of Washington in Seattle. Ten participants randomly received a placebo, while the other 30 participants received 11-beta-MNTDC at two dose levels: 200 mg (14 participants) and 400 mg (16 participants). The men took their assigned drug or placebo once daily with food for 28 days.

For men who received 11-beta-MNTDC, analyses indicate the average circulating testosterone level decreased as low as in androgen deficiency; however, no severe side effects were reported. The drug’s side effects were mild and included acne, fatigue, or headache. Although five participants reported mildly reduced sex drive, and two men reported mild erectile dysfunction, there was no reported decrease in sexual activity. None of the participants stopped taking the active drug because of side effects.1

“Our results suggest that this pill, which combines two hormonal activities in one, will decrease sperm production while preserving libido,” says study co-senior investigator, Christina Wang, MD. Wang is the associate director of the UCLA Clinical and Translational Science Institute at Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center.

Effects from low testosterone levels were minimal, notes co-senior investigator, Stephanie Page, MD, PhD, professor of medicine at the University of Washington. Although the study drug can mimic testosterone through the rest of the body, the concentration in the testes is not high enough to support sperm production, Page said in a press statement.

Researchers reported that levels of luteinizing hormone and follicle-
stimulating hormone, which are required for sperm production, decreased significantly when the study drug was used compared to placebo. The drug’s effects were reversible after treatment stopped, analyses indicate.1

Since 11-beta-MNTDC would require at least three 60- to 90-day periods to affect sperm production, 28 days of treatment is too little time to observe optimal sperm suppression, said Wang in a press statement. Researchers plan longer studies. If research indicates effectiveness, testing will move forward in sexually active couples.

Other Options in the Pipeline

Scientists at the two research centers are proceeding with other potential male contraceptive options. One approach focuses on an oral form of dimethandrolone undecanoate (DMAU). In early research, doses of 200 mg or less were found to markedly suppress serum testosterone,
luteinizing hormone, and follicle-stimulating hormone.2

“The goal is to find the compound that has the fewest side effects and is the most effective,” notes Page. “We are developing two oral drugs in parallel in an attempt to move the field forward.”

Further along in the research pipeline is a potential male contraceptive in gel form, supported by the National Institute of Child Health and Human Development (NICHD) and the Population Council. The gel, which contains testosterone and a progestin compound known as segesterone acetate (Nestorone), is applied to the back and shoulders and absorbed through the skin. The progestin reduces sperm production to low or nonexistent levels by blocking natural testosterone production in the testes. The replacement testosterone maintains functions, including normal sex drive, that depend on adequate blood levels of the hormone.

Scientists at Los Angeles BioMed Research Institute at Harbor-UCLA Medical Center and the University of Washington will coordinate research from seven other clinical centers. The Phase II study, now in the enrollment phase, will last 24 months and involve 450 men. The endpoint will be contraception efficacy in the female partner.

Men who enroll in the study will use the study gel daily for four to 12 weeks to determine participants’ tolerance of the formulation and to ensure that they encounter no unacceptable side effects. If the sperm levels have not decreased adequately, participants will continue using the gel for up to 16 weeks. Once participants’ sperm levels are sufficient for contraception, the participants will move to the efficacy phase, which is designed to study the formulation’s contraceptive effectiveness. This phase will last 52 weeks and calls for couples to rely solely on the male partner’s application of the gel for pregnancy prevention. Men will remain in the study for observation for 24 weeks after they discontinue use of the gel.

The time for a male contraceptive is long overdue. Results of a 2005 international survey indicate that a large percentage of men are interested in trying new reversible forms of male contraception.3 According to recent data, nearly 60% of unmarried men ages 15-44 relied on a condom, vasectomy, or withdrawal at last intercourse.4

“Many women cannot use hormonal contraception and male contraceptive methods are limited to vasectomy and condoms,” says Diana Blithe, PhD, chief of the NICHD Contraceptive Development Program. “A safe, highly effective and reversible method of male contraception would fill an important public health need.”

REFERENCES

  1. Yuen F, Thirumalai A, Pham C, et al. The novel androgen 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) effectively suppresses gonadotropins and testosterone in healthy men: A potential oral male hormonal contraceptive. Presented at ENDO 2019: New Orleans; March 2019.
  2. Thirumalai A, Ceponis J, Amory JK, et al. Effects of 28 days of oral dimethandrolone undecanoate in healthy men: A prototype male pill.
    J Clin Endocrinol Metab 2019;104:423-432.
  3. Heinemann K, Saad F, Wiesemes M, et al. Attitudes toward male fertility control: Results of a multinational survey on four continents. Hum Reprod 2005;20:549-556.
  4. Daniels K, Abma JC. Unmarried men’s contraceptive use at recent sexual intercourse: United States, 2011-2015. NCHS Data Brief 2017;(284):1-8.