A daily oral dose of 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) for 28 days suppressed endogenous testosterone and gonadotropin production in healthy men and may be a potential oral male contraceptive, according to study results presented at the Endocrine Society’s annual meeting, ENDO 2019, held March 23-26 in New Orleans, Louisiana.
Investigators conducted a placebo-controlled, double-blinded study at 2 medical academic centers. Participants were healthy men age 18 to 50 years. They were randomly assigned to receive either 11β-MNTDC 200 mg (n = 14), 11β-MNTDC 400 mg (n = 16), or placebo (n = 10) once a day for 28 days. Investigators conducted twice weekly assessments to monitor vital signs, electrocardiogram activity, QTc intervals, liver function tests, hematocrit, lipids, and adverse events. Serial blood samples were obtained on day 1 and 28 to assess pharmacokinetic and pharmacodynamic effects of the medication, such as 24-hour serum drug concentration and suppression of testosterone, luteinizing hormone, and follicle-stimulating hormone. In addition, standardized questionnaires were utilized to examine mood and sexual function at baseline, day 28, and at the end of the study period.
In participants who received 11β-MNTDC, there was a dose-proportional increase in serum 11β-MNTDC and 11β-MNT concentrations over 24 hours. On day 28, researchers observed significant suppression of 24-hour average serum concentrations in men receiving 11β-MNTDC for testosterone (200-mg dose, 22.3 ng/dL; 400-mg dose, 7.6 ng/dL; placebo, 461.1 ng/dL), luteinizing hormone (200-mg dose, 1.9 IU/L; 400-mg dose, 0.3 IU/L; placebo, 6.0 IU/L), and follicle-stimulating hormone (200-mg dose, 1.2 IU/L; 400-mg dose, 0.2 IU/L; placebo, 3.1 IU/L).
The oral medication was well-tolerated and no serious adverse events were reported. The most commonly reported treatment-related adverse events were fatigue, headache, acne, decreased libido, and mild erectile dysfunction in participants assigned to 11β-MNTDC. On clinical assessment, no significant changes in blood pressure, electrocardiogram activity, QTc, or liver enzymes were observed. There were dose-related increases in weight (200-mg dose, 1.3 kg; 400-mg dose, 1.9 kg), hematocrit (200-mg dose, 1.2%; 400-mg dose, 1.0%), and low-density lipoprotein cholesterol (200-mg dose, 10 mg/dL; 400-mg dose, 18 mg/dL) and a decrease in high-density lipoprotein cholesterol (200-mg dose, 9 mg/dL; 400-mg dose, 11.5 mg/dL).
In participants assigned to 11β-MNTDC 400 mg, the sexual desire score was reduced, but there were no changes in sexual activity.
Investigators concluded that “these results warrant further evaluation of 11β-MNTDC as a potential oral male contraceptive.”
Funding for this study was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, which is developing 11β-MNTDC.
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; March 23-26, 2019; New Orleans, LA. Abstract SUN-LB042.