Effects of 28 days of oral dimethandrolone undecanoate in healthy men: A Prototype male pill

Abstract

Context: Dimethandrolone (DMA) has androgenic and progestational activity in pre-clinical studies. Single oral doses of DMA undecanoate (DMAU) were well-tolerated and reversibly suppressed serum LH and testosterone (T) in men. Objective: Assess safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of oral DMAU. Design: Double-blind, randomized, placebo-controlled study. Setting: Two academic medical centers. Participants: Healthy men (18-50 years). Interventions: 100 men received DMAU (0, 100, 200 or 400mg, formulated in castor oil/benzyl benzoate (C) or powder (P)) for 28 days. Subjects underwent 24-h PK blood sampling on days 1 and 28, and twice weekly ambulatory visits throughout treatment. Main outcome measures: Primary outcomes were safety and tolerability parameters (vitals, laboratory data, mood and sexual function scores) and adverse events. Secondary outcomes were drug PK profiles and PD effects (serum LH, FSH, sex-hormones). Results: 82 subjects completed the study and were included in the analysis. There were no serious adverse events. No clinically significant changes developed in safety laboratory parameters. A significant dose effect was seen for weight, hematocrit, HDL-C, QTc, and sexual desire. Serum 24h average concentrations of DMAU and DMA showed dose-related increases (p<0.001). All six subjects in the P400 group and 12/13 subjects in the C400 group achieved marked suppression of both LH and FSH (<1.0 IU/L) and serum T (<50 ng/dL). Conclusions: Daily oral administration of DMAU for 28 days in healthy men is well tolerated. Doses of ≥200 mg markedly suppress serum T, LH and FSH. These results support further testing of DMAU as a male contraceptive.