Effects of 28 Days of Oral Dimethandrolone Undecanoate in Healthy Men: A Prototype Male Pill

Abstract

Context: Dimethandrolone (DMA) has androgenic and progestational activity. 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 to 50 years).

Interventions: One hundred men received DMAU [0, 100, 200, or 400 mg, formulated in castor oil/benzyl benzoate (C) or powder (P)] for 28 days. Subjects underwent 24-hour PK 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, and sex hormones).

Results: Eighty-two 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, high-density lipoprotein cholesterol, corrected QT interval, and sexual desire. Serum 24-hour average concentrations of DMAU and DMA showed dose-related increases (P < 0.001). All six subjects in the P400 group and 12 of 13 subjects in the C400 group achieved marked suppression of 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.

Trial registration: ClinicalTrials.gov NCT01382069.

Figure 1.

Pharmacokinetic parameters of DMAU and DMA by treatment group. (a) Serum DMAU concentrations over 24 h on d 1 and 28, trough DMAU concentrations measured twice-weekly during treatment and at recovery visits. (b) Average serum DMAU concentrations (C Average) and maximum serum DMAU concentrations (C Max) on d 1 and 28. (c) Serum DMA concentrations during 24-h stays on d 1 and 28 along with trough DMA concentrations twice weekly during treatment and at recovery visits. (d) Average Serum DMA concentrations and maximum serum DMA concentrations on d 1 and 28. Striped bars represent powder formulation in (b). In (b), serum DMAU concentrations are shown in logarithmic scale to fit full range of values. All values are means ± SEM.

Figure 2.

Serum sex hormone concentrations by treatment group. (a) Serum LH concentrations during 24-h stays on d 1 and 28, at twice-weekly visits during treatment, and during recovery. (b) Serum FSH concentrations during 24-h stays on d 1 and 28 along with FSH concentrations at twice-weekly visits during treatment and during recovery. (c) Serum total T concentrations during 24-h stays on d 1 and 28 along with T concentrations at twice-weekly visits during treatment and during recovery. (d) Calculated free T concentrations during 24-h stays on d 1 and 28 along with calculated free T concentrations at twice-weekly visits during treatment and during recovery. (e) Serum estradiol (E2) concentrations on d 1 and 28 along with estradiol concentrations at twice-weekly visits during treatment and during recovery. (f) Serum SHBG concentrations on d 1 and 28 along with SHBG concentrations at twice-weekly visits during treatment and during recovery. Dashed gray lines represent normal reference range for each hormone. LLOQ, lower limit of quantification for the assay. All values are means ± SEM.