Dimethandrolone Undecanoate, a Novel, Nonaromatizable Androgen, Increases P1NP in Healthy Men Over 28 Days

Abstract

Context: Dimethandrolone undecanoate (DMAU) is being developed as a male contraceptive. Daily oral administration of DMAU, a potent androgen that is not aromatized, markedly suppresses serum testosterone (T) and estradiol (E2) in healthy men. E2 deficiency can increase bone resorption in men.

Objective: This work aimed to assess changes in bone turnover markers with DMAU administration in a 28-day study.

Design: A randomized, double-blind, placebo-controlled study was conducted.

Setting: This study took place at 2 academic medical centers.

Participants: Healthy men, age 18 to50 years (n = 81), participated.

Intervention: Men received 0, 100, 200, or 400 mg of oral DMAU for 28 days. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and procollagen type I amino-terminal propeptide (P1NP; bone formation marker) were measured on days 1 and 28.

Main outcome measures: Changes in bone turnover markers and serum hormones over the treatment period were measured.

Results: On day 28, median serum T and E2 were markedly suppressed in all treatment groups vs placebo (P < .001 for both). Percentage change (%) in serum P1NP significantly differed across treatment groups (P = .007): Serum P1NP significantly increased in the 200 mg (5%, interquartile range [IQR] -7% to 27%) and 400 mg (22%, IQR -1% to 40%) groups relative to placebo (-8%, IQR -20% to 0%). Change (%) in serum CTX did not differ between groups (P = .09).

Conclusions: DMAU administration for 28 days to healthy men leads to marked suppression of serum T and E2, yet increases P1NP, a serum marker of bone formation. Longer-term studies of the potent androgen DMAU are warranted to determine its impact on bone health in men.

Trial registration: ClinicalTrials.gov NCT01382069.

Keywords: androgen; bone formation marker.

© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Comparison of percentage changes in bone turnover markers in various groups by end of treatment (median, interquartile range). This figure shows a box and whiskers plot of the percentage change in serum concentrations of A, procollagen type I amino-terminal propeptide (P1NP) and B, C-terminal telopeptide of type I collagen (CTX) by the end of treatment in various groups: placebo (blue), dimethandrolone (DMA) undecanoate (DMAU) 100 mg (red), DMAU 200 mg (green), and DMAU 400 mg (purple). *P less than .01 (significant pairwise comparisons) on Mann-Whitney U test, adjusted for multiple comparisons.

Figure 2.

Serum bone turnover markers before and after treatment by group (median, interquartile range). This figure shows serum concentrations of procollagen type I amino-terminal propeptide (P1NP; A, C, E, and G) and C-terminal telopeptide of type I collagen (CTX; B, D, F, and H) in various groups: A and B, placebo; C and D, dimethandrolone undecanoate (DMAU) 100 mg; E and F, DMAU 200 mg; and G and H, DMAU 400 mg on day 1 (in blue; before treatment start) and day 28 (in red; end of treatment). *P less than .05 on Wilcoxon signed-rank test for within-group change.