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

J Clin Endocrinol Metab. 2021 Jan 1;106(1):e171-e181. doi: 10.1210/clinem/dgaa761.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alkaline Phosphatase / blood
  • Biomarkers / blood
  • Bone Remodeling / drug effects*
  • Collagen Type I / blood
  • Contraceptive Agents, Male / pharmacology
  • Double-Blind Method
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Nandrolone / analogs & derivatives*
  • Nandrolone / pharmacology
  • Peptide Fragments / blood*
  • Peptides / blood
  • Placebos
  • Procollagen / blood*
  • Time Factors
  • United States
  • Up-Regulation / drug effects
  • Young Adult

Substances

  • Biomarkers
  • Collagen Type I
  • Contraceptive Agents, Male
  • Peptide Fragments
  • Peptides
  • Placebos
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • dimethandrolone-undecanoate
  • procollagen Type I N-terminal peptide
  • Nandrolone
  • ALPL protein, human
  • Alkaline Phosphatase

Associated data

  • ClinicalTrials.gov/NCT01382069