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

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.