Effects of E2/P4 oral capsules on bone turnover in women with vasomotor symptoms

Abstract

Objective: To evaluate bone turnover markers (BTM) in the REPLENISH trial (NCT01942668).

Methods: REPLENISH evaluated oral estradiol/progesterone (E2/P4) for the treatment of moderate to severe vasomotor symptoms (VMS) in postmenopausal women with a uterus. Eligible women for this analysis had ≥50 moderate to severe VMS/wk, were <5 years since last menstrual period, and had BTM measurements at baseline, and months 6 and 12. Percent changes for three BTM (bone-specific alkaline phosphatase [BSAP], C-terminal telopeptide of type I collagen [CTX-1], and N-terminal propeptide of type I procollagen [P1NP]) assessed by immunoassay methods were evaluated from baseline to months 6 and 12 for the 1 mg E2/100 mg P4, 0.5 mg E2/100 mg P4, and placebo groups.

Results: A total of 157 women (40-61 y, 69% White) were analyzed. Mean baseline values ranged from 14.0 to 14.3 U/L for BSAP, 0.34 to 0.39 ng/mL for CTX-1, and 76.9 to 79.3 ng/mL for PINP. Mean differences in percent change from baseline for both E2/P4 doses versus placebo significantly decreased at months 6 and 12 and ranged from -8% to -16% for BSAP (all, P < 0.05), -30% to -41% for CTX-1 (all, P ≤ 0.001), and -14% to -29% for PINP (all, P < 0.01).

Conclusions: REPLENISH data provide support for a potential skeletal benefit of E2/P4 when it is used for the treatment of moderate to severe VMS. Further studies are warranted.

Conflict of interest statement

Financial disclosures/conflicts of interest: M.R.M. consults for Amgen and Myovant; and has served on the speaker's bureau of Amgen. R.K. consults for Amgen, Astellas, and TherapeuticsMD; and has served on the speaker's bureau of TherapeuticsMD. S.G., B.B., and S.M. are employees of TherapeuticsMD with stock/stock options. G.C. consults to multiple pharmaceutical companies including but not limited to TherapeuticsMD and has stock options from TherapeuticsMD.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.

Figures

FIG. 1

Percent changes from baseline in (A) BSAP, (B) P1NP, and (C) CTX-1. aP < 0.05; bP < 0.01; cP < 0.001 versus placebo; dP < 0.05 versus 0.5 mg E2/100 mg P4; en = 46 for P1NP and CTX-1; fn = 53 for CTX-1. BSAP, bone-specific alkaline phosphatase; CTX-1, C-terminal telopeptide of type I collagen; E2, estradiol; P1NP, N-terminal propeptide of type I procollagen; P4, progesterone.