Effects of combined 17β-estradiol and progesterone on weight and blood pressure in postmenopausal women of the REPLENISH trial

Denise R Black, Mary Jane Minkin, Shelli Graham, Brian Bernick, Sebastian Mirkin, Denise R Black, Mary Jane Minkin, Shelli Graham, Brian Bernick, Sebastian Mirkin

Abstract

Objective: To examine the impact of a single-capsule 17β-estradiol (E2)/progesterone (P4) on weight and blood pressure (BP) when treating moderate to severe vasomotor symptoms in postmenopausal women with a uterus.

Methods: Healthy postmenopausal women with a uterus (aged 40-65, body mass index ≤34 kg/m2, BP ≤140/90 mm Hg) were randomized to daily E2/P4 (mg/mg; 1/100, 0.5/100, 0.5/50, 0.25/50) or placebo in the phase 3 REPLENISH trial (NCT01942668). Changes in weight and BP from baseline to month 12 were evaluated. Potentially clinically important changes were defined as increases or decreases from baseline in weight by ≥15% and ≥11.3 kg, systolic BP by ≥20 mm Hg (absolute value ≥160 or ≤90 mm Hg), and diastolic BP by ≥15 mm Hg (absolute value ≥90 or ≤60 mm Hg).

Results: Overall mean changes in weight and BP from baseline to month 12 with E2/P4 were modest and generally not statistically or clinically significant versus placebo. Incidence of potentially clinically important changes was low for weight (E2/P4 vs placebo: 1.1-2.6% vs 2.2%), systolic BP (0.3-1.1% vs 1.1%), and diastolic BP (1.4-4.2% vs 3.2%). A small number of women had treatment-related, treatment-emergent adverse events of weight gain (1.4-2.6% vs 1.3%) or hypertension (0.2-1.2% vs 0%). Few women who discontinued E2/P4 had weight gain (1.6%) or hypertension (0.6%) as a primary reason. Efficacy profile on VMS was consistent with previous findings and not modified by body mass index.

Conclusions: Twelve-month use of E2/P4 had no clinically meaningful impact on weight or BP in postmenopausal women of the REPLENISH study.

Conflict of interest statement

Financial disclosure/conflicts of interest: Dr. Black consults for and/or is on the advisory board of BioSyent, Duchesnay, and Pfizer. Dr. Minkin consults for AMAG, Duchesnay, Pfizer, and TherapeuticsMD. Drs. Graham, Bernick and Mirkin are employees of TherapeuticsMD with stock/stock options.

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society.

Figures

FIG. 1
FIG. 1
Disposition of participants in the safety population and the MITT-VMS substudy. E2, 17β-estradiol; MITT-VMS, modified intent-to-treat vasomotor symptoms substudy; P4, progesterone.
FIG. 2
FIG. 2
Changes in weight from baseline to month 12. (A) Comparison of mean body weight at baseline and at month 12. (B) Comparison of incidence of PCI weight change in different treatment groups. E2, 17β-estradiol; P4, progesterone; PCI, potentially clinically important.
FIG. 3
FIG. 3
Changes in sitting BP from baseline to month 12. Comparison of mean BP at baseline and at month 12 for systolic BP (A) and diastolic BP (B). Comparison of incidence of PCI changes in systolic BP (C) and diastolic BP (D). BP, blood pressure; E2, 17β-estradiol; MITT-VMS, modified intent-to-treat vasomotor symptoms substudy; P4, progesterone; PCI, potentially clinically important.
FIG. 4
FIG. 4
Mean changes (±SD) from baseline in frequency (A) and severity (B) of moderate to severe VMS in different BMI subgroups at week 12. P value was calculated for each active dose versus placebo. BMI, body mass index; E2, 17β-estradiol; P4, progesterone; PCI, potentially clinically important; VMS, vasomotor symptoms.

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