REPLENISH: Hormone pill for vasomotor symptoms delivers no substantial effect on weight, BP
Use of a single-capsule 17β-estradiol (E2)/progesterone (P4) to treat vasomotor symptoms does not appear to produce unwanted changes in body weight and blood pressure (BP) in postmenopausal women, according to data from the phase III REPLENISH trial.
Changes in the two parameters after a year of treatment were modest, without clinically meaningful differences when compared with placebo, the investigators said.
The analysis included 1,835 healthy postmenopausal women (average of 5.8 years since menopause) who had taken at least one dose of the E2/P4 (daily dose: 1 mg/100 mg, 0.5 mg/100 mg, 0.5 mg/50 mg, 0.25 mg/50 mg) or placebo during the study. Their mean age was 54.6 years, mean weight was 72.0 kg, and mean body mass index was 26.7 kg/m2. Mean systolic and diastolic BP ranged from 118.9 to 120.5 mm Hg and 75.7 to 76.3 mm Hg, respectively, across the treatment groups.
At month 12 of follow-up, only a fraction of women in both treatment arms showed potentially clinically important increase in weight (1.1–2.6 percent vs 2.2 percent) and elevations in systolic (0.3–1.1 percent vs 1.1 percent) and diastolic BP (1.4–4.2 percent vs 3.2 percent). [Menopause 2020;doi:10.1097/GME.0000000000001659]
As an adverse event related to E2/P4, weight gain and hypertension occurred at low frequencies (1.4–2.6 percent and 0.2–1.2 percent, respectively) and led to few study discontinuations (1.6 percent and 0.6 percent, respectively).
Efficacy results at week 12 revealed that compared with placebo, E2/P4 yielded superior improvements in both the severity and frequency of vasomotor symptoms regardless of body mass index.
“A common belief of women is that hormone therapy may bring undesired weight gain. Small gains in weight appear to be common in midlife women,” the investigators said.
Other randomized controlled trials of hormone therapy in postmenopausal women aged 42–52 years recorded an average of 0.4 to 2.1 kg increase in body weight over a follow-up of up to 3 years. These numbers were not significant when compared with that gained on placebo. [J Clin Endocrinol Metab 1997;82:1549-1556; Menopause 2004;11:306-314; Am J Epidemiol 2004;160:912-922]
“Prevention of unfavourable increases in BP is [also] important for postmenopausal women [given that] BP is one of the risk factors for cardiovascular diseases,” they said.
Together with previously reported efficacy and safety data, the results on weight and BP from the REPLENISH trial demonstrated that E2/P4 exerts no detrimental effects on cardiovascular disease risk factors, according to the investigators. [Obstet Gynecol 2018;132:161-170; Climacteric 2019;22:610-616]