SAT-239 Bioidentical Estradiol and Progesterone Improved Hot Flushes, Night Sweats and Sweating

In the phase 3 REPLENISH trial of postmenopausal women with a uterus, TX-001HR (TherapeuticsMD, Boca Raton, FL), an oral 17β-estradiol-progesterone (E2/P4) softgel capsule, reduced moderate to severe hot flush frequency and severity and improved quality of life outcomes, while protecting the endometrium. The objective of this analysis was to further determine the effects of the E2/P4 capsules versus placebo on vasomotor symptoms (VMS) as assessed by the menopause-specific quality of life (MENQOL) questionnaire. In the REPLENISH trial (NCT01942668), women with moderate to severe hot flushes (≥7/day or ≥50/week) were randomized 1:1:1:1:1 to daily E2/P4 (mg/mg) of 1/100 (FDA approved as BIJUVA(TM)), 0.5/100, 0.5/50, 0.25/50, or placebo (VMS substudy). Other women (with fewer VMS) were randomized 1:1:1:1 to active E2/P4 doses only. Three of the 29 items in the MENQOL questionnaire assess vasomotor symptoms: hot flushes, night sweats, and sweating. The symptoms, if experienced, were rated using a 7-item Likert scale ranging from “Not at all bothered” (score of 2) to “Extremely bothered” (score of 8); if not experienced, the score was 1. Changes from baseline to week 12, and months 6 and 12 in these 3 items were assessed in the overall efficacy population (MITT) and VMS (MITT-VMS) substudy population. Women were randomized to daily doses of E2/P4 (mg/mg) 1/100 (n=415), 0.5/100 (n=424), 0.5/50 (n=421), 0.25/50 (n=424) or placebo (n=151). Participants (mean age of 55 years and mean BMI of 27 kg/m(2)) were primarily white (65%) or black (32%). Mean baseline scores ranged from 6.7 to 7.4 for hot flushes, 6.1 to 7.1 for night sweats, and 6.0 to 6.9 for sweating. In the MITT population, women treated with all E2/P4 doses had significantly more favorable improvements from baseline in their hot flushes (range of significant mean changes with E2/P4 vs placebo, -2.9 to -4.3 vs -1.9 to -2.7), night sweats (-3.1 to -4.0 vs -2.4 to -3.0) and sweating (-2.8 to -3.6 vs -2.3 to -3.2) scores at week 12, and months 6 and 12 (all, P≤0.002). Similarly, significant improvements from baseline with E2/P4 vs placebo (all, P≤0.030) were observed in the MITT-VMS substudy population for hot flushes (-3.0 to -4.4 vs -1.9 to -2.7), night sweats (-3.3 to -4.4 vs -2.4 to -3.0), and sweating (-3.1 to -4.2 vs -2.3 to -3.2), except for those treated with the lowest E2/P4 dose (0.25 mg E2/50 mg P4) at months 6 and 12 for sweating. In the REPLENISH trial, compared with placebo, postmenopausal women treated with E2/P4 had significant improvements in their hot flushes, night sweats and sweating as assessed by MENQOL. Benefits continued for up to 12 months of treatment. These results with this first oral hormone therapy formulation combining bioidentical estradiol and progesterone in a single capsule are consistent with the primary REPLENISH results demonstrating efficacy for the treatment of moderate to severe vasomotor symptoms in menopausal women with a uterus.