Low-dose and ultra-low-dose estradiol and dydrogesterone in postmenopause: an analysis by body mass index.

OBJECTIVE: Oral, low-dose and ultra-low-dose continuous combined 17β-estradiol (E) plus dydrogesterone (D) reduce vasomotor symptoms (VMS) in postmenopausal women. METHODS: Two phase 3, double-blind studies were included. In the European study, postmenopausal women were randomized 2:1:2 to receive E0.5 mg/D2.5 mg (ultra-low dose), E1 mg/D5 mg (low dose) or placebo for 13 weeks. In the Chinese study, women were randomized 1:1 to receive E0.5 mg/D2.5 mg or placebo for 12 weeks. Post-hoc endpoints assessed in body mass index (BMI) subgroups (<25 kg/m 2 ; ≥25 kg/m 2 ) included number of hot flushes and moderate-to-severe hot flushes per day, and the proportion of women with amenorrhea. RESULTS: A total of 640 women were included. At the end of treatment, the mean (95% confidence interval) numbers of daily hot flushes were significantly lower ( p ≤ 0.05) for all treatment groups versus placebo, with E0.5 mg/D2.5 mg (BMI < 25 kg/m 2 : 2.5 [1.9, 3.1]; BMI ≥ 25 kg/m 2 : 3.2 [2.5, 3.8]) and E1 mg/D5 mg versus placebo (BMI < 25 kg/m 2 : 2.7 [1.2, 4.2]; BMI ≥ 25 kg/m 2 : 2.3 [1.1, 3.5]) than with placebo (BMI < 25 kg/m 2 : 4.4 [3.8, 50]; BMI ≥ 25 kg/m 2 : 4.2 [3.6, 4.9]). A similar pattern was seen for moderate-to-severe hot flushes. The amenorrhea rate was high (79-98%) across both studies and BMI subgroups. CONCLUSION: Oral, ultra-low-dose continuous combined E0.5 mg/D2.5 mg and low-dose continuous combined E1 mg/D5 mg alleviated postmenopausal VMS compared with placebo, irrespective of BMI.