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

Oral, low-dose and ultra-low-dose continuous combined 17β-estradiol (E) plus dydrogesterone (D) reduce vasomotor symptoms (VMS) in postmenopausal women. 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 (&lt;25 kg/m²; ≥25 kg/m²) included number of hot flushes and moderate-to-severe hot flushes per day, and the proportion of women with amenorrhea. 640 women were included. At end of treatment, mean (standard deviation) numbers of daily hot flushes were significantly lower (<i>p</i>≤0.05) for all treatment groups versus placebo: E0.5mg/D2.5mg [BMI &lt;25: 2.6 (2.6); BMI ≥25: 3.0 (2.9)]; E1mg/D5mg [BMI &lt;25: 2.1 (2.2); BMI ≥25: 1.9 (2.2)]; and placebo [BMI &lt;25: 4.5 (4.5); BMI ≥25: 4.1 (4.0)]. A similar pattern was seen for moderate-to-severe hot flushes. The amenorrhea rate was high (79–98%) across both studies and BMI subgroups. 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.