Low-dose estradiol for climacteric symptoms in Japanese women: a randomized, controlled trial

Objectives To investigate two different doses of oral estradiol to reduce the number of hot flushes in Japanese women with climacteric symptoms. Methods Women (n = 211) aged 40-64 years who had experienced natural menopause or bilateral oophorectomy, with >= three moderate/severe hot flushes per day in the week before study, were randomized to receive micronized estradiol (E2) 0.5 or 1.0 mg or placebo once daily for 8 weeks. The primary efficacy endpoint was percentage change in mean daily number of hot flushes over 7 days from baseline to final examination. Results Percentage change in mean daily number of hot flushes at final examination was similar for E2 0.5 mg and E2 1.0 mg (-79.58 +/- 28.29% vs. -82.49 +/- 25.31%, p = 0.555) but was significantly lower with placebo (-57.89 +/- 34.15%, p < 0.001 vs. E2, both doses). There was no significant difference in number of treatment-related adverse events occurring in the E2 0.5 and 1.0 mg groups (25% and 36.6%, respectively). The higher E2 dose showed more pronounced effects on symptom severity. Conclusions The dose of 0.5 mg/day was effective as the oral E2 starting dose for treatment of hot flushes in Japanese women.