A multicenter, prospective, randomized, double-blind, placebo-controlled study to investigate the efficacy of a continuous-combined hormone therapy preparation containing 1mg estradiol valerate/2mg dienogest on hot flushes in postmenopausal women

Abstract

Objectives: To evaluate the effects of an estrogen-reduced, continuous-combined hormone therapy preparation (HT) containing 1mg estradiol valerate (1EV) and 2mg dienogest (2DNG) on the number of moderate and severe hot flushes.

Methods: This study compared the effects of an oral continuous-combined HT containing 1mg EV and 2mg DNG (1EV/2DNG) with those of placebo. The planned treatment duration was 12 weeks. Data were obtained from 324 postmenopausal women. The primary efficacy variable was the individual relative change of the mean number of moderate and severe hot flushes per week. Weeks 5-12 of treatment were compared with the 2 weeks preceding the treatment phase.

Results: Moderate and severe hot flushes were reduced by 80.8+/-30.9% in the 1EV/2DNG group and by 41.5+/-39.4% in the placebo group. This difference was statistically significant (p<0.0001; Wilcoxon's rank sum test). The incidence of all types of hot flushes (mild+moderate+severe) was reduced by 75.2+/-30.2% under 1EV/2DNG and by 35.3+/-37.0% under placebo. In the subset of non-hysterectomized women, exposure to 1EV/2DNG led to 2.4+/-6.2 days with bleeding in the reference period of 84 days of treatment, versus 0.3+/-1.3 days in the placebo group. The safety profile of 1EV/2DNG was very similar to that of placebo.

Conclusions: Continuous-combined HT preparation with 1mg EV and 2mg DNG induced a significant reduction of moderate and severe hot flushes compared to placebo (p<0.0001). Thus, this low-estrogen preparation is an effective and safe option for HT.