A 1-year comparison of the efficacy and clinical tolerance in postmenopausal women of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone

This double-blind, randomized, multi-center study compared the efficacy and clinical tolerance of a combined formulation containing 2 mg estradiol (E2 ) and 0.5 mg trimegestone (TMG) with a standard hormone replacement therapy containing estradiol valerate (E2V) and norgestrel (NG) in the treatment o f climacteric symptoms. The study was conducted over 13 cycles, each of 28 days, and involved 634 subjects, of whom 481 completed the study, The prima ry efficacy variable was the percentage of subjects who showed at least a 5 0% reduction from baseline in the mean daily number of hot flushes in cycle 3. This was observed in 98.5% of the subjects in the E2 + TMG group and 93 .3% of the subjects in the E2V + NG group (95% confidence interval of the d ifference, -8.6, -1.9). Significant differences in favor of the E2 + TMG co mbination were observed in the reduction in the mean daily number and sever ity cf hot flushes, and in the percentage of subjects who had hot flushes a t baseline but no hot flushes during treatment. There were no significant d ifferences between the treatments in the Kupperman index and in urogenital signs or symptoms. Treatment with the E2 + TMG combination was well tolerat ed and the incidences of adverse events were similar in the two treatment g roups. Breast pain was the main adverse event, possibly related to treatmen t that resulted in discontinuation. The mean number of bleeding days per cy cle was significantly lower with the E2 + TMG combination than with the E2V + NG combination. The incidences of endometrial hyperplasia were low and c omparable in both treatment groups. It was concluded that the E2 + TMG comb ination was either equivalent or superior to the E2V + NG combination in th e treatment of hot flushes and other climacteric symptoms, and that its ble eding profile was favorable.