Objective: To determine the efficacy and tolerability of two strengths of percutaneous 17beta-estradiol in a hydroalcoholic gel and placebo in controlling vasomotor symptoms of menopause.
Design: A total of 221 postmenopausal women were assigned randomly to treatment with percutaneous 17beta-estradiol gel 1.25 g (containing 0.75 mg of estradiol) or 2.5 g (containing 1.5 mg of estradiol) or placebo gel applied once daily for 12 weeks. The primary efficacy variable was the mean change from baseline in the frequency of moderate/severe hot flushes. In addition, the mean changes from baseline in the frequency and severity of all hot flushes were assessed. Safety and tolerability were evaluated from endometrial biopsy, adverse events, and laboratory tests.
Results: A significant reduction (P < 0.05) in the mean frequency of moderate-to-severe hot flushes and mean frequency and severity of all hot flushes was observed with both 17beta-estradiol gel groups compared with placebo. The mean number of moderate-to-severe hot flushes at the end of the study with 17beta-estradiol gel 2.5 g, 17beta-estradiol gel 1.25 g, and placebo gel was 2.0, 2.8 and 5.2, respectively. The overall incidence of adverse events was not significantly different among groups, though a higher incidence of estrogen-related adverse events was reported with the 17beta-estradiol gel 2.5-g dose.
Conclusions: 17beta-estradiol gel was effective and well tolerated for alleviating moderate-to-severe hot flushes in postmenopausal women. Therapy may be initiated with the 1.25-g dose with an increase to the 2.5-g dose if needed.