Randomised, controlled comparison of transdermal estradiol with oral conjugated estrogens for the relief of hot flushes

Objective and Design: This multicentre, double-blind, randomised, controlled trial evaluated the efficacy of continuous low-dose transdermal estradiol (E2-TDS) compared with oral conjugated equine estrogens (CEE) in decreasing the frequency and severity of hot flushes in postmenopausal women. Patients and Methods: The study enrolled 193 postmenopausal women at 19 centres. Healthy postmenopausal females, aged 45 years or older, who experienced moderate or severe hot flushes (at least 7 daily or 60 weekly) during the screening period were randomised to receive either oral CEE0.3 mg/day or an estradiol patch delivering0.025 mg/day for 12 weeks. Patients were assessed after three 28-day cycles. The primary efficacy variable was the frequency and severity of hot flushes. Results: The mean weekly number of hot flushes, as well as the severity of hot flushes, decreased significantly across all cycles for both treatment groups. Results were comparable at all time-points. By the end of the study, the mean (± standard deviation) weekly number of hot flushes had decreased from 94.1 ± 39.4 at baseline to 29.0 ± 34.3 (69%) in the E2-TDS group, and from 94.1 ± 58.7 to 31.4 ± 76.9 (68%) in the CEE group. Lipid changes in this 3-month study were small and not generally clinically significant. Treatment-related adverse events were similar in both treatment groups and only 6 patients treated with CEE and 5 patients treated with E2-TDS discontinued therapy because of adverse events. Conclusions: Low-dose E2-TDS (0.025 mg/day) was shown to be an effective method of relieving hot flushes in postmenopausal women, with efficacy comparable to CEE0.3 mg/day.