Low-dose transdermal estradiol for vasomotor symptoms: a systematic review

This review aims to determine the effectiveness of low-dose transdermal estrogen versus placebo in postmenopausal women with moderate to severe hot flashes.

We conducted a systematic review of studies by searching Medline and EMBASE using the following inclusion criteria: double-blind, placebo-controlled, randomized controlled trials conducted in postmenopausal women with at least 7 hot flashes per day and/or at least 50 hot flashes per week. All included studies used estrogen formulations below the equivalent dose of 0.05 mg of 17β-estradiol.

Nine studies met all inclusion criteria. Seven of nine studies had low risk of bias, whereas two studies had high risk of bias. Low-dose transdermal estrogen in all dose ranges was more likely than placebo to decrease the daily number of hot flashes. Meta-analysis was not performed as only three of the nine studies included measures of variance; weighted means were used to summarize the data. Results were divided into three groups by decreasing estrogen dose range (0.037-0.045, 0.020-0.029, and 0.003-0.125 mg). The mean daily decrease in the number of hot flashes from baseline was 9.36, 7.91, and 7.07, respectively. The mean daily decrease in the placebo groups was 5.07. Eight of the nine studies reported P values comparing each estrogen dose to placebo; all were significant at P < 0.05.

Although publication bias cannot be excluded, risk of bias and heterogeneity among studies are low. There is strong evidence to conclude that low-dose transdermal estrogen at any dose is more effective than placebo in decreasing the daily number of moderate to severe hot flashes.