Less is more when it comes to E2 for hot flushes

As little as 0.014 mg/d trans dermal 17ß-estradiol (E2) is enough to significantly reduce the number of moderate and severe hot flushes in postmenopausal women, according to the results of a randomized, double-blind, placebo-controlled multicenter trial.

Healthy postmenopausal women aged 40 years and older who experienced at least 50 hot flushes per week applied transdermal patches containing either a combination of 0.023 mg/d 17ß–estradiol and 0.0075 mg/d levonorgestrel, 0.014 mg/d E2 alone, or placebo for 12 weeks.

Compared with placebo, the average number of moderate and severe hot flushes per week was reduced by 51.8 episodes (P<0.001) in the combination group and by 38.46 (P<0.001) in the microdose E2 group. Almost half (41.3%) of the women receiving the microdose of E2 had a 75% or greater reduction from baseline in hot flush frequency (P=0.003) versus 24.2% of the women receiving placebo. And relief was provided quickly: mean reduction in frequency of hot flushes was 50% by week 2, 70% by week 4, 90% by week 8, and 95% by week 12, with side effects comparable to those experienced by the women receiving placebo.

Bachmann GA, Schaefers M, Uddin A, et al. Lowest effective transdermal 17ß-estradiol dose for relief of hot flushes in postmenopausal women: a randomized controlled trial. Obstet Gynecol. 2007;110:771-779.

Commentary from Nanette F. Santoro, MD, Professor and Director, Division of Reproductive Endocrinology, Department of Ob/Gyn and Women's Health, Albert Einstein College of Medicine, Bronx, NY.

This very interesting trial clearly demonstrates marked subjective improvement in vasomotor symptoms compared with placebo at a surprisingly low dose of estradiol. The 41% 'responder' rate suggests that many women may find significant relief of their hot flushes at hormone doses previously considered homeopathic.