17 beta-estradiol/levonorgestrel transdermal system.

Abstract

Hormone replacement therapy with continuous 17 beta-estradiol/levonorgestrel (estradiol/levonorgestrel), administered once weekly as a transdermal system, has shown efficacy in the treatment of vasomotor symptoms associated with menopause. Transdermal estradiol/levonorgestrel (4.4/2.74 and 4.5/3.75mg) significantly reduced the mean weekly (primary endpoint) and daily number of hot flashes (flushes) compared with placebo in a 12-week, randomized, double-blind trial in postmenopausal women (both of the dosages used are higher than the approved dosage). The same endpoints were also numerically reduced from baseline by estradiol/levonorgestrel (4.4/1.39 [approved dosage], 4.4/2.74, and 4.5/3.75mg), as well as 17 beta-estradiol (estradiol) in a substudy of a 12-month randomized trial in postmenopausal women; however, there were no significant between-group differences. Estradiol/levonorgestrel also reduced the mean daily maximal severity of hot flashes. In the 12-week study, mean daily hot flash severity improved from severe to mild for estradiol/levonorgestrel recipients, but remained moderately severe for placebo recipients. None of the recipients of estradiol/levonorgestrel 4.4/1.39mg and 12.8% of women treated with estradiol developed endometrial hyperplasia (primary endpoint) in a large, 12-month, randomized, double-blind trial in postmenopausal women. Over 12 months, estradiol/levonorgestrel and estradiol significantly improved mean quality-of-life total scores (women's health questionnaire) from baseline; there were no significant between-group differences. The estradiol/levonorgestrel transdermal system was generally well tolerated. In two trials, application-site reactions were common in all treatment groups (estradiol/levonorgestrel, estradiol, and placebo).