Efficacy of continuous sequential transdermal estradiol and norethindrone acetate in relieving vasomotor symptoms associated with menopause, ,

Objective: This study was undertaken to evaluate the efficacy and tolerability of a combination estradiol plus norethindrone acetate transdermal delivery system given in a continuous sequential regimen with transdermal estradiol versus placebo in the treatment of vasomotor symptoms of menopause. Study Design: This was a 12-week double-blind trial of 220 healthy postmenopausal women with ≥8 moderate to severe hot flushes and sweating episodes per day. Women were randomly assigned to wear transdermal placebo patches or a transdermal patch releasing 50 μg/d 17β-estradiol alone (Vivelle) for days 1 to 14 of each cycle and a combination patch releasing 50 μg/d 17β-estradiol plus 1 of 3 dosage levels (140, 250, or 400 μg/d) of norethindrone acetate (CombiPatch) for days 15 through 28. Results: There was a significant (P< .001) reduction by the second week in the mean number of daily hot flushes from baseline to end point with all 3 doses of estradiol plus norethindrone acetate compared with placebo. Significant (P< .001) reductions in the mean intensity of hot flushes and sweating were also noted with estradiol plus norethindrone acetate compared with placebo. The incidences of adverse events with all 3 doses of estradiol plus norethindrone acetate and with placebo were comparable. Conclusion: An estradiol plus norethindrone acetate transdermal delivery system administered in a continuous sequential regimen with transdermal estradiol was well tolerated and effective for the treatment of moderate to severe vasomotor symptoms in postmenopausal women. (Am J Obstet Gynecol 2000;182:7-12.)