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 tolerabil ity of a combination estradiol plus norethindrone acetate transdermal deliv ery system given in a continuous sequential regimen with transdermal estrad iol versus placebo in the treatment of vasomotor symptoms of menopause. STUDY DESIGN: This was a 12-week double-blind trial of 220 healthy postmeno pausal women with greater than or equal to 8 moderate to severe hot flushes and sweating episodes per day. Women were randomly assigned to wear transd ermal placebo patches or a transdermal patch releasing 50 mu g/d 17 beta-es tradiol alone (Vivelle) for days 1 to 14 of each cycle and a combination pa tch releasing 50 mu g/d 17 beta-estradiol plus 1 of 3 dosage levels (140, 2 50, or 400 mu g/d) of norethindrone acetate (CombiPatch) for days 15 throug h 28. RESULTS: There was a significant (P < .001) reduction by the second were 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. Signi ficant (P < .001) reductions in the mean intensity of hot flushes and sweat ing were also noted with estradiol plus norethindrone acetate compared with placebo. The incidences of adverse events with all 3 doses of estradiol pl us norethindrone acetate and with placebo were comparable. CONCLUSION: An estradiol plus norethindrone acetate transdermal delivery sy stem administered in a continuous sequential regimen with transdermal estra diol was well tolerated and effective for the treatment of moderate to seve re vasomotor symptoms in postmenopausal women.