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.


METHODS
This was a 12-week double-blind trial of 220 healthy postmenopausal women with > or = 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 microg/d 17beta-estradiol alone (Vivelle) for days 1 to 14 of each cycle and a combination patch releasing 50 microg/d 17beta-estradiol plus 1 of 3 dosage levels (140, 250, or 400 microg/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.


CONCLUSIONS
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.
Notelovitz
M
M
Women's Health Center and Rhône-Poulenc Rorer Pharmaceuticals Inc, Colllegeville, PA, USA.
Cassel
D
D
Hille
D
D
Furst
K W
KW
Dain
M P
MP
VandePol
C
C
Skarinsky
D
D
D000279:Administration, Cutaneous; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects; D015914:Estrogen Replacement Therapy; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D010919:Placebos; D045167:Progesterone Congeners / Q000008:administration & dosage* / Q000009:adverse effects; D013546:Sweating
D010919:Placebos; D045167:Progesterone Congeners; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone