Norethindrone acetate and estradiol-induced endometrial hyperplasia.
OBJECTIVE
To identify the lowest effective continuous dose of norethindrone acetate that significantly reduces 12-month incidence of endometrial hyperplasia associated with unopposed 17beta-estradiol (E2), 1 mg.


METHODS
In a double-masked, randomized, multicenter study, 1176 healthy postmenopausal women 45 years of age or older without evidence of endometrial abnormalities were given 12 months of treatment with unopposed E2, 1 mg, or continuous-combined regimens of E2, 1 mg, and norethindrone acetate, 0.1 mg, 0.25 mg, or 0.5 mg. Endometrial histology was evaluated at the end of the treatment period.


RESULTS
Continuous-combined E2-norethindrone acetate regimens significantly reduced 12-month incidence of endometrial hyperplasia compared with unopposed E2 1 mg (P <.001). Endometrial hyperplasia occurred in 14.6% of women treated with unopposed E2 1 mg, whereas in all continuous-combined groups, the rate decreased to less than 1%. Among patients who received E2-norethindrone acetate 0.1 mg, incidence was 0.8%; among those who received 0.25 mg and 0.5 mg, it was 0.4%.


CONCLUSIONS
Continuous norethindrone acetate at doses as low as 0.1 mg combined with E2 1 mg effectively negated risk for endometrial hyperplasia associated with unopposed E2 1 mg, at least for the first year of therapy.
Kurman
R J
RJ
Department of Gynecology and Obstetrics The Johns Hopkins Hospital, Baltimore, Maryland 21287, USA.
Félix
J C
JC
Archer
D F
DF
Nanavati
N
N
Arce
J
J
Moyer
D L
DL
D002979:Climacteric / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004714:Endometrial Hyperplasia / Q000139:chemically induced / Q000517:prevention & control*; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate
D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone