Norethindrone acetate and estradiol-induced endometrial hyperplasia.

Abstract

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%.

CONCLUSION:

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.

• Authors: R J Kurman, J C Félix, D F Archer, N Nanavati, J Arce, D L Moyer
• Journal: Obstetrics and gynecology (Obstet Gynecol) Vol. 96 Issue 3 Pg. 373-9 (Sep 2000) ISSN: 0029-7844 [Print] United States
• PMID: 10960628 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Estradiol
• Norethindrone Acetate
• Norethindrone

Topics

• Climacteric (drug effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination
• Endometrial Hyperplasia (chemically induced, prevention & control)
• Estradiol (administration & dosage, adverse effects)
• Estrogen Replacement Therapy
• Female
• Humans
• Middle Aged
• Norethindrone (administration & dosage, adverse effects, analogs & derivatives)
• Norethindrone Acetate