Postmenopausal uterine bleeding profiles with two forms of continuous combined hormone replacement therapy

UMMS Affiliation

Department of Obstetrics and Gynecology

Publication Date


Document Type



Aged; Double-Blind Method; Drug Combinations; Estradiol; Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Female; Humans; Medroxyprogesterone Acetate; Middle Aged; Norethindrone; Postmenopause; Progestins; Uterine Hemorrhage


Obstetrics and Gynecology


OBJECTIVE: This study was designed to compare the bleeding profiles of conjugated equine estrogens 0.625 mg in combination with 2.5 mg medroxyprogesterone acetate (Prempro; CEE/MPA group), the most widely prescribed continuous combined hormone replacement therapy (CCHRT) in the United States, with 17beta-estradiol 1 mg combined with 0.5 mg norethindrone acetate (Activella; E(2)/NETA group), a newly available CCHRT preparation, over a 6-month period.

DESIGN: This study was a prospective, randomized, multicenter, double-blind, controlled trial. A total of 438 healthy postmenopausal women were randomized and received treatment (Activella n = 217, Prempro n = 221). Each woman recorded bleeding diaries daily. Total cholesterol, triglycerides, and endometrial biopsies were obtained at screening and end-of-trial visits.

RESULTS: The more favorable bleeding profile was found in the E(2)/NETA (Activella) group. The differences in bleeding patterns were most marked in the first 3 months of treatment in women who were 1-2 years from last menses, with no bleeding in 71.4% vs. 40.0%; ( p = 0.005) and with no bleeding and no spotting in 54.8% vs. 17.1%; (p = 0.001). Triglycerides fell by 8.5% in the E(2)/NETA group and increased by 11.7% in the CEE/MPA group (p < 0.001). Total cholesterol declined by 9.1% and 6.9%, respectively.

CONCLUSION: The most important factor in the continuation of HRT is uterine bleeding. E(2)/NETA has significantly less bleeding than the most commonly prescribed CCHRT CEE/MPA, therefore; E(2)/NETA should be associated with improved continuation rates. The patient taking E(2)/NETA will receive effective treatment for her menopausal symptoms with less bleeding.


Menopause. 2002 Jan-Feb;9(1):16-22. Link to article on publisher's website

Journal/Book/Conference Title

Menopause (New York, N.Y.)


At the time of publication, Julia Johnson was not yet affiliated with the University of Massachusetts Medical School.

Related Resources

Link to Article in PubMed

PubMed ID