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

Johnson, Julia V. MD1; Davidson, Michael MD2; Archer, David MD3; Bachmann, Gloria MD4


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 17β-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.

Author Information

From the 1 Department of Obstetrics and Gynecology, University of Vermont College of Medicine, Burlington, Vermont, 2 Chicago Center for Clinical Research, Chicago, Illinois, 3 Clinical Research Center, Eastern Virginia Medical School, Norfolk, Virginia, and the 4 Department of Obstetrics and Gynecology and Reproductive Sciences, University of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School.

Received June 18, 2001;

revised and accepted September 5, 2001.

Address reprint requests to Julia V. Johnson, MD, University of Vermont College of Medicine, Department of Obstetrics and Gynecology, Given Building, Burlington, Vermont 05405. E-Mail:

The Activella Study Group: G. Bachmann, R. K. Bath, M. B. Block, B. F. Booker, S. S. Brady, D. P. Buser, S. Christian, M. Davidson, S. Drosman, S. A. Funk, H. L. Geisberg, P. R. Goldstein, M. Greenwald, M. A. Heuer, J. V. Johnson, W. D. Koltun, J. P. Lenihan, D. C. McCluskey, W. S. McKenzie, M. Nunez, G. Parker, M. Reynolds, S. Rosenblatt, L. Speroff, S. Turner, R. L. Weinstein, S. Weiss, R. Wilson.

©2002The North American Menopause Society