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Comparative controlled trial of a novel oral estrogen therapy, estradiol acetate, for relief of menopause symptoms

Utian, Wulf H MD, PhD1; Speroff, Leon MD2; Ellman, Herman MD3; Dart, Clint4

doi: 10.1097/01.gme.0000184220.63459.a8

Objective: To compare the efficacy and tolerability of a new oral estradiol prodrug, estradiol acetate, with micronized estradiol or conjugated equine estrogens for alleviation of postmenopausal vasomotor and urogenital symptoms.

Design: A total of 249 postmenopausal women experiencing seven or more moderate or severe vasomotor symptoms daily for 1 week or 60 or more symptoms in 1 week were randomized to 0.9 mg of estradiol acetate (n = 79), 1 mg of micronized estradiol (n = 85), or 0.625 mg of conjugated equine estrogens therapy (n = 85). Efficacy endpoints were the change in frequency and severity of vasomotor symptoms from baseline to week 12, participant-assessed urogenital symptoms, and investigator-assessed signs of vaginal atrophy. Efficacy results were considered equivalent if estradiol acetate was at least 80% as effective as estradiol and conjugated estrogens.

Results: At week 12, frequency of vasomotor symptoms decreased comparably in all groups, and at weeks 4 and 12, the decrease in frequency of symptoms was statistically equivalent for estradiol acetate and conjugated estrogens. Severity of vasomotor symptoms also improved comparably for all groups, with least squares mean decreases of 1.05 for estradiol acetate, 1.34 for estradiol, and 1.17 for conjugated estrogens at week 12. Urogenital symptoms and vaginal signs showed similar improvement in all groups. Overall, the majority of adverse events were mild or moderate and consistent with estrogen therapy.

Conclusion: Estradiol acetate 0.9 mg was comparable to 1 mg of estradiol and 0.625 mg of conjugated equine estrogens in reducing the number and severity of vasomotor and urogenital symptoms in postmenopausal women. Oral estradiol acetate was well tolerated.

In a head-to-head comparative study, a novel new estradiol prodrug, estradiol acetate, proved equally efficacious to conjugated equine estrogens in reducing the number and severity of vasomotor and urogenital symptoms in postmenopausal women.

From the 1Department of Gynecology, Cleveland Clinic, Case University; 2Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR; 3Warner Chilcott, Inc., Rockaway, NJ; and 4Health Decisions, Inc.

Received December 21, 2004, revised and accepted March 24, 2005.

This study was supported by Warner Chilcott, Inc., which has developed this product.

Address correspondence to: Wulf H. Utian, MD, PhD, Executive Director, The North American Menopause Society, 5900 Landerbrook Drive, Suite 195, Mayfield Heights, OH 44124. E-mail:

©2005The North American Menopause Society