Objective: The aim of this study was to assess vasomotor and other menopausal symptoms before starting estrogens or placebo, 1 year later, again at trial closure, and after stopping estrogens or placebo. The role of baseline symptoms and age was examined, as was the frequency and determinants of hormone use and symptom management strategies after discontinuing conjugated equine estrogens (CEE) or placebo.
Methods: Intent-to-treat analyses of 10,739 postmenopausal women before and 1 year after randomization to CEE or placebo at 40 clinical centers and a cohort analysis of participants (n = 3,496) who continued taking assigned study pills up to trial closure and completed symptom surveys shortly before (mean, 7.4 ± 1.1 y from baseline) and after (mean, 306 ± 55 d after trial closure) stopping pills were performed. Generalized linear regression modeled vasomotor symptoms, vaginal dryness, breast tenderness, pain/stiffness, and mood swings as a function of treatment assignment and baseline symptoms, before and after stopping study pills.
Results: Approximately one third of participants reported at least one moderate to severe symptom at baseline. Fewer symptoms were reported with increasing age, except joint pain/stiffness, which was similar among age groups. At 1 year, hot flashes, night sweats, and vaginal dryness were reduced by CEE, whereas breast tenderness was increased. Breast tenderness was also significantly higher in the CEE group at trial closure. After stopping, vasomotor symptoms were reported by significantly more women who had reported symptoms at baseline, compared with those who had not, and by significantly more participants assigned to CEE (9.8%) versus placebo (3.2%); however, among women with no moderate or severe symptoms at baseline, more than five times as many reported hot flashes after stopping CEE (7.2%) versus placebo (1.5%).
Conclusions: CEE significantly reduced vasomotor symptoms and vaginal dryness in women with baseline symptoms but increased breast tenderness. The likelihood of experiencing symptoms was significantly higher after stopping CEE than placebo regardless of baseline symptom status. These potential effects should be considered before initiating CEE to relieve menopausal symptoms.
This study shows that conjugated equine estrogens (CEE) significantly reduced vasomotor symptoms and vaginal dryness in women with baseline symptoms but increased breast tenderness. The likelihood of experiencing symptoms was significantly higher after stopping CEE than placebo regardless of baseline symptom status. These potential effects should be considered before initiating CEE to relieve menopausal symptoms.
From the 1Department of Family and Community Medicine, University of Nevada School of Medicine, Reno, NV; 2Fred Hutchinson Cancer Research Center, Seattle, WA; 3Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI; 4Family and Child Nursing, University of Washington, Seattle, WA; 5The North American Menopause Society, Cleveland, OH; 6University Women's Care Inc., Detroit, MI; 7Department of Preventive Medicine, School of Medicine Health Sciences Center, State University of New York at Stony Brook, Stony Brook, NY; 8Division of Preventive and Behavioral Medicine, University of Massachusetts Medical College, Worcester, MA; 9Stanford Prevention Research Center Hoover Pavilion, Stanford, CA; and 10Lawrence J. Ellison Ambulatory Care Center, University of California Davis Health System, Sacramento, CA.
Received September 21, 2009; revised and accepted January 19, 2010.
Author contributions: Drs. Brunner and Stefanick and Mr. Aragaki had full access to all of the data and take full responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Barnaabei, Brunner, Stefanick, Cochrane, Ockene, Woods. Acquisition of data: Brunner, Gass, Hendrix, Lane, Ockene, Stefanick, Woods. Analysis and interpretation of the data: Aragaki, Barnabei, Brunner, Cochrane, Lane, Ockene, Stefanick, Woods. Drafting of the manuscript: Barnabei, Brunner, Stefanick, Ockene. Critical revision of the manuscript for important intellectual content: Aragaki, Barnabei, Brunner, Cochrane, Gass, Hendrix, Lane, Ockene, Stefanick, Woods, Yasmeen. Statistical analysis: Aragaki. Obtained funding: Brunner, Gass, Hendrix, Lane, Ockene, Stefanick. Administrative, technical, or material support: Cochrane. Study supervision: Brunner, Gass, Hendrix, Lane, Ockene, Stefanick.
Funding/support: The Women's Health Initiative program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services.
Financial disclosure/conflicts of interest: Dr. Gass reports that she has received funding support for multisite clinical trials from Procter & Gamble Pharmaceuticals, Roche, and Wyeth Pharmaceuticals and honoraria from Aventis, Eli Lilly & Co., Esprit Pharma, GlaxoSmithKline, Novartis, Merck & Co. Inc., Procter & Gamble Pharmaceuticals, Roche, Upsher-Smith Laboratories Inc., and Wyeth Pharmaceuticals Inc. Otherwise, no other authors reported financial conflicts. The National Institutes of Health had input into the design and conduct of the study and in the review and approval of this article.
Address correspondence to: Robert L. Brunner, PhD, Department of Family and Community Medicine, University of Nevada School of Medicine, Reno, NV 89511. E-mail: firstname.lastname@example.org