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Scientific Review

Heidi D. Nelson, MD, MPH

JAMA. 2004;291:1610-1620.

Context  Recommendations for postmenopausal hormone therapy have changed since the Women's Health Initiative indicated that estrogen was harmful for use in disease prevention; however, treatment of menopausal symptoms with low-dose estrogen remains an approved indication for use.

Objective  To compare the short-term efficacy and adverse effects of 2 commonly used estrogens, conjugated equine estrogen (CEE) and 17-estradiol, for reducing menopausal hot flashes by systematically reviewing randomized controlled trials.

Data Sources  MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and Cochrane Controlled Trials Registry were searched from the database start dates to July 2003 using database-specific key words. Reference lists of published articles, experts, and pharmaceutical manufacturers were also consulted.

Study Selection  English-language abstracts of double-blind, randomized, placebo-controlled trials and systematic evidence reviews of oral CEE and oral and transdermal 17-estradiol, and treatment of menopausal hot flashes and their adverse effects.

Data Extraction  Study design, population characteristics, eligibility criteria, interventions, withdrawals, adverse effects, and results for each outcome. Study quality was assessed using predefined criteria based on parameters developed with the US Preventive Services Task Force and the UK National Health Services Centre.

Data Synthesis  A total of 32 trials including 4 head-to-head comparisons met inclusion criteria; 14 trials met criteria for meta-analysis. All estrogen agents significantly reduced the weekly number of hot flashes compared with placebo (CEE, 1 trial: mean change, –19.1; 95% confidence interval [CI], –33.0 to –5.1; oral 17-estradiol, 5 trials: pooled weighted mean difference, –16.8; 95% CI, –23.4 to –10.2; transdermal 17-estradiol, 6 trials: pooled weighted mean difference, –22.4; 95% CI, –35.9 to –10.4); differences between agents were not significant. Breast tenderness and atypical vaginal bleeding were the most frequently reported adverse effects among estrogen users. The influence of progestin or progesterone use, cyclic and continuous regimens, and differences in adverse effects could not be determined.

Conclusion  Conjugated equine estrogen and 17-estradiol have consistent and comparable effects on treatment of menopausal hot flashes and may have similar short-term adverse effects.

Author Affiliations: Oregon Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology, and Department of Medicine, Oregon Health and Science University, Portland.

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