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.
To compare the short-term efficacy and adverse effects of 2 commonly
used estrogens, conjugated equine estrogen (CEE) and 17β-estradiol, for
reducing menopausal hot flashes by systematically reviewing randomized controlled
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.
English-language abstracts of double-blind, randomized, placebo-controlled
trials and systematic evidence reviews of oral CEE and oral and transdermal
17β-estradiol, and treatment of menopausal hot flashes and their adverse
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
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 17β-estradiol, 5 trials: pooled weighted mean difference, –16.8;
95% CI, –23.4 to –10.2; transdermal 17β-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.
Conjugated equine estrogen and 17β-estradiol have consistent and
comparable effects on treatment of menopausal hot flashes and may have similar
short-term adverse effects.