Hum. Reprod. Advance Access originally published online on March 8, 2007
Human Reproduction 2007 22(6):1769-1777; doi:10.1093/humrep/dem031
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Estrogen affects post-menopausal women differently than estrogen plus progestin replacement therapy
1 Department of Medicine 2 Center for Clinical Epidemiology and Biostatistics 3 Department of Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA 4 Department of Obstetrics and Gynecology
5 To whom correspondence should be addressed at: University of Pennsylvania School of Medicine, 295 John Morgan Building, 36th and Hamilton Walk, Philadelphia, PA 19104, USA. Tel.: +215 898 2270; Fax: +215 573 0280; E-mail: tannen{at}mail.med.upenn.edu
BACKGROUND: In the Women's Health Initiative Randomized Controlled Trial (WHI RCT), estrogen-only treatment compared with combined estrogen–progestin treatment resulted in less coronary artery disease, no increase in breast cancer and no reduction in colorectal cancer. Since we previously reasonably replicated the combined estrogen–progestin WHI RCT using the UK General Practice Research Database (GPRD), estrogen-only treatment was investigated using a similar methodology.
METHODS: This GPRD study simulated the estrogen-only WHI RCT of women who had undergone a hysterectomy except for randomization. The primary analysis examined 11 572 unexposed and 6890 Exposed women (aged 55–79) treated with conjugated equine estrogen and was compared with the combined estrogen–progestin GPRD study.
RESULTS: At baseline, women with a hysterectomy exhibited more cardiovascular disease than those with an intact uterus. In the estrogen-only GPRD study, adjusted hazard ratios (HRs) were 0.50 (0.38–0.67) for myocardial infarction (MI), 1.13 (0.91–1.41) for breast cancer, and 1.18 (0.72–1.92) for colorectal cancer. Compared to the HRs in the estrogen–progestin GPRD study, the estrogen-only results are significantly lower for MI and breast cancer and higher for colon cancer, a pattern similar to the WHI RCT study comparisons.
CONCLUSIONS: This study confirms that post-menopausal women in the overall population respond differently to estrogen-only treatment compared with estrogen–progestin treatment, due to different hormone regimens and/or increased cardiovascular disease in hysterectomized women.
Key words: cohort studies/coronary heart disease/hormone replacement therapy/hysterectomy/menopause
Submitted on December 5, 2006; resubmitted on January 12, 2006; accepted on January 18, 2007.