Estrogen affects post-menopausal women differently than estrogen plus progestin replacement therapy

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.