Sengwee Toh, ScD; Jacques E. Rossouw, MD; Miguel A. Hernán, MD, DrPH
Potential Conflicts of Interest: None disclosed.
Toh S, Rossouw JE, Hernán MA. Menopausal Hormone Therapy and Risk for Cardiovascular Disease in the WHI Trial. Ann Intern Med. 2010;153:61-62. doi: 10.7326/0003-4819-153-1-201007060-00022
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Published: Ann Intern Med. 2010;153(1):61-62.
We agree with Dr. Harman and colleagues about the importance of both the timing of initiation of postmenopausal hormone therapy and the duration of treatment in relation to CHD, a point we made in our article. Unlike several analyses of observational studies, the WHI estrogen plus progestin trial found no benefit of postmenopausal hormone therapy on either CHD risk or mortality. In contrast, the WHI findings were consistent with observational analyses for stroke, venous thromboembolism, breast cancer (increased risk), hip fractures, and colorectal cancer (decreased risk) (1). Subsequent reanalyses of the observational data (2, 3) suggest that an early harmful effect of estrogen plus progestin therapy on CHD may explain the randomized-observational discrepancy: The WHI trial fully captured the early events, whereas several previous analyses of observational data did not. Our analyses of data from WHI and the Nurses' Health Study indicate that women who started estrogen plus progestin therapy long after menopause had a greater CHD risk during at least the first 8 years of treatment and that women who started therapy within 10 years after menopause did not have a lower CHD risk during the first 3 to 6 years of treatment (3). In fact, as Drs. Pines and Sturdee point out, our findings are also consistent with a small increase in the short-term CHD risk in these younger women. Regardless of whether one chooses to emphasize the lack of early benefit (as we did in our article) or the possibility of early harm, the insufficient evidence for long-term CHD benefit, plus the adverse effects on stroke, venous thromboembolism, and breast cancer, argue against returning to estrogen plus progestin therapy (at least not the regimen studied in the WHI) as a viable option for the prevention of chronic diseases.
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