Jerome L. Sullivan, MD, PhD
Potential Conflicts of Interest: None disclosed.
Sullivan J.; Menopausal Hormone Therapy and Risk for Cardiovascular Disease in the WHI Trial. Ann Intern Med. 2010;153:61. doi: 10.7326/0003-4819-153-1-201007060-00021
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Published: Ann Intern Med. 2010;153(1):61.
TO THE EDITOR:
The WHI was based on an expectation of no less than a 30% reduction in CVD mortality in women receiving hormone replacement therapy (HRT) (1). With the “timing hypothesis” effectively eliminated by Toh and colleagues (2), the meaning of the results of the trial should be revisited. Failure to show any reduction in mortality, let alone a 30% reduction, has far-reaching implications beyond the recommendation that HRT not be used for prevention of CVD. The large expected decrease in disease was related to the much lower CVD rates of menstruating women. The fact that the WHI found no mortality decrease with HRT, even in newly postmenopausal women, raises questions about the belief that menstruating women are protected from CVD by the direct effects of female hormones. The working conclusion seems to be that young women are protected by their hormones but that, at whatever age menopause occurs, this protection is lost. An alternative, simpler view consistent with WHI findings is that female hormones confer a small cardiovascular risk at any age. In other words, risk is lower in young, menstruating women despite the disease-promoting effects of female hormones. Premenopausal women may be protected by some other factor that, when lost after menopause, makes this increased risk apparent in those receiving HRT. An alternative protective factor in menstruating women has been proposed (3–6).
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