To the Editor: Dr Rossouw and colleagues1 analyzed postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause; they used combined data for conjugated equine estrogen (CEE) therapy and CEE plus medroxyprogesterone acetate (CEE + MPA) from the Women's Health Initiative (WHI). The hazard ratios (HRs) for coronary heart disease (CHD) based on years since menopause were 0.76 (<10 years), 1.10 (10-19 years), and 1.28 (≥20 years) (P for trend = .02). The corresponding values for CEE were 0.48, 0.96, and 1.12 (P for trend = .15); for CCE + MPA the estimates were 0.88, 1.23, and 1.66 (P for trend =.05).
For CEE + MPA, the HRs may have been overestimated.2 - 3 At baseline, the women were informed that a primary outcome was CHD, and during follow-up 44% and 6.7% of the CCE + MPA and placebo recipients, respectively, became unblinded to treatment assignment, mostly because of persistent vaginal bleeding.4 After about 3 years of follow-up, and again 1 year later, they were informed that an increased risk of CHD had been identified. Therefore, mild or atypical episodes of myocardial infarction (eg, “indigestion”) might have been diagnosed more commonly among the CEE + MPA participants compared with the placebo participants.
It is thus possible that a protective effect of CEE + MPA among recently menopausal women was present, but underestimated, and that there was no subsequent increase in the risk. Unblinding occurred in less than 2% of the CEE recipients because they had undergone hysterectomy,5 and although the data were less statistically robust because of smaller numbers, they were compatible with that possibility.
As has been suggested before,2 - 3 the HRs for CEE + MPA should be investigated among recipients who remained blinded.
Financial Disclosures: Dr Shapiro reported past consulting with Schering and Organon, and current consulting with Bayer/Schering and Organon, manufacturers of hormonal products used in the treatment of menopausal women, for which he has received compensation.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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