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In Reply: Drs Brinton and Nilsen cite their cellular-level research indicating that MPA interferes with the protective effects of CEE on neurons, and conclude that their data are consistent with our findings regarding an increased risk for AD associated with CEE plus MPA (as compared with placebo). We agree that their data provide one possible hypothesis regarding a mechanism that may have contributed to a null finding and, perhaps, to our negative finding. However, we strongly disagree with their conclusion regarding the demonstrated benefits of estrogen alone in preventing AD. In our analysis we did not isolate the unique contribution of MPA on global cognitive functioning or probable dementia (including AD). At the end of the study we do plan to compare the effect of CEE alone (vs placebo) with that of CEE plus MPA on the incidence of dementia. Until then, however, we consider this as only an intriguing . . . [Full Text of this Article]

Sally A. Shumaker, PhD; Stephen R. Rapp, PhD; Mark A. Espeland, PhD; Robert B. Wallace, MD; Susan L. Hendrix, DO; Victor W. Henderson, MD, MS; Margery L. Gass, MD; Leon Thal, MD

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