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March 5, 2003

Estrogen Replacement and Risk of Alzheimer Disease—Reply

Author Affiliations

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2003;289(9):1100-1102. doi:10.1001/jama.289.9.1100-a

To the Editor: Dr Zandi and colleagues1 found that postmenopausal estrogen replacement therapy (ERT) reduced the risk of Alzheimer disease (AD), but only among long-term users of ERT. It is possible, however, that some of this trend may be mediated by indirect effects of estrogen. In particular, serum concentrations of gonadotropins, luteinizing hormone, and follicle-stimulating hormone are sensitive to changes in estrogen, since gonadotropins are the primary regulator of estrogen production. In postmenopausal women, the loss of estrogen results in a significant increase in circulating gonadotropin concentrations.2 Conversely, when women take ERT, gonadotropin concentrations are suppressed due to the inhibitory feedback of estrogen on the hypothalamic-pituitary-gonadal axis.3 Thus, the effects of ERT may be related to hormones other than estrogen.

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