Letters Section Editor: Stephen J. Lurie,
MD, PhD, Senior Editor.
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.
Smith MA, Perry G, Atwood CS, Bowen RL. Estrogen Replacement and Risk of Alzheimer Disease—Reply. JAMA. 2003;289(9):1100-1102. doi:10.1001/jama.289.9.1100-a