Letters Section Editor: Stephen J. Lurie,
MD, PhD, Senior Editor.
To the Editor: Dr Shumaker and colleagues1 from the Women's Health Initiative Memory Study
(WHIMS) reported that combined equine estrogen (CEE) plus medroxyprogesterone
acetate (MPA) increased the risk for probable dementia in postmenopausal women
aged 65 years or older. They also found that this regimen did not prevent
mild cognitive impairment. These findings are consistent with our data that
MPA antagonizes the neuroprotective and memory mechanisms of estrogen.2- 4 These studies,
conducted while the WHIMS trial was in progress, indicate that progestins
have differing profiles of biochemical and genomic activation that lead to
differential effects on beneficial estrogen-inducible mechanisms.5 Results of these analyses could be used to predict
efficacy of hormone therapy formulations for prevention of Alzheimer disease
(AD). The challenge remains to develop a therapeutic strategy for promoting
the beneficial effects of estrogen in the brain while preventing untoward
consequences of estrogen in other organ systems.
Brinton RD, Nilsen J. Effects of Estrogen Plus Progestin on Risk of Dementia—Reply. JAMA. 2003;290(13):1706-1708. doi:10.1001/jama.290.13.1706-a