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Robert B. Gibbs, Does Short-Term Estrogen Therapy Produce Lasting Benefits in Brain?, Endocrinology, Volume 151, Issue 3, 1 March 2010, Pages 843–845, https://doi.org/10.1210/en.2009-1453
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The question of whether estrogen therapy should be used in postmenopausal women is a topic filled with controversy and debate. In vitro and animal studies clearly show that estrogens (most often 17β-estradiol) are neuroprotective (1), can enhance hippocampal and cortical function (2), improve cognitive performance (3), and prevent or reduce age-related cognitive decline (4, 5). Estrogen therapy, however, is not without risks. These include increased production of liver proteins such as sex hormone-binding globulin and C-reactive protein as well as increased risk of thromboembolism and stroke and breast and uterine cancers (6–9). Although positive effects on cognitive performance have been observed (10), negative results also have been reported. For example, the recent Women’s Health Initiative Memory Study showed an increased (∼2-fold) risk of dementia among women receiving the combination of oral conjugated equine estrogens and medroxyprogesterone acetate (11) and a trend toward increased risk of dementia among women receiving conjugated equine estrogens alone (12). This was a very large study of over 7000 women with a mean age of 69 yr. Another recent study likewise showed increased risk of cognitive decline among long-term users of estrogen therapy, particularly among women who initiated therapy at older ages (13). These findings have raised serious concerns about the long-term use of estrogen therapy in older postmenopausal women. As a result, women who are prescribed therapy for the treatment of menopausal symptoms are encouraged to limit therapy to the lowest possible dose and duration.
