The very large and long-running Women's Health Initiative study surprised everyone when it produced its finding that hormone therapy generally increased rather than decreased stroke risk as well as other health problems. But one explanation for that finding might be that many of the women only received hormone replacement therapy years after menopause. There are indications that timing is crucial.
This new rat study involved female rats equivalent to human 60-65 year olds, about a decade past menopause. An enzyme called CHIP (carboxyl terminus of Hsc70 interacting protein) was found to increase binding with estrogen receptors, resulting in about half the receptors getting hauled to the cell's proteosome to be chopped up and degraded. When some of the aged rats were later treated with estrogen, mortality increased. When middle-aged rats were treated with estrogen, on the other hand, results were positive.
In other words, putting in extra estrogen after the number of estrogen receptors in the brain has been dramatically decreased is a bad idea.
While this study focused on mortality, other research has produced similar conflicting results as to whether estrogen therapy helps fight age-related cognitive impairment in women (see my report). It’s interesting to note that this effect only occurred in the hippocampus — estrogen receptors in the uterus were unaffected.
(2011). C terminus of Hsc70-interacting protein (CHIP)-mediated degradation of hippocampal estrogen receptor-α and the critical period hypothesis of estrogen neuroprotection.
Proceedings of the National Academy of Sciences. 108(35), E617 -E624 - E617 -E624.