Window of Opportunity of Estrogen Therapy for Neuroprotection

Catchy title for a workshop, no? It certainly caught my eye, but alas it was over and done with months ago, and I only heard about it this month.

Not too late, however, for me to share the gist of the message with you, namely that there is ample evidence that estrogen is brain protective--i.e. can decrease your risk of progressing from the occasional menopause moment into a permanent demented state of mind as the years go by--but only if estrogen supplementation is initiated at a time when your brain is still functioning normally.

Actually, this is not new news at all. Researchers have known for years that estrogen plays a critical role in brain function, particularly in those parts of the anterior brain known as the forebrain where memories are formed and complex functions such as learning and multi-tasking are initiated. Diminishing estrogen levels during that lovely adventure known as perimenopause are, therefore, often associated with problems in verbal memory (finding the right word at the right time and using it correctly) as well as difficulty in mastering new skills. Ever tried to teach an old lady how to use e-mail? And if you've spent any time in nursing homes, you are well aware that the majority of the residents are female and a large number of them are struggling with dementia.*

Doctors at the Mayo Clinic studied women who underwent oophorectomies (removal of one or both ovaries) before the age of menopause and compared their brain health through the years following surgery as compared with a group of subjects who hung onto their ovaries through a natural menopause.(1) Removing the ovaries at the time of a hysterectomy done for any reason (such as fibroids or abnormal menstrual bleeding) used to be a common practice in order to protect against the possibility of future ovarian cancer. Since the findings of the Women's Health Initiative made headline news in 2002, the use of estrogen therapy following such surgery has become increasingly uncommon.

Those women who underwent bilateral oophorectomy (both ovaries removed) before menopause were 1.5 times more likely to develop dementia as they aged than the control subjects who did not undergo surgery. And the younger the age at which they experienced loss of ovarian function (and thus loss of estrogen), the more likely they were to develop profound problems with cognitive functioning. Subsequent analysis of the data from the Mayo Clinic group as well as from other studies showed that oophorectomized women who received estrogen therapy until age 50--more or less the time of natural menopause--had a normal risk of dementia.(2) In other words, they were no more likely to develop Alzheimer's disease than women going through menopause in the normal fashion. Furthermore, menopausal women who took hormone therapy initiated at the time of menopause and continued for 10 years, i.e. from ages 50-60, had a reduced risk of dementia.

The scary news, however, regarding hormone therapy and dementia, came from the Women's Health Initiative which looked at the health effects of hormone supplementation in a group of post-menopausal women with an average age of 63 many of whom were a decade or more past menopause. The sub-study that looked at HRT and brain health called the Women's Health Initiative Memory Study (WHIMS) found that those women in the group who initiated HRT (and remember, this was a group specifically chosen for the characteristic that none of them had ever been on HRT prior to the study) years past menopause were significantly more likely to develop dementia.

Scientists have dubbed this the Timing Hypothesis of cognitive aging with respect to the protective qualities of estrogen. Take it early while your brain is still functioning normally, and it is protective. Take it later after you've begun to develop vascular changes from atherosclerosis or the protein plaques of Alzheimer's, and it not only won't protect, it might in fact accelerate the process.

More on the possible mechanisms for this dual effect of estrogen on brain tissue--protective early on and detrimental as aging progresses--in future posts.
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*Whereas the male residents, if there are any, are more than likely suffering from Parkinson's disease, a brain dysfunction much more common in men than women.
(1) Rocca, WA, et al. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 2007 Sep 11;69(11):1074-83.
(2) Rocca, WA, et al. Oopherectomy, Menopause, Estrogen, and Brain Aging: The Timing Hypothesis. Neurodegenerative Disease.