Estrogen and the Menopausal Brain

In Volume 1,8 of the Wise Brain Bulletin, in a list of possible interventions for improving memory, I wrote: “For women entering menopause, consider taking estrogen.”

Not surprisingly, I got a few thoughtful comments about that line, and I appreciated them. Hormone replacement therapy (HRT) is controversial, so I’d like to unpack the complexities of that subject. In this issue, I will summarize data regarding post-menopausal estrogen replacement and the brain. In the next issue or two, I will review the concerns associated with the risks of using estrogen replacement (and related methodological problems), and how to minimize them.

Some Neurological Benefits of Estrogen

In general, animal studies on laboratory rats and primates have shown that estrogen promotes brain cell survival, growth, and regeneration. Studies with human subjects have compared the brains of post-menopausal women who did or did not take estrogen. Without estrogen, the women’s brains were characterized by “age-related shrinkage.” But with HRT, these brain regions remained normally sized:

  • Prefrontal cortex (planning, judgment, decision-making)
  • Parietal cortex (sensory processing)
  • Temporal lobes (language, emotion)

Different research – the Baltimore Longitudinal Study of Aging – found that women on HRT had greater blood flow to the hippocampus and other regions important for verbal memory. They also performed better on vertical and visual memory tests than women who had never been treated with hormones. Overall, these scans again showed that estrogen seems to reduce the usual shrinkage of the brain with age. Other researchers – this time at UCLA – found that women who had used estrogen therapy were less depressed and angry than those not on HRT, and they performed better on tests of verbal fluency.

Last, in my clinical experience, many women love the effects of estrogen replacement for mood and cognitive clarity. (And to be clear, my license does not allow me to prescribe hormones, so I have no incentive to hold this view.)


On the other hand, in 2002, the Women’s Health Initiative (WHI) study found that women who took Prempro, a combination of estrogen from mare (horse) urine and a synthetic progestin, had a small increased risk of breast cancer, stroke, and dementia. Since that finding hit the headlines, hormone therapy has been up in the air.

The WHI has been roundly criticized in many academic and clinical quarters, largely on methodological grounds, and I will review those analyses in the next issue of the Bulletin. To summarize and potentially over-simplify a very complex subject, the bottom line of the evidence so far is that not supplementing estrogen and HRT both carry risks that must be evaluated on an individual basis; many women will probably conclude that the net balance of risks and benefits appears to favor HRT– if properly done – but some women will decide that the balance in their own case tilts against HRT.


In this light, the key questions are:

  • How can a woman assess her health risks from not supplementing estrogen, and her health risks from HRT?
  • How can a woman reduce her health risks from HRT, while preserving its benefits?

In another post, I’ll try to answer these.

Category : Articles &Hormones &Memory Posted on January 3, 2012

One Comment → “Estrogen and the Menopausal Brain”

  1. Williamtok
    7 years ago

    I appreciate you sharing this article.Thanks Again. Really Cool. ebeeefefkefk Hodgkins


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