Study: Hormone Therapy May Not Hurt — Or Help — Menopausal Brains


Here’s the good news for women on hormone therapy for menopause: A new study suggests it will not increase your risk of dementia or otherwise hurt your brain health.

Now here’s the bad news for women on hormone therapy: It doesn’t look like it will improve your brain health either.

I think of this as the period of the Great Shake-Out on hormone therapy. First came the Fountain of Youth period, with some doctors handing out estrogen and progestin like candy to women during and after menopause.

Then, about a decade ago, came seminal Women’s Health Initiative findings that hormone therapy could carry daunting risks, including higher rates of heart attacks, dementia and cancer in older women.

Research led to a new hypothesis, the “Window of Opportunity” theory: That if women started hormone therapy earlier, more like in their fifties than in their sixties or seventies, they might reap benefits with fewer risks. For heart disease, there’s extensive evidence that is indeed the case.

Now, the “WHIMSY” study — for Women’s Health Initiative Memory Study in Younger Women — just out in the journal JAMA Internal Medicine, does seem to bear out somewhat the earlier-window theory when it comes to brain health. At least when it comes to avoiding harm.

Dr. Fran Grodstein of Brigham and Women’s Hospital, who researches the long-term health effects of hormone therapy but was not involved with this latest study, wrote in a commentary accompanying the paper:

Dr. Fran Grodstein of Brigham and Women's Hospital (Courtesy)

Dr. Fran Grodstein of Brigham and Women’s Hospital (Courtesy)

“Approximately 10 years ago, the Women’s Health Initiative Memory Study (WHIMS) found that postmenopausal hormone therapy in older women caused nearly two-fold increases in dementia risk, worse rates of cognitive decline over time, and decreased brain volume on magnetic resonance imaging, compared with placebo treatment.”

But the new study, which looked at over 1300 post-menopausal women who started taking estrogen in their fifties, found no such heightened risks after seven years.

It didn’t find any brain benefits either, though.

Dr. Grodstein sums up:

“The most important point is that the original Women’s Health Initiative, which looked at the effects of hormone therapy on brain health in older women, had found multiple ways … that hormone therapy caused harm to the brain. specifically in older women.”

The upshot of this new WHIMSY study “is that they now looked at the question in much younger women,” and the results are “reassuring to women and doctors, in that they should not be very afraid of damage to brain health being an unwanted side effect.”

Some researchers had hoped that hormones would actually improve brain health in younger women, she said, but the study did not clearly point to any such benefits.

“I would say, though,” she added, “in contrast to heart disease, where there’s a fair amount of evidence, for brain health there isn’t remotely near that amount of evidence. So I’d say while WHIMSY didn’t help make the point that it could be beneficial, we don’t know yet. and more research is needed to determine whether hormone therapy near menopause might improve brain health.”

I asked Dr. Grodstein to comment about the swinging hormone-therapy pendulum, and the annoyance that many of us feel when medical studies tell us first one thing and then another:

“It is incredibly challenging,” she acknowledged, “and I think somehow, the public has to start recognizing that we’re extremely complex beings, and in terms of the science, we’re only slowly learning how our bodies work.”

“Definitive answers are very hard to get…Hormones act on virtually every part of our body, and understanding the interactions, and why they lead to different things in different parts of our body, and even to different things in the same parts of our body as we age — it’s unfortunate, and it’s not a satisfying answer, but it’s incredibly complex, and we’re only slowly unraveling the details.”

“What happens is that each study basically teaches us something new, and at the same time opens up ten new questions. So that’s just something we all have to learn to live with. It’s not a satisfying answer and it’s no more satisfying for people doing the research than for those trying to apply it.”

Readers? Do you feel your annoyance giving way to empathy? Any hormonal questions? Further reading:

Managing Menopause: Top Takeaways After Ten Years
Five New Rules Of Hormone Therapy For Menopause
Hormone Replacement Therapy 10 Years Later: Calls For ‘Rational Use’

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  • Barbara

    I’m wondering about starting to take HRT after a year lay off. Have been taking it since I was surgically menopausal over 30 years ago! I feel diminished for not taking them this last year and want to resume. I have hypertension and am medicated for it.

  • LMZ

    I may sound simple or simplistic, but I have a question: while we search for the magic )bullet for healthy brains as we age (and we may never find it), can we assume that an active and engaged life style is still a decent (not perfect, but somewhat strong) predictor of brain health, more than than anything we know so far? (active and engaged life style for me includes moderate physical activity integrated with your daily tasks, minimal time spent sitting anywhere, curiosity and learning something new as a regular mindset, enjoying community, family and friends, value sleep, trying to improve you sleep if not good enough, and of course varied, colorful meals full of veggies fruit, seafood and some whole grain in moderation…. yes, simple, but apparently not really where we are right now… ) Thank you.

  • CF Fan

    Two things – this study did indeed show that cognition OVERALL was unaffected, but specifically women taking estrogen alone seemed to have experienced lasting decrements in verbal fluency years after cessation of therapy. Also, PRIOR HRT users may have been adversely affected.

    I take issue with the proclamation that the timing hypothesis is somehow settled for heart disease and that a benefit exists. The fact is that it is still unproven. The WHI was not designed to test for age effects and even so, no significant age differences were found, no matter how you spin it. Also, the more recent KEEPS did NOT show a slowing of atherosclerosis in newly menopausal women taking estrogen. Heart attacks are uncommon in newly menopausal women and estrogen trials would have to go on for 20-30 years to prove the timing hypothesis. That research is never going to happen. And subjecting younger women to HRT’s confirmed risks of cancer, strokes and blood clots makes no sense, just to prove a theory – one, might I add, that never really existed until HERS and WHI dethroned HRT as some all purpose elixir of youth.