Your Brain On (And Off) Estrogen

This is Dr. Lisa Mosconi. She’s a professor of Neuroscience in Neurology and Radiology, and is one of the 1% most influential scientists of the 21st century. That’s not a random number or an exaggeration; it has to do with citation metrics collated over 20 years:

A standardized citation metrics author database annotated for scientific field

What does she want us to know?

Women’s brains age differently from men’s

This is largely, of course, due to menopause, and as such is a generalization, but it’s a statistically safe generalization, because:

• Most women go through menopause—and most women who don’t, avoid it by dying pre-menopause, so the aging also does not occur in those cases
• Menopause is very rarely treated immediately—not least of all because menopause is diagnosed officially when it has been one year since one’s last period, so there’s almost always a year of “probably” first, and often numerous years, in the case of periods slowing down before stopping
• Menopausal HRT is great, but doesn’t completely negate that menopause occurred—because of the delay in starting HRT, some damage can be done already and can take years to reverse.

Medicated and unmedicated menopause proceed very differently from each other, and this fact has historically caused obfuscation of a lot of research into age-related neurodegeneration.

For example, it is well-established that women get Alzheimer’s at nearly twice the rate than men do, and deteriorate more rapidly after onset, too.

Superficially, one might conclude “estrogen is to blame” or maybe “the xx-chromosomal karyotype is to blame”.

The opposite, however, is true with regard to estrogen—estrogen appears to be a protective factor in women’s neurological health, which is why increased neurodegeneration occurs when estrogen levels decline (for example, in menopause).

For a full rundown on this, see:

Alzheimer’s Sex Differences May Not Be What They Appear

It’s not about the extra X

Dr. Mosconi examines this in detail in her book “The XX Brain”. To summarize and oversimplify a little: the XX karyotype by itself makes no difference, or more accurately, the XY karyotype by itself makes no difference (because biologically speaking, female physiological attributes are more “default” than male ones; it is only 12,000ish* years of culture that has flipped the social script on this).

*Why 12,000ish years? It’s because patriarchalism largely began with settled agriculture, for reasons that are fascinating but beyond the scope of this article, which is about health science, not archeology.

The topic of “which is biologically default” is relevant, because the XY karyotype (usually) informs the body “ignore previous instructions about ovaries, and adjust slightly to make them into testes instead”, which in turn (usually) results in a testosterone-driven system instead of an estrogen-driven system. And that is what makes the difference to the brain.

One way we can see that it’s about the hormones not the chromosomes, is in cases of androgen insensitivity syndrome, in which the natal “congratulations, it’s a girl” pronouncement may later result in a surprise if it turns out she had XY chromosomes all along, but the androgenic instructions never got delivered successfully, so she popped out with fairly typical female organs. And, relevantly for Dr. Mosconi, a typically female brain that will age in a typically female fashion, because it’s driven by estrogen, regardless of the Y-chromosome.

The good news

The good news from all of this is that while we can’t (with current science, anyway) do much about our chromosomes, we can do plenty about our hormones, and also, the results of changes in same.

Remember, Dr. Mosconi is not an endocrinologist, nor a gynecologist, but a neurologist. As such, she makes the case for how a true interdisciplinary team for treating menopause should not confined to the narrow fields usually associated with “bikini medicine”, but should take into account that a lot of menopause-related changes are neurological in nature.

We recently reviewed another book by Dr. Mosconi:

The Menopause Brain – by Dr. Lisa Mosconi

…and as we noted there, many sources will mention “brain fog” as a symptom of menopause, Dr. Mosconi can (and will) point to a shadowy patch on a brain scan and say “that’s the brain fog, there”.

And so on, for other symptoms that are often dismissed as “all in your head”, as though that’s a perfectly acceptable place for problems to be.

This is critical, because it’s treating real neurological things as the real things they are.

Dr. Mosconi’s advice, beyond HRT

Dr. Mosconi notes that brain health tends to dip during perimenopause but often recovers, showing the brain’s resilience to hormonal shifts. As such, all is not lost if for whatever reason, hormone replacement therapy isn’t a viable option for you.

Estrogen plays a crucial role in brain energy, and women’s declining estrogen levels during menopause increase the need for antioxidants to protect brain health—something not often talked about.

Specifically, Dr. Mosconi tells us, women need more antioxidants and have different metabolic responses to diets compared to men.*

*Yes, even though men usually have negligible estrogen, because their body (and thus brain, being also part of their body) is running on testosterone instead, which is something that will only happen if either you are producing normal male amounts of testosterone (requires normal male testes) or you are taking normal male amounts of testosterone (requires big bottles of testosterone; this isn’t the kind of thing you can get from a low dose of testogel as sometimes prescribed as part of menopausal HRT to perk your metabolism up).

Note: despite women being a slight majority on Earth, and despite an aging population in wealthy nations, meaning “a perimenopausal woman” is thus the statistically average person in, for example, the US, and despite the biological primacy of femaleness… Medicine still mostly looks to men as the “default person”, which in this case can result in seriously low-balled estimates of what antioxidants are needed.

In terms of supplements, therefore, she recommends:

• Antioxidants: key for brain health, especially in women. Rich sources include fruits (especially berries) and vegetables. Then there’s the world’s most-consumed antioxidant, which is…
• Coffee: Italian-style espresso has the highest antioxidant power. Adding a bit of fat (e.g. oat milk) helps release caffeine more slowly, reducing jitters. Taking it alongside l-theanine also “flattens the curve” and thus improves its overall benefits.
• Flavonoids: important for both men and women but particularly essential for women. Found in many fruits and vegetables.
• Chocolate: dark chocolate is an excellent source of antioxidants and flavonoids!
• Turmeric: a natural neuroprotectant with anti-inflammatory properties, best boosted by taking with black pepper, which improves absorption as well as having many great qualities of its own.
• B Vitamins: B6, B9, and B12 are essential for anti-aging and brain health; deficiency in B6 is rare, while deficiency in B9 (folate) and especially B12 is very common later in life.
• Vitamins C & E: important antioxidants, but caution is needed with fat-soluble vitamins to avoid toxicity.
• Omega-3s: important for brain health; can be consumed in the diet, but supplements may be necessary.
• Caution with zinc: zinc can support immunity and endocrine health (and thus, indirectly, brain health) but may be harmful in excess, particularly for brain health.
• Probiotics & Prebiotics: beneficial for gut health, and in Dr. Mosconi’s opinion, hard to get sufficient amounts from diet alone.

For more pointers, you might want to check out the MIND diet, that is to say, the “Mediterranean-DASH Intervention for Neurodegenerative Delay” upgrade to make the Mediterranean diet even brain-healthier than it is by default:

Four Ways To Upgrade The Mediterranean Diet

Want to know more from Dr. Mosconi?

Here’s her TED talk:

Click Here If The Embedded Video Doesn’t Load Automatically!

Enjoy!