The menopause hormone study vilified as harmful enrolled women averaging 63—over a decade after menopause
The study that tainted menopausal hormone therapy enrolled women averaging 63, over a decade past average menopause at 51. It tested whether adding hormones years later is safe, not whether to use them during menopause itself.
The video won't play here. Listen to the audio instead:
The argument · tap a timestamp to hear it
Home brain stimulation devices took 25 years to win FDA approval
TMS requires professional personnel in a clinic—expensive equipment available only at specialized centers. TDCS uses milder current and can become a wearable device for home use. This technology took 25 years to develop before FDA approval last year for treating depression, and commercial rollout began this month—the first affordable, non-drug option for depression that patients can do at home.
— Jenny SmithHormones were once the reason women were excluded from brain stimulation trials
Estrogen and progesterone alter how the brain responds to TMS; the medical field treated this as a ‘problem’—women at different cycle phases were excluded because hormone fluctuations would confound results. That logic is now reversed: if hormones affect how TMS works, then brain stimulation likely works both ways on hormone-related mood and pain issues, making women the population that should be studied separately. Pregnant and postpartum mood disorders already exclude pregnant women from drug trials out of fetal safety fears; these are exactly the patients most needing non-drug options.
— Jenny SmithDevices sold as wellness gadgets are the same hardware from clinical trials
TDCS devices that stimulate both the motor cortex (pain) and dorsolateral prefrontal cortex (mood) are already sold over-the-counter in the US. Manufacturers market them as ‘unassessed wellness aids’ to sidestep drug-device regulation. But as Jenny points out, this is the identical technology used in a large randomized controlled trial of pregnant women in Canada—one side has rigorous randomized trials under regulatory supervision, while the other side has the same hardware available on store shelves.
— Jenny SmithA seven-woman trial showed TMS can intentionally modulate reproductive hormones
A City College engineer noticed that deep brain stimulation for Parkinson's occasionally altered cortisol levels unexpectedly, prompting the question: can we deliberately use TMS to control hormones? She targeted indirect stimulation of the hypothalamus—the source of ‘master hormones’ like luteinizing hormone and follicle-stimulating hormone. The trial included 7 women; only 1 showed a completely robust response, but the direction proved viable. The next step is testing in people with low luteinizing hormone and absent menstruation, which could offer an option beyond fertility drugs.
— Jenny SmithThe research condemned as harmful actually tested only one of 200+ hormone formulas
The Women's Health Initiative (WHI) study in the early 2000s found that menopausal hormone therapy increased risks of breast cancer, cardiovascular disease, and dementia, leading to early trial termination and nearly shutting down the entire field. But Lisa Galea points out the study tested only one of 200+ formulations on the market, and participants averaged 63—over a decade older than average menopause age 51. The research actually answered ‘is it safe to add hormones years after menopause?’ not ‘should women use hormones during menopause?’ These are entirely different questions.
— Lisa GaleaWomen experiencing hot flashes were actively discouraged from the landmark study
An often-overlooked detail in WHI: women with obvious hot flashes and night sweats (medically called vasomotor symptoms) were steered away from participation—yet about 80% of women experience these symptoms. This meant the ‘representative’ study systematically excluded the very population most in need of observation. Subsequent reanalysis showed much of the observed risk increase came from the synthetic progestin used in that trial, or only appeared in older subgroups (some participants in their 70s).
— Lisa GaleaSurgical menopause and early menopause, not symptom severity, carry the real health risks
Menopause is not one thing: there is natural menopause and surgical menopause from bilateral oophorectomy. Galea says the strongest link to later cardiovascular disease and dementia risk comes from early menopause age and surgical menopause—not from how severe symptoms are. She traces this individual variation to multiple estrogen receptor types—at least three classical receptors, plus GPER (G protein-coupled estrogen receptor), whose distribution and sensitivity vary from person to person. That is why ‘my menopause is nothing like my mother's or my daughter's.’
— Lisa GaleaWomen with prior depression or anxiety face over 50% risk during menopause transition
New-onset anxiety and depression in perimenopause affect roughly 10% to 30% of women, but if someone already has a depression or anxiety history—and women are diagnosed 2–3 times more often than men before menopause—risk exceeds 50%. Brain fog complaints reach 80%, splitting into two types: one affecting prefrontal executive function (forgetfulness), the other affecting temporal lobe word retrieval and episodic memory. Recent work found transdermal hormone delivery performs better on episodic-memory tests, while oral delivery favors executive function—suggesting delivery method itself should be a precision-medicine variable.
— Lisa GaleaIn their own words · checked verbatim
So with the TDCS, the big buzz, the big excitement at the conference was that finally after 25 years of this technology being in development, it was finally approved by the FDA last year.
Jenny Smith3:10
The device that's being tried that hits both the motor cortex and the dorsolateral prefrontal cortex is actually available over the counter in the United States. And they didn't wait. It's marketed as a non-evaluated, quote unquote, wellness aid.
Jenny Smith9:17
And this researcher, who's a device engineer, wanted to see if hormone levels could be deliberately altered using TMS.
Jenny Smith11:19
So this big study came out, the Women's Health Initiative study, which actually showed a lot of detrimental effects of menopause hormone therapy. But it was one particular kind of menopause hormone therapy. There are over 200.
Lisa Galea19:30
The fact that they were on average 63 years of age, which is average age of menopause is 51. So you're talking more than a decade past menopause.
Lisa Galea20:30
we have 2,500 papers on estradiol and the brain. And so do we need any more, which I think is really an interesting comment.
Lisa Galea27:46
Our menopause is not all one thing.
Lisa Galea34:02
And it's more than a moment. We need a seismic shift.
Lisa Galea35:50
Figures
| Post-menopausal years as share of lifespan | 39% | 17:30 |
| Average length of perimenopause | ~7 years (range 2–10 years) | 18:30 |
| Average age of WHI study participants | 63 | 20:30 |
| Average age of menopause | 51 | 20:30 |
| Share of women experiencing vasomotor symptoms | ~80% | 20:30 |
| North American menopause research funding as share of total research budget | 0.2% | 27:46 |
| Existing papers on estradiol and the brain | 2500 | 27:46 |
| Existing papers on breast cancer | 2 million | 27:46 |
| Number of existing menopausal hormone therapy formulations | 200+ | 19:30 |
| Incidence of new anxiety/depression during perimenopause | 10%–30% (over 50% with prior history) | 30:51 |
Glossary
- TMS
- Transcranial magnetic stimulation: non-invasive technique using magnetic fields to stimulate brain neurons, commonly used to treat depression.
- TDCS
- Transcranial direct current stimulation: non-invasive technique using mild direct current to stimulate the brain, gentler than TMS, usable at home.
- SAINT
- Intensive TMS protocol with multiple sessions daily for five consecutive days.
- Women's Health Initiative (WHI)
- Large clinical trial from the early 2000s that assessed risks of menopausal hormone therapy.
- Vasomotor symptoms
- Hot flashes and night sweats, common symptoms during menopause.
- GPER
- G protein-coupled estrogen receptor: a class of estrogen receptors discovered recently, distinct from classical estrogen receptors.
How to listen
Women over 35, those interested in perimenopause and reproductive health, and researchers and investors in neuromodulation and women's health products.
14:24–16:29 contains program ads and journal highlights; you can skip directly.