#711

@RapAdmin Has anyone discovered a way to obtain 17alpha estradiol? Seems like it should be available through India or perhaps a compounding pharmacy?

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#712

Not that I’ve heard of. @DrFraser had mentioned some time ago that he heard of some group that may be providing it at some point in the future, but that was quite a while ago - Any updates Dr. Fraser?

#713
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#714

Yes the gentleman that I was talking with on this and yes, it was going to be synthesized in a for human use form, off shore. It’s been a while since I’ve had contact with him however. When I get an update, I’ll share what I can.

Of course there are multiple groups that synthesize it — but all are selling only to verified research labs or academic institutions.
Here are examples:

https://www.sigmaaldrich.com/US/en/product/sigma/e8750?srsltid=AfmBOopa4WlKpzFoHwNtTaVAtM3DoH6mMSAzJSWmoeOc-abu_vAj-VZD

I’m contacting a few of the compounding pharmacies I work with as I heard that some might be willing to synthesize it. If I get any positive response from any of them, I’ll post that.

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#715
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#716

https://english.elpais.com/health/2025-06-22/how-to-avoid-age-related-cognitive-deterioration.htm

And a story on ozempic helping avoid dementia…

lhttps://www.medicalnewstoday.com/articles/can-ozempic-weight-loss-diabetes-help-lower-risk-vascular-dementia

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#717

My favorite PharmD at a compounding pharmacy says he might be able to get this. He wants to know what formulation (tablet, injection)… I think tablet would be most consistent with what I know, then he has asked on dosing.
Does anyone have a good source for how to dose this?

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#718

There is this review (paywalled and I don’t have access through my institution).

Review of the effects of 17α-estradiol in humans: a less feminizing estrogen with neuroprotective potential

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.20284

AI says the dose that has been tested and determined to be non-feminizing in Men is 2mg/day but this may be well below the dose for longevity. Mouse dose was “4.8 mg 17aE2/kg (4.8 ppm) diet”.

Here is a Resus macaque study that suggests a dose of 0.20 mg/kg/day while tolerated, resulted in “significant feminization” (that would be 14 mg / day for a 70 kg. human). They explain in the study that the mouse dose above equates to 0.92 -1.15 mg /kg/day which translates to a primate dose of 0.2 to 0.3 mg/kg/day. They also suggest that the feminization may be do to bolus dosing and isomerization to beta estradiol and that future studies may want to use transdermal patches to avoid the feminization effects.

Assessing tolerability and physiological responses to 17α-estradiol administration in male rhesus macaques - PMC.

Not much help and I was unaware that higher doses were feminizing as I believe the studies in mice and rats did not show feminization. It sounds like all we know is that 2mg/day was non-feminizing and tolerated in humans.

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#719

I would guess a transdermal formulation would be best.

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#720

Thanks @59vw and @dicarlo2 for giving input.

I think the doses being used that showed longevity benefit were potentially feminizing.

On route - does oral 17 alpha estradiol result in liver enzyme induction and cause individuals to be at increased risk of thrombosis (DVT/PE) like oral standard estradiol does? It looks like that question is probably known - and looks like it is probably safe in that regard.

Topical brings in another complexity on absorption, how to measure, and what a normal level would be? Even with known quantities of of 17 beta estradiol (the one we use now for female HRT) in patches has required a lot of work to get consistent absorption. The compounded creams that individuals use result in serum levels all over the place, depending upon how they compound it - and at least we can easily and cheaply measure this in 17 beta, but not 17 alpha.

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#721

On route - does oral 17 alpha estradiol result in liver enzyme induction and cause individuals to be at increased risk of thrombosis (DVT/PE) like oral standard estradiol does? It looks like that question is probably known - and looks like it is probably safe in that regard.

Good question, I’m not sure it has been tested enough in humans to know.

Re route, the macaque paper hypothesizes that estrogen receptors are getting saturated with bolus dosing and unconjugated molecules are isomerizing to beta-estradiol. They found significantly higher beta-estradiol in animals that received alpha-estradiol.

#722

On 17 alpha estradiol, my cost $3 per 2 mg tablet. I’m just not sure we know enough on this, but yes, it can be done.

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#723

Scientists can tell how fast you’re aging from a single brain scan

New aging clock can predict risk for dementia, other age-related diseases years before symptoms appear

“The way we age as we get older is quite distinct from how many times we’ve traveled around the sun,” said Ahmad Hariri, professor of psychology and neuroscience at Duke University.

Now, scientists at Duke, Harvard and the University of Otago in New Zealand have developed a freely available tool that can tell how fast someone is aging, and while they’re still reasonably healthy – by looking at a snapshot of their brain.

From a single MRI brain scan, the tool can estimate your risk in midlife for chronic diseases that typically emerge decades later. That information could help motivate lifestyle and dietary changes that improve health.

In older people, the tool can predict whether someone will develop dementia or other age-related diseases years before symptoms appear, when they might have a better shot at slowing the course of disease.

“What’s really cool about this is that we’ve captured how fast people are aging using data collected in midlife,” Hariri said. “And it’s helping us predict diagnosis of dementia among people who are much older.”

The results were published July 1 in the journal Nature Aging.

https://www.eurekalert.org/news-releases/1089381

Open access paper:

DunedinPACNI estimates the longitudinal Pace of Aging from a single brain image to track health and diseas

To understand how aging affects functional decline and increases disease risk, it is necessary to develop measures of how fast a person is aging. Using data from the Dunedin Study, we introduce an accurate and reliable measure for the rate of longitudinal aging derived from cross-sectional brain magnetic resonance imaging, that is, the Dunedin Pace of Aging Calculated from NeuroImaging (DunedinPACNI). Exporting this measure to the Alzheimer’s Disease Neuroimaging Initiative, UK Biobank and BrainLat datasets revealed that faster DunedinPACNI predicted cognitive impairment, accelerated brain atrophy and conversion to diagnosed dementia. Faster DunedinPACNI also predicted physical frailty, poor health, future chronic diseases and mortality in older adults. When compared to brain age gap, DunedinPACNI was similarly or more strongly related to clinical outcomes. DunedinPACNI is a next-generation brain magnetic resonance imaging biomarker that can help researchers explore aging effects on health outcomes and evaluate the effectiveness of antiaging strategies.

https://www.nature.com/articles/s43587-025-00897-z

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#724

@DrFraser
Can we, and by we, I mean you :slight_smile:, apply this tech to our existing brain MRI’s ?

#725

I’m new to the forum here, so first off hello to everyone!

I found this piece by Crissman Loomis to be quite interesting. It suggests that 45% of dementia cases could be avoided/prevented with lifestyle interventions. It includes many great suggestions around exercise, sauna, dietary patterns, coffee, alcohol, etc. What is perhaps lesser appreciated is the controversy around the protective effects of education, and how factors like air pollution, hearing, and social connections matter.

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#726

The code is available on github with what appear to be good instructions on how to use it. I asked ChatGPT if I could somehow convert the SimonONE results to the format the algorithm expects and it sounded like it should be possible with all free software. I have not attempted yet though.

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#727

Ok, @dicarlo2, be my canary… after you figure it out, let me know! I have the same Simon one mri. Thanks!

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#728

@drew_ab Hi, and welcome to the forum! Thanks for posting this resource. Feel free to join in any conversations about topics that interest you regarding longevity or rapamycin.

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#729

On getting brain analysis on an MRI, I have some people use Brainkey.ai

I believe it is free and does a good job of mapping out each area of the brain and giving %tiles, etc.

Those %tiles and also atrophy/white matter changes would all have to be part of the calculation - but I suspect it is proprietary and licensed, just like Dunedin PACE.

We’ll have to see what @dicarlo2 figures out.

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#730
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