17-Alpha Estradiol - Another Top Anti-Aging Drug

17aEstradiols

17 Alpha Estradiol is probably the second best-performing longevity drug after rapamycin. We wish it was a supplement, but you can only buy it as drug or chemical right now. We’ve identified sources and pricing / cost below but its hard to get. Apollo ventures has announced that it is seeking to develop 17 alpha estradiol as a human drug which is great, but it will likely greatly increase the cost.

In the National Institute on Aging’s ITP life extension studies it was shown that:

  • It Extends healthy lifespan (in mice) by up to 28%
  • 17α-Estradiol seems to work just as well in late middle age as if you start it at an earlier age
  • 17α-Estradiol only works in males for lifespan extension
  • It resulted in their muscles getting stronger, improved glucose tolerance, and positive changes in muscular structure

While 17 alpha estradiol is not yet available as a drug, it is almost identical to the estradiol / estrogen that women take for hormone replacement therapy. But, 17 alpha estradiol is different in some very important aspects.

17α-estradiol is a naturally-occurring isomer of 17β-estradiol (commonly referred to as estrogen or oestrogen, the primary female sex hormone in women. In contrast to 17β-estradiol, 17α-estradiol is thought to be a non-feminizing estrogen - so if taken by a male, it will not cause the male to develop female-like physical characteristics. All human studies done to date have been completed safely, with no adverse events reported.

A small phase 1 clinical study of 17α-Estradiol (see full paper below) suggested it was safe in people, with no reported side effects. Moreover, it has been reported that the regular estrogen hormone pills that women take contain a significant amount (typically around 5%) of 17α-Estradiol (in addition to the 17β-estradiol that is the primary active ingredient) so it is a compound that has already been in use by millions of people for the past 20+ years.

17AlphaEstDose

Also, the phase 1 clinical study noted:

In addition to the phase I trial described below, there are several published studies of the administration of 17α-E2 to humans by oral, sublingual, s.c., intravenous, or topical routes. These include studies with single oral doses ranging up to 70 mg, and a 12-week study at 2 mg p.o. per day. No adverse events have been reported. (See a list and links to all these earlier 17a-estradiol human studies at bottom of this post)

Note: One chemistry professor friend I spoke to regarding 17-alpha estradiol as an anti-aging compound suggested that the only concern he would have about it is that since 17-alpha and 17-beta estradiol are usually manufactured together (they are just chiral, i.e. right hand/left hand versions, of the same molecule), in any purchase of 17-alpha estradiol there will be some 17-beta estradiol, so the issue is how much there is of the beta version. 17-Beta estradiol is 10 fold more active than the 17-alpha estradiol. So, even with small percentages (e.g. 1 to 3% of the total purchase is 17-beta estradiol, you could see some feminizing effects from taking what is purchased as 97% to 99% “17-alpha estradiol”. So, I suspect that this would be the key side effect to watch for if taking this compound longer term. Also, the this also suggests that the greater purity of the 17-a estradiol sample, the lower the likelihood of excess 17-beta estradiol. The other key unknown with 17-alpha estradiol is the optimal dose for humans / males. Given the lack of side-effects and the wide range of dosing tried so far (albeit in a limited and short-term fashion) it seems like a reasonably strategy for biohackers might be to start low (at 50 μg/day), and slowly increase. The highest dose tested that I’ve seen is the 70mg dose.

17α-Estradiol is also sold in some countries for topical use for hair regrowth. Galderma has a product called Ell-Cranell that it sells around the world for his purpose. It doesn’t seem to be particularly effective in this application, similar to minoxidil.

17α-Estradiol in NIA ITP Program, Discussion with Richard Miller

The following information is sourced from the Peter Attia / Richard Miller podcast:

What was the genesis behind the plan to investigate 17α-Estradiol?

Richard Miller tells Peter Attia that a pharmacologist named James Simpkins has studied estrogen receptors and suggested investigating 17α-Estradiol. He had tried to make a compound that was like estrogen—17β-estradiol—which is generically crudely referred to as estrogen. Estrogens are widely used as medications, mainly in hormonal contraception, hormone replacement therapy, and to treat gender dysphoria in transgender women and other transfeminine individuals as part of feminizing hormone therapy.

James Simpkins synthesized 17α-Estradiol—very much the same compound except for one of the bonds tilts up instead of tilting down. And in his studies mostly in tissue culture cells, he found that yes, it was tenfold less active compared to 17β-estradiol (the compound which most people refer to as the estrogen used in hormone replacement therapy).

When he gave it to mice, he found it was non-feminizing: So when you give it to male mice, it did not induce the secondary sexual characteristics that the stronger estrogens, like 17 beta- estradiol, estrogen would do. His idea was that giving estrogen to male mice might make them live as long as female mice (female mice live 5-10% longer than males) AND this compound called 17α-Estradiol will be good for males because “no man wants to look feminine” even if he lives as long as a women.

National Institute on Aging, ITP studies – 17α-Estradiol

The first attempt—cohort 5—used a low dose (4.8 ppm) and it extended median survival in males, but not maximum lifespan. In the next ITP study using 17-Alpha Estradiol —cohort 7—they gave a dose 3 times higher (14.4 parts per million) and it extended the measure of maximum longevity , as well as median longevity at all three sites for male mice, but not for females. In this study the males not only lived longer than regular old males, they lived longer than regular females. Dr. Rich Miller suggests that they have some clues as to why it works only in males, but they don’t know for sure. He said that their hope is that they can try to figure out a way to get around that obstacle and to get it to work in females as well. 17-Alpha Estradiol was also studied by the ITP in cohort 12 but the results have not yet been published.

Peter Attia asked if there an IND (Investigational New Drug application) for this compound?

Rich Miller suggested that there is a lot of attention being devoted to developing novel estrogenic compounds and “I’ll bet a great chunk of it is kept quiet by pharmaceutical firms”.

How to Buy / Purchase 17α-Estradiol:
17α-Estradiol is easily available from Lab / Reagent supply resellers at low cost (for people who work in biology / chemistry labs or academic institutions or companies). I hear people are being successful in acquiring this via friends who are academics where they can order these materials, or own smaller companies that can order chemicals like this). Please post your personal results with 17-alpha estradiol below in the comments. I see people are posting below about their acquisitions of this exciting new compound already…

CAS Number: 57-91-0
Cayman Chemical: 17α-Estradiol / CAS 57-91-0, $160/gram
Sigma Aldrich: 17α-Estradiol / CAS 57-91-0, $650 per gram
BioMol: 17α-Estradiol / CAS 57-91-0, €200 Euros/gram

The Most Interesting Research Studies on 17α-Estradiol

National Institutes on Aging, ITP Life Extension Study on 17α-Estradiol

acel.12496.pdf (1.2 MB)

Development of 17α-Estradiol as a Neuroprotective Therapeutic Agent Rationale and Results from a Phase I Clinical Study

17AlphaEstradioldykens2005.pdf (801.1 KB)

Review of the Effects of 17-Alpha Estradiol in Humans: A Less Feminizing Estrogen With Neuroprotective Potential

17AlphaEstradiolmoos2009.pdf (213.3 KB)

Alzheimers Drug Discovery Foundation Report on 17α-Estradiol from 2021:
17α-Estradiol_UPDATE.pdf (415.6 KB)

Older Human Studies of 17-Alpha Estradiol

WILLIAMS, K.I. & D.S. LAYNE. 1967. Metabolism of 17-alpha-estradiol-6,7-3H by nonpregnant women. J. Clin. Endocrinol. Metab. 27: 159–164.

SCHROEDER, J., et al. 1997. Estradiol-17-alpha—a reasonable hormone replacement for the aging male? Maturitas 27(supplementary): 216.

HOBE, G., R. SCHON, N. GONCHAROV, et al. 2002. Some new aspects of 17alpha-estradiol metabolism in man. Steroids 67: 883–893.

BREUER H. & E. SCHOTT. 1966. Studies of the metabolism of 17 alpha-estradiol in man. J. Clin. Endocrinol. Metab. 26: 533–536.

LAURITZEN, C. 1969. Estrogenic activity of 17alpha-estradiol, equilin, equilenin, and their sulfoconjugates in experimental animals and in man. Symposion der Deutschen Gesellschaft fuer Endokrinologie 15: 142–144.

MEYER, W.J. 3rd, D.H. HENNEMAN, H.R. KEISER & F.C. BARTTER. 1976. 17 alpha estradiol: separation of estrogen effect on collagen from other clinical and biochemical effects in man. Res. Commun. Chem. Pathol. Pharmacol. 13:685–695.

[ORFANOS, C.E. & L. VOGELS. 1980. Local therapy of androgenetic alopecia with 17 alpha-estradiol. A controlled, randomized double-blind study (author’s translation)]. Dermatologica 161: 124–132.

OETTEL, M., M. DOREN, R. HELLER, et al. 1996. Estrogens and antioxidative capacity. Klimakterium und Hormonsubstituzion. Proceedings of Internationales Greifwalder Menopause Symposium, June 22-23: 109–118.

OETTEL, M. 1999. Estrogens and antiestrogens in the male. In Estrogens and Antiestrogens. II Pharmacology and Clinical Application of Estrogens and Antiestrogens. M. Oettel and E. Schillinger, Eds.: 505–571. Springer. Berlin.

Studies of Estradiol in Men - breuer1966.pdf (444.3 KB)

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An easier/cheaper way to get it is just to take estradiol prescription (just say you’re gender dysphoric). Then stop it/discontinue once you notice breast development (and cycle as such)

Yes - that would definitely be the quick and easy approach. But many of us aren’t going to like the results I suspect (see image and paper below). The cost of alpha-17 estradiol is not very high actually - see the quotes from the lab supply companies included in the post. Yes - you are correct in that its not very easy to get - you have to know someone who works at a biology / chemistry organization to order it.

Source:

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Tofu has estrogen like chemicals. If you eat tofu it’s possible you could live longer. I remember reading that if you eat four impossible burgers a week you could grow breasts, :laughing:.

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Any new clues or updates on dosage for humans, or any reports you’ve found of self-experimentation?

The formulations for topical hair loss applications seem to be around 0.25mg/ml — does it make sense that just 1ml of topical solution is close to the upper limit for the oral dose listed above?

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I think the best thing anyone has to go off of are the human safety trials that were done earlier. Here are the calculations of that range and then going up higher.

Daily Dosing (micrograms, ug) 50 100 200 400 800
Total Annual Dosing (ug) 18,250 36,500 73,000 146,000 292,000
Total Dose /Person/Year (g) 0.01825 0.0365 0.073 0.146 0.292
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standard dose for women of 17-Beta estradiol is 625 micrograms (.625 milligrams) per day.

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The more I study these papers, the more I’m unsure of the dosing that would be appropriate for 17-alpha estradiol. The phase 1 clinical study was just a series of single dose tests with 8 women with pre and post bloodwork done. These single doses seem really high - 50g, 100g and 200g… but other papers had tested as high as 70g single dose, so perhaps its real. But such high doses seem unlikely in an ongoing, daily dosing scenario.

While the existing dosing for women of for 17-beta estradiol might be a starting point, its really hard to know what the comparable dosing would be for men, and for 17-alpha estradiol.

In the ITP studies they started out at similar dosing levels for the mice as they did for rapamycin - 4.8ppm, and then 14.4ppm (see below). So - if we take equivalent dosing that people use with rapamycin, we’d be starting at a low dose of 2 or 3 mg/day, and at a high dose as high as 30mg or 40mg, and even to 90mg per day.

Below are the calculations for what the total annual cost of taking lab reagent 17a-estradiol in roughly these doses would look like:

Daily Dosing (miligrams, mg) 2 3 5 10 20 40
Total Annual Dosing (mg) 730 1,095 1,825 3,650 7,300 14,600
Total Dose /Person/Year (g) 0.73 1.095 1.825 3.65 7.3 14.6
Total Cost ($160/gram) $116.80 $175.20 $292.00 $584.00 $1,168.00 $2,336.00

And here was the rapamycin dosing in the mice:

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A rumor brought to you by the American Beef Association :wink:

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When I researched this compound, I found that is used as a topical hair loss treatment here in Belgium together with minoxidil, made by a compounding pharmacy. I am thinking of getting this, since I already use minoxidil. That way, I could get 2,5 mg topical per day.

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That might help with hair growth - but I doubt the topical 17alpha estradiol will get into the blood stream, so it won’t help you with systemic 17a estradiol.

In topical rapamycin studies they’ve done they found that the rapamycin did not enter the blood stream.

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There already are topical testosterone gel and topical 17 beta estradiol gel, and the chemical structure of 17alpha estradiol is similar to them, I wonder if 17alpha estradiol have the potential to be topical use? Are there any clinical data?

Dr Brad Stanfield recently mentioned 17 alpha estradiol , but the information of it is still scarce
Have you experimented yourself 17alpha estradiol yet? Can you share your personal experience to us?

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“The transdermal of estradiol in an alcohol solution is unfortunately only 10%” according to the wiki article on estradiol. So I think a better option to have 2 mg tablets made by a pharmacy in my case. But first I will look for some more information on the subject

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In the phase 1 clinical study in humans for 17alpha estradiol they just mixed the powder in purified water.

I haven’t tried it, but I’m sure other people have.

Good to see 17 Alpha Estradiol getting some coverage:

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I’ve just bought 17-alpha estradiol from Chinese reseller
You don’t need to be in labs or academic institutions, they also sell compounds to individuals

The price is $228 USD/gram, purity >=98%
Thanks for your dosing equivalent table, that’s very handy
I plan to take 17-alpha estradiol on 2mg/day

Are there any cautions I need to know before taking it?

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I’ve heard of too many bad experiences with Chinese resellers of supplements, chemicals and drugs to have any confidence in any product coming out of there that has not been tested and validated by an independent 3rd party lab. I recommend you read this post and watch the video attached to it.

Other than that - I think all the material in this thread - from the top post on down, covers most of the known research and tests done on 17 alpha estradiol.

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I’ve hit some dead ends trying to get manufacturers to send it to me. Went through a whole process of trying to prove I was a lab, but they wouldn’t send in the end.

What type of information did they want to see to validate your lab status?