17 Alpha Estradiol: Use and Dosing Experiences

Today, our lab finally got 17 alpha estradiol, 1g, from Cayman chemical. The chemical was not water soluble. But it dissolved in DMSO, albeit a bit long (~3min) vortexing was required for full dissolve in room temperature. I used 50mg of the compound with 1mL of DMSO, and diluted into 100% MCT oil, with a total volume of 150mL, giving 0.33mg of 17aE2 per 1mL. I planned to drink the solution 3mL per day (1mg 17aE2 per day). As the compound is hydrophobic and water insoluble, I guess that taking 17aE2 as powder state might be less effective in terms of bioavailability.

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Dissolving 17aE2 reminded me my experience 5 years ago using rapamycin (raw material for mice experiment) that was also very very insoluble in water in the end required 100% DMSO, heat, and sonication.

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Just thought that as 17aE2 shares some downstream mechanisms with rapa, it might be a nice and safe filler between intermittent rapa dosage - at the trough level of rapa.

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Hi Dr. Ecsta, welcome to the site and thanks for posting about your experiences with 17 alpha estradiol.

I’m confused about the water insolubilty that you’ve run into. In the phase 1 clinical trial Development of 17α-Estradiol as a Neuroprotective Therapeutic Agent Rationale and Results from a Phase I Clinical Study (included in the first post of this thread) it mentions

“Subjects were given 17* α*-E2 as an oral solution containing either 50 g, 100 g, or 200 g of 17α-E2, dissolved in 50 mL of purified water”

Any thoughts on why your sample of 17 alpha estradiol is not water soluble, while the compound used in the phase 1 clinical study was?

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Hi, I used the compound in the link, and tried to dissolve 10mg 17aE2 in 50mL distilled water(DW), which was unsuccessful. 1mg in 50mL DW was also unsuccessful (after vortexing + heat etc). I tested wheter fully dissolved 17aE2 in DMSO could be diluted in DW, but crystals were formed. Hence I used 100% MCT oil as a diluting solution, not DW. Considering the studied solubility of E2 (https://pubs.acs.org/doi/10.1021/je050318c), much lower concentration in DW might be achievable.

Aqueous Solubilities of Estrone, 17β-Estradiol, 17α-Ethynylestradiol, and Bisphenol A

https://pubs.acs.org/doi/10.1021/je050318c

Full Paper PDF Here: Sci-Hub | Aqueous Solubilities of Estrone, 17β-Estradiol, 17α-Ethynylestradiol, and Bisphenol A | 10.1021/je050318c

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Oh, and by the way. Please do pre-testing (bloodwork, and perhaps some epigenetic or biological age calculations) before starting A17estradiol, and then at some point after (e.g. 6 months), so we can see if there is any measurable difference… A Friendly, Biological Age Reduction Competition?

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Heard from another doctor who is trying 17 alpha estradiol and he says… for disolving / administration of the compound:

50% ethanol sublingual is cheapest

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Can you please share your exact dosing strategy and dosing level for 17-alpha estradiol? How much 17aE, how often?

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Thanks for the suggestion. However, as I have been taking lots of things for the last 8 years (since I became 30) including SGLT2 inhibitors voglibose, metformin and rapamycin (mostly in sequencial manner) so it might be less informative and interpretation will be messy.

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I started from 1mg per day and after 3 consecutive days experiencing unexpected acne in my face, descending to 0.5mg per day. Will update on this.

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Hi DrEcsta

Do you notice some other effects ?

Thanks

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Today, I dissolved 17 alpha estradiol in 50% ethanol and put them on sublingual for 2 mins, then spitted it out.

Originally, I planned keeping it in the mouth for 5 mins, but 50% ethanol on my sublingual was so hot and irritating, so I only kept it for 2 mins. High concentration ethanol hurt my oral mucosa, and I had numb tongue for more than 30 mins.

Do anyone have experience of sublingual administration with ethanol? I don’t know if this is a correct way for the sublingual administration, I don’t know if 2 mins on sublingual is too long or too short? And should I dilute 50% ethanol to lower concentration?

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Does anyone know if 17-Estradiol is broken down by digestion before it can be absorbed?
If so, I guess injecting would be a better route of administration?
Any info on cost? It is one compound I would like to try but very hard to obtain.

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Cost is in the first post of this thread. But you have to work in a lab to order it.

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Alfatradiol (17-alpha estradiol) is marketed under the brand names Avicis, Avixis, Ell-Cranell Alpha, and Pantostin. In Pantostin, it is dissolve in propan-2-ol ( Isopropyl alcohol ), a toxic compound. At ambiant temperature, Isopropyl alcohol evaporates. Inhalation of the vapors can also be toxic. My understanding is that 17-alpha estradiol do not evaporate in this process. There is 0,25mg of alfatradiol per ml of solution.

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Yes - but this is topical use, not the systemic use like in the NIA ITP program that resulted in the mice living much longer.

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Some info from another doctor I know who’s been looking into 17-alpha estradiol:

I know 17bE2 is practically insoluble in water, so I was originally looking into using extra virgin olive oil (or maybe MCT oil + antioxidant might be better since EVOO is much more “fragile”) with a dark bottle and oxygen absorber, which would take out the oxygen that could degrade the 17aE2 in presence of light/UV. Then one could add say lauroyl macroglycerides as surfactant, lecithin as homogenizer, and finally optional cosolvent like glycerol. This is just to make sure it is homogeneous and doesn’t precipitate at all over say a few months - which could mess up with dosing. Have the study on hand for 17aE2 aqueous solution?

17aE2 is even stable while heating vegetable oil at 100 C.
Effect of cooking on concentrations of β-estradiol and metabolites in model matrices and beef - PubMed

I’d also point out sublingual option could save at ~1/5 the cost, since it would probably be much more expensive if more pure though - so savings without user error like injections would probably make it more available to everyone if they end up charging say 5x the price for 10 gram “wholesale” which could be $3k a year per oral.

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In the long-term we males who are interested in using 17-alpha estradiol are going to want to make sure there is very low levels of 17-beta estradiol (the feminizing hormone typically used in hormone replacement therapy by women).

So the issue of testing comes up when thinking about this drug. Specifically, testing for the percent of alpha vs. beta estradiol in the product you are buying.

Some of the conversation on this topic:

The problem is I wonder how they claim to do it purity-wise. Sounds like they want to keep the process hush. Been a while since I did a wet lab in organic synthesis for ligand synthesis, so I’d have to dust off some old O chem and A chem books. I suspect 99%+ enantiomer selectivity should be possible though and should be easy to use a tiny amount to send out for a ng/mL sample in a lab for HPLC-UV to test for their claim of essentially 100% purity. Was wondering what your chem professor thought, if he’s willing to comment.

and the response from my Chem professor friend:

Shouldn’t need too much sample to conduct the test.

However, diastereomers can be difficult to separate, even by HPLC. The lab may require some background work unless there is an available SOP for a- and b- estradiol assay. I would imagine that the lab will ask for high purity samples of both a- and b- estradiol as refence materials.

You would need to consult with the lab; and maybe a couple of labs for alternate opinions.

and…

Also, 100% is somewhat nebulous. It could mean that the estradiol is 100% a- or b-, but has some other stuff as carrier (water, saline, buffer, other steroids not estradiol, etc).

Or it could mean that the sample is actually 100% estradiol (a- or b-), with no other compounds (no fillers, excess proteins, saline, buffers, etc)

My thoughts are that it is a high % of one diastereomer in a mix that contains many other chemicals including byproducts, buffers, water, etc.

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Thanks for updating the information of 17-Alpha Estradiol, I think there are too few people using 17-Alpha Estradiol right now, according to the survey in this site, only 1% users in this site have experience in 17-Alpha Estradiol.

I wish there are more advice and feedback from people and MD, it looks like 17-Alpha Estradiol will not be available for the next decade, do you know whether there is any company developing 17-Alpha Estradiol as drug? And what’s the estimated time for FDA to approve 17-Alpha Estradiol for prescription Rapamycin User Survey #2 - Please Respond

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Hi All

I have procured a source of 99.5% pure 17alpha estradiol in pharmaceutical cream delivery base provided in a pump bottle of 100mg/50ml with a 2mg/1ml delivery per pump.

We are planning on a small trial for proof of efficacy and safety

Markers to include:
Serum or urine 17a estradiol levels**
Serum Chemistry
GlycanAge Immune Age
TruDiagnostic Pace of Aging
Precision Analytics Comprehensive Urine Hormone Metabolic
CNS Vital Signs

I have everything lined up except for a lab to assess 17alpha estradiol levels. Our best guess for a starting dose would be 8 to 12mg per week. Ideally this could be a twice weekly dose but we may want to go with 1 pump 5 to 6 days weekly. Before starting the trial we would need some PK data to pick
a dosing protocol.

If anyone knows of a lab or can be of help finding a lab, I would greatly appreciate it. I have sent some emails out to researchers of some more recent papers. So hoping I will get a response.

Thoughts? Ideas? Feel free to message me directly at 805.724.6446

Thanks

Rick Cohen, M.D.

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