Estriol Experiment: Human Male: N of 1

[Jin]

The doc started me on femoston conti but my boobs were tender from it. Im on Angeliq now and so far it seems better. Hit and miss

[Tom_Clark]

Hi Jin, hormones almost by definition are very powerful and from what I’ve heard and read it’s tricky, and that’s with men taking men’s hormones and women taking women hormones. So this estriol thing for me is walking on thin ice. But as of yet I don’t have sore nipples and my libido is holding up, so that’s a win. My testosterone levels were never great, but it never bothered me. I did a baseline and also I’ve got some of the results from the first week of dosing, progesterone and estradiol up very slightly, waiting on estriol and testosterone. The two markers being slightly up, but still well below top reference range for men, means maintain Full Sail Ahead.

[Tom_Clark]

@Jin

femoston

Jin I saw femoston was progesterone and estradiol. My estradiol was 17pg baseline 21pg after week of dosing. Progesterone was less than 0.5 ng both times which I think is below the measurement level for men. So I’m not worried. If testosterone ends up dumping with this first reading, I’ll need to rethink carefully, but it will ultimately depend on how I’m physiologically functioning, so far so good.

[Jin]

It looks like they use a pretty shotgun approach of 1:5 estrogen to progesterone, but with the new tab of 1:2 I feel great and the breast tenderness issue has gone. Lol

[Tom_Clark]

October 25, 2024 T+11d
3mg Estriol
SHBG results:
T+0d 20nm/L
T+8d 30nm/L
An unmistakable 50% increase
Baseline 20nm/L is on the low side, but low might be good because then there’s more free testosterone, and its quite low for my age, perhaps remarkably so.
While 30nm/L isn’t high or low, it’s a more “normal” range, but still below average for my age.
From Martin Emlinger Reference intervals for testosterone, androstenedione and SHBG levels in healthy females and males from birth until old age - PubMed
From 17 to 70 “the median SHBG levels increased steadily in men from 20.8 to 44.5 nmol/l”.

Awaiting testosterone result. If its crashed I’ll have some hard decisions to make. I really want to run this for 4 weeks to give estriol a fair chance to show effects on the Levine Age Score. I think/hope that estriol won’t make permanent degradations to my male hormonal system.

The determining factors will be the level of any decrease, and the effects on my physiological state; libido, titty soreness, energy levels; all pure judgment calls. That’s the nature of sailing uncharted seas in a small boat.

[Tom_Clark]

October 26, 2024 T+12d
3mg Estriol
Yesterday I was considering going to a bolus, all pills at once, now I’m considering keeping the 0.5x6 dosing after getting the latest hormone results shown below. I had avoided giving my exact numbers before because they were low, but functionally I was fine, so I wasn’t too concerned. But now the numbers have changed in a strange way and are both obtuse and uninterpretable (to me), and generalized descriptions are insufficient, so here they are. At the end of the experiment I’ll attach all final lab reports. The two tests shown were pre-dosing and T+7d
Testosterone Total (ng/dL) 200==>281
Testosterone Free (pg/mL) 36 ==>44.7
Progesterone (ng/mL) 0.6==> Less than 0.5
Estradiol (pg/mL) 17==>21
SHGB (nm/L) 20==>30

[Neo]

Do you know the test to test variability of these - a lot of the swings could just be normal noise/sample error - not sure, just saying something to look into as I need my blood work bouncing around quite a bit even when I have not changed any variables)

[AgentSmith]

@Tom_Clark

The two tests shown were pre-dosing and T+7d
Testosterone Total (ng/dL) 200==>281
Testosterone Free (pg/mL) 36 ==>44.7
Progesterone (ng/mL) 0.6==> Less than 0.5
Estradiol (pg/mL) 17==>21
SHGB (nm/L) 20==>30

What specific testosterone tests did you order? The cheap immunoassay tests get you a ballpark total T result, but aren’t as accurate as LC/MS, and the free testosterone results are even less reliable unless you paid for equilibrium dialysis. Calculated free T from Vermeulen can also differ by quite a bit. Here’s a guy who compared some methods: Calculate Free Testosterone with TruT by FPT | Page 7 | Excel Male TRT Forum

[Tom_Clark]

AS, I’m just using the tests from UltaLabs, around $100. I added on FS and LH for the next tests this coming Mon/Tues. I was worried about decreasing Tes levels because while I have no issues at present, I’m so close to the the lower reference edge of free Tes, that any measurable decline, could have noticeable effects. And estriol is a female hormone, so yeah, there were risks. With this paradoxical increase, I’ve got some room to breath. I’ll look through the thread you listed and try to get a better idea of some of the nuances to Tes testing.

I was mentally prepared for an emergency stop, but with no negative physiological side effects, and crude but positive numerical data, its full sail ahead.

Scehduled again for Monday, as well as estriol.

[Tom_Clark]

Estriol blood test came back and no change!
Guesses:

1. Bogus product
2. Estriol was “all chewed up” by the SHBG, liver, kidneys
3. Lab error
   My take on the 3 possibilities:
   A) The product looks good. People aren’t making fake copies because there is really no market for it. Why make fakes if there is no market and no real money invovled? Label, packaging, all good. Could have been exposed to high heat?
   B) Its possible I suppose but I seem to recall a MS study with estriol and the dosing was 8mg designed to target a blood level of mid-pregnancy which is way way more than baseline.
   C) Lab error very unlikely.

I perceive no extraordinary danger. No physiological degradation in exercise, mood, libido. No remarkable or alarming blood signals. I’m increasing the dose to 6mg a day, somewhat above what they gave the mice, I believe.

[Imitation_Black]

What was the brand of estriol you got?

If possible could you take a photo of the box?

Was is “Ovestin” by “Schering-Plough”?

Also maybe try putting it in enteric capsules and see if that helps?

[DrFraser]

Oral estrogens … not anything I’d ever Rx. Needlessly induces liver enzymes and increases risk of DVT, PE, probably stroke. Topical estrogens eliminate this risk as are the only ones I’ll Rx.
Also, why take a synthetic progestin? Best practice is micronized progesterone at bedtime as it is a GABA agonist and helps to restore sleep.
This is something I do daily in my practice and am always concerned when I see an oral estrogen used or a non-bioidentical progestin.

[Tom_Clark]

October 27th 2024
Increasing to 6mg bolus dose

Sensitivity of the common Estriol Test
0.2ng/mL or 200pg/mL, i.e. it only reads values above 200pg/mL

From “https://en.wikipedia.org/wiki/Estriol_(medication)”
“Estriol levels at term are normally between 5,000 and 20,000/pg/mL”
From: “Pharmacokinetics and pharmacodynamics of three dosages of oestriol after continuous vaginal ring administration for 21 days in healthy, postmenopausal women - PMC”
"The oestriol plasma concentrations is about 7.9 pg/ml in days 5–7 and 11.1 pg/m ln days 20–22 of the regular female cycle.”
Comment: Makes clear the test I’m using is only designed for pregnant women. And for wiki, it looks like a decent entry.

From: "Efficacy and safety of oral estriol for managing postmenopausal symptoms. By Kentaro Takahashi”
“investigators have been able to initiate very little carcinogenesis in animal studies unless large doses (200 –500 mcg/kg per day) were used on a continuous basis”
Comment: For me 200mcgx70kg==14000mcg==14mg, so not that much headroom

From: “Estriol: Safety and Efficacy by Kathleen A. Head, N.D.”
It may be that estriol’s effect on the endometrium has less to do with the dose and more to do with the frequency of administration, with more frequent dosages being more likely to contribute to endometrial hyperplasia.
Comment: This suggests a bolus dose, which I’ve also seen suggested other papers.

From wiki: Estriol (medication) - Wikipedia**
Comment: This indicates 2hr post dose while fasting will be the max. But it still won’t register on the crude common test that just says less than 0.2ng/mL

All of which begs the question “What’s u gonna do sailor-boy?”
6mg bolus dose now through next test.
But I won’t get my results until the day before the following and final test.
So if the 6mg doesn’t get above the test minimum, I’ll do 9mg bolus on the last day of the test to try to get some reading from which I can extrapolate downward.

[Tom_Clark]

Yes, I understand. Best Wishes,
RowingAgainstTheStream

[Thorin]

I think this is an important question for you to consider, Tom Clark.

If the tests are imprecise, you may be measuring testing noise more than anything else.

Also there is a diurnal pattern to testosterone release, so in general one wants to test at consistent times of day. Early in the morning is supposed to be close to the peak, I believe. I mention this only in case you were unaware of it.

Another thought: your starting testosterone level is on the low end of the typical range. I don’t know if this matters in any way, but it is possible that you don’t “look like” the typical animal tested, so extrapolating results from a population of presumably “typical” animals to you might be a challenge. We have both a different species (from mice to man) and also different starting androgen levels (from typical to lowish). Whether this matters, I have no clue.

Anyway, what you are doing is interesting, and I thank you for sharing your thinking and results. Best wishes and good luck!

[Tom_Clark]

No, I will never discuss anything that would involve another party. This is my deal, its on me.

[Tom_Clark]

I’ve finished dosing and blood testing on the estriol experiment. I’ve kept a diary of possible minor “symptoms” as they came up and I’ll summarize and post along with all blood tests when I get back from a 10 day road trip. The last “regular” dose was the 4th. The 5th was a “wash-out” day. Around sunrise on the 6th I had blood drawn for the Levine Calculator.

Since I wanted to get a reading on estriol blood levels and since the test’s lower detection level is 100picograms, at 11am on the 6th I took large 12mg bolus of Estriol and had the blood drawn about 2.5hrs later, for the hormone panels, including estriol. This should create a level above 100picograms (possibly as much as 240picograms) if the product is legit. During the test my regular dosing ranged from 0.5mg at the beginning to 4mg the last week.

The lab results will trickle in over the next week, and a few came back this morning. FSH was the only one that was elevated out of range. I had not tested it pre-dosing or at the one week mark, so this is my first reading, but it is definitely high and my limited understanding is that estriol should decrease FSH. So I have no idea why or how this came to be. Possibilities:

1. I’ve always had high FSH but didn’t know it??? But I think this is unlikely. My libido, functioning and anatomy are fine.
2. The test is wrong. Unlikely
3. Something about the wash-out day and then the bolus dose. Could it have been a re-bound effect? The first study referenced below used doses of 2mg. Could supra doses have contrary effects? Quite possible.
4. The product I’m taking is bogus or the wrong compound. The bolus dose estriol reading should settle that issue. Typically the estriol lab results takes a full week. I think the lab is in Puerto Rico.

Oh and I saw written confirmation that the ITP study used common estriol(E3) from one of the dozen or so authors of the study. So now I would bet anyone $30K at 3 to 1 odds, your favor, that ITP used Estriol(E3)

I apologize about my rather cranky attitude as this trial began. I had to get out of the harbor with faith that I was using a good form of the proper substance. But its over now, back safely I’ve done what I set out to do, so I’m happy.
The two great unknowns as I started this were;

1. did ITP use E3 and
2. is my product any good

I’ll know in about a week if I was correct in my belief that the product was good.

Studies indicating estrogens decrease FSH
Estrogen replacement therapy in postmenopausal women: a study of the efficacy of estriol and changes in plasma gonadotropin levels - PubMed ←specifically studies estriol
https://emedicine.medscape.com/article/118810-overview?form=fpf
https://academic.oup.com/jcem/article-abstract/88/11/5405/2656711?redirectedFrom=fulltext

[RapAdmin]

I’ve heard back from a person who is very knowledgeable about these types of compounds and they are saying that the compound used in the ITP study is just the regular estriol, and while different nomenclature is sometimes used, its not any sort of unique or different variation of the compound. So - this should give us more confidence as we consider personal testing with this product.

[AnUser]

There’s like 20 authors on this paper, what’s going on at the NIH that they miss this? What about peer review?

It looks like to me maybe someone wrote ‘estradiol’, rather than ‘estriol’, then they CTRL+H to replace it, which replaced the term everywhere. Is it common to invent seemingly new terms like 16-hydroxyestriol without the α (alpha), and without "…estradiol’?

[RapAdmin]

Its impossible for us to know for sure, but its not inconceivable that they might have done a little deliberate obfuscation here on the naming to reduce the rapid uptake of the compound by biohackers.

I’ve spoken by email with Richard Miller and I don’t get the feeling that they are necessarily super supportive of the biohacker crowd immediately translating their research into practice, and they may even be getting pressure from their funders (e.g. the NIH) to make their research a little less “translational friendly”. The NIH is a very methodical, conservative group generally and while I’m not one for conspiracy theories, it wouldn’t be too much of a stretch to think that they (the NIH) is concerned about people harming themselves by rushing in too quickly to try translating the research on their own bodies.

I have no data to support this theory - but it wouldn’t surprise me if there are groups or people within the NIH pushing back on the ITP because its getting a lot of press / publicity, but the research is still just in mice and there could be a risk of harm to people if large numbers of people start testing on themselves.

Rapamycin is a drug that has gone from the fringes of research, into the mainstream press and quite wide-scale adoption, over the past 5 years, largely on the backs of the ITP research. I can imagine that some people in the NIH may not view this as a necessarily positive development given the lack of large-scale human clinical trials in healthy human populations (of course, this may never happen because rapamycin is a generic drug).