Estriol Experiment: Human Male: N of 1

#35

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.

2 Likes
#36

Yes, I understand. Best Wishes,
RowingAgainstTheStream

2 Likes
#37

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!

3 Likes
#38

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

#39

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

7 Likes
#40

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.

6 Likes
17 Alpha Estradiol: Use and Dosing Experiences
#41

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’?

1 Like
#42

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).

3 Likes
#43

I know I asked this question before, but since there’s a good possibility that the product was not legitimate or otherwise not any good, then I think it would be of great public interest what brand you used.

Actually, it would be of public interest which brand you used if it turned out that the product worked.

I planned on added estriol to my longevity stack and to be honest your results (or seemingly lack-there-of thus far) have put me off from making the investment.

Surely you can tell us the brand without compromising the info of the supplier.

1 Like
#44

An old woman on youtube just gave it up. Save this video. Some things are being disappeared . I’m off on the road, good luck bros. It’s Interleukin-6.

5 Likes
#45

Still on the road in a desert but my final lab results are in: First Look:

  1. Product is good, its real E3
  2. Levine markers trending slightly lower overall, And noticeable cumulative negative effect on gross score.
  3. Changes on classic hormone markers. End testosterone markers lower Some noticeable decrease in libido after last large bolus dose
  4. End result? I certainly don’t recommend for what I call the TesBros, i.e those taking exogenous testosterone.
    Through most of the experiment my libido was fine, but I’m taking huge amounts of PDE5; 2x20mgCialis/wk and 3x100mgSildenifil/wk and I have an unusual jelqing routine.Thus my results are not extrapolable.
    BUT No titty soreness;)

Plan going forward? I need to check hormones in a couple of weeks to see if they have rebounded, which I expect.
Then if OK, I’ll do a monthly weekend 3 days of 4mg each day.

Of course this is NOT a recommendation or suggestion for general use. If anything this is a cautionary tale. Remember what our richest cuz did with our dearest luv rapa?
There be dragons.

3 Likes
#46

Did you have the pills tested, or are you basing this on bloodwork you got showing higher estriol levels?

#47

Blood work, complicated, composing long post on it now.

1 Like
#48

Final Blood Work Summary
I had 3 blood draws for this experiment: pre-dosing, 1 week, and the final 3rd week. The first 2 draws were just sex hormones. The final draw included lipids/met plus I added on FSH and LH. The first week I ramped from 1mg to 3mg. Weeks 2 and 3, I ramped from 3mg to 6mg. At the end of the 3rd week I stopped dosing, took my lipid/met tests the next morning, came home, took 12mg, waited 2 hours, and had the final hormone test draw. I did not do a full blood panel except at the end, as I’d had 2 or 3 just this year. I only decided to add FSH and LH after reading about their importance. At first, I was mainly concerned with testosterone and the estrogens.

image
image883×542 104 KB

Levine Markers
As I mentioned previously, most of my Levine markers went in the wrong direction by small amounts, which resulted in a pheno calculated age score about 11 years younger than my bio age. I tested twice earlier this year at 14 and 15 years younger.

Minor Out of Range Issues
Other red out-of-range values that I didn’t consider particularly important:

  1. Sodium and chloride slightly low: I don’t eat much salt, and they’ve been borderline low for several years, sometimes slipping into the red reference range as they did for this test.
  2. RBC, hemoglobin, and hematocrit slightly low: They’ve been slightly low for about 2 years. My PCP isn’t worried about it. I take VitB and iron and never feel general fatigue. Although it could be bone cancer or multiple myeloma, which my mother died from, I took a blood marker test for MM a while back, and it came back negative.
  3. Urine glucose high: I take dapagliflozin.

Hormones
The sex hormones are difficult to interpret, but the numbers look “bad.” They weren’t that great to begin with. However, I have never felt physiologically inadequate, and for most of the test, my libido was fine. The last few days there was a noticeable decrease in tumescence, but still sufficient rigidity for “functionality.” After the bolus dose, we went on a brutal week-long desert cross-country trip with little sleep, intermittent food, and water. Even considering those “distractions,” I would judge my libido as being impaired for 5 or 6 days after the bolus dose, i.e., minimal morning erections. It’s been a very long time since I’ve had sex behind an outhouse in the desert, and regardless of any exogenous estriol intake, and in any case, considering the sunburn, snakes, gravel, sand, and splinters, at this decade of my life, I’m in no shape or mood for it. So there’s a lot of “noise” around these “impressions” and despite these confounding factors, from my perspective, there’s a clear decrease in libido with large doses.

Next steps?
I’ll check my hormones in a month or so. Then I might try a few weeks at low dose (1 or 2 mg) to see what my hormones look like. Recall that after a week at low dose most of my hormones looked better, so I’m not giving this baby up yet.

A post script, if you please.
“S’io credesse che mia risposta fosse / a persona che mai tornasse al mondo, / questa fiamma staria senza piu scosse. / Ma perciocchè giammai di questo fondo / non tornò vivo alcun, s’i’odo il vero, / senz’ tema d’infamia ti rispondo.”

4 Likes
#49

Final estriol blood test 2hrs after 12mg, I had estimated a reading of 180-240 picograms.

image
image911×186 14.5 KB

This final mega-dose registered on the blood test as less than 200 picograms while the reference range is less than 180 picograms. The first two tests came back with less than 100 picograms which I interpreted to be the lower limit of quantification. Thus I interpret this final reading to mean between 180 and 200 picograms, which is in-line with what I had anticipated based on the MS-estriol experiment. Also it’s weird that the “0.20” is in green. It is clearly greater than the 0.18 reference range. And the last test mentions “dilution” meaning a “qualitative” type test.
Their thinking could be as follows:
Everybody knows this is a crude wide bandwidth color interpretation reading and your actual level definitely is less than 0.20 and could be somewhat lower, but we’re not really sure. It is probably above 0.18, but even if it’s over a little bit, it’s close enough to be OK, so we’ll give it a green, since we really don’t know and its not way high. And besides you’re a man, and so this is a silly test so we’re not going to complicate things by making it red.

Which is really sloppy scientific rationalization, but that is the only way I can see to explain the number being green even if above reference range.
Here is a screenshot of what the first two estriol tests showed:

image
image929×212 12.8 KB

So I really don’t know exactly what it means.

3 Likes
#50

PostScript:
Today I’m starting to finally feel that “my strength is back”. I had a 2 day break from the gym and when I went back this morning, my muscles felt strong, I felt strong.

I am still still “weaker” than before the experiement in that I had to cut the weight back, but I think I can ramp up to former loads fairly quickly, perhaps 2 weeks. Plus physiologically, mentally, and “drive”-wise, I finally feel restored.

There was the serious confounding factor of the desert trip, and that is difficult to filter out or account for, but still my perception is that the 2 week higher dose period combined with the final large bolus dose decreased my energy levels and made me more fatiqued and “weaker”.

At some point I’ll dive back in with a lower dose and different time spans, but I’ve got to catch up on my monthly rapamycin that I missed last month.

A Happy Thanksgiving to All!

5 Likes
#51

In this Youtube video Dr Andrew Winge tells he takes 1mg oral estradiol for the cardiovascular benefits, he is of course on TRT with a total testosteron of 1200 ng/dl. He plans to increase to 2mg

3 Likes
#52

I have patients on BiEst which is estradiol and estriol. They are topical and are absorbed, and are over the counter. If just giving Estriol you can go with this. This also avoids any theoretic risk of liver enzyme induction and increased venous thrombotic events (this is primarily with oral estradiol)
Given that the T1/2 of Estriol (E3) is 5-10 hours, application twice daily should give a reasonable steady state after 5 days and allow a reasonable blood test maybe 5 hours after applying the last dose.
Here is the estriol product I use (on Women) but is real estriol (and it’s cheap!) 84 doses for $23
I’m not advocating for men to use this at this stage, but it is a very weak estrogen and if the ITP says it is a winner - everyone can decide what to do.

@Ludovic I’d say this doctor is incredibly out of date, as no one who is up to date uses oral estradiol. Topical is the safe route. If his testosterone is 1200 (and the total isn’t really the relevant figure, it is only the free that matters) then he should have plenty of estradiol anyway and be more likely to need to be on an aromatase inhibitor to prevent the estradiol from being too high. I like men’s estradiol in the mid 20’s to low 30’s. If higher, we get feminizing effects and if lower excess cognitive decline and osteoporosis.
I guess if I had a man with adequate testosterone who was low on estradiol, I’d first see if I could bump his testosterone up (as estradiol is principally formed from testosterone) and if that failed, I’d have to consider adding some low dose topical E2 (estradiol), but I’ve not ever seen this in practice.

8 Likes
#53

I didn’t know about that brand. I used incurin, dog medicine, for the first test. I’ve recovered from my last foolhardy experiement and I’m starting another one; 2 months of 3mg E3 for Fri/Sat/Sun alternating with 3mg of rapa Fri/Sat/Sun, single dose in the morning. Full blood work pre-dosing with sex hormone lab work after 2nd weekend of E3. If they’re “bad” I’ll either decrease dosing or abort.
On the last go-around, aside from all the libido stuff, the loss of appetite, was really pronounced and significant, so I asked Grok, who came up with a pretty good analysis:
" You’re spot on—estriol does indeed have a higher binding affinity for ERβ (estrogen receptor beta) compared to ERα (estrogen receptor alpha), and that difference could absolutely be relevant to the effects you’re exploring, like the satiety and weight loss in that man’s case or the mouse trial. Let’s dive into why this matters.

ERα and ERβ are both nuclear receptors that mediate estrogen’s effects, but they’re distributed differently across tissues and often havedistinct—or even opposing—roles. ERα is more dominant in reproductive tissues (like the uterus) and is heavily involved in energy storage and fat accumulation. ERβ, on the other hand, is more prevalent in the brain (including the hypothalamus), skeletal muscle, and some metabolic tissues, and it’s often linked to energy expenditure and leaner body composition. Estriol’s preference for ERβ—roughly 3- to 5-fold higher affinity than for ERα, depending on the study—means its actions might lean toward those ERβ-driven effects.

In the brain, ERβ is expressed in key appetite-regulating areas like the arcuate nucleus and paraventricular nucleus of the hypothalamus. Activating ERβ here can suppress food intake by enhancing satiety signals, much like what that man described: eating a little, feeling full, and losing the urge to eat more. Research in mice backs this up—ERβ agonists (compounds that specifically target ERβ) have been shown to reduce food intake and body weight without the estrogenic “side effects” (like uterine growth) tied to ERα. Estriol, favoring ERβ, could’ve hit this sweet spot in his brain, dialing down hunger more selectively than a stronger ERα binder like estradiol might.

For the mouse trial, this ERβ bias could explain the weight loss despite ad libitum feeding. If estriol nudged ERβ in the hypothalamus, the mice might’ve felt sated sooner or less driven to eat, subtly cutting their intake. Alternatively, ERβ activation in peripheral tissues—like muscle or brown fat—might’ve boosted energy expenditure, burning more calories even if they ate normally. Studies with ERβ knockout mice show they tend to gain fat and eat more, suggesting ERβ naturally keeps appetite and weight in check. Estriol’s affinity could’ve tapped into that mechanism.

The ERβ preference might also mean fewer ERα-driven downsides. ERα activation can promote fat storage and, at high doses, nausea or other side effects (more common with estradiol). Estriol’s weaker ERα binding could explain why that man didn’t feel sick—just less hungry—while still losing weight. It’s a cleaner satiety effect, less muddied by systemic estrogenic noise.

That said, estriol isn’t an exclusive ERβ agonist—it still hits ERα, just less potently—so some effects might overlap. But the β-leaning affinity likely tilts its profile toward appetite suppression and metabolic tweaks over, say, fat retention. Does this ERβ angle feel like it fits the puzzle you’re working on? It could be a key to why estriol stands out in these scenarios."

#54

I think this AI is hallucinating, mouse that have ERα knocked out gain weight much more easily. I have seen at least two studies:

It puzzles me that estriol is the winner in the ITP but it has a much more ERβ preference.

Have you seen any metabolic benefits in your current or past experiments? Glucose, TG, liver enzimes, etc?