#1

In three days, I plan on beginning an estriol trial. The basics are:
1. Pre-dosing blood tests (E3, E1, Progesterone, Testosterone-free & total)
2. Initial dosing of 0.5 mg estriol for 7 days
3. Retest of blood markers
4. Increase dose to 1.0 mg if no indications from informal markers
5. Informal markers are libido and before and after photos of nipple, breast size, tenderness, and color
6. Receive results of 2nd blood test; if under 30pg estriol and no negative signs from informal markers, continue 1 mg dosing and retest at the 2-week mark
7. If over 30 milligrams, consider decreasing dose and/or frequency, or stopping if notable negative informal markers arise.
I have dozens of questions, concerns, and observations that I will post as the experiment goes along. The three most important are:

  1. I’m basing these actions on the reports of the latest ITP results, which I finally purchased. For weeks leading up to this, I had struggled with the chemical definition of estriol, i.e., was 16-hydroxyestriol just plain old estriol, E3? I am now certain, or at least certain enough to begin this experiment, that E3 has many names, but both estriol and 16-hydroxyestriol are the same thing. If I am incorrect, please advise, thank you in advance.
  2. I hate to make an experiment more complicated with added supplements, and the only case would be if that additional procedure or supplement was to make the experiment safer and less likely to have potentially serious negative side effects. It is my limited understanding that there are two estrogen receptors, alpha and beta, and that estriol has a greater affinity for the beta receptor. The alpha receptor leads to greater and more pronounced feminization effects. Thus, improved binding of estriol to the beta receptor and decreased binding to the alpha receptor would be desirable, and it is my understanding that genistein from soy might do this. I’ll research this idea over the next few days. If there are any other supplements that you think should be avoided or consumed beneficially, please comment.
  3. The most important concern is safety. Obviously, I’m on uncharted grounds, stumbling about in a fog. Still yet, I don’t perceive this short, low-dose experiment as particularly “dangerous.” It is my impression that the blood biomarkers and informal “signs and symptoms” will alert me in time to cease and avoid any permanent damage. If you perceive potential hazards, particularly severe and/or permanent, I would appreciate your advice, concern, or even vitriolic criticism. (Except sarcasm, I can’t stand sarcasm, or puns for that matter, no puns :slight_smile:
    Here is the copyrighted ITP article I’ll be liberally but lawfully quoting from in coming updates:
    Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin | GeroScience
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E3 Experiment: Low-Dose Intermittent, N=1
#2

Sounds interesting. It looks like you’re primarily testing for side effects? Any way to test for positive effects other than waiting to see if you live longer?

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#3

I was wondering the same thing as you a while back and did come to think that any kind of estriol (E3) would probably be a good enough replacement. For the record, pure estriol is not the same thing as what the ITP used though. Check this thread out: Next estrogen that extended male mice lifespan 16 alpha-hydroxyestradiol - does anyone knows anything about this? - #8 by Neo

To be clear is this straight estriol (E3)?

  • It’s 16-hydroxy estriol

Why did you pick 16-hydroxyl estriol as opposed to 4-hydroxy, 2-hydroxy, or just pure estriol?

  • Rich doesn’t know the answer, we could ask Mike Garratt
  • Maybe it was commercial availability
  • Maybe it was prior studies of toxicity in mice
  • Mike has his reasons, and Rich read the application three years ago and doesn’t remember what specifically led him to suggest this compound
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#4

Thank you L for addressing this issue. I literally spent dozens of hours researching this critical question. I mean if you take the wrong drug by accident, it is a diaster waiting to happen, what mathematicians would dryly call a non-trivival question. Your exact quote caused me about a dozen hours of confustion. This is a direct quote from the ITP paper. The font could be copyrighted, but the issue is one of scientific and public concern, so fair use:
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This screenshot is from Cambridge Isotope Laboratories. Please note the astericks on the left hand side of the diagram. These represent C13 for metabolic tracing, high dollar stuff.

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Next look at the chemical structure for estriol from wiki
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Also comparing the molecular weight, I found that the high dollar C13 version was 3 units higher than the wiki estriol. Each C13 unit is a molar 1 more than regular C12, so you get a 3 higher molecular weight.
All that being said I wouldn’t bet my life on it, I wouldn’t bet the farm, but I might bet some sore titties. Hey this is serious. I could be wrong, but still leaning 60/40 to them being the same.

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#5

This is a long form quote from the paper:
“A metabolomic screen of hepatic responses to 17aE2 showed that estriol-3-sulfate and 16-oxoestradiol 3-sulfate were increased approximately 100-fold in the livers of 17aE2-treated male mice but were minimally changed in females. Estriol-3-sulfate and 16-oxoestradiol 3-sulfate are both products of the conversion of 17aE2 to estriol, of which estriol-3-sulfate is the main sulfated form. This indicates that 17-α-estradiol under-goes sex-specific metabolism to other estrogens in mice and suggests that estriol might be involved in some of the male-specific anti-aging benefits of17aE2 treatment. We, therefore, speculated that treating mice directly with estriol might produce a lifespan benefit similar to that seen in 17aE2-treated males, but do so in both sexes.”

The money quote is "suggests that estriol might be involved in some of the male-specific anti-aging benefits of17aE2 treatment. We, therefore, speculated that treating mice directly with estriol "
It doesn’t say estriol derivative or estriol analog or estriol biosimilar, it says estriol. The use of the word “directly” leaves no doubt. To a native English speaker it is clear that “directly” means the exact substance estriol, not a metabolite, or precusor, or biosimilar.
All that being said I’m still not 100% certain,

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#6

Great point. I can’t think of any specific biomarkers. Nebulous subjective feelings? Shiny hair? I do the Levine Calculator test periodically. You would think that a substance that prepares a mother to give birth and a child to come into the world would have some measurable effects. Wasn’t child birth one of the leading causes of female death until quite recently? And wasn’t delivery one of the main times of infant death? When (or if) I settle into a routine with estriol, I’ll do a Levine calculator score, but you are correct that more specific markers would be beneficial.

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#7

Fascinating experiment! You may want to look at the basic glucose, lipid profile, and hsCRP blood work to see if anything improves.

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#8

It’s important (to me the lab rat) to have this right.
Here is the youtube video and here is a screenshot.
(Despite this “evidence” I’m not 100% convinced, maybe 90%, but that is just the nature of navigating in a strange and distant land, without charts or good compasses or clocks.

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From this video by Optispan, out of the mouth of Matt Kaeberlein

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#9

Tminus2
Regarding progress on the 3 main issues:

  1. Chemical identification: Is OH_Est==E3? Using Optispan as a recognized authority I see two youtube videos:
    281 ‒ Longevity drugs, aging biomarkers, and updated findings from the Interventions Testing Program
    This video is long and from about 10 months ago. It seems to definitely indicates that OH_EST is not the same as E3. However my opinion is that if you parse the words very carefully, it does not actually state that, but rather infers it. (I did not have sex with that woman, true but misleading) Yes it is a subtle distinction and open to interpretation and misinterpretation.
    The second video is Estriol Shown to Increase Lifespan as Winner of Intervention Testing Program
    This is a newer video only about 3 months old. Starting at the 5 second mark linked in the following URL, I think he clearly says that 16 alpha-hyrdoxyestriol IS estriol. I simply do not see any other way to parse his words.(https://www.youtube.com/watch?v=1DQEuT0dtWk&t=5sP)
  2. ER beta agonists, i.e. soy/genistein: This boat has too many moving parts as it is. Throwing another potentially powerful substance into the mix is dangerous. I may be foolish, but I’m not reckless:) So messing with the underlying receptors is a no go on this trip.
  3. BioMarkers: I’ve got the hormone labs scheduled. DeStrider made the excellent suggestion to also test traditional blood markers that go into the Levine Calculator. If the experiment continues past the initial 3-4 weeks launch, I will definitely start looking at the big picture. Right now I’m just focused on not crashing and sinking this boat before I get out of the bay.

Over the next 2 days I’ll try to figure out “how” to take the E3, i.e, with a meal, with fats, empty stomach, time of day, etc. I recall seeing a European label for E3 and I don’t recall that it listed rigorous directions for time of day ingestion, but I need to double check on that.

Despite all these unknowns, this boat is sailing on-time.

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#10

Guys, the researchers that actually do the work and who’s names are on the research papers, are usually very open to helping clarify things like this. Has anyone reached out to these people? (Not Rich Miller, because he’s too far up the chain of command, but the others who are actually doing the work
)

From here: Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin | GeroScience

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#11

I’m too close to it. It’s one thing to talk about theoretical possibilities and hypotheses. But it’s another thing to talk to someone who just had their pre-dosing blood work drawn and then consumed 0.5 mg of estriol. I don’t want to put these guys on the spot. They are doing a great job on the ITP that will benefit us and all of humanity, and the world owes them a debt of gratitude. A few of them might be happy that some brave fools are pushing the bounds. But I suspect most are more prudent. Science has its bounds and customs and protocols and this does not include cowboys. Perhaps I’m just naturally paranoid, but I’m still alive, so I’ll follow my instinct for the good of myself and these kind random scientists.

But the boat has sailed. Got the pre-dosing blood work, went with the 1/2 mg dose, the 1 mg pill was scored and cut nicely with a razor blade.

The ingestion/absorption dynamics are not a straight line, so I’ve got to figure that out. I took pre-dose photos of my chest/nipples, which my wife found amusing. I won’t get the pre-dose results until Friday or Monday. I need to think through how long after dosing to get the next blood draw. It’s fairly quickly excreted, so 24 hours after dosing will be hard to interpret. The mice got it in chow so it was nearly continuous dosing. There are many unknowns and I would love to hear what the random scientists think, but I can sail this boat on my own as needed.

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#12

I can tell you that Dr. Miller probably won’t assist with dosing questions based on personal experience. You may get some of the guys below him to give you some insights into dosing, but remember that they’re working with mice. But, it couldn’t hurt to ask.

#13

Why aren’t you using what they actually tested? 17α-Estradiol (17αE2)

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#14

T+7
First remarkable event/impression/reaction: My appetite has crashed. If I don’t think of food I’m not hungry and don’t have hunger pangs or cravings. If I sit down with food, it tastes good. I enjoy the sense of eating, but I don’t really want much. I’m happy after a few bites. After a few bites I could go for a few more hours, maybe 4hrs, without really wanting food. I need to consciously sit there and eat because I know I need the nutrition, and I consciously eat a few more bites to get to what I normally would consider a very small meal or a snack.

I’m mid-150’s, drifting to lower 150’s. I always considered 156 my “fighting weight” from my senior year of high school. I could see drifting down to my freshman year weight of 138, without really thinking much about it, or trying. It seems that I might drift to the 140’s despite my knowledge and attempts to keep my intake up.

The ITP article noted significant weight loss starting in middle age and I had read the report so I was aware of the phenomena and it could just be my expectation of weight loss. But it doesn’t seem that way to me. Of course this is the classic observer/observed paradox, but I “feel” that the effect is real and not psychosomatic.

I was shocked by looking at the mice’s weight loss graphs, something like 30% loss. What struck me was that the females lost about 30% also. That alone should have given them a 10% boost in lifespan, rather than the 7% decline. That means the net hit they got was 17%. That’s a big hit.

I’m keeping a diary of minor events/impressions, but this one was the first one that really stands out.

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#15

T+8
Remarkable side effect: Watery stools. I’ve had them for a few days, but I have a high oil intake; fish oil, astaxanthin (suspended in sunflower oil 8x12mg) and if I don’t get the proper amount of bulk and time it right, then I’ll have oily loose stool. So that’s what I thought was wrong. But apparently estrogens and stomach problems are a well know issue.

I vaguely recall my mother urging my teen-age sister to eat oatmeal and I asked why, and got no reply, couldn’t figure it out. So I guess I’ll try oatmeal. Ordering some oat bran to mix with steel cut oats, soaked overnight, basically eat raw, mildly heated before serving.

If that doesn’t work I’ll need to re-evaluate long term use. There’s loperamide, but I don’t want to go down that route.
There is always pulsing (intermittent dosing) and micro-dosing. I’m at 3mg currently. I can handle the stomach issues for a few weeks. I really want to give it a fair chance to effect blood markers.

Is the weight loss, partially or wholly due to watery quick gut transit times?

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#16

I agree that it appears that he is saying it is not E3. If he wanted to be perfectly clear he would have answered, “No, it is xyz”. So technically he did not answer the question. Example “Is this a website?” answer “This is an information sharing system”. Why would he do that? I think he might have been under pressure to keep the cat in the hat, but old men will ramble. Still he didn’t spill the beans. Why would the powers that be want to maintain this confusion? There might be a little bit of money in it, someday. I checked out the authors and many of them were tightly involved with private companies that dealt with longevity. Some of those companies might be interested in this chemical. And we’re in a capitalist competitive economic system. Knowledge is power and first mover has the advantage, and the fewer the competitors the better, and regulatory capture is a proven path to profitablity. But at least one of the authors was an old man, and sometimes old men will do what they’re pressured to do, but spill the beans in subtle ways as they ramble on.

#17

If you want to be even more confused, when they say “16-α-hydroxyestriol” in the beginning of the paper, there are no matches for that on pubmed. It’s only 16-α-hydroxyestradiol or 16-α-hydroxyestrol. The title of the paper is also 16-hydroxyestriol without the α (alpha), and that I can only find two matches, which includes this paper.

On the Mouse Phenome Database, which they link in the ITP study article, it also says 16-α-hydroxyestriol but also known as 16-α-hydroxyestradiol, with a link to the Wikipedia article on the Estriol medication, which is the 16-hydroxy version of estradiol.

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If I go to their supplier at Sigma-Aldrich Chemical, I can’t find 16-α-hydroxyestriol. But I can find 16-α-hydroxyestradiol and I can’t find 16-hydroxyestriol.

The ITP website says 16 alpha-hydroxyestradiol, though.

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I think it’s the Estriol medication.

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#18

Thank you AnUser. You’ve found several very convincing lines of evidence that I was unaware of. It is fairly well established that 16 alpha-hydroxyestradiol is a synonym for estriol. The use of 16 alpha-hydroxyestriol is unique to this paper. Also the term OH_EST is unique. A benevolent interpretation is that since there are perhaps a dozen naming conventions for the estrogens, a simplified approach describing simple common human estriol with these other higher unique terms is warranted for the following reasons:

OH_EST is a logical synonym because EST stands for estradiol, the premiere and primary estrogen. Estriol has an extra OH on it, so OH_EST clearly stands for hydrodoxy-estradiol, a well known synonym for estriol.

16 alpha-hydroxyestriol is a logical synonym for estriol because the unique thing about estriol and the thing that differentiates estriol from the queen of estrogens, estradiol, is the hydroxy group in the 16 position. Thus addition of “16 alpha-hydroxy” makes it clear that we are talking about the common, imprecise term estriol, but in a higher more precise scientific language in which laypeople are untrained, unskilled and ignorant.

Of course such explanations or reasoning are gas-lighting and paltering. Are we to imagine that these well educated scholars and businessmen are bumbling rambling fools who honestly believe such foolishness? I believe it is more likely that there was some intent in such clear obfuscation of perhaps the most critical term or word in the entire paper.

And perhaps it was a benevolent intent. Perhaps they purposely muddled the most important word or fact in the entire paper to protect an old man from himself, who might perform unsupervised self-experimentation. Their possible concern is touching but unwarranted and unwelcome. I am N of 1 and I’m sailing this boat.

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#20

Hi Tom. This may be totally irrelevant, but after I’d noticed muscle loss and tiredness, I asked the doc to put me on HRT (I’m 62yrs) and have had massive improvements in mood - sleep - gut health - memory. I know this unequivocally, because I moved to Turkey 2 months ago and they didn’t have the HRT I was looking for - so I went cold Turkey for 2 weeks. The brain fog was hideous, my mood was low to fluctuant and my bowels unpleasant (enough said). In addition my sleep was completely disrupted. Yes I know a zillion other influences may have been very relevant but since 3 days ago when I found a replacement HRT, I feel like a million $, So yeah it could (actually No) could not be incidental. I am also a female so throw that in the mix. :smile:

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#21

What does HRT look like for a female? or is it specialized based on everyone’s needs/indicators?

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