On Estrone and Estradiol Conversion

Here’s what I know. One group of enzymes - 17β-HSD. Many isotypes affecting estrogens and androgens: HSD17B1, B2, B4, B6, B7 and so on. Some of them are widely distributed (general expression: liver, brain, heart, adipose tissue, etc.), some are located in specific tissues and abundant (so they act only specifically for a tissue, like for retina). It’s very hard to predict the exact effect of it’s group final activity (conversion to one compound or another), because of massive isoform distinction within a group and their unpredictable distribution.

That’s what they do: estrone <-> estradiol (a reversible redox reaction depended on NADPH/NAD+).

That’s the answer for a question - “and what about endogenous estradiol reservoir?”. I mean, the reaction above, partly. A given isoform density and activity decides in which direction it runs. An excess of one of the two reagents will be metabolised in matter of hours, at most, and this is not the only reaction affecting those reagents, obviously (most importantly the excess must be removed from the body, mainly with urine).

What I mean… It’s so complicated that I can’t tell you WHY EXACTLY AND WHEN something happens with those two and no one will tell you for sure.

What’s also known for sure is, Le Chatelier’s principle affects your body constantly. You give a woman an oral E2 - her estrone levels increases in matter of minutes. After E2 is removed - her estrone level decreases proportionately fast and is back on it’s level. The equilibrium of the reaction depends on the substrate concentration, so the effect - the issue of an enzyme activity is a secondary matter here in short-term. Yes, the same about your E2 peak and related side effects from supraphysiological TEST level. That’s a reaction of aromatization, same principle - more substrate, more product, equilibrium maintained.

There’s the thing. An AI helps you to inhibit the reaction of aromatization if you need it, so less product is made and more substrate in your blood. You can’t inhibit your 17β-HSD, because you have no drug to do that. More E2 leads to more estrone, and vice versa, that’s it. Nothing about magical customization of your tissues to move an excess of estradiol to estrone in SHORT-TERM. The magic happens in LONG-TERM (matter of weeks, at least) - your body restructures it’s enzyme machinery and do it’s best to let your hormones be in correct proportions. What’s worse - the fact comes from anecdotal evidence, mainly.

That’s why using an AI is an option and works great AD HOC. You cycle often - you definitely want an AI to react as fast as possible and enjoy the benefits of AAS.

Not using an AI would work great too, but much later - so long, that you will be depressed (and how long exactly - nobody knows!), but not necessarily. Good for TRT (not for everybody), definitely bad for frequent AAS rotation.

Things clarified?

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My response upcoming is a very simple way of putting it, but one of my arguements against using AI’s on cycle is, if you’re already messing with natural physiology, why fuck with hormonal ratios. E conversion is a natural byproduct of T, thus you can’t expect to maintain physiological E status on high doses of T. Same principle with Estradiol and estrone, you can’t expect to have one elevated but not the other, that’s just not how the bodies natural physiology works, why further mess with it?

I’ve never had symptoms from letting my E run wild no matter the dose of test I use, I guess that’s just me.

Good post tho, you’re an extremely valuable addition to this community :slight_smile:

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I have a question and I hope you know how much I respect you. I hope you know that this is a sincere question and if it’s none of my business you’ll tell me to kindly sod off.

So what I notice when my e2 gets a little too high is not physical but emotional issues. I will cry at a sappy movie. Hell, I cried when Goose dies in Top Gun (spoiler alert for a 30+ year old movie). I don’t like how I feel emotionally when my e2 gets too high. My question: Is it possible that you personally don’t notice it as much because you’re on the spectrum? You mentioned it before and I wonder if it colors your view of things differently than it does for someone else.

My feelings don’t get hurt that easily haha.

I assume you’re talking about a percieved lack of ability to feel certain emotions. I certainly do feel things like sadness, empathy, love etc. I just have trouble identifying said emotions. I’m talking more about symptoms like high blood pressure, gynocomastia, excess water retention. I don’t notice symptoms like this. If I was significantly more emotional, you’re right I probably wouldn’t notice it because I wouldn’t be able to tell.

I’d argue that sometimes I feel just as much, if not more than regular people (not to say I’m not normal) when it comes to emotion. Esp when it comes to empathizing with certain people’s struggles. That being said this is very difficult for me to describe, and I don’t have a great grasp on many emotions. If you met me in real life you’d never be able to tell I was on the spectrum… Until you make a joke and then I can’t tell whether you’re kidding or not. I spend a lot of time joking around, however a lot of people don’t understand my sense of humour as it’s on the strange side.

Currently in bed but there’s a mosquito hovering above me and I can hear it dammit. I went to sleep for a couple hrs, woke up and no joke I have been bitten about 15 times… How does one mosquito even do that? Doesn’t seem possible

Edit: the mosquito landed on my neck, I slapped it, partially hitting it. But it got awaaaayyyy :frowning:

It’s still HERE! Just landed on my shoulder

You simplify it too much, mate. Your organism isn’t so smart to keep things always that way so you can be happy - it wants to survive and live as long as possible first, some biochemical reactions and some organs are still primitive and often require pharmacological intervention. By injecting TEST your body’s hormonal concentrations and behavior will never be close to natural because of, e.g. different manner of secretion (pulsative vs few times a week). How your body could be adapted to more or less exacerbated spikes of TEST in your blood? No way, it won’t happen. Your liver function, renal excretion, body fat, sleep time, mental status change, and so on. HPTA was regulating things well enough, you’ve “messed it” enough by injecting TEST, now you have to deal with it, often with necessity of polytherapy.

I believe that slight alternations of E2/E1 ratio happen because there’re mechanisms to do so. But as I’ve mentioned - it takes time of negative feedback loop to work (at best weeks). AI works almost immediately (matter of hours).

The problem is, people can’t dose their AI. That’s why I’ve created this topic: Estrogenic Side Effects No More - #9 by unreal24278

It’s really hard to crash your estrogens if you can manipulate your dosage of anastrozole by 0.05 mg, but it requires patience.