Trt protocal - advice needed

[AH2261]

Hey guys,

I was hoping someone could help me pinpoint what they believe may be going on. I've been on trt for several years and have come to the conclusion that an AI is required for me to minimize high E symptoms. I am due for some bloods in the next 3-4 weeks, but figured in the meantime I'd share to see if anyone can provide any guidance. I am currently on 50mg e4d and I notice that the estro spokes i get from each injection carry me almost to the next, so basically I take .25 24hrs from inj, and start feeling my best right before my next shot, and it apperas the cycle then continues, to the point where I almost don't even want to take the 2nd shot for the week since i'm feeling good. What is that saying if i feel best after inj on day 3-4? The first two days post injection I'm dealing with high E2, oily skin, ED, etc. I'm thinking my .25 post ijection isn't driving my E2 down enough, since i've taken .25 on day 1 after inj and day 2 just to keep it at bay.

Any idea if i should possible increase my AI dose more , and or should move my shot out to E5 OR E6 day? I can't imagine the dose i;m taking it too much.

 

[Systemlord]

I've been on trt for several years and have come to the conclusion that an AI is required for me to minimize high E symptoms.

The majority of men that think their symptoms are related to estrogen are in fact not. TRT changes blood plasma volume and changes the way your body reabsorbs sodium in the kidneys.

This increases fluid in the body, and since AI’s cause fluid loss from lowering estrogen, symptoms disappear. The AI a bandaid.

If your body fat percentage is higher, you may retain more fluid due to metabolic disturbances.

It also seems like the best course of action is to run labs, see where you are, then maybe reduce your dosage, or inject smaller more frequent doses, to minimize the hormonal spikes leading up to peak.

 

[AH2261]

Thank you for the quick response. I'm very into fitness/nutrition and maintaining relatively low BF year round, so even though the water retention is only a few lbs I notice it. I'm not too concerned with that as much as the higher E causing Ed issues..ability to maintain, I pop an AI and usually morning wood, etc. I can also tell when estrogen is high since I can take as much cialis as you can imagine and doesn't work. That and oily skin have always been sign for me. My last labs I was at 60 estro. Never thought I'd need to go lower than 100mg a week, but I guess less is more for many.

 

[Systemlord]

I can also tell when estrogen is high since I can take as much cialis as you can imagine and doesn't work.

Cialis doesn’t work well for me if ferritin is low normal iron. Also a study shows Cialis changes T:E2 ratios, favoring testosterone.

Estrogen is always the scapegoat. Why does everything have to be estrogen related, why can’t it just be too much testosterone causing your symptoms?

Come clean, where does your Total T and Free T currently sit?

 

[AH2261]

I'm not sure what aspect of my testerone would be off. All free and total have been in middle/upper ranges during time on trt. I just know that I've never felt right being abortion 40ish E, regardless of Test levels. The fact that I can take an AI and performance and overall sex drive sky rocket...not sure what to make of that. Clearly no expert , so I'm sure there's a lot of validity to all that you've stated as well.

 

[Systemlord]

All free and total have been in middle/upper ranges during time on trt.

There’s no context, like when labs are drawn in relation to your injections, measuring at peak, midpoint or trough?

 

[AH2261]

always measured at trough. Maybe I should consider m/w/f schedule or nust lower my dose to Mayne 90mg week vs 100 I'm at.

 

[Systemlord]

I am currently on 50mg e4d

Maybe I should consider m/w/f schedule or nust lower my dose to Mayne 90mg week vs 100 I'm at.

No, you’re not on 100 mg weekly, more like 87.5 mg per week, because you’re injecting every 4 days (4+4=8), a week is 7 days.

You divide 100 by 8, and come up with 12.5 mg per day x 7 is 87.5 mg per week.

So 45 mg every 4 days is 78.75 mg per week.

I still believe you need smaller injections, more often, like 20 mg every other day, that’s every 2 days.

Maybe you even need daily shots, based on your sensitivity to exogenous testosterone.

I also don’t think you should target high normal testosterone. You want to maintain a near static 450-550 and you can achieve this injecting frequently. This eliminates the hormonal spikes, which I believe is causing your symptoms.

Back when I was on injections, I maintained a near static 425-450 level injecting 7 mg daily, the best I ever felt on injections, and if it wasn’t for my Gilbert syndrome, a liver disorder, which has a difficult time clearing out dead red blood cells, or bilirubin, that would have been optimal for me.

 

[AH2261]

I use to do smaller injections more frequently, M/W/F, I actually recently switched to my current protocol few months ago. Main reason I switched was due to test being well over 1500 total and free high out of range at 120mg. My doc believed I just wasn't processing test and frequent injections were having a compounding effect driving test and estro up. My estro was 65 when I did labs. I probably should of maintained the same dosing schedule and just lowered the dose. Instead, I switched go E3.5 to E4 day at a lower dose.

 

[Systemlord]

My doc believed I just wasn't processing test and frequent injections were having a compounding effect driving test and estro up.

It’s all about the dosage, daily shots usually requires much less Test. I got about the same Test levels on 7 mg daily as I did on 20 mg EOD.

The most notable difference was in my E2 levels, 28 versus 49.

Sorry, but your doc sounds like someone with little experience in this area of medicine.

Sadly a lot of docs are only good for the TRT script, but beyond that they are all but useless in guiding treatment.

The reason to inject a large amount of Test infrequently is to compensate for the decline in levels over longer periods of time, so frequent dosing requires less overall Test.

A good starting place is 10-15 mg per day.

 

[aneuman]

I use to do smaller injections more frequently, M/W/F, I actually recently switched to my current protocol few months ago. Main reason I switched was due to test being well over 1500 total and free high out of range at 120mg. My doc believed I just wasn't processing test and frequent injections were having a compounding effect driving test and estro up. My estro was 65 when I did labs.

Regardless what most people say anecdotally (and I value anecdotes) most studies I've read say that estradiol levels in males are tightly controlled between 20-30 pg/ml. I know some people have 40, and 60 and +80 pg/ml and feel like 20 year olds, good for them, but it seems most 25-39 year olds are actually in that range.

Age-Specific Serum Total and Free Estradiol Concentrations in Healthy Men in US Nationally Representative Samples​

You could discuss with your doctor lowering the dosage, or lowering the dosage and increasing the frequency, or maybe you do need an AI. One size does not fit all.

And yes, estradiol outside the normal range (both high and low) is associated with sexual dysfunction in males.

Estradiol is an independent risk factor for organic erectile dysfunction in eugonadal young men​

Different levels of estradiol are correlated with sexual dysfunction in adult men​

The most optimistic study regarding higher levers of estradiol (>50pg/ml) was by Ramasamy. "Most compelling is the fact that in men with serum testosterone <300 ng dl-1, sexual drive was seen to be markedly higher when estradiol levels were >5 ng dl-1", but it also mentions that "exposure to estradiol in the mature penis leads to increased vascular permeability with increased ED."

The role of estradiol in male reproductive function​

I probably should have maintained the same dosing schedule and just lowered the dose. Instead, I switched go E3.5 to E4 day at a lower dose.

I think this is a sensible conclusion. Since you've been on TRT for several years, I assume you have some labs that correlate with point in times where you were feeling good, your performance was good, etc. What were the levels of T/FT/E2 when that happened? I'd try to replicate that scenario to see if things improve.

 

[RobRoy]

Regardless what most people say anecdotally (and I value anecdotes) most studies I've read say that estradiol levels in males are tightly controlled between 20-30 pg/ml. I know some people have 40, and 60 and +80 pg/ml and feel like 20 year olds, good for them, but it seems most 25-39 year olds are actually in that range.

Age-Specific Serum Total and Free Estradiol Concentrations in Healthy Men in US Nationally Representative Samples​

You could discuss with your doctor lowering the dosage, or lowering the dosage and increasing the frequency, or maybe you do need an AI. One size does not fit all.

And yes, estradiol outside the normal range (both high and low) is associated with sexual dysfunction in males.

Estradiol is an independent risk factor for organic erectile dysfunction in eugonadal young men​

Different levels of estradiol are correlated with sexual dysfunction in adult men​

The most optimistic study regarding higher levers of estradiol (>50pg/ml) was by Ramasamy. "Most compelling is the fact that in men with serum testosterone <300 ng dl-1, sexual drive was seen to be markedly higher when estradiol levels were >5 ng dl-1", but it also mentions that "exposure to estradiol in the mature penis leads to increased vascular permeability with increased ED."

The role of estradiol in male reproductive function​

I think this is a sensible conclusion. Since you've been on TRT for several years, I assume you have some labs that correlate with point in times where you were feeling good, your performance was good, etc. What were the levels of T/FT/E2 when that happened? I'd try to replicate that scenario to see if things improve.

Everything you have posted is a baseline study. It has nothing to do with raising estradiol by giving testosterone. In every study that mean we're giving testosterone get raised estradiol (unless it was a study where they were blocking estradiol). In all of those studies where they gave testosterone and therefore raised estradiol it did not result in erectile dysfunction. But when you give testosterone and block estradiol, those studies did result in adverse effects such as erectile dysfunction. Testosterone works through its active metabolites which are DHT and estradiol. When you block those active metabolites you block the beneficial effects of testosterone at the tissue level where they are generated. What you measure in the serum does not reflect the levels in the tissues of either estradiol or DHT. People are making adjustments on serum levels that don't have an effect at the tissue level when on testosterone.
The reason for this highlights fundamentally important control mechanisms in androgen target tissues that finely regulate pathways for androgen synthesis and degra- dation to maintain DHT homeostasis. These in- tracellular processes do not appear to be affected by circulating DHT concentrations. Circulating levels of DHT in response to testosterone do not correlate with those found an androgen sensitive tissues such as the prostate, adipose tissue, and muscle due to local regulatory mechanisms that tightly control intracellular androgen homeostasis.
Same holds true for estrogen.
In comparing blood levels of E2 and testosterone with biologic effects, it is important to recognize that E2 is produced locally from aromatase in target tissues and acts in a paracrine fashion (Simpson 2003). In healthy men and in studies of medically castrated men undergoing graded testosterone add-back, serum levels of E2 reflect the total E2 that has diffused into the blood from all tissues having been synthesized by aromatase and escaped local tissue metabolism. These blood levels, no matter how
accurately measured, are an indirect reflection of total estrogen signalling which is further locally modulated by sulphoconjugation and deconjugation of estrogens (Song 2001).
So when we take an aromatase inhibitor or a five alpha reductase inhibitor we will decrease levels in the serum but most importantly we're decreasing them in the tissues where they're needed therefore we are blocking the beneficial effects of testosterone in the tissues and that's why we see negative effects with aromatase inhibitors and five alpha reductase inhibitor's.
So what you're measuring in the serum with regard to DHT and estradiol when you're on testosterone does not have an effect in the tissues themselves because estradiol and DHT are generated intracellularly. Their levels are tightly controlled intracellularly. So men on testosterone are completely different than baseline studies or observations in men that are not on testosterone. They are not the same and it is comparing apples to oranges

 

[Jerajera]

But when you give testosterone and block estradiol, those studies did result in adverse effects such as erectile dysfunction

Genuinely curious, any such studies in which the men were given less than an absurd amount of AI (e.g 1mg/day) that completely crashed their E2? Just enough let's say to get their (sensitive) E2 within 20-30pg/mL?

 

[TLR]

Everything you have posted is a baseline study. It has nothing to do with raising estradiol by giving testosterone. In every study that mean we're giving testosterone get raised estradiol (unless it was a study where they were blocking estradiol). In all of those studies where they gave testosterone and therefore raised estradiol it did not result in erectile dysfunction. But when you give testosterone and block estradiol, those studies did result in adverse effects such as erectile dysfunction. Testosterone works through its active metabolites which are DHT and estradiol. When you block those active metabolites you block the beneficial effects of testosterone at the tissue level where they are generated. What you measure in the serum does not reflect the levels in the tissues of either estradiol or DHT. People are making adjustments on serum levels that don't have an effect at the tissue level when on testosterone.
The reason for this highlights fundamentally important control mechanisms in androgen target tissues that finely regulate pathways for androgen synthesis and degra- dation to maintain DHT homeostasis. These in- tracellular processes do not appear to be affected by circulating DHT concentrations. Circulating levels of DHT in response to testosterone do not correlate with those found an androgen sensitive tissues such as the prostate, adipose tissue, and muscle due to local regulatory mechanisms that tightly control intracellular androgen homeostasis.
Same holds true for estrogen.
In comparing blood levels of E2 and testosterone with biologic effects, it is important to recognize that E2 is produced locally from aromatase in target tissues and acts in a paracrine fashion (Simpson 2003). In healthy men and in studies of medically castrated men undergoing graded testosterone add-back, serum levels of E2 reflect the total E2 that has diffused into the blood from all tissues having been synthesized by aromatase and escaped local tissue metabolism. These blood levels, no matter how
accurately measured, are an indirect reflection of total estrogen signalling which is further locally modulated by sulphoconjugation and deconjugation of estrogens (Song 2001).
So when we take an aromatase inhibitor or a five alpha reductase inhibitor we will decrease levels in the serum but most importantly we're decreasing them in the tissues where they're needed therefore we are blocking the beneficial effects of testosterone in the tissues and that's why we see negative effects with aromatase inhibitors and five alpha reductase inhibitor's.
So what you're measuring in the serum with regard to DHT and estradiol when you're on testosterone does not have an effect in the tissues themselves because estradiol and DHT are generated intracellularly. Their levels are tightly controlled intracellularly. So men on testosterone are completely different than baseline studies or observations in men that are not on testosterone. They are not the same and it is comparing apples to oranges

In your clinical experience have you ever seen a guy that was just sensitive to Supra physiologic levels of estradiol and didn’t tolerate it well? For me, it seems anytime my E2 gets higher it affects erectile function (soft erections). If that (or any other negative effects) happen, do you just lower the dose of T?

 

[Systemlord]

In your clinical experience have you ever seen a guy that was just sensitive to Supra physiologic levels of estradiol and didn’t tolerate it well?

How do you determine whether or not it’s estrogen that’s causing your symptoms?

If your answer is the use of an AI, that’s not good enough, because TRT affecting your kidneys reabsorption of sodium,, which is what commonly causes fluid retention in TRT patients, as well as blood pressure increases that could lead to anxiety.

AI’s are a bandaid and may provide relief even though estrogen is not the cause. TRT also causes plasma volume increases in addition to changing the way your body reabsorbs sodium.

The latter is under appreciated and often ignored, and estrogen is the scapegoat.

 

[TLR]

How do you determine whether or not it’s estrogen that’s causing your symptoms?

If your answer is the use of an AI, that’s not good enough, because TRT affecting your kidneys reabsorption of sodium,, which is what commonly causes fluid retention in TRT patients, as well as blood pressure increases that could lead to anxiety.

AI’s are a bandaid and may provide relief even though estrogen is not the cause. TRT also causes plasma volume increases in addition to changing the way your body reabsorbs sodium.

The latter is under appreciated and often ignored, and estrogen is the scapegoat.

I don’t take an AI…Ive just noticed during times when I’ve increased my dose it naturally rises and when it gets elevated I get soft erections….and, anecdotally there are several men who state using a small dose of AI to lower their E2 results in better overall feeling and erection quality. I don’t believe an AI should be standard practice on TRT, however, we all say quite frequently that we are all different and different testosterone levels affect each person differently. I don’t see how estradiol can be any different and some men are not a lot more sensitive to its effects.

 

[Systemlord]

I don’t see how estradiol can be any different and some men are not a lot more sensitive to its effects.

The only way to know is if you instead take a water pill and if you get the same symptom relief as when using an AI, then you know.

 

[RobRoy]

In your clinical experience have you ever seen a guy that was just sensitive to Supra physiologic levels of estradiol and didn’t tolerate it well? For me, it seems anytime my E2 gets higher it affects erectile function (soft erections). If that (or any other negative effects) happen, do you just lower the dose of T?

The individual has a choice. You're blaming it on estradiol but it's not. It's just a surrogate number that you're following but when you take testosterone and raise levels and levels of estradiol, testosterone, and DHT, along with serotonin and others etc. What a man's levels get too high too quickly then we can see some erectile dysfunction initially. That is treated by either lowering the dose until it resolves and then SLOWLY raising the dose. Firstly, if the patient was doing well at the lower dose with strong directions and symptomatic improvement there's no need to raise the dose to super physiologic levels. Secondly if he does have symptoms that may improve with increasing testosterone then you would raise it very slowly. The problem is a lot of men even though they hate doctors basing treatment on levels they themselves tend to aim for levels which they may not need for symptomatic resolution. One man may need a very high level to resolve symptoms and another very little. Second way to overcome the erectile dysfunction you're getting is to just give it time. It typically will resolve in in a few months at most but most men will not have the patience to give it that time. It happened to me and I trusted in my provider and I just gave it time to work an it couldn't be any better.
So a man can just either lower his dose and then move up slowly if necessary (daily testosterone no matter what the delivery) or simply give it time (1-3 months)to resolve on its own which it always does once the body acclimates to the new levels.
Lastly, make sure you're not aiming for a number yourself and that you're raising your levels that will realistically resolve remaining symptoms. Too many men want to use testosterone to resolve every symptom they have and it's not going to do that. It will only resolve symptoms related to deficient testosterone in that individual. Some men are extremely responsive to testosterone and a little bit goes a long way while others take a lot to go a little way

 

[Gman86]

The whole E2 side effects convo is still a very fascinating one to me. I’m not sure what to make of it, tbh. Both sides have good points. And even though I put WAY more weight into real life anecdotes, than studies and/ or what science tries to explain what should be going on, I will admit that it’s not easy for anyone to try and extrapolate what’s going on in these anecdotes of men taking an ai and seeing objective improvements in sexual function, and also improvements in other areas, such as mood and energy, for examples. There’s absolutely no denying that many men have had this experience, and relatively quickly once they take the ai. This is not disputable. It’s happened hundreds and hundreds of times to men on HRT, and again, just can’t be denied. Obviously doesn’t happen everytime, but I’ve read with my own eyes hundreds and hundreds of anecdotes over the years of men taking an ai and seeing improvements in areas such as sexual function, mood, energy, sleep, well being, etc. There’s just no way all these anecdotes can be chalked up to coincidence or dumb luck or what not

What I’m interested in is the why this occurs. What exactly is happening in the body that gives some men improvements when they take an ai. Is it as simple as their E2 comes down a bit, while androgens remain the same, thus improving their T to E ratio, and then consequently feeling better and/ or seeing sexual improvements? I want it to be this simple, but I’m really not sure if it is. I’m legit dying to know tho, I can tell u that! Lol

Another thing to consider, which hopefully might help narrow down what’s going on, would be the fact that it’s extremely common to see men take a DHT derivative, mainly masteron, primobolan and/ or Proviron, and see moderate to drastic improvements in libido, and often times erections as well, but mainly libido. It’s undeniable that DHT derivatives have the reputation to improve sexual function, and often times well being and energy. The question is, however, what mechanism of action from these compounds are causing these improvements? Is it mostly the lowering of E2, or at least the minimizing of E2 effects, while either keeping total androgens the same, or with certain DHT derivatives actually increasing total androgens? Is it mostly the fact that they can give the person similar effects as increasing their DHT level would give them? Is it the combo of lowering E2/ decreasing E2‘s effects, increasing total androgens, and giving the person DHT like benefits all at the same time? Obv there’s a big difference in the mechanism of action between an ai and a DHT derivative, but I can’t help but try to connect what they both might have in common, and why they can sometimes result in similar effects with some guys. Obv not always. I just wonder how much of the sexual improvements from both come from their shared quality of lowering E2. That’s obv the only thing they have in common, as far as I know.

Doss anyone know whether an ai can increase DHT or not? Like if anastrozole decreases the amount of test that gets converted into E2, does that mean there’s more test available to be converted into DHT? Or would the amount of test that’s being converted into DHT remain the same?

 

[Gman86]

And to complicate things further, why have I seen so many guys do better on a nandrolone based protocol, with a tiny bit of test to boost E2 a bit, than they did on a test based protocol? Seems like a lot of guys that try it do better on it than a test based protocol. And guys on a nandrolone based protocol tend to do their best when they keep their E2 relatively low, while keeping their androgens moderate to high. Which makes me think there in fact is something to keeping androgens moderate to high, while keeping E2 low to moderate. AKA having a pretty high androgen to E2 ratio. Higher than the ratio they would have on straight testosterone without manipulating their E2 levels in any way. AKA what some would consider their bodies preferred/ “natural“ test to E2 ratio