E2: what is "high" and "low"

[sirgawain]

I see so many threads saying "if my E2 is too high or too low I get <x> symptom" but no numbers that show what that really is. My current routine, as an example, is 140 of T per week, injected once and 1mg of AI, once a week. It puts me at 980 at the low (day before shot) for T, and E2 of around 30. My libido still sucks.

So, what is "low" vs. what is "too high?"

 

[Nelson Vergel]

I hope I explain things clearly here. E2 levels depend on T levels.

High Estradiol in Men: Myths and Realities

Discover the dangers of high estradiol in men and learn how to identify when levels are too high. Explore more on our blog at DiscountedLabs.com

www.discountedlabs.com

 

[sirgawain]

Kinda. I still don't see a "when your E2 reaches this level, you should consider an AI" explanation. So in my case, I've *always* been on an AI, so I have no idea what E2 looks like without it.

When I started TRT, I was at 503 T, 25.4 E2

A few months later, my T moved to 988, E2 was 35 (and I was taking .25 AI, weekly)

Six months later, T was at 1080, E2 at 39.1, doc moved me up in AI to 1mg a week)

Two months after that, T was at 961, E2 at 24.1

So I've always had an AI and don't know what I feel like without it, or how high I'd be with E2 without the AI. I also know that in spite of the awesome body changes with the T, my libido has not seen the equal awesomeness in change. My dick and my libido remain a giant blah. As I reported that, the doc just kept pushing the AI higher to get the E2 down. I'm not sure that was the right call.

 

[Nelson Vergel]

Since most men make the decision of taking an AI based on the assumption that they have high estradiol when they are retaining water, are moody, or have sensitive nipples (and most do not get a sensitive estradiol test), we really have no data on how much higher from the 0.4% aromatization can be present before "high estradiol symptoms" are there. We also don't have a study that gives men on TRT an AI to measure such perceived symptoms. In fact, all we have is speculation about those symptoms (not a single study).

If you feel better on anastrozole at whatever dose you take, then that is what is important as long as you do not bring your sensitive E2 under 15 pg/mL. That, we know!

We have lots of information on what happens when you "crash your estradiol" in this forum.

 

[sirgawain]

I don't know if I feel better on AI or off. I have never been "off AI" while doing T, so I can only compare to pre-T. Libido still where it was which is what lead me to T in the first place. My doctor's reaction has been to push the E2 down further, yet a lot of other doctors say I shouldn't be on it in the first place. So f-ing confusing and frustrating when medical people can't agree on a protocol.

 

[Nelson Vergel]

No one can agree on an AI protocol because there is not a single study that shows if or how well they work. Estradiol is important for libido. And libido has a lot of factors that influence it. It’s easy to treat ED, but low libido is another story.

hCG is the only thing that raises my libido and makes me want to seek sex. I have been around for over 25 years in the TRT field and have yet found anything better. But some guys hate it. We are all so different.

 

[Charliebizz]

I've personally never felt a difference in libido with big changes in e2 according to lab work What I do notice is in my tt and ft. Numbers. Too high t I feel like crap all around. When I'm in my sweete spot libido is really good. And too low libido takes a big hit but still can have some good days

 

[Cataceous]

To answer the question more generally it should be divided into two parts: What is high estradiol in an absolute sense? and What is high estradiol relative to testosterone? Starting with the absolute question, we can look at statistics for estradiol in normal men. We find that estradiol peaks at around 30 pg/mL at about age 30. The standard deviation is about 8 pg/mL. This gives a measure of how extreme it is to be at higher levels.

Above SDs	E2 Level (pg/mL)	Odds in normal population
2	> 46	1 in 44
3	> 54	1 in 741
4	> 62	1 in 31,574
5	> 70	1 in 3,488,556

By this measure it's getting to be quite unusual to have estradiol over 50 pg/mL in a normal population of healthy young men.

To consider whether estradiol is high relative to testosterone we can look at the weight ratios in plasma as a percent. I don't have a specific citation for this, but I doubt there'd be much disagreement that the normal range for E2/T in men is about 0.3-0.6%. If your aromatization rate is above this range then it's probably fair to say that your estradiol is relatively high compared to testosterone.

It's pretty well accepted that having high estradiol in a relative sense is problematic. For example, in susceptible individuals it may contribute to gynecomastia. It's less clear at this point if high absolute levels of estradiol are also a problem. There are not so many reports of acute issues, and we simply don't have the data to say if chronically high estradiol is harmful or not. Anyone running high levels long-term is participating in the experiment. In any case, those on TRT with high absolute estradiol have a simple solution that doesn't involve AIs: lower the dose to better emulate normal physiology.

 

[tareload]

To answer the question more generally it should be divided into two parts: What is high estradiol in an absolute sense? and What is high estradiol relative to testosterone? Starting with the absolute question, we can look at statistics for estradiol in normal men. We find that estradiol peaks at around 30 pg/mL at about age 30. The standard deviation is about 8 pg/mL. This gives a measure of how extreme it is to be at higher levels.

Above SDs	E2 Level (pg/mL)	Odds in normal population
2	> 46	1 in 44
3	> 54	1 in 741
4	> 62	1 in 31,574
5	> 70	1 in 3,488,556

By this measure it's getting to be quite unusual to have estradiol over 50 pg/mL in a normal population of healthy young men.


To consider whether estradiol is high relative to testosterone we can look at the weight ratios in plasma as a percent. I don't have a specific citation for this, but I doubt there'd be much disagreement that the normal range for E2/T in men is about 0.3-0.6%. If your aromatization rate is above this range then it's probably fair to say that your estradiol is relatively high compared to testosterone.

It's pretty well accepted that having high estradiol in a relative sense is problematic. For example, in susceptible individuals it may contribute to gynecomastia. It's less clear at this point if high absolute levels of estradiol are also a problem. There are not so many reports of acute issues, and we simply don't have the data to say if chronically high estradiol is harmful or not. Anyone running high levels long-term is participating in the experiment. In any case, those on TRT with high absolute estradiol have a simple solution that doesn't involve AIs: lower the dose to better emulate normal physiology.

Most excellent contribution. From a few years ago with the confusion that one of Rouzier's videos caused:

Are These Side Effects from HCG and/or Anastrozole?

Hi, great question. I’ve listened to the lectures and I understand how this comment can be frustrating: It’s going to be extremely difficult for someone not trained in the field to try to make sense of this. This issue is further clouded by the fact that no distinction between RIA and LC/MS...

forums.t-nation.com

 

[xqfq]

To address sirgawain's question more directly -

There is strong evidence[1] that testosterone treatment improves age-related libido loss in men. The men in the studies that this evidence is based on did not use an aromatase inhibitor with their therapy. So if you are struggling with libido, you may want to discuss trying testosterone without an AI, or perhaps with less AI, for some period of time with your physician.

1. "Evidence" here meaning medical evidence from very large, randomized trials, meta-analysis, etc. The American College of Physicians, a major group that sets guidelines and recommendations for treatment for american physicians, published a paper outlining this - https://www.acpjournals.org/doi/full/10.7326/M19-0882. There are of course likely many other benefits to testosterone therapy, but other possible benefits haven't been studied in the same level of detail (e.g. mood, energy levels), or studies were not powered or designed appropriately.

 

[TorontoTRT]

Your E2 is too low for your total test. Hence no libido. Drop the AI all together.

 

[bennettjc]

To answer the question more generally it should be divided into two parts: What is high estradiol in an absolute sense? and What is high estradiol relative to testosterone? Starting with the absolute question, we can look at statistics for estradiol in normal men. We find that estradiol peaks at around 30 pg/mL at about age 30. The standard deviation is about 8 pg/mL. This gives a measure of how extreme it is to be at higher levels.

Above SDs	E2 Level (pg/mL)	Odds in normal population
2	> 46	1 in 44
3	> 54	1 in 741
4	> 62	1 in 31,574
5	> 70	1 in 3,488,556

By this measure it's getting to be quite unusual to have estradiol over 50 pg/mL in a normal population of healthy young men.


To consider whether estradiol is high relative to testosterone we can look at the weight ratios in plasma as a percent. I don't have a specific citation for this, but I doubt there'd be much disagreement that the normal range for E2/T in men is about 0.3-0.6%. If your aromatization rate is above this range then it's probably fair to say that your estradiol is relatively high compared to testosterone.

It's pretty well accepted that having high estradiol in a relative sense is problematic. For example, in susceptible individuals it may contribute to gynecomastia. It's less clear at this point if high absolute levels of estradiol are also a problem. There are not so many reports of acute issues, and we simply don't have the data to say if chronically high estradiol is harmful or not. Anyone running high levels long-term is participating in the experiment. In any case, those on TRT with high absolute estradiol have a simple solution that doesn't involve AIs: lower the dose to better emulate normal physiology.

Good Afternoon,
You wrote " in susceptible individuals it may contribute to gynecomastia. " Do you know if there are any studies regarding this issue? I ask because I may be grappling with this issue.
Thanks

 

[JimGainz]

My E2 has also been all over the place - as low as single digits (at .5 mg -week Arimidex) and as high as 90 (with no AI).
My last labs had me at 60 with a total T of 960 and that was with .125 mg Ai split into two weekly doses. Never felt better so I’m leaving things alone.

 

[Cataceous]

Good Afternoon,
You wrote " in susceptible individuals it may contribute to gynecomastia. " Do you know if there are any studies regarding this issue? I ask because I may be grappling with this issue.
Thanks

Seem to be quite a few:

gynecomastia testosterone estradiol ratio - Search Results - PubMed

gynecomastia testosterone estradiol ratio - Search Results - PubMed

pubmed.ncbi.nlm.nih.gov

Some snippets from the first few hits:

​

... gynecomastia is common in men ... and is considered to be due to an increased estradiol/testosterone ratio.​

​

Ketoconazole-induced increase in estradiol-testosterone ratio. Probable explanation for gynecomastia.​

​

The E2/TTE ratio may be a helpful tool in diagnosing gynecomastia.​

​

During puberty, there is often a transient relative imbalance between estrogen and testosterone, leading to gynecomastia.​

​

An imbalance in the ratio of estrogen to androgen tissue levels is postulated as a major cause in the development of gynecomastia.​

 

[bennettjc]

Thanks for replying.

But I should have been more specific given the topic here is "Testosterone Side Effect Management." To rephrase can someone point me to any studies regarding any relationship between estradiol (relative to testosterone) and gynecomastia... in men taking exogenous testosterone? I suppose one could extrapolate from what has been written about the issue not in the context of TRT. But I am more interested in unique situation of TRT. I did try googling but had no luck.

Of historical interest I did find this paper espousing the value of an aromatase inhibitor in reversing gynecomastia in TRT. One of the two authors is our hero Dr. Morentaler! Alas it is case report with an n of 2. Treatment of testosterone-induced gynecomastia with the aromatase inhibitor, anastrozole

Some recent numbers: Total Testosterone = 1050ng/dl. Free Testosterone (LabCorp Diffusion Method) = 44ng/dl. Estradiol (LabCorp Sensitive Method) = 86pg/ml. I don't take the AI. I do take HCG.

Do I have symptoms related to E2? Possibly. Despite 20lbs weight loss since starting (good) TRT, it does seem that my breasts are more prominent. I am aware of the distinction between glandular tissue and adipose tissue.

The topic is gynecomastia but I will say, as an aside, that since being on (good) TRT I am exceedingly more emotional. I cry at songs. I cry at professional wrestling!

Best,
Bennett

 

[Cataceous]

TRT is associated with external, physical changes in the men. Exogenous testosterone is known to cause an imbalance in the hypothalamic-pituitary axis. As such, testosterone can be converted to estrogen by aromatization. Excess estrogens may lead to gynecomastia and/or breast pain, both of which may be seen in 10-25% of men on TRT.[66] The ratio of estradiol to androgens is the key factor in the development of gynecomastia rather than absolute increases in androgens themselves.[66] Clinicians must be aware of non-iatrogenic causes of gynecomastia and therefore the appropriate work-up should be sought out to rule out other pathology, especially if there is any breast tenderness or unilateral gynecomastia. Only a few case-reports describe a relationship between male breast cancer and TRT.[38,39]

Risks of testosterone replacement therapy in men - PMC

Testosterone replacement therapy (TRT) is a widely used treatment for men with symptomatic hypogonadism. The benefits seen with TRT, such as increased libido and energy level, beneficial effects on bone density, strength and muscle as well as ...

www.ncbi.nlm.nih.gov

Your aromatization rate is over 0.8%, certainly on the high side. Most likely it's the hCG that's pushing it up. Excess emotionalism is a common symptom.

 

[bennettjc]

Thanks! Looking forward to reading reference #38 - subtitled "A warning to endocrinologists."

Cataceous - I am not picking on you.. I promise!! But regarding emotionalism, as it were, I tried searching on that as well and had no luck finding data. Definitely nothing involving emotionality in TRT associated with E2/T. Or associated with increased E2 in men in general. Certainly it seems to be the case anecdotally.

 

[madman]

Good Afternoon,
You wrote " in susceptible individuals it may contribute to gynecomastia. " Do you know if there are any studies regarding this issue? I ask because I may be grappling with this issue.
Thanks

At What point Does Estrogen get high enough to start encouraging Gyno production?

www.excelmale.com

Gynecomastia Evaluation and Treatment: EAA clinical practice guidelines (2019)


INTRODUCTION—DEFINITION

Gynecomastia (GM) is a benign proliferation of glandular tissue of the breast in men. The term is derived from the Greek words ‘gyneka’ (woman) and ‘mastos’ (breast). GM can be unilateral or bilateral, most commonly the latter (Nuttall, 1979; Mieritz et al., 2017). GM has to be distinguished from pseudogynecomastia (i.e., lipomastia), which is characterized by excess fat deposition without glandular proliferation. GM is a common condition with a prevalence that varies widely between 32 and 65%, depending on the age of the subjects studied and the criteria used for GM definition (Braunstein, 2007). GM shows three discrete peaks throughout a man’s lifespan: the first peak is observed during infancy, the second during puberty, and the third in middle-aged and elderly men (Nachtigall, 1965; Knorr & Bidlingmaier, 1975; Nuttall, 1979). The purpose of the assessment of GM should be the detection of underlying pathological conditions and the discrimination from other breast lumps that mimic GM, particularly breast cancer.

 

[Gman86]

My E2 has also been all over the place - as low as single digits (at .5 mg -week Arimidex) and as high as 90 (with no AI).
My last labs had me at 60 with a total T of 960 and that was with .125 mg Ai split into two weekly doses. Never felt better so I’m leaving things alone.

What’s the rest of ur protocol currently looking like?

 

[M.J]

No one can agree on an AI protocol because there is not a single study that shows if or how well they work. Estradiol is important for libido. And libido has a lot of factors that influence it. It’s easy to treat ED, but low libido is another story.

hCG is the only thing that raises my libido and makes me want to seek sex. I have been around for over 25 years in the TRT field and have yet found anything better. But some guys hate it. We are all so different.

Raising libido is what I am searching for at lest makes me want to seek sex.

I am trying now to lower hcg from 500eod to 200 or even 100.