Dr Neal Rouzien's Position on Hematocrit and Estradiol Management

[Tommy Wall]

Hi Nelson,I just saw your post from yesterday of MD Neal Rouzien´s lecture. It sounds a bit of "too good to be true" or what it is your opinion about his speach?No more worries about higher levels of Estradiol, Hematocrit etc.. Would appreciate your input on his lecture.

 

[Gene Devine]

I personally know TRT Physician's who attend this exact lecture and they walked away thinking he was "out of his mind" on his position on elevated E2 levels in men.

There are just to many studies out there that present that elevated E2 levels in men can cause pathologies even when no symptoms are present.

Elevated E2 can be very insidious in men if not kept in check.

 

[Nelson Vergel]

I strongly disagree with him about his views about not managing hematocrit. He is opening himself up for medical malpractice. We know that higher hematocrit increases cardiovascular risks from studies that provided EPO to anemic patients.

Stroke Severity and Stroke Risk Factors Correlate with Blood Viscosity

 

[Nelson Vergel]

I agree with him on estradiol. Estradiol of over 30 pg/mL can be only problematic in men with low testosterone (under 350 ng/dL)

This is the ONLY study that links higher mortality with higher estradiol. I am attaching the paper. Most men had T around 350 ng/dL.

STUDY LOOKING AT EFFECT OF ESTRADIOL ON MORTALITY IN MEN:

This study found that estradiol levels of < 21.80 pg/ml and > 30.11 pg/ml resulted in greater mortality in men.


Abstract

CONTEXT:

Androgen deficiency is common in men with chronic heart failure (HF) and is associated with increased morbidity and mortality. Estrogens are formed by the aromatization of androgens; therefore, abnormal estrogen metabolism would be anticipated in HF.


OBJECTIVE:

To examine the relationship between serum concentration of estradiol and mortality in men with chronic HF and reduced left ventricular ejection fraction (LVEF).


DESIGN, SETTING, AND PARTICIPANTS:

A prospective observational study at 2 tertiary cardiology centers (Wroclaw and Zabrze, Poland) of 501 men (mean [SD] age, 58 [12] years) with chronic HF, LVEF of 28% (SD, 8%), and New York Heart Association [NYHA] classes 1, 2, 3, and 4 of 52, 231, 181, and 37, respectively, who were recruited between January 1, 2002, and May 31, 2006. Cohort was divided into quintiles of serum estradiol

quintile 1, < 12.90 pg/mL;
quintile 2, 12.90-21.79 pg/mL;
quintile 3, 21.80-30.11 pg/mL;
quintile 4, 30.12-37.39 pg/mL;
and quintile 5, > or = 37.40 pg/mL.

Quintile 3 was considered prospectively as the reference group.


MAIN OUTCOME MEASURES:

Serum concentrations of estradiol and androgens (total testosterone and dehydroepiandrosterone sulfate [DHEA-S]) were measured using immunoassays.


RESULTS:

Among 501 men with chronic HF, 171 deaths (34%) occurred during the 3-year follow-up. Compared with quintile 3, men in the lowest and highest estradiol quintiles had increased mortality (adjusted hazard ratio

---

, 4.17; 95% confidence interval [CI], 2.33-7.45 and HR, 2.33; 95% CI, 1.30-4.18; respectively; P < .001). These 2 quintiles had different clinical characteristics (quintile 1: increased serum total testosterone, decreased serum DHEA-S, advanced NYHA class, impaired renal function, and decreased total fat tissue mass; and quintile 5: increased serum bilirubin and liver enzymes, and decreased serum sodium; all P < .05 vs quintile 3). For increasing estradiol quintiles, 3-year survival rates adjusted for clinical variables and androgens were 44.6% (95% CI, 24.4%-63.0%), 65.8% (95% CI, 47.3%-79.2%), 82.4% (95% CI, 69.4%-90.2%), 79.0% (95% CI, 65.5%-87.6%), and 63.6% (95% CI, 46.6%-76.5%); respectively (P < .001).

Reference:

Circulating estradiol and mortality in men with systolic chronic heart failure.
JAMA 2009 May 13;301(18):1892-901.

 

[MG123]

Anyone who thinks polycythemia is nothing to worry about should not have a license to practice medicine. Just my opinion.

 

[MG123]

In regards to estradiol, I think that it should be considered independently of testosterone, whether testosterone is low, normal, or high. Just like Gene stated above, elevated E2 levels can cause bad problems in men. E2 can be elevated no matter what the testosterone level is. If you have total testosterone of 1000 and E2 of 60, you would still have elevated E2 regardless of the testosterone level.

 

[Re-Ride]

When this E2 business is finally sorted will someone kindly shoot me a pm? Thanks!

 

[ecdysone]

I strongly disagree with him about his views about not managing hematocrit. He is opening himself up for medical malpractice. We know that higher hematocrit increases cardiovascular risks from studies that provided EPO to anemic patients.

I think you may be missing his premise. While the correlation of high hematocrit to cardiovascular risk is true, he would claim (and may be correct) that disease conditions causing high hematocrit also have the "added baggage" of elevated platelet levels and other clotting factors. If the elevation of hematocrit is solely due to erythocytosis (caused by testosterone administration) then significantly higher levels of hematocrit/hemoglobin may be perfectly safe. This phenomena might well explain why people living at high altitudes can safely tolerate hemoglobin levels >20 g/dL.

On the E2 issue, he is not claiming that levels >30-40 are not "elevated" but that they are of no consequence if testosterone levels are also higher. The test:E2 ratio is much more important than the actual values. Maybe a good model for this is young men where their E2 levels tend to peak at >45, but are accompanied with correspondingly higher testosterone levels.

 

[midlifealpha]

Dr. Crisler shut me down for having high RBC, Hematocrit, and Hemoglobin. My bloodwork was posted at one point. He wanted to wait two weeks after therapeutic phlebotomy to get re-tested. If you consider the total amount of time it was probably between 3-4 weeks without test. However it did it fact reduce to normal levels. If it's going to be a problem I'm hoping I can get the phebotomy every so often without having to shut down T for so long I feel like shit. Now I had T it wasn't a question of waiting for Defy to ship it (would not ship until I passed and met with Nurse) I just felt like I should follow the rules. To me it seemed serious enough to lay off.

Now once I was cleared yesterday I took a shot right away I didn't wait for the shipment to arrive (which should be Friday).

 

[Vince Carter]

I've still never seen a definitive high E2 number, lab ranges are a sample of the population and can't be trusted. E2 unchecked and out of control I concur with but I don't believe a sensitive E2 of say, 40, is a limit requiring intervention as an issue in and of itself. As in treating a number vs treating the patient.

 

[Vince Carter]

Dr. Crisler shut me down for having high RBC, Hematocrit, and Hemoglobin. My bloodwork was posted at one point. He wanted to wait two weeks after therapeutic phlebotomy to get re-tested. If you consider the total amount of time it was probably between 3-4 weeks without test. However it did it fact reduce to normal levels. If it's going to be a problem I'm hoping I can get the phebotomy every so often without having to shut down T for so long I feel like shit. Now I had T it wasn't a question of waiting for Defy to ship it (would not ship until I passed and met with Nurse) I just felt like I should follow the rules. To me it seemed serious enough to lay off.

Now once I was cleared yesterday I took a shot right away I didn't wait for the shipment to arrive (which should be Friday).

What we're your numbers that he cut you off cold turkey, if I might ask?

 

[CoastWatcher]

I've still never seen a definitive high E2 number, lab ranges are a sample of the population and can't be trusted. E2 unchecked and out of control I concur with but I don't believe a sensitive E2 of say, 40, is a limit requiring intervention as an issue in and of itself. As in treating a number vs treating the patient.

I fully agree with this, Vince. In my own case, i had to relax and quit reacting to a number. I learned I felt just fine with an E2 in the high 30s to low 40s. On the occasion that it climbed higher I went to every-other-day injections and brought it back into line.

 

[midlifealpha]

What we're your numbers that he cut you off cold turkey, if I might ask?

RBC - 6.23
Hemoglobin - 18.0
Hematocrit - 51.8

I think the issue was with all three being out of range (high) he wanted to get it under control.

The most recent test was:

RBC - 5.40
Hemoglobin - 15.4
Hematocrit - 46.2

 

[Helboi]

Why would he cut you off at those numbers and not just send you for a therapeutic phlebotomy? That's surprising to me. Seems...hasty.

 

[jfullam]

Prior to starting TRT (with Defy), my E2 was 16.9, Total T was 263 and Free T was 5.9. After 8 weeks on my protocol, which is 60mg Test Cyp 2x per week subq and 100iu HCG daily subq, my E2 was at 51.6, Total T was at 756, and Free T was 23.3. All my energy and recovery came back after settling in on the treatment and I have felt very good since. At my 8 week consult with defy, even though my E2 was little high, we decided to stay the course and not introduce an AI (since I was feeling fantastic).
I decided to do another set of blood work at 12 weeks and was surprised at the results: E2 was 66.1, Total T was 1045 and Free T was 38.4. I am now at 14 weeks and I continue to feel really good, but the high E2 makes me nervous, though I am not sensing any of the common symptoms. To by safe, I decided to cut back on my HCG and I am now taking 125iu 3x per week, not certain how that will affect my E2 numbers. If I continue to feel good, my plan is to do another blood test in mid-December and see where my E2 is at. By the way, my Hematocrit, RBC, and Hemaglobin numbers have remained in a good range throughout treatment.

 

[Nelson Vergel]

Here is the transcript of his talk:

PART 1

Neal: ... Is Neal Rouzier and I wish to thank MedQuest Pharmacy for sponsoring this talk this morning. This is going to be 3 lectures crammed into one and I hope to provide for you the most important slide presentation and medical journal articles that you're going to get this entire conference. I will make these slides available to everyone. The last slide will give you that information to contact me and I'll be happy to provide these slides, and the slide presentation to you so that you too may use this slide presentation to your medical staff or anyone else you wish to speak to. This presentation, hopefully, will clear up some doubts as to why we do what we do.
I'm going to talk about a couple of myths this morning, myths that we always see and hear on a daily basis that are not necessarily supported by any good evidence-based literature or science or study, but yet we still do those things because someone once, or I heard somebody say once, "Well, my peers do that, so I must do it too." Nevertheless, what I'm about to present to you is evidence-based medicine to show you why we should what we do, and why we shouldn't do what we commonly do. This topic is going to be primarily for hormones in men, and related to testosterone, estrogen. Are they good, bad or indifferent?
This is the article that set the world on fire, which is the recent article from JAMA of November of last year that demonstrated that testosterone administration, although they didn't really guarantee administration, they guaranteed that they had a prescription for it; resulted in an increased incidence of myocardial infarction and death. This article has turned the anti-aging world on its head because we've got 40 years of others articles and studies showing just the opposite, but nevertheless, since this article appeared, our patients are very concerned about it because they see advertisements on the television at night that if you had a heart attack while you're taking testosterone "contact this attorney firm because we can get you the money you deserve because, what happened is, you had a heart attack and you took testosterone," which couldn't be further from the truth, but that's reality.
The critique of this article, and this is the lecture that I gave to my medical staff, and all my medical staff were concerned also about, "Well, what do we tell our patients?" In the discussion section of this JAMA article, it mentions that this is the only study that showed this adverse outcome, and it was in a select group of individuals. An outcome that we haven't seen in any other study, which is true. However, this was an observational study and all of the randomized controlled trials ... This was not a randomized control trial. All of the randomized controlled trials have shown the opposite outcome. Either no effect or protection against heart attacks.
Even though this article was profound in its statement, 4 years of other past studies, and articles, and randomized controlled trials do not show that. Since all of the studies show the opposite and one study does not negate all prior studies, and there were some definite biases in these studies, I will refer you to the third week ... Excuse me. The first week of March in JAMA, where the editorial comments criticized this article for the use or misuse, shall we say, of their study criteria. This is a perfect example of, if you torture the data long enough, you'll be able to prove anything you want. I will go further into those criticisms, but I suggest that we do not change anything that we have been doing based on one study that has significant flaws and biases.
We'll hear doctor Morgentaler talk about that too. When all of the studies in the past demonstrate protection against heart disease and stroke, and I have included about 20 articles from the literature in this talk that prove that. All of the articles to date, the randomized controlled trials, demonstrate improved longevity in those that are treated with testosterone, but increased morbidity and mortality in those men that were not treated with testosterone. Which group would you like to be in? If you really look at the other side of the coin, despite of the fact that you see advertisements on television for attorneys' firms looking to sue somebody because you had a heart attack with testosterone, I can take the opposite approach and say, "You have a significant increased risk of heart attacks, strokes and death if you did not take testosterone."
That's what the majority of the studies show and prove. A randomized controlled trial would have much more power than this observational study an all of these other studies were randomized trials. Also the problem with an observational study is it does not prove causation. It's an interesting observation but, as I'll get into later on, observation does not prove causation. An interventional study in a blinded fashion is so much more powerful and there are studies that are blinded and randomized controlled trials that prove that testosterone not only does not cause harm, but it protects against heart attacks and death. Therefore observational studies can't really prove causation as RCTs do. What we should take away from this study is what the researchers state in the last paragraph of the article.
That more studies are necessary before definitive conclusions can be made as to the cause and effect of testosterone causing an increased risk of MA. Also treatment decisions should not be based solely on one study that was negative, but rather on a trend of studies. Unfortunately the editorial comment section did not express this clearly. Just because one study shows a negative outcome does not mean that we should jump to conclusions based on that one study and throw about 40 years prior studies that show beneficial protection. Had this study been published years ago, 40 years, and all subsequent studies since then proved protection against cardiovascular disease, then this study probably would have been ignored and forgotten.
However, since it's a recent study, we tend to believe and reject all the past studies that show the exact opposite outcome. That's the way our mind works, unfortunately. We throw the baby out with the bath water, but we shouldn't do that. Nevertheless, one study does not negate many other studies to show opposite results and beneficial effects, so I will log this study on a negative slide for testosterone results, but it is only one such study on this slide besides the recent PLOS ONE study that was a very similar outcome. This is in contrast to all the other very powerful, much more scientific randomized controlled trials that showed benefits of testosterone administration.
I've put together a list of articles that I present to my medical staff, as well as to patients, as well as to other doctors, that demonstrate the various mechanisms by which testosterone is protecting the heart and brain against heart disease, against stroke, against dementia, and against plaque deposition causing arteriosclerosis that's causing that plaque rupture. If indeed, although we don't see this in 40 years studies, if indeed there was thrombotic mechanism to testosterone, then we could prevent thrombosis, just like in women, if we protected against the plaque buildup in the first place, which means if you administered testosterone to the world, we wouldn't have that plaque buildup that results in that plaque rupture.
The data in the literature is overwhelming in favor of a protective effect of testosterone in men. This recent study, although it's interesting and intriguing, does not change any of the evidence that I present, nor does it change my treatment strategies that I've been using for 20 years now. Until more studies demonstrate the same harm, I'll continue to follow the scientific literature that demonstrates benefit, and not follow one negative study that had significant flaws and biases in that study. As per the suggestion of the authors, they state that more studies needed to evaluate these results, and I agree.
I recommend to patients and physicians that they continue the same identical treatment based on all prior studies that show benefit in spite of the this one negative study. Certain statements deserve comment. The authors do note that other trials and other meta-analyses, studies of multiple studies, do not demonstrate adverse cardiovascular outcomes with testosterone administration. The trend so far in the literature has been a protective effects as the trials demonstrate that testosterone therapy improves a number of intermediate outcomes in cardiac risk factors. In the interventional trials, there's a decrease in heart attacks and also, in the interventional trials, we see all the reasons and beneficial effects of administering testosterone over the last 40 years, that provide protection.
The new JAMA study is the first and only study to demonstrate harm and should therefore be interpreted carefully in light of all the other studies demonstrating opposite results. In addition, the results of this study differ from a retrospective study that was done Shores et al. Same identical patient population group, same identical data set, same identical method of analysis. This showed a 39% reduction in mortality risk amongst patients treated with testosterone, which again suggest that we should use caution in coming to conclusions based on only this present study. An identical study 2 years prior to that came up with completely the opposite results, but that's how our brain works. Of course when our patients see those advertisements on television, they get scared.
Then they go, "I asked my doctor. My doctor scared me. He said I should stop testosterone." Different confounders and biases might account for the discrepancy that we see in this study. There's multiple limitations of this study that are noted by the authors and certainly by the critiques from the March issue of JAMA. All in all it's an intriguing study with unexpected results that are in dis-concordance with all of the prior studies and really, it should not influence our current therapy. It's one that really begs for more study. What about all the past studies, though? Should we ignore those? No. For those patients and physicians that are unfamiliar with the current literature on testosterone therapy, I've included several articles that I'll review for you on testosterone replacement therapy.
First are the studies that review mortality in men treated with testosterone compared to control groups. So far, in every study to date we see protection against myocardial infarction, protection against cerebral vascular disease, protection against all cause death including cancer. There's fewer heart attacks, cancer, and reduced mortality in men treated with testosterone in contrast to the current study. So many patients ... I shouldn't say so many. So many patients have considered stopping the testosterone because their doctor scared them, but the doctors are not aware of, nor are the patients aware of, the fear of heart attack, strokes, and reduction to all cause of mortality, even from cancer, that we seen in all these studies.
Other studies go on to prove that low levels of testosterone increase morbidity and mortality in contrast to men with testosterone levels at the higher quartiles. If you want to increase your risk of mortality, keep your testosterone levels low. If you want to protect against morbidity and mortality that we see as we age, then having higher levels of testosterone in every study have been beneficial and protective. Low levels of testosterone are predictive of an increase in all-cause mortality. That includes cancer. Why? Because of the decrease in visceral fat that see with testosterone administration and the protection against the insulin resistance that we get, so it's not just heart disease that we protect against. It's a multitude of other diseases and illnesses to. Where would you like your testosterone levels to be?
Where the majority of the literature shows better protection against dying or very, very low, where all the literature shows significant increase morbidity and mortality when you keep your levels low? Other articles demonstrate that all the physiologic benefits of testosterone administration were on cholesterol. It lowers the bad ones and it raises the good ones across the board. Lipoproteins. It lows the bad ones and it raises the good ones across the board. It improves insulin sensitivity. It reduces insulin resistance. It protects against diabetes. It lowers inflammatory cytokines. C-reactive protein, interleukin 6, tumor necrosis factor alpha are all lowered with testosterone. There's no drug that does that.
It protects against endothelial dysfunction in every study. It protects against plaque development and it also results in plaque reversal. There's no drug out there does that unless you use very high dose statins, but nevertheless there was quite a few studies in our literature showing that testosterone and estrogen result in plaque reversal. The current NAG study, the elite study giving oral estrogen to women, their in-point is carotid intima-media thickness. It's plaque reversal. What a great drug it is. If we could only come up with a drug that did that. Boy, it would sell like hot cakes, but we've got them, but we ignore them.
It protects against memory loss. It protects against Alzheimer's disease. It helps improve mood, cognition, energy, muscle mass. Fat mass is melted. It protects against osteoporosis and bone loss. It treats erectile dysfunction, sexual dysfunction, and is beneficial in decreasing all-cause mortality. Wow. I told my patients, "If you want to increase the risk of these things, then stop your testosterone, but if you want to protect against all of these things, then you should continue your testosterone." Patients will say, "But my doctor scared me. What I wanted to do is hear from you doctor, because I understand you, and I trust you, and I know you're expert in this. I just needed to hear it from the horse's mouth." Well, you too can help with your patients, cope with this stress that they're having, and if you want to increase the risk of getting all of these things, then stop the testosterone.
That's the risk that you'll take when you stop the testosterone, or if you don't take it in the first place. "But my doctor said." Your doctor doesn't understand. Your doctor doesn't understand this literature. Do you really want to stop the testosterone based on one negative study and risk all of these other things? I'm not and I don't recommend that patients do either. What are the consequences of stopping or not taking testosterone? That's listed in the first paragraph. Extremely important. Multiple studies demonstrate beneficial effects of testosterone replacement therapy on quality of life as well as disease protection. It's amazing the data from testosterone replacement therapy on reduction of body fat, insulin levels, insulin resistance, diabetes, inflammation and vascular disease that we tend to ignore.
It's such a great drug that's pretty much ignored by most of the cardiovascular world, which is really a shame. Testosterone serves to maintain health in every system of the body. Levels of testosterone in the low to mid-normal range are associated with an increase of illness as listed above. "Yeah, but the level is normal. You don't need to treat it because it's normal." Yes, but it's not optimal. There's a difference. I did it with an endocrinologist last night. He says, "It's really interesting that the endocrine world views hormone replacement as replacement." He says, "I don't replace hormones. I optimize them. There's a difference." Normal is not where you want to be. Normal is an average of a population.
If you want to be normal and die like everyone else, then keep your levels normal. If you want to protect against disease and illness, then you need to optimize all of your hormones. It was very refreshing to hear an endocrinologist make these statements. Don't forget, the pun is intended, the protection against Alzheimer's disease and dementia in every study to date. Why does testosterone protect against Alzheimer's disease? We'll get to that in a minute. I'm going to fly through these articles. I don't put these articles up here for you to look at right now, and write down the references and what they say. I'm just showing you all the articles that are available to you in the slide presentation.
All you have to do is contact me and I'll give you this presentation in PowerPoint so you can present to your medical staff, or to your patients, or whomever you want. This is a summary of these articles. I'm going to fly through them, but I'm going to make interesting points out of each one of those studies. This is a study by Shores et al recently done 2 years ago. It's an observational cohort of men with low testosterone levels. They got testosterone treatment and it was associated decreased mortality compared to no testosterone treatment at all. Completely opposite results. Same identical patient group and method of analysis, but completely different results.
Again, these are observational studies and you cannot extrapolate cause and effect from an observational study. You have to do a randomized trial to study that. Low testosterone levels predict an increase in all-cause mortality during long-term follow-up. Are there any long-term studies? Yeah, there's lots of long-term studies. There's also replacement in this study, improved survivals in men with type 2 diabetes. Endogenous testosterone concentrations at baseline are inversely related to mortality due to all causes. Cardiovascular disease and cancer. Low testosterone predicts mortality from cardiovascular disease.
Prevention of androgen deficiency improves cardiovascular outcomes so far in every study to date, except for the recent JAMA study. Low testosterone levels correlate with increased risk of cardiovascular mortality in every study. A lot of it has to do with the metabolic components associated with that risk. Low levels are associated with increased all-cause death, cancer included. It's not the same study. These are multiple studies basically showing the same effect. Deficiency in testosterone is associated with increased all-cause mortality. There's evidence that testosterone deficiency syndrome is associated with all-cause mortality particularly cardiovascular disease. Why do they do these studies and what should we get out of these studies?
Testosterone is an independent predictor of mortality in men. Where would you like your levels to be? It protects. It also protects against the plaque rupture as well as the plaque deposition. Another study. The lower the testosterone the greater the risk of all-cause mortality and cancer. Different studies. Men in the highest testosterone quartile had a 30% lower risk of death. Men in the lower quartile had the 40% more likely increased risk of dying. Where would you like your levels to be? Based on these studies it's almost malpractice to keep your levels low as opposite to optimal. The evidence overall particular from large recent studies points to testosterone having a pathologic role in cardiovascular disease, and there's no evidence of replacement increases cardiovascular risk. Every study, there's no increased risk of it.
Only protective effects. "Yeah, but that one study ..." One study does not negate 40 years of prior studies. Low levels are associated with all-cause mortality including cancer. If they're a predictive marker, where would you like your levels to be? Testosterone insufficiency is associated risk of dying over 20 years. This is a long-term study published in the Annals of Internal Medicine. In patients with heart failure, when treated with testosterone, there was a significant increase in exercise capacity. In addition to that, there's no significant adverse cardiovascular events in these studies. These are interventional trials. They're not observation.
They're interventional trials to show this. Major cardiovascular events have been studied. Low testosterone levels associated with a significant increased risk of major events. Low levels are independently associated with increased CHF mortality. Where would you like your levels to be? I find very few cardiologists on my staff administering testosterone because they're afraid of their peers. Well, that's out of my specialty. It's out of my realm, but yet that's all out of the cardiovascular literature. Concentration of testosterone is inversely associated with carotid intima-media thickness. Don't you think, doctor Cardiologist, that you would like to decrease that plaque? "Well, he's on a statin." I know that, but he's still developing plaque and all the studies will show you, but yet all these studies show there's a tremendous improvement in plaque deposition with testosterone administration.
"That's beyond my scope of practice." It's beyond your scope of practice to protect against cardiovascular disease? Quite a few studies showing the same thing. A decrease in all-cause mortality. Finally you get bored with this and say, "Wow, there's a tremendous amount of data out there supporting the use of it and a tremendous among of data showing that if you don't treat it, then you're increasing the risk of drying for multiple causes." That's the cardiovascular literature showing that, despite of the fact that some physicians and patients are misled to believe that testosterone is harmful. It's not. Interventional studies show protection. Long-term studies show protection. Low levels in every study to date are associated with an increased risk of morbidity and mortality. It's not harmful. It's protective. That's the first part of this lecture.
The second part of this lecture as to do with estrogen in men. I heard a couple of lectures yesterday allude to the reason that we're starting to see this increased risk of myocardial infarctions based on this one study. If you truly believe that study, which you shouldn't, when you go back and look at the study the criticism is, the raw data actually shows protections against heart attacks, but when they plug it into their statistical analysis formula, it shows an increase, but the raw data by itself shows protection against heart attacks. It's hard to conceptualize that, but that's what they did. Yeah, there's still a lot of people out there saying, "It's the estrogen." You read Life Extension. "It's the estrogen."
They didn't control the estrogen and we know that, since estrogen causes heart attacks in women, it must also cause it in men, so that's why you want to keep your levels low. How do we make that jump and that extrapolation? You cannot extrapolate. You should not extrapolate. Don't extrapolate. You have to study it. You have to study it to then prove it. You cannot extrapolate, but yet I hear everyone extrapolating, "You got to keep the estrogen low because it causes heart attacks and that's what we see in women." Okay. We've got 40 years of studies giving testosterone to men that raises estrogen levels. Please show me one study, I'm waiting, where raising estrogen in men is harmful. "That one study that showed that there's a high level of estrogen associated with heart disease." That's not what I asked.
I asked, give me a study where we raise testosterone. What you're quoting is an observational study. Give me one study where we raise estrogen in men, by either giving testosterone or giving estrogen, that results in harm. Okay, give me a study where we lower estrogen in men and has shown to be protective and beneficial. I'm waiting. You mean there aren't any? Then why do you lower estrogen? "Well, because someone said and this study here shows that in men, when the level is high, there's an increased risk of heart disease." Okay- Let me go through a couple of slides and explain to you the difference between observation, association and causation.
In order for you to understand the second lecture, you have to understand the difference between observation, association and causation. There's also this study. Show that premenopausal women with elevated testosterone levels are at increased risk of breast cancer. Do you give testosterone to women? Yeah, of course you do. It says right here that you're going to increase the risk of cancer in those women. Why would you do that? Why do you continue to give testosterone to women if this study shows that the high levels are associated with a breast cancer risk? The reasons associated with an increased risk of breast cancer is because that's what you see on premenopausal women with PCOS that have high testosterone levels. Yeah, that's what's caused them the breast cancer. No, it's not.
It's the insulin resistance, inflammatory cytokines in the visceral fat that are increasing the risk of breast cancer and uterine cancer. "Yeah, but there's an association." Does not prove causation. How do you prove causation? You study it. In part two, the course that I teach on cancer, every study to date, when we administer testosterone to women, in interventional trials, it protects against breast cancer. Testosterone is apoptotic to cancer cells. I'll give you that lecture tomorrow. "Yeah, but it says here ..." That's an association. Don't extrapolate association to causation. In order to prove causation you have to do an interventional study intervene, give them testosterone and see what happens.
In every study when we give testosterone to women, its apoptotic cancer cells, it protects against it. Some of you may be old enough like me. If remember what we gave patients with metastatic breast cancer. IM injections of testosterone. Guess what happened? It significantly decreased the metastasis from breast cancer. Another study shows that postmenopausal women that have high baseline estrogen are at risk for breast cancer. Another study showing that estrogen is harmful and causes breast cancer. It says it right there. What is it that you don't understand about that? Do you give estrogen to women? Yeah, you do. Well, you're causing breast cancer according to this study.
According to the Women's Health Initiative study and the [Dennis 00:28:07] trial, [Annie Lee 00:28:10] trial, and the CORA study, and the West trial, giving estrogen to women not only did not increase the risk of cancer, but it decreases the risk of cancer in the breast. "Yeah, but this one right here says that high ..." That's an association. Women with increased visceral fat produce more estrone, produce higher levels of estrogen. "Yeah, that's that estrogen that's causing the breast cancer." No, that's an association. It's not causation. How do you prove causation? You administer estrogen to women. Any study out there showing that? No. Then why do you? "Because the study says." That's an association, but if you'll notice it says, "Increased BMI," the first letters up here. Body mass index increases, associated with increased risk of breast cancer and it raises estrogen.
That's an association. It does not prove causation. To prove causation you administer. We don't see that in these studies. Levels of endogenous hormones estrogen are strongly associated with breast cancer risk in postmenopausal women. Then why do you give estrogen to women if it's associated with an increased risk of breast cancer? Do you give estrogen to women? Yes. What is it you don't understand about this study? This is a re-analysis of 9 prospective studies. What you don't understand is this is an association and the association is, the higher the estrogen baseline, the greater the risk, but there's also a greater risk of heart disease, and a greater risk of stroke, and a greater risk of diabetes.

 

[Nelson Vergel]

PART 2

That's triggering this increased risk of all cancers, not just breast cancer, but yet we associated with estrogen and say, "That's the estrogen that caused it." No, it's not. Interventional studies do not show that. Don't extrapolate an association to prove causation. You can't do that with testosterone and estrogen in women. Higher concentrations of estrogen, again, are associated with increased risk of breast cancer in postmenopausal women. Study after study shows baseline levels. These are not treatments, it's an association of a baseline level. Don't extrapolate it. If you're going to extrapolate it, you got to prove it. You got to do an interventional study and give estrogen to see if it causes it. So far we don't see that.
Now let's go to men. Men with higher estradiol levels had an increased risk of diabetes and heart disease. "Aha. See? It's that estrogen that causes that increase in belly fat." No, it's not. It's the increase in visceral fat that increases estrone production, which increases your estrogen levels. It's an association. It doesn't prove causation. How do you prove causation? You got to administer estrogen. Okay, let's see what happens. This is a study that's quoted by Life Extension and many other groups. "Aha. See? High level estrogen are associated with an increased risk of mortality and heart failure. Is that estrogen that's causing that problem." No, it's not. That's an observation. To prove causation you've got to intervene.
So far in interventional studies we don't see that. Participants with metabolic syndrome have high free and total estradiol, "which proves that estrogen causes that problem." No, that's an observation. It doesn't prove causation, but everyone will extrapolate the association proving causation. You can't do that. Mean body mass index is associated with high estrogen levels in men. "Maybe that estradiol that's causing that increase in heart disease." No, it's the increase in BMI and you always see this in men that how increased visceral fat, not in normal weight men. Obesity amongst aging men is associated with insulin resistance and hyperinsulinemia, as well as an increase in estrogen, but we've extrapolated and said that estrogen that's harmful, that's causing the belly fat. No, it's not.
It's the belly fat that's increasing the risk of high estrogen. It's just the opposite. Higher levels of estradiol are associated with lower risk of cardiovascular events in normal men. Oops. Now we're starting to see the opposite. Again that's an association. How do you prove causation? You have to intervene. Studies suggest that circulating sex hormones including estrogen have a beneficial effect on cardiovascular disease in men. All right. Now we see the opposite effect, but again it's an association. You got to prove it by administering estrogen. Okay, well let's look at this. In men that take LHRH agonists we wipe out the testosterone, we wipe out their estrogen, and when we do, we increase cardiovascular risk.
In every study so far, when we give LHRH agonists, there's an increased risk of death in these men. Thank god they didn't die from the prostate cancer, but they did die. We killed them. How do you then reverse that? In this study here they gave transnormal to improve the cardiovascular outcomes that are associated with poor outcomes with androgen deprivation therapy. Now we're intervening. Any study out there, where we give estrogen to men, that's harmful? No. "Yeah, but these studies ..." That's an association. These are interventional trials to prove whether there is harm or not. There's not. In this study transnormal estrogen was given and lowers the cholesterol. It raises the HDL and has a positive effect on all lipoproteins. It lowers the bad ones and raises the good ones, and it decreases mortality rates.
Estrogen administration to men has a positive effect on all lipo-parameters and decreases mortality rates in those that did not get estrogen. That's an interventional trial. Are there any interventional trials when we raise estrogen in men that's harmful? No. Are there any interventional trials where we raise estrogen in men are beneficial? Yes, every one. Then why do you lower estrogen? Because gynecomastia. Yeah, but what about the increase in heart disease? It's widely accepted that in women estrogen provide protection against the development of cardiovascular disease and we see the same thing now in men. It's the aromatization into estrogen that's protect them. That is protective.
Estrogen supplementation, this is an interventional trial, was done with estradiol. Blood pressure has decreased. HDL increased. There's a positive effect in all lipo-parameters. Their well-being improved. The side effects from the LHRH agonists were eliminated. This study demonstrates that the suppression of endogenous estrogen with aromatase inhibitor anastrozole results in impairment of flow-mediated dilatation of the blood vessels in men. Is there any study? Okay, we've done interventional. We've given estrogen. There was protective effects. It doesn't cause harm. Was there any studies showing that lowering estrogen in men is harmful? Yes. Was there any study showing that raising estrogen in men is beneficial? Yes.
Any study showing that lowering estrogen in men is beneficial? No. Then why do you lower it? We administer aromatase inhibitor Testlac to prevent the normal conversion of testosterone into estradiol, and then we studied to see what happened. In men that received the aromatase inhibitor, estradiol levels were profoundly suppressed, and as a result the HDL was suppressed. LDL went up. All of the lipoproteins has a negative effect. The bad apolipoprotein B increased. The good apolipoprotein A decreased. There's an adverse effect in all lipo-parameters when we block estrogen in men with aromatase inhibitor. Then why do you do it?
I gave this lecture a couple of years ago and there was a member of the audience that stood up and said, "We only want to lower it a little bit." Okay. We only want to lower HDL a little bit. We only want to raise LDL a little bit. We only want to adverse the effect lipoproteins a little bit. That makes no sense. It's physiologic levels of estradiol men that are important to maintain plasma levels of HDL. When you block it and lower it there's a harmful effect in all lipo-parameters. Then why do you do it? We only want to do it a little bit. The estrogen that's only produced in men has a cardio-protective effect. Different studies. In men with aromatase deficiencies, you see low levels of HDL. How do you get that up? You give them estrogen.
There're also adverse effects on libido and sexual function. How do you improve that? You give them estrogen. Estrogen acts along with testosterone to help maintain insulin sensitivity and when you block estrogen you increase insulin resistance. Why would you then do that? Elevated levels of estradiol reduce the risk of cardiovascular disease in men over 50 years of age. Why do you then block it? "We only want to block it a little bit." You only want to increase the risk of heart disease a little bit? In healthy men subjected to estrogen suppression what we saw is an adverse effect in cardiovascular disease in all lipo-parameters. In this study here they gave men aromatase inhibitors to increase testosterone levels.
What they found was the low levels appeared to decrease bone mineral density. You want to inhibit bone formation? Block estrogen. "We only want to block it a little bit." You only want to inhibit bones a little bit? In this study here they gave aromatase inhibitors to men and they looked at verbal memory and cognition. When you block the estrogen you significantly had an adverse effect on memory and cognition. In those that were not block, that the estrogen level was kept high, had improvement. Memory and verbal improvement depends on the level of estradiol. "We only want to block it a little bit." You only want to decrease memory and cognition a little bit?
This is a great article from JCEM. Despite the numerous publications from our group and others regarding the role of estrogen in bone metabolism in men, none of my colleagues inquire or seem to care one way or another about the estradiol levels. It's only the testosterone levels that they're concerned about, and estrogen is irrelevant. In this study here, bone mineral density decreased in those treated with anastrozole. There's a 50% increase in testosterone levels with anastrozole, but there's also a 20% reduction in estradiol and a significant adverse effect in bone. All recent studies show that same thing. When you block estrogen you have a harmful effect and fractures in bones. Relatively small reductions in estradiol appear to have a significant effect on bone mineral density and bone loss.
"We only want to block it a little bit." You only want to decrease bones significantly? Why would you do that. High estradiol levels are associated with maximum skeletal benefits. There's also evidence for estrogen in regulating body composition. In men, when you blocked estrogen, there was an increase in body fat. These findings indicate that aromatization of testosterone and estrogen is critical not only for bone preservation, but also for body composition and body fat. I hear everyone else going around, "You got to block estrogen because you want to get rid of the belly fat." No, that's just opposite. When you block estrogen, you increase belly fat. "We want to block the estrogen because it causes heart disease." No, it doesn't.
In summary, whereas the concept of using aromatase blocker to enhance endogenous testosterone production was an attractive one, what we see is that there's an adverse effect on bone and an adverse effect on body composition by increasing visceral fat. These findings suggest that as males, we should perhaps be just as interested in our estradiol levels as we are in our testosterone levels. "We only want to block it a little bit." We only want to cause a little bit of harm. Patients that get LHRH agonists wipe out testosterone and estrogen. It causes an increased risk of dying. In all of these studies, when you give estrogen to men, it reverses that.
"I thought estrogen causes prostate cancer." No, it doesn't. It's been an armamentarium for treatment of prostate cancer for over 50 years. I used it as a resident way back when. I have several dozen men that I actively treat with estrogen that have prostate cancer spread beyond their capsule, and I have these men up to 50 years have been treated with estrogen without any progression of their disease. With LHRH agonists you get testosterone and independent tumors. Despite of the fact that you wipe out the testosterone, the tumor continues to grow and then they die. When you use estrogen it has a positive effect on cancers. It has a significant anti-angiogenic and a pro-apoptotic effect on prostate cancer cells.
It's a great treatment for prostate cancer, but I see everyone out there blocking estrogen because estrogen causes prostate cancer. No, it does. It's been a treatment for it for years, and if you say that you completely do not understand the medical literature. Estrogen have an added anti-cancer effect not otherwise seen with conventional LHRH agonists because of its androgen suppressive effect, but because of the pro-apoptotic and anti-angiogenic effect. In this study they gave 1 milligram of estradiol. When they gave LHRH agonists they lost bone. When they gave estrogen that bone loss, the [NTX 00:41:35] reversed. Moods improved, they were healthy, they got cardiovascular protection and they no longer had bone loss, and they no longer had the side effects of loss of estrogen.
Transdermal estradiol therapy effectively causes a tumor response. Transdermal estrogen improves androgen deprivation symptoms and improves quality of life scores, and improves bone density, and it protects against heart attacks and heart disease. It costs a tenth of the agonists, but I see everyone out there blocking estrogen because you fear it because someone said. Show me the evidence that it's harmful. "Someone said." No, I want evidence. I want to a study showing that raising it is harmful and causes cancer, and every study shows that it protects against cancer. The opposite. The risk of prostate cancer was 30% lower for a doubling of the concentration of estradiol. When you want to increase your risk of prostate cancer, lower your estrogen.
If you want to protect against that cancer, then raise your estrogen up as per study. High levels of testosterone and high levels of estrogen are associated with a reduced risk of prostate cancer and the aggressiveness of a cancer. Then why do you want to block? "We only want to block it a little bit." You only want to increase prostate cancer risk a little bit? Men with low levels of estrogen, estradiol are at risk for fractures in every study to date, and an increase in morbidity and mortality. Elderly men with low estradiol levels have an increased risk of mortality. Lowest levels of estrogen show the highest risk of mortality. Why would you block it? "We only want to block it a little bit." You only want to increase mortality a little bit? Yeah.
Then why do you block it? "Because someone said." Where's the evidence, where's the literature to support that someone says it's correct, when all the literature is just the opposite? This is a great study, if you haven't seen this study. This is something the New England Journal of Medicine 2014, last year. The article was on blocking estrogen in men. Androgen deficiency accounts for a decrease in lean muscle mass. Of course. But estrogen deficiency also has an adverse effect by an increase in body fat and a decrease in sexual function when you block it. Why would you block it? "We only want to block it a little bit." When testosterone levels falls so does estradiol levels. The potential role of concomitant decline in estrogen is typically ignored and estrogen deficiency is a responsible for the pathogenesis and consequence of male hypogonadism, but we fail to understand that and appreciate it.
Why did they publish a study in the New England Journal of Medicine? The effects of testosterone on aromatase inhibition on body composition were as follows. When you blocked estrogen in this group, there was significant increase in subcutaneous and visceral fat. Why would you do that? "We only want to block it a little bit." You only want to increase subcutaneous fat and visceral fat a little bit? Yeah. That makes no sense. Inhibition of estrogen synthesis also results in guess what? Significant decrease in sexual desire and erectile dysfunction. Why would you do that? "We only want to increase erectile dysfunction a little bit and we only want to decrease libido a little bit." That's why we block estrogen. Why would you do that?
"We only want to do it a little bit." Wow. Changes in body fat were associated with estradiol levels. The lower the level, the greater the body fat. Because increase in visceral fat reduces insulin sensitivity and is associated with diabetes, the metabolic syndrome, and mark an increase in intra-abdominal fat from aromatase inhibition, [pertains 00:45:40] an increase in cardiovascular risk and diabetes. Why would you do that? "We only want to do it a little bit." Our finding that estrogen has a fundamental role in the regulation of body fat and sexual function, coupled with the evidence from prior studies, show the same thing. A crucial role of estrogen in bone metabolism, a crucial role in body fat, increase in the risk of heart disease.
This suggests that measuring estradiol levels may be helpful in assessing the risk of sexual dysfunction and bone loss in men. Don't block it. My time is up. This next session you can look at in this slide presentation and it reviews polycythemia. We all know that testosterone causes polycythemia and it's harmful. No, it doesn't. It causes eritrocytosis. I recently presented this to my hematology group and they all sort of sat puzzled. They said, "High red blood cells cause an increased risk of clotting." Well, in this study, there's 200 million people that live in altitude that have eritrocytosis and some people with hemoglobin levels greater than 21.
Excessive eritrocytosis is what's it's called. Do [we lobotomize 00:46:53] those people. Do we tell all those people that live in altitude to rush to the beach, and live at the beach because they're going to get heart attacks and strokes? Because they have eritrocytosis? What we've done is we've extrapolated the harm of poly which is a blood cell dyscrasia that's easily diagnosed with a JAP2 gene test, to be harmful and it causes eritrocytosis. Polycythemia [varies 00:47:18] increased red cells, white cells and platelets, and platelet accounts is what's causing the clotting, not the high red blood cells. Nowhere in the world do we see in a increase risk of clotting in people that have eritrocytosis that live in altitude or that have COPD.
Yet I hear commentators lecture and say, "You got to lobotomize them every 3 months because you got to get that red blood cell down, because that causes clotting and clumping." No, it does not. I saw a patient recently from Cenegenics who's a physician, Cenegenics physician who had extreme fatigue. His iron level was 5 and his ferritin level was 5 ,and he couldn't figure out why he felt so bad. IV Venofer completely reversed that. He felt great within a week, but yet we're still taught you got to get that red blood cell count down. When I confronted one of my hematologist with this she said, "Giving testosterone is different than having high altitude eritrocytosis. It's completely different."
If you look at the studies that I showed here, the mechanism for eritrocytosis in people that live in altitude is? The testosterone levels go up significantly and that's what's causing the eritrocytosis, not an increased erythropoietin. Having said that, I hope that was fun. Doctor Morgentaler is going to speak after this. I will go outside and answer any questions that you may have. Contact me if you wish in order to get the slide presentation. This is the numbers that you want to copy down. You can email me and my email address is [email protected]. If you're interested in the hormone courses that we teach, you can go to nealrouzier.com and look up the different courses. There's 4 different parts that we teach similar to the presentation that I've given today. I hope it was fun. Enjoy your stay. I'll answer any questions outside if you wish. Have a good day. Thank you.

 

[Gene Devine]

If a man on TRT complains to their Practitioner of having symptoms of elevated estrogen levels...and we know what they are...and the Practitioner confirms this with the correct blood work laboratory analysis and then proceeds to prescribe a low dose AI to bring the serum levels back down to optimal levels the man will usually respond and as a result feel much better and be healthier at the same time.

This happens every day for TRT Physicians' who are trained in such medical management.

You can post all you want about what you want but it's the clinician's on the front line who see the realities of the such and know how to manage E2 correctly for those men with elevated levels and who are symptomatic.

Who wants to live on TRT and feel like shit if their E2 is elevated and not do something about it???

 

[Nelson Vergel]

Gene

I can tell you have not read the paper that I posted a while ago. Please take the time to read it. Have you ever considered that what you have been told about estradiol is wrong?

[h=2]Estrogen in Men: Best Review Paper[/b]Best review paper on the role of estrogen (estradiol in particular) in men and the use of anastrozole.
Attached Images estradiol in men review paper.pdf (403.8 KB, 17

 

[Palermitano]

I personally know TRT Physician's who attend this exact lecture and they walked away thinking he was "out of his mind" on his position on elevated E2 levels in men.

There are just to many studies out there that present that elevated E2 levels in men can cause pathologies even when no symptoms are present.

Elevated E2 can be very insidious in men if not kept in check.

This has been a concern of mine. Ive been on TRT for several years and have been walking around with sensitive E2 levels at 60+, yet no symptoms what so ever, I feel great. I felt relieved when I heard Dr Rouzier's lecture.