Should We Be Managing Estradiol and Hematocrit in Men on Testosterone Replacement?

[J. Keith Nichols MD]

Let's try to clear up some confusion here. No need to debate what the E2 level in a young male going through puberty would be but yes it can run >70. This is not the point. The point is that a level of 70 is not harmful to men. The harm to men is with blocking estrogen. After 50 years of administering IM T to men which significantly raises E2 levels , there is not a study which showed the harm of raising E2. Also, what study has showed benefit to lowering E2 levels? None. The harm is when E2 is blocked. NEJM 2013 Sep 12:369(11): 1011-1022 "Gonadal steroids and body composition, strength, and sexual function in men". There are 2 ways to lower estrogen

1. Aromatase inhibitors

2. Androgen deprivation therapy (ADT)

I could fill several pages on the negative effects of ADT which totally wipes out both T and E2 (google it). It is used in the treatment of prostate cancer. These men then develop osteoporosis, sexual dysfunction, obesity, insulin resistance, diabetes, metabolic syndrome, cognitive dysfunction, dyslipidemia, and a significantly increased risk of cardiovascular mortality. If they don't die of prostate cancer we kill them in another way and believe me these men want to die because their quality of life is zero. When these men are treated with E2 it dramatically improves their quality of life. They don't become osteoporotic, their lipid profiles remain good, the have improved cognition, and they maintain the cardioprotective effects of estradiol. Also, E2 is apoptotic and anti angiogenic to prostate cancer cells. E2 has just as many important functions in men as it does women...we just don't need as much.

Next issue, method of delivery. I have no problems with the differing methods of delivery. I have used pellets, injections, gels, and compounded creams in myself and my patients. There are some studies that show no effect and some that show a negative effect on HDLS with injections: Clinical journal of sports medicine 1996 jul; Vol 6 "Changes in lipoprotein-lipid levels in normal men following administration of increasing doses of testosterone cypionate".

I am not anti injections but just like with so many other treatments there is sometimes a better way. I treat numerous men each week who are on injections. They are all skeptical at first but most are referred in from their male friends. Once they make a switch to our method of delivery I have not had a single patient go back to injections. Let be say again I am not anti injectable T. I will give it if they want. I use a 200mg/gm compounded cream in a HRT base (or lipoderm) and it is applied BID to the testicles (yes I said testicles as there is 4-5x greater absorption). I treat symptoms and adjust dose until symptom improvement. I aim for optimal...not normal. Normal is basically the average for a population of sick people that a pathologist at a lab randomly assigns. Do you think with these lab values they go out and test only the most healthy in shape people? All of my male patients have a free T from 30-50 some even higher depending on their optimal. This usually correlates with a total of 1500-2000 .I use LabCorp but not too long ago they changed their reagent where you could not get a accurate free T level. We specifically order a T free/total equilibrium ultra filtration test so I get a actual number. Labcorp's normal range" is basically 5-21. Everyone gets caught up in a number and I am treating patients and optimizing their T levels. Not one single patient has had to take a AI. Their levels are consistent day to day and the only way that could be reproduced with injections is with daily low dose injections. So get T the way you can, but also be open to alternative methods. Find a MD that is not caught up in a number on a piece of paper but instead is focused on your symptoms and optimizing your levels to what works best for you. I'll ask anyone on this board would you rather be normal or optimal?

There is another subject that I will address in the near future and that is the issue of polycythemia. T DOES NOT cause polycythemia. It causes a physiologic erythrocytosis just like what occurs at high altitude. That is why our Olympic training center is at high altitude...to take advantage of the erythrocytosis. Polycythemia Vera is a blood disorder where there is a increase in all blood components...most importantly is the increase in platelets which clot. TRT does not cause a increase in platelets. There is absolutely no need to donate blood due to your erythrocytosis. It is not PV. Measure anyone's blood that lives at high altitude and they will have a high H/H. Patients with COPD have high H/H and we are not bleeding them. This is just another one of the falsehoods that gets propagated like blocking estradiol.

 

[Nelson Vergel]

I am glad you joined us, Dr. Nichols. I agree with your comments on estradiol. You have probably seen my videos and articles in which I say that most men should not be taking an AI on TRT. It is a myth that has been hard to stop even after 5 years of my trying to educate men!

Here are my thoughts on estradiol management:

Role of Estradiol in Men and Its Management


I have coached men using creams as you described and they are doing great. Some are using a 20% T cream twice per day on their scrotum for better DHT and libido and attaining total T over 700 ng/dL.

We can start a new thread to discuss your comment on erythrocytosis. I am in complete disagreement with you on that one. We started a thread here a few months ago:

Dr Crisler Now Says No Blood Donation is Needed When Hematocrit is High

By the way, guys, here is some info on Dr Nichols (maybe he can expand a little for us to get to know more details about his work)

http://www.t1institute.com/physicians-Nichols.php

 

[J. Keith Nichols MD]

Thanks so much. The only reason I joined your website is that you are one of the few that seems to get the big picture. We all should continue to learn and grow and be willing wo change our way of thinking if the medical evidence supports a change in what we have been previously taught. Once we learn something one way it is just human nature to resist any change . It's the world is flat mentality. I am glad you understand the importance of estradiol in men (and women) and that is why I am here. Your last video with the urologist was unfortunately not good in promoting maintaining estradiol levels in men. Not from you but from the urologist. He mistakenly extrapolated the adverse effects with Premarin and provera to estradiol. No RCT to date has shown harm with E2. The problem is that physicians and others use the word estrogen loosely without ever distinguishing between "which" estrogen. They are not the same but they get used interchangeably which is wrong. Premarin is Conjugated equine estrogen (only 15% estradiol) and estradiol is 100%17beta estradiol. The same issue occurs with polycythemia Vera and erythrocytosis. They are not the same but erythrocytosis gets propagated as being the same as PV. I will put the evidence together to support what I am saying and post it on the forum. Google the H/H of a Sherpa. Are they being told to donate blood or dying of blood clots while climbing Mt. Everest? Look at the Tour de France athletes that abused T and epogen. Not one died of a heart attack, stroke, or DVT. The reason is that increasing ones H/H is not polycythemia Vera.

 

[user_joe]

I'm not going to pretend I can debate any of this, but I find it interesting.

What is half life of the compounded cream you use Dr. Nichols?

the reason I ask is you mentioned TT levels of 1500-2000 and also needing to inject daily to get steady levels like with a cream. I did just that at 250mg/wk test cyp split into 7 daily injections. I ended up with a TT of 1700, but e2 was most certainly a problem. I had every symptom just about, and only an AI made me feel better.

Im wondering if the longer half life of the ester allows more of it to convert to e2 to be a problem, and you have avoided that with the cream.

 

[sportsfan8724]

Very informative information Dr. Nichols. Glad to have you here! Are you saying running the normal free and total testosterone by labcorp isn't accurate enough for free t or isn't that a huge thing to worry about as long as the free testosterone levels are keep elevated?

 

[J. Keith Nichols MD]

Yes we seen the spike with the injectable form of T causing more of a problem with E2. The half life is approximately 12 hours with the compounded cream. As I have stated, I use the cream (experimented with all methods of delivery) and all my patients the same without any issues with E2. Have not had a single issue to date with mastalgia or other symptoms of E2 excess, but if that did occur I would prescribe a AI for a few weeks until symptoms resolve and then discontinue.

 

[J. Keith Nichols MD]

The first thing to look for is symptom improvement after starting TRT. The problem recently with labCorp is that they changed the reagent so now when you order a free T you will get a response of "too high to measure". The same thing just happened with the testing of a women's progesterone. I find that my patients are most optimal at a free T level of 30-50 and some even higher (it's just a number and I am treating symptoms ). With the current test it won't give you those numbers so we have to order a equilibrium ultra filtration test which is a more specialized test and will give me the actual free T level no matter what the value. Believe me, we have no complaints when a free T is maintained at a optimal level 24/7. So in summary, the total T is insignificant really. It is the free T you are looking to optimize. If your free T Is in a optimal range don't worry about total. The most simple test that I tell my patients is if they are having consistent morning erections. If you are then you are optimal. This will also start another thread but don't look to lower your SHBG. The higher the better. I can send you all the studies. You don't want to lower SHBG to raise T, you just increase the T dosage. When you increase your T you also increase your E2 which also increases SHBG and all three are beneficial. Just follow your free T and get that 30-50 and I assure you you will not worry about your E2 or SHBG

 

[Dr Justin Saya MD]

Welcome Dr Nichols. Always happy to have a colleague join the community and I hope you find that all views are welcome with cordial and educational discussion.

Where do you see your patient's DHT levels running? I frequently use low dose transdermal directly to the scrotum specifically for patients needing a boost in DHT. However, just yesterday had a patient come in for their first consult with me...was applying 100mg BID directly to scrotum and DHT level was 460ng/dL (for the community - reference is 30-85ng/dL...though we all know the flaws of "reference" range, but it provides some context). He indeed had total T >1500, free T 41, estradiol (LC/MS-MS) 50 and was not doing very well subjectively. I adjusted him to a lower dose of T cyp on a BIW basis and incorporated HCG into his regimen. I suspect, based on past similar cases, he will improve. Curious if you are prescribing HCG with your patient base?

 

[Vince]

Dr Nichols, Welcome to Excelmale. I'm excited to read all of your posting and future ones.

 

[J. Keith Nichols MD]

Dr Saya,
i replied to your post but I don't see that my responses have been posted. Could you please confirm you got them? If not, I will repost.
Thanks
Keith

 

[Will Brink]

Thanks so much. The only reason I joined your website is that you are one of the few that seems to get the big picture. We all should continue to learn and grow and be willing wo change our way of thinking if the medical evidence supports a change in what we have been previously taught. Once we learn something one way it is just human nature to resist any change . It's the world is flat mentality. I am glad you understand the importance of estradiol in men (and women) and that is why I am here. Your last video with the urologist was unfortunately not good in promoting maintaining estradiol levels in men. Not from you but from the urologist. He mistakenly extrapolated the adverse effects with Premarin and provera to estradiol. No RCT to date has shown harm with E2. The problem is that physicians and others use the word estrogen loosely without ever distinguishing between "which" estrogen. They are not the same but they get used interchangeably which is wrong. Premarin is Conjugated equine estrogen (only 15% estradiol) and estradiol is 100%17beta estradiol. The same issue occurs with polycythemia Vera and erythrocytosis. They are not the same but erythrocytosis gets propagated as being the same as PV. I will put the evidence together to support what I am saying and post it on the forum. Google the H/H of a Sherpa. Are they being told to donate blood or dying of blood clots while climbing Mt. Everest? Look at the Tour de France athletes that abused T and epogen. Not one died of a heart attack, stroke, or DVT. The reason is that increasing ones H/H is not polycythemia Vera.

Actually, there's been a fair number of who have. Just recently:

"Belgian cyclist Daan Myngheer died on Monday night after the 22-year-old suffered a heart attack during the opening stage of the Critérium International in Corsica on Saturday." (1)

Belgian Frederiek Nolf, 21, died in February 2009 in his hotel while competing in the Tour of Qatar, while France’s Fabrice Salanson, 23, suffered a heart attack and died in his sleep in 2003 during the Tour of Germany.

It's not common granted, and that's not proof per se of EPO use being the cause, but it should be noted it happens. I have not read what the tox reports were on them, etc. They also use amphetamines and other drugs. Additional:

https://www.outsideonline.com/1822676/spinning-their-graves



(1) http://www.telegraph.co.uk/cycling/...-myngheer-dies-from-heart-attack-suffered-at/

 

[CoastWatcher]

Dr Saya,
i replied to your post but I don't see that my responses have been posted. Could you please confirm you got them? If not, I will repost.
Thanks
Keith

Dr. Nichols,

As a moderator, I checked and don't know what happened to the comments you posted in response to Dr. Saya. I apologize for the glitch.

 

[J. Keith Nichols MD]

I have to say that in over 50 years of T use and studies it has not been show to cause heart attacks, strokes, or DVTs (excluding some of the recent extrnely flawed studies that have retracted). So if 50 years of studies without incident are correct, then you can be assured there are other causes for their premature deaths. When we speak of medical TRT, it can't be compared to TRT abuse as seen with athletes looking for performance enhancement only. You are most likely correct that their are other substances not mentioned that played a role. Right now it is a association that has not been proven to be causative. I think that you bring up a very interesting point though. The problem with distinguishing the difference between medical TRT and steroid abuse. Most of the recommendations that still get propagated falsely are from the steroid abuse community such as blocking estrogen. Of course we don't utilize epogen as part of TRT, but I will in the very near future show you the difference Between TRT >H/H and polycythemia Vera and the flaws in the studies that caused this false belief that they are the same.

 

[Will Brink]

I have to say that in over 50 years of T use and studies it has not been show to cause heart attacks, strokes, or DVTs (excluding some of the recent extrnely flawed studies that have retracted). So if 50 years of studies without incident are correct, then you can be assured there are other causes for their premature deaths. When we speak of medical TRT, it can't be compared to TRT abuse as seen with athletes looking for performance enhancement only. You are most likely correct that their are other substances not mentioned that played a role. Right now it is a association that has not been proven to be causative. I think that you bring up a very interesting point though. The problem with distinguishing the difference between medical TRT and steroid abuse. Most of the recommendations that still get propagated falsely are from the steroid abuse community such as blocking estrogen. Of course we don't utilize epogen as part of TRT, but I will in the very near future show you the difference Between TRT >H/H and polycythemia Vera and the flaws in the studies that caused this false belief that they are the same.

I don't disagree with what you're saying, but I am saying the statement regarding the high level cyclists is not factually true. What seems to kill them is unclear, but they are otherwise very healthy young men so be it the EPO, T, etc, I can't say.

The Sherpas are really a different animal altogether and have had millennium to adapt to that environment.

My point being, neither perhaps a good example per se of your main point RE between TRT >H/H and polycythemia Vera

 

[J. Keith Nichols MD]

Polycythemia Vera is a blood disorder with a increase in all components. Most importantly platelets. Erythrocytosis is a increase in H/H not platelets. Platelets clot not H/H. I have to repeat. In over 50 years of TRT there has been no increase in heart attacks, strokes, orDVTs. We can't ignore these decades of studies. Recent flawed studies (we can discuss) dont undo 50 years of research with TRT being safe. The reason you believe H/H causes issues is because of the false interchangeable wording. In these studies where there was a increase in cardiac events with high H/H they actually had polycythemia Vera but use the words erythrocytosis and polycythemia Vera as if they are the same which does nothing but confuse us. instead of disecting the words and missing the bigger point such as with the sherpas (although if we are making it point that high H/H causes heart attacks, strokes, or DVT then adaptation has nothing to do with it. A sherpas H/H is elevated and if that caused heart attacks then that would be occurring "thick blood is thick blood" right?) the mechanism that causes a increase in H/H at altitude is the same as with TRT. I guess I could just have easily said measure all the people living in Denver and compare their H/H to the people living in Panama City Florida. Also, look at patients with COPD. They have significantly elevated H/H and we don't bleed them. Why, because it is a physiologic erythrocytosis not polycythemia Vera. I will say over and over again the confusion lies in physicians using these words interchangeably

 

[Sean Mosher]

This was an awesome exchange of good information!

 

[Tom Larabee]

Dr Saya,
i replied to your post but I don't see that my responses have been posted. Could you please confirm you got them? If not, I will repost.
Thanks
Keith

Dr. Nichols - If possible can you reply to Dr. Saya's post again as we would all be interested regarding the DHT levels of your patients using the cream you are using on the testicles. Also if you are using HCG in your protocol's

 

[J. Keith Nichols MD]

Welcome Dr Nichols. Always happy to have a colleague join the community and I hope you find that all views are welcome with cordial and educational discussion.

Where do you see your patient's DHT levels running? I frequently use low dose transdermal directly to the scrotum specifically for patients needing a boost in DHT. However, just yesterday had a patient come in for their first consult with me...was applying 100mg BID directly to scrotum and DHT level was 460ng/dL (for the community - reference is 30-85ng/dL...though we all know the flaws of "reference" range, but it provides some context). He indeed had total T >1500, free T 41, estradiol (LC/MS-MS) 50 and was not doing very well subjectively. I adjusted him to a lower dose of T cyp on a BIW basis and incorporated HCG into his regimen. I suspect, based on past similar cases, he will improve. Curious if you are prescribing HCG with your patient base?

Dr Saya,
Thanks so much for the welcome. It's my pleasure to be able to interact with you gentlemen. Your question opens up a excellent opportunity for me to hopefully give you a good answer but also to discuss related issues.
Firstly, I would have to ask about your patient a little more with regard to what symptoms he was experiencing when he is "not doing very well subjectively". The reason I would ask is to gain a little further insight into the possibility that some of his symptoms may not be completely T related. I bring this up because in addition to optimizing testosterone I am optimizing DHEA, Vit D3, and especially free T3. We will just assume he is already eating appropriately, exercising, utilizing appropriate supplements etc... I can't stress the importance of optimizing free T3. I do everything I can to decrease their fatigue, improve energy and sexual function, and most importantly for their long term health decrease their visceral body fat. The best way I have found to decrease visceral body fat is T, not blocking E2, DHEA, and optimizing free T3 ( I usually aim for a range of 4-7 or until symptoms improve) and of course exercise. I follow their lipid profiles (small particles as well) and their insulin resistance. Nothing is better than seeing them removed from their statins, anti hypertensives, and metformin etc... I feel that the success I have with TRT is not just the T....but the thyroid as well. So I don't know if all of these other issues were addressed with your new patient by his previous provider
Secondly, something that doesn't get mentioned very much but is extremely important is the timing of lab testing. I measure all my men patients 5 hours after application and dosages are adjusted accordingly. Measuring labs and making adjustments obtained with varying times after application is a recipe for disaster . This is also a consideration with new patients that are already on HRT by another provider.
Lastly, your patient and his labs. Let's assume (which is bad I know) that his DHEA and free T3 are exactly where we would want them (doubtful his thyroid is optimal though). I would have increased his T dosage to 150 mg bid ( 200mg/gm concentration in a HRT or lidoderm base) so 3/4 gm applied to clean, dry, shaven area of testicles bid. I would then remeasure and follow up in 4 weeks 5 hours after application. I think what may have been concerning to you is that with a T level of 1500 and a free T level of 41 you assume that with those levels he should be doing great and therefore felt the need to make a change. I run into those numbers weekly and the patient does better by just simply increasing the dosage and optimizing the other hormones. Most MDs get scared by an number but in my practice and my personal experience most just start to begin to feel better at 1500. You just can't measure a persons receptor sensitivity so T in the 1800-2000 range don't bother me nor does a free T at 50. The patients feel great without any issues of E2 excess. I did not feel good when I had the numbers of your patient and I personally am optimal with a T level of almost 2000 and free T of 50. I am treating symptoms in my patients and hit home the concept of optimal. I ask them all the time "Do you want to be normal or optimal?". I do not regularly check DHT levels and I have not had to add Hcg to my patients treatment, but if they needed it I would certainly do it. I just haven't had that patient yet. When you aggressively optimize freeT and freeT3 and don't block E2 they do very well

 

[Vince Carter]

Ive been pondering my entire youth spent out West in Nevada and Arizona that my HGB/HCT numbers being what they are are physiologically my normal given that I grew up at Elevation, at least thru 13 years old. When I was 18, I did spend 8 weeks in Denver Colorado for follow-on training with the Air Force and I do not recall that I had the altitude adjustment that so many others had (thinner air).

 

[user_joe]

Dr. Nichols - If possible can you reply to Dr. Saya's post again as we would all be interested regarding the DHT levels of your patients using the cream you are using on the testicles. Also if you are using HCG in your protocol's

I agree. This is one of the most interesting threads in a long time. It's a very different approach from pretty much what every other Dr I have read up on recommends.

I wonder why literally 95% of the time I read about someone's experience with a gel or cream, compounded or not, they do not routinely see TT levels like mentioned. Maybe at first, but then efficiency goes down. They switch to injections. Rarely if ever have I read of someone with e2 issues on topical, and DHT is usually on the high end. My Dr was recommending a compounded topical from Empower to start, but I stayed away due to those reasons.

Just a couple more topics pics thrown into the much. Appreciate the info.