Can Testosterone Induce Blood Clots and Thrombosis? Interview with Dr Charles Glueck

In my work collecting information for ExcelMale.com, I review abstracts daily on latest studies related to testosterone, men's health, nutrition, and more. I am always looking for studies that stand out and are no just repetitions of what we have seen before. Contrarian data to what I assume we know is what motivates me to read. In particular, I am looking for negative data and results in studies using testosterone. I have been using this hormone since 1993 to save my life and its quality and have not had any side effects. However, I know everyone is different and some people may have genetic or other variations that may make them susceptible to at least one side effect.

Good read:

What to do if you have a blood clot

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The first time I read a paper than mentioned thrombosis risk in people on testosterone replacement (read abstract at the end of this article), my goal is to get in contact with the author. Dr Charles Glueck was kind to reply for my request for an interview to help me educate physicians and patients. He is a graduate from Harvard and Western Reserve Universities and has over 35 years of medical practice and have produced over 600 publications. He is currently the Medical Director of the Jewish Hospital Cholesterol Center. To say that he has credentials is an understatement.

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I am impressed by his willingness to help anyone who may be concerned about this issue (he provides contact information below)

Here is the short interview:

Dr Glueck, Thank you so much for agreeing to educate my readers about your research.

Can you give give us a brief background of why you were interested in looking into thrombophilia and thrombosis in people on testosterone replacement therapy? Can you explain those terms to us?

Dr Glueck: As physicians who deal with deep venous thrombosis (DVT) and pulmonary embolus (PE), as well as blood clots in the eyes (central retinal vein and central retinal artery thrombosis), and ischemic stroke, and arterial blood clots, we realized that many of our referrals had started exogenous conventional testosterone therapy before sustaining their blood clots. Because we were very experienced with the diagnosis of thrombophilia and hypofibrinolysis, we hypothesized that the exogenous testosterone was interacting with underlying coagulation disorders producing the blood clots. We have now proven this in multiple publications.

In your best estimate or opinion, what is the incidence of this problem in men on testosterone replacement?

Dr Glueck: The incidence of DVT-PE or other clots in men on T therapy is not known, but our best estimates are that about 1-2% of men taking T will develop blood clots related to underlying inherited clotting abnormalities or to acquired thrombophilia (the antiphospholipid antibody syndrome). These men who landed in the hospital with dangerous and potentially lethal blood clots in the deep veins of the legs or in the lungs developed these clots within three months of starting testosterone therapy. None of them knew previously that they had an inherited clotting disorder that put them at greater risk for developing clots, nor did their providers test them before putting them on testosterone therapy.

You suggest that "thrombophilia should be ruled out before administration of exogeneous testosterone". How can that be done and are the tests commercially available or research tools? You used these tests in your study: factor V Leiden heterozygosity, high factors VIII and XI, high homocysteine, low antithrombin III, the lupus anticoagulant, high anticardiolipin antibody lgG, and the hypofibrinolytic 4G4G mutation of the PAI-l gene. Should all be performed? Would these tests be reimbursed by insurance and, if not, what do you think the retail value would be?

Dr Glueck: The 4 tests we would do include Factor V Leiden, Prothrombin gene, Factor VIII and Factor XI, all routinely available commercially at Lab Corp and Quest (big national labs), and at almost all regional labs as well. In our experience these tests are routinely covered by insurance. If not covered, I would estimate that the cost would be expensive, $800.

You also suggest a link between high estradiol with thrombophilia. Can you explain this finding? Would anastrozole or other E2 inhibitor improve outcome if used with TRT?


Dr Glueck: We have data to show that when T is aromatized in the body to estradiol (E2), the high E2 may be the agent which directly interacts with the underlying thrombophilia to produce the clots. We do not have enough data to know whether Arimidex used to lower E2 would be protective, but we know that Arimidex alone is prothrombotic in all of the thrombophilias and hence, probably not a good idea.

In your opinion, should all men on TRT be on low dose aspirin?

Dr Glueck: Low dose aspirin would have no effect on the clotting events seen in men on T who have underlying thrombophilia and I would not recommend it.

Are you planning to do any further studies on this troubling issue?

Dr. Gluek: We are working hard to better understand this troubling issue. If any of your readers have had DVT-PE or other clots while taking exogenous T, or during hCG or clomid therapy to raise T, we would be glad to help them out with expert consultative advice free of charge. Have them contact us by email ([email protected]) or by phone (513-924-8250) fax (513-924-8273) and we will advise them on what blood samples to have drawn, and how to deal with their problem. All of their information will, of course, be entirely private and totally confidential. We will also be glad to work with their doctors in their local communities.

Thank you so much for your time and I will be contacting you in a few months to see if you have any updated data for us.


____________________________________________

ClincAppl Thromb Hemost. 2014 Jan;20(1):22-30. Epub 2013 Apr 23.


Testosterone, thrombophilia, and thrombosis.

Glueck CJ, Richardson-Royer C, Schultz R, Burger T, Labitue F, Riaz MK, Padda J, Bowe D, Goldenberg N, Wang P.


Abstract

We describe thrombosis, deep venous thrombosis (DVT) pulmonary embolism (PE; n = 9) and hip-knee osteonecrosis (n = 5) that developed after testosterone therapy (median 11 months) in 14 previously healthy patients (13 men and 1 woman; 13 Caucasian and 1 African American), with no antecedent thrombosis and previously undiagnosed thrombophilia-hypofibrinolysis. Of the 14 patients, 3 were found to be factor V Leiden heterozygotes, 3 had high factor VIII, 3 had plasminogen activator inhibitor 1 4G4G homozygosity, 2 had high factor XI, 2 had high homocysteine, 1 had low antithrombin III, 1 had the lupus anticoagulant, 1 had high anticardiolipin antibody Immunoglobulin G, and 1 had no clotting abnormalities. In 4 men with thrombophilia, DVT-PE recurred when testosterone was continued despite therapeutic international normalized ratio on warfarin. In 60 men on testosterone, 20 (33%) had high estradiol (E2 >42.6 pg/mL). When exogenous testosterone is aromatized to E2, and E2-induced thrombophilia is superimposed on thrombophilia-hypofibrinolysis, thrombosis occurs. The DVT-PE and osteonecrosis after starting testosterone are associated with previously undiagnosed thrombophilia-hypofibrinolysis. Thrombophilia should be ruled out before administration of exogenous testosterone.

Click here for part 2:

Article: Second Interview with Dr Charles Glueck About Testosterone and DVT
 
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Please describe exactly which coagulation disorders you have been diagnosed with from your lab tests. How long have you been on TRT while you were also on Eliquis? What dose of Eliquis are you taking and what is your dose of TRT? Also, I'm curious, did you ask Dr. G about the latest studies which contradict all of his previous work that we posted here?

This is literally what Dr G emailed me after he went over the lab work he requested:

"You have an acquired thrombophilia called the Lupus anticoagulant. This almost never is associated with the disease Lupus, and unless you have arthritis, joint pain, sun sensitivity, and a facial rash, would not worry about that. It is now clear that the blood clot which you had was related to the interaction of the testosterone with the lupus anticoagulant. As long as the lupus anticoagulant is present, ANY EXOGENOUS TESTOSTERONE IS CONTRAINDCATED, due to a huge increase in the risk of blood clotting. CJ Glueck MD"

I took the same blood results to my prescribing doctor and he said, in his opinion, I am going to clot whether I am on TRT or not. This was in March of this year. He started me on Eliquis and rechecked my leg about 12 weeks later. The superficial blood clots were gone.

I take 5 mg of Eliquis twice a day.

I am prescribed 200 mg of TRT but usually take 120 to 160 mg a week.

I did not challenge Dr G regarding any of the new studies my prescribing doc mentioned. I figured he was aware of them or would come across them. Also, he does all this free of charge for us so I did not want to come across as disrespectful after asking for his help.

Just to add: I started completely over with another cardiologist today just for a second opinion.
 
This is literally what Dr G emailed me after he went over the lab work he requested:

"You have an acquired thrombophilia called the Lupus anticoagulant. This almost never is associated with the disease Lupus, and unless you have arthritis, joint pain, sun sensitivity, and a facial rash, would not worry about that. It is now clear that the blood clot which you had was related to the interaction of the testosterone with the lupus anticoagulant. As long as the lupus anticoagulant is present, ANY EXOGENOUS TESTOSTERONE IS CONTRAINDCATED, due to a huge increase in the risk of blood clotting. CJ Glueck MD"

I took the same blood results to my prescribing doctor and he said, in his opinion, I am going to clot whether I am on TRT or not. This was in March of this year. He started me on Eliquis and rechecked my leg about 12 weeks later. The superficial blood clots were gone.

I take 5 mg of Eliquis twice a day.

I am prescribed 200 mg of TRT but usually take 120 to 160 mg a week.

I did not challenge Dr G regarding any of the new studies my prescribing doc mentioned. I figured he was aware of them or would come across them. Also, he does all this free of charge for us so I did not want to come across as disrespectful after asking for his help.

Just to add: I started completely over with another cardiologist today just for a second opinion.

Thanks for getting back. Good you're getting a 2nd opinion, but I would be surprised if a cardiologist will have the knowledge base you need when it comes to HRT in general, as most will just side with all the crap studies that say TRT causes strokes, heart attacks, and clots.

I agree with your prescribing doc. TRT is not necessarily the trigger and I find it nothing more than an assumption on Dr. G's part that your episode was related to an interaction between the TRT and LA. So, you're still on TRT and Eliquis? Did you ever stop the T? How long had you been on it when you had the clot and was that prior to being on Eliquis or any anticoagulant? Since that clot, have you experienced any new ones? What's your age? Had you experienced any clots prior to taking T? Any chance you knew what your RBCs. MCT, HGB and E2 were when the clot presented? Glueck says that E2 >42 is the major thrombogenic trigger. So, my question would be.....so long as you make sure and keep serum E2 levels <42 + anticoagulant prophylaxis, then would the so-called risk of clot induction from TRT be minimized? I don't think anyone can answer that with any certainty at this point.
 
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So, you're still on TRT and Eliquis? Did you ever stop the T? How long had you been on it when you had the clot and was that prior to being on Eliquis or any anticoagulant? Since that clot, have you experienced any new ones? What's your age? Had you experienced any clots prior to taking T?

I did stop the TRT when I first found out about the the clots in my leg. This was summer of last year. I had probably been on TRT around two years at that point.

Since starting Eliquis, my prescribing doc has not found any more clots in either leg. Though, that does not mean the rest of my body is clot free.

I am 40.

No clots prior to taking T (that I know of).

Here is the wrench! I was in the hospital for five days in late May. I got the clot signs and symptoms the day after I was released. Five days of sitting and laying on my ass may have played a large part.
 
I did stop the TRT when I first found out about the the clots in my leg. This was summer of last year. I had probably been on TRT around two years at that point.

Since starting Eliquis, my prescribing doc has not found any more clots in either leg. Though, that does not mean the rest of my body is clot free.

I am 40.

No clots prior to taking T (that I know of).

Here is the wrench! I was in the hospital for five days in late May. I got the clot signs and symptoms the day after I was released. Five days of sitting and laying on my ass may have played a large part.

How long have you been on Eliquis? Did you also look into the other newer class anticoagulants, Xarelto and Pradaxa?

Unless you were dx'd with a DVT or PE, there's no reason for you to have been hospitalized, as a clot in a superficial vein is not life-threatening. Maybe I'm missing something more here? Were you in the ER at first?
 
How long have you been on Eliquis? Did you also look into the other newer class anticoagulants, Xarelto and Pradaxa?

I can't remember exactly. I want to say around March of this year.

Unless you were dx'd with a DVT or PE, there's no reason for you to have been hospitalized, as a clot in a superficial vein is not life-threatening. Maybe I'm missing something more here? Were you in the ER at first?

Sorry, I was in the hospital in May of last year for diverticulitis. As of May 2014, I had no symptoms or any ideas of any blood clots. Off the top of my head, I want to say I started TRT in March of 2013 with a gel. I felt my first blood clot symptom the day I left the hospital. The clots weren't discovered officially until June 2014. I didn't take all of this info to my prescribing doctor until the beginning of this year. Not sure if that paints a better picture.
 
Does anyone know what test they used for the estradiol of 42.6. There are 3levels of sensitivity at labcorp. The test just prior to my dvt and PE was 40 on the extra-sensitive. On testosterone for 8 months.His lab sheet he sent to me was regular estradiol. I would have been way above 42 on that test. Only tested for 3clotting tests and they were negative except 1 parent on a MTHR GENE
 
According to Glueck, E2 >42 is a far more thrombogenic risk than elevated HCT/polycythemia. Once must watch for both to prevent DVT/PEs.


well recently got bloods done and this caught my eye again due to my levels:

WENT OFF TEST FOR A LENGTH OF TIME SO I COULD GET A BASELINE, AND IT MIGHT HAVE ACTUALLY BEEN LOWER SCORE HAD I BEEN ABLE TO GET TO QUEST EARLIER THAN 9 AM...

total test 268
free test 40

ESTROGEN SENSITIVE....22!!!!!

HCT 55: SCALE 38.5-50
HEMOGLOBIN 17.6 SCALE 13.2-17.1
RBC 6.1 SCALE:4.20-5.80


I HATE HOW DIFFERENT GROUPS WHO TAKE YOUR BLOOD HAVE DIFFERENT SCALES, WHERE AS MY LAST CRIT SCALE WAS 44-52 AND THIS IS COMPLETELY LIKE 6-7 POINTS LOWER FROM QUEST ..... MAKES NO DAMN SENSE TO ME HOW THERE ISNT A SET PARAMETER FOR BW....
 
does anyone know what test they used for the estradiol of 42.6. There are 3levels of sensitivity at labcorp. The test just prior to my dvt and pe was 40 on the extra-sensitive. On testosterone for 8 months.his lab sheet he sent to me was regular estradiol. I would have been way above 42 on that test. Only tested for 3clotting tests and they were negative except 1 parent on a mthr gene

my old doctor had me doing an estrodial testing of 0-160 and the new doc is estrogen sensitive lc/ms/ms

in actuality there a a ton more that can be done not just three...
 
I am not getting the rest of his testing done at this time because of fear. In the ER they told me this is often a sign of a hidden cancer. So, if I get the testing done and I am negative on everything, I will concentrate on the cancer possibility. It look like between 6 months and a year that risk rapidly decreases. Then I will finish the genetic testing.it has only been 5 Weeks for me. The risk is somewhere between 3-10%, with newer studies skewing to the lower end.

My last test was all normal except my rbcs had increased to 5.6, not polycythremia but much higher. Maybe that with high E2 is what kicked this up. I had taken my first arimidex in months within a few days of the PE.
 
I am not getting the rest of his testing done at this time because of fear. In the ER they told me this is often a sign of a hidden cancer. So, if I get the testing done and I am negative on everything, I will concentrate on the cancer possibility. It look like between 6 months and a year that risk rapidly decreases. Then I will finish the genetic testing.it has only been 5 Weeks for me. The risk is somewhere between 3-10%, with newer studies skewing to the lower end.

My last test was all normal except my rbcs had increased to 5.6, not polycythremia but much higher. Maybe that with high E2 is what kicked this up. I had taken my first arimidex in months within a few days of the PE.

ok please tell me what exactly is a hidden sign of cancer?? rbc's at 5.6??? man cmon mine are sitting at 6, WHICH IS HIGH, bro ur rbc's are still lower than the max... on my scale it was 4.20-5.80....5.6??? where are u getting these bw tests done and by what scale are they using? labcorp and quest values on said blood tests are both different... im very confused on why anyone is saying a hidden cancer towards anything ur going thru, i apologize if im out of line, but just very confused...
 
I know my RBCs are below max, it was just a large increase for me. In cases where they can not find a cause for the dvt or PE, the cause can be an unknown cancer. Cancers are thrombogenic. It may even be undetectable at the time of the clot. The vast majority of cancers show up in a year.Testing for it such as a CT test and full assessment at the time of the clot will find 2 out of 3 cancers. Remember this is at most 1 in 10 cases. That has been going down, probably due to routine cancer screening telling more people they already have cancer. In the last 15 years the rate of hidden cancer is about 4%

I am only freaking because some studies say testosterone does not cause clots. I have one more CT on Monday, everything has been negative. After that I have to not think about it. My E2 was in the 40s at the time of my clot. That was the ultrasensitive test. On Dr Gleucks form he only asks for the regular E2 test.My experience shows I probably would have been much higher on the regular E 2 test

Did you have a clot?
 
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Where did you get this info that E2 was more thrombogenic

he said doc g stated it.... but as we know some of what doc g is now saying is contradicting to what he said here... so confusion sets in amongst us all...


i wish doc g would chime in here tbh...
 
I know my RBCs are below max, it was just a large increase for me. In cases where they can not find a cause for the dvt or PE, the cause can be an unknown cancer. Cancers are thrombogenic. It may even be undetectable at the time of the clot. The vast majority of cancers show up in a year.Testing for it such as a CT test and full assessment at the time of the clot will find 2 out of 3 cancers. Remember this is at most 1 in 10 cases. That has been going down, probably due to routine cancer screening telling more people they already have cancer. In the last 15 years the rate of hidden cancer is about 4%

I am only freaking because some studies say testosterone does not cause clots. I have one more CT on Monday, everything has been negative. After that I have to not think about it. My E2 was in the 40s at the time of my clot. That was the ultrasensitive test. On Dr Gleucks form he only asks for the regular E2 test.My experience shows I probably would have been much higher on the regular E 2 test

Did you have a clot?

i thought i did 2 times, but they said nope, did a d-dimer test and ultrasounds of veins and artery down left leg 2 times, nothing... which im thankfull for...sorry man didnt mean to sound harsh or anything im just wondering if ur freakin a bit, and yes u have right to be a bit on edge, with all this stuff as of late with clots, and all this other stuff, even tho my test was low, i might say forget it and come off t all together and just focus on health and optimizing my adrenal glands, thyroid, preg and dhea..... there HAS to be a root cause for low t, it cant just be everyone everywhere at the same dang time,,, something is in the water, and foods, and its not good for us...arsenic, floruide etc...

another route one may try to go, is chelation therapy? (prononounced key lation) RESEARCH CHELATION THERAPY, EDTA FOR IRON (HEMATOCRIT, RBC'S ETC) AND phosphatidylcholine FOR CHOLESTEROL
 
I chatted via email a week ago. He said it is far more likely this is testosterone than cancer related. It does not help that I am going through testosterone withdrawal. Fatique and anxiety are constant. I feel like dead man walking half the time.

I am 46 , so if you are younger your chance of cancer is even lower. I had a chat with an oncologist. Based on one steady my max risk is 2 percent and after my CT just under 1%. That scan is Monday. The real reason I am freaking out is I have had a sore throat for 4 months and they see nothing. I can convince myself it is cancer easily. I could sweat 1-2% fairly well if I was not in constant pain with no explanation
 
I chatted via email a week ago. He said it is far more likely this is testosterone than cancer related. It does not help that I am going through testosterone withdrawal. Fatique and anxiety are constant. I feel like dead man walking half the time.

I am 46 , so if you are younger your chance of cancer is even lower. I had a chat with an oncologist. Based on one steady my max risk is 2 percent and after my CT just under 1%. That scan is Monday. The real reason I am freaking out is I have had a sore throat for 4 months and they see nothing. I can convince myself it is cancer easily. I could sweat 1-2% fairly well if I was not in constant pain with no explanation

ok a sour throat? strep perhaps? thyroid issue?? also get ur adrenal glands checked, i got a doc whom i found on another forum who is working with me right now and i did a 24 saliva test and BAM came back that on a scale of 9 being worst for adrenal failure mine was a damn 7!!!

i went cold turkey withought test from last october to april 2015, talk about feeling shitty


with ur throat, have u ever smoked or chewed tobacco? get a throat scope done man and get some answers unless thats what the doc is doing monday???

throat soreness for a month, do u have any allergies? any meds ur taking might be interacting with each other???

just shooten some suggestions out
 
ok a sour throat? strep perhaps? thyroid issue?? also get ur adrenal glands checked, i got a doc whom i found on another forum who is working with me right now and i did a 24 saliva test and BAM came back that on a scale of 9 being worst for adrenal failure mine was a damn 7!!!

i went cold turkey withought test from last october to april 2015, talk about feeling shitty


with ur throat, have u ever smoked or chewed tobacco? get a throat scope done man and get some answers unless thats what the doc is doing monday???

throat soreness for a month, do u have any allergies? any meds ur taking might be interacting with each other???

just shooten some suggestions out

Don't get me started. I have seen more Docs than I can count in 4 months. I have no thyroid. I had milder pain 3 years ago and they yanked it out thinking it was cancer. It was not. I keep going and have been scoped, They note some sores that come and go ( different areas), slightly red and irritated and one tonsil is marginally inflamed.

They even biopsied it once, but she missed the spot she wanted. I then clotted and was thrown on coumadin, so no biopsies until I am off that I have not done any tobacco, Binge drink about once a decade for a few weeks at a time. So alcohol should not be much of a factor, because I do not drink in between.

I have terrible allergies and was just started on singular 4 days ago. That may be helping with the pain, but is making me hoarse a bit. I was just told I am allergic to everything and that severe allergies can inflame a tonsil.

So, I asked about reflux and they said that and allergies are probably the cause, but they are not sure.So here I am in the ER (thinking I have pneumonia as I waited 2 days to go in) They are telling me I have a clot and that cancer can cause this and do I have cancer. Man, ignorance is bliss. I wish they had not told me. Monday is a CT, she wil;l do a biopsy if needed but I have to stop the coumadin for week.
 
I have 1 gene MTHFR C667T and a homcysteine of 9, Could that be an issue. As I posted elsewhere. My estardiol was in the 40s and I was dehydrated
 
Don't get me started. I have seen more Docs than I can count in 4 months. I have no thyroid. I had milder pain 3 years ago and they yanked it out thinking it was cancer. It was not. I keep going and have been scoped, They note some sores that come and go ( different areas), slightly red and irritated and one tonsil is marginally inflamed.

They even biopsied it once, but she missed the spot she wanted. I then clotted and was thrown on coumadin, so no biopsies until I am off that I have not done any tobacco, Binge drink about once a decade for a few weeks at a time. So alcohol should not be much of a factor, because I do not drink in between.

I have terrible allergies and was just started on singular 4 days ago. That may be helping with the pain, but is making me hoarse a bit. I was just told I am allergic to everything and that severe allergies can inflame a tonsil.

So, I asked about reflux and they said that and allergies are probably the cause, but they are not sure.So here I am in the ER (thinking I have pneumonia as I waited 2 days to go in) They are telling me I have a clot and that cancer can cause this and do I have cancer. Man, ignorance is bliss. I wish they had not told me. Monday is a CT, she wil;l do a biopsy if needed but I have to stop the coumadin for week.

wow man, yeah thru the ringer and back sounds like me and im only 37.... tbh u need to relax a bit, and get ur adrenals looked at, they can cause a lot of stuff, wow so no thyroid and enflamed tonsils...could it be perhaps ur thyroid meds? what r u on for thyroid meds? im just trying to possibly help a bit, im not a doc or anything even close there are better people on here than i in all realms of the human bodie, but im taking interest as it is interesting to me ...
 

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