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

Nelson Vergel

Founder, ExcelMale.com
Testosterone, thrombophilia, thrombosis.

Glueck CJ, et al. Blood Coagul Fibrinolysis. 2014.

Authors
Glueck CJ1, Friedman J, Hafeez A, Hassan A, Wang P.

Author information

1 Thrombosis Center

b Internal Medicine Residency Program, Jewish Hospital of Cincinnati, Cincinnati, Ohio, USA.
Citation

Blood Coagul Fibrinolysis. 2014 Oct;25(7):683-7. doi: 10.1097/MBC.0000000000000126.

Abstract

We assessed previously undiagnosed thrombophilia-hypofibrinolysis in 11 testosterone (T)-taking men, five of whom developed deep venous thrombosis (DVT), four pulmonary embolism, one spinal cord infarction, and one osteonecrosis 3.5 months (median) after starting T gel (50-160 mg/day) or T intramuscular (50-250 mg/week). In the order of referral because of thrombosis after starting T, thrombophilia-hypofibrinolysis was studied in 11 men, and, separately, in two control groups without thrombosis - 44 healthy normal male controls and 39 healthy men taking T. Nine men had DVT or DVT-pulmonary embolism after 3.5 months (median) on T, one spinal cord infarction after 5 days on T, and one had osteonecrosis (knee and then hip osteonecrosis after 6 and 18 months on T). Four of the 11 men (36%) had high factor VIII (≥150%) vs. one of 42 (2%) controls (P = 0.005), and vs. one of 25 (4%) T-controls, (P = 0.023). Of the 11 men, two (18%) had factor V Leiden heterozygosity vs. none of 44 controls, (P = 0.04) and vs. none of 39 T-controls(P = 0.045). Of the 11 men, three had 4G4G plasminogen activator inhibitor-1 homozygosity, one prothrombin G20210A heterozygosity, one low protein S, and one high factor XI. When T was continued, second DVT-pulmonary embolism recurred in three of 11 men despite adequate anticoagulation. T interacts with thrombophilia-hypofibrinolysis leading to thrombosis. Men sustaining DVT-pulmonary embolism-osteonecrosis on T should be studied for thrombophilia. Continuation of T in thrombophilic men appears to be contraindicated because of recurrent thrombosis despite adequate anticoagulation. Before starting T, to prevent T-associated thrombosis, we recommend measures of factor V Leiden, factor VIII, and the prothrombin gene.
 
Testosterone, thrombophilia, thrombosis.

Glueck CJ, et al. Blood Coagul Fibrinolysis. 2014.

Authors
Glueck CJ1, Friedman J, Hafeez A, Hassan A, Wang P.

Author information

1 Thrombosis Center

b Internal Medicine Residency Program, Jewish Hospital of Cincinnati, Cincinnati, Ohio, USA.
Citation

Blood Coagul Fibrinolysis. 2014 Oct;25(7):683-7. doi: 10.1097/MBC.0000000000000126.

Abstract

We assessed previously undiagnosed thrombophilia-hypofibrinolysis in 11 testosterone (T)-taking men, five of whom developed deep venous thrombosis (DVT), four pulmonary embolism, one spinal cord infarction, and one osteonecrosis 3.5 months (median) after starting T gel (50-160 mg/day) or T intramuscular (50-250 mg/week). In the order of referral because of thrombosis after starting T, thrombophilia-hypofibrinolysis was studied in 11 men, and, separately, in two control groups without thrombosis - 44 healthy normal male controls and 39 healthy men taking T. Nine men had DVT or DVT-pulmonary embolism after 3.5 months (median) on T, one spinal cord infarction after 5 days on T, and one had osteonecrosis (knee and then hip osteonecrosis after 6 and 18 months on T). Four of the 11 men (36%) had high factor VIII (≥150%) vs. one of 42 (2%) controls (P = 0.005), and vs. one of 25 (4%) T-controls, (P = 0.023). Of the 11 men, two (18%) had factor V Leiden heterozygosity vs. none of 44 controls, (P = 0.04) and vs. none of 39 T-controls(P = 0.045). Of the 11 men, three had 4G4G plasminogen activator inhibitor-1 homozygosity, one prothrombin G20210A heterozygosity, one low protein S, and one high factor XI. When T was continued, second DVT-pulmonary embolism recurred in three of 11 men despite adequate anticoagulation. T interacts with thrombophilia-hypofibrinolysis leading to thrombosis. Men sustaining DVT-pulmonary embolism-osteonecrosis on T should be studied for thrombophilia. Continuation of T in thrombophilic men appears to be contraindicated because of recurrent thrombosis despite adequate anticoagulation. Before starting T, to prevent T-associated thrombosis, we recommend measures of factor V Leiden, factor VIII, and the prothrombin gene.

"When T was continued, second DVT-pulmonary embolism recurred in three of 11 men despite adequate anticoagulation."

These studies keep duplicating the same theme: that there is a clear danger in using exogenous TRT in anyone who is prone to any type of thrombophilia (clotting disorder) which may or may not be known unless the patient is thoroughly tested, hopefully prior to TRT administration. Even with blood thinners, one can still be at risk. The bottom line is that an alternative agent needs to be developed that (i) induces ENDOGENOUS production of T, and (ii) has none of the side effects associated with exogenous TRT. Clomid and the as yet to be approved drug for secondary hypogonadism, Androxal (enclomiphene citrate), come to mind since they are effective T secretagogues, but they are synthetic chemicals not recognized by the body and we don't know the long-term side effects. So, we are still stuck.
 

miked123

Member
Ugh, this blows and I completely sympathize with the frustration others here are facing.

I was just about to start exogenous T, but thankfully saw this thread as I was waiting for my doc to send me my prescription. I've never had a clot, but a 1-2% risk was too much of a gamble for me, and the $400 - $500 (with insurance) for the labs was a paltry sum relative to not dying.

I had all the tests ordered by Dr. Glueck, here's what he said:

Three reasons why taking exogenous testosterone would put you at risk for deep venous thrombosis, pulmonary embolus:
1. High factor VIII, probably inherited
2. 4G4G homozygosity for the PAI-1 gene, inherited
3. MTHFR C677T and A1298C compound heterozygosity, inherited.

Some follow up questions I asked him:

1. Is there any medication (ex Xarelto) or supplements (ex Rutin) that you believe could prevent thrombotic events were I to take exogenous testosterone? Anything promising on the horizon?

2. If I do not go onto testosterone therapy, would you still recommend some kind of daily anti-coagulant, ex Xarelto or Warfarin?

3. The doctor also prescribed thyroid medication, I think it was Synthroid or Armour Thyroid. Do those types of medications also increase the risk of thrombotic events? To the same or lesser extent than testosterone?

His answers:

1. DO NOT EVER TAKE exogenous testosterone, HCG, clomid, or any other drug to increase testosterone levels along with concurrent anticoagulation. Of our first 58 published cases like yours, 8 of them continued or restarted testosterone along with coumadin, xarelto, or eliquis, and ALL 8 had second and third DVT-PE, including one near death. Anticoagulation WILL NOT PROTECT YOU if you start testosterone therapy.
2. If you do not take testosterone, I would not recommend coumadin, xarelto, or eliquis, and aspirin will not provide any real benefit.
3. Thyroid has no effect, one way or another.

Some further questions:

Given what I've inherited, is DVT-PE only a problem in the presence of exogenous test? Do you recommend any regular labs or any medication to prevent DVT-PE? Are there certain symptoms you believe are reliable early warning signs?

His answers:

You do not need to worry about inherited thrombophilia which would be a problem only in the following circumstances:
1. exogenous testosterone, clomid or HCG
2. orthopedic surgery hips, knees, feet. Were that to be done, you should be anticoagulated 12 hours after surgery with eliquis 2.5 mg twice per day for 1 month, provided that there were contraindications to osteonecrosis.
3. abdominal open surgery, would also require anticoagulation after surgery, as per #2

============

Interesting that he believes thyroid medication would have no effect.
 
Ugh, this blows and I completely sympathize with the frustration others here are facing.

I was just about to start exogenous T, but thankfully saw this thread as I was waiting for my doc to send me my prescription. I've never had a clot, but a 1-2% risk was too much of a gamble for me, and the $400 - $500 (with insurance) for the labs was a paltry sum relative to not dying.

I had all the tests ordered by Dr. Glueck, here's what he said:



Some follow up questions I asked him:

1. Is there any medication (ex Xarelto) or supplements (ex Rutin) that you believe could prevent thrombotic events were I to take exogenous testosterone? Anything promising on the horizon?

2. If I do not go onto testosterone therapy, would you still recommend some kind of daily anti-coagulant, ex Xarelto or Warfarin?

3. The doctor also prescribed thyroid medication, I think it was Synthroid or Armour Thyroid. Do those types of medications also increase the risk of thrombotic events? To the same or lesser extent than testosterone?

His answers:



Some further questions:

Given what I've inherited, is DVT-PE only a problem in the presence of exogenous test? Do you recommend any regular labs or any medication to prevent DVT-PE? Are there certain symptoms you believe are reliable early warning signs?

His answers:



============

Interesting that he believes thyroid medication would have no effect.

You didn't state your labs results or what your clotting disorder you've inherited is. Please advise.

If you look back on my posts, I have had a history of clots back in 2012 which both cleared on their own, although I was on a short-term course of warfarin. I am now on Xarelto 10mg as a prophylaxis against DVT-PE, but I was not on TRT, clomid, AAS, hCG at the time of the clots and am not on TRT now, so his statement about not worrying about inherited thrombophilia makes no sense. You STILL have to treat certain thrombophilia, depending on which one, regardless.

The only HRT I take is DHEA and desiccated thyroid. Since my own Total T averages in 500s, it isn't worth the risk for that extra 200-400 at this point to do TRT. My goal is to wait until a better agents comes on the market that do not exhibit the risk side effect profile of exogenous TRT. For those of us who are not hypogonadal but want to ENHANCE as oppose to REPLACE endogenous T to youthful physiologic levels, I don't think TRT can continue to be the best answer. What we need to come up with is TET (Testosterone Enhancement Therapy) for those with TT of at least 500 that want to improve their natural endogenous levels for that extra boost, not stomp out an already decent level, and avoid the HPTA suppression and side effects associated with frank TRT.

According to Glueck, anticoagulant prophylaxis does not prevent the possibility of a DVT-PE as he indicates in his papers which is unfortunate. It is not his belief. It is what has been demonstrated in actual studies.

Familial thrombophilia is not an easy diagnosis unless it is clear cut, i.e. elevated Factor VIII is NOT always inherited/familial. It is an acute phase reactant that can also be elevated from inflammation, stress, TOO MUCH THYROID HORMONE (i.e. hyperthyroidism) and even intense exercise (I have a ton of studies to prove it). Repeat testing over many months may be the only way to determine a more accurate diagnosis of familial FVIII. I fall into that category. I can have high FVIII for 3 labs in a row, and then, by some miracle, it is within range again. My thoughts: excess exogenous thyroid hormone (T3 or T4) sets in motion the coagulation cascade which can induce thrombosis as shown in the literature.

What he fails to mention is that there are no studies that show a male with higher circulating levels of endogenous T is prone to clots any more than that of one who has lower levels, so it's not so much the T itself as it is the mechanism by which the T is enhanced and to supra physiologic levels that then increases the risk mechanism. I have flat out asked him twice about clomid - since it works by endogenous stimulation of T via FSH/LH and he never replied. If you studied his work, the #1 trigger point in thrombogenesis is elevated E2 as I posted on upthread.

Also, MTHFR C677T homozygosity has only been shown to be a thrombotic risk factor if homocysteine level is elevated. That is controlled via ample doses of methyfolate, methylB12, NAC, TMG, choline, etc. I have a friend who is on TRT and is homozygous and has had no incidence of thrombotic events.

While Glueck's studies show a subset of prone individuals with inherited risk factors for thrombophilia to have had presented with actual events from TRT and other agent administration, Glueck almost seems to be on an anti-TRT campaign. And the worst of it, he offers no alternative for those who are truly hypogonadal and have no quality of life because they need TRT, yet also have a clotting disorder. WTF does he expect them to do? Have a lesser QOL, but stay alive? That's an unacceptable result we're left with.
 
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D

DeMegaMan619

Guest
Association Between Testosterone Supplementation Therapy and Thrombotic Events in Elderly Men

http://www.goldjournal.net/article/S0090-4295(15)00405-7/abstract

Yet another recent study in opposition Glueck's work which shows no difference in terms of thrombotic risk factors (clots) between those on TRT and not on TRT.

After completing Dr Glueck's blood orders, he highly recommended I d/c TRT. I have a history of superficial blood clots and took him serious. I took the blood results, and his recommendation, to the Dr that prescribed my TRT. He told me about several studies that had just come out. He said, according to my blood work, I am a clotter and will probably develop them on or off TRT. He recommended I continue TRT and also continue Eliques. Eliques help me pass my superficial clots fair quickly. He hasn't found any since I started the drug.
 
After completing Dr Glueck's blood orders, he highly recommended I d/c TRT. I have a history of superficial blood clots and took him serious. I took the blood results, and his recommendation, to the Dr that prescribed my TRT. He told me about several studies that had just come out. He said, according to my blood work, I am a clotter and will probably develop them on or off TRT. He recommended I continue TRT and also continue Eliques. Eliques help me pass my superficial clots fair quickly. He hasn't found any since I started the drug.

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?
 

J2048b

Member
with all these findings as of late, who is right? the newer studies contradict what doc g has been saying and researching for years, BUT within the newer studies how do they compare with the doctor's studies? ie example:

duration of studies, age of people in them, amounts used, health of each individual?

it has been shown a few times where studies have come out, only to find out the men involved already had previous heart attacks and so on....
 
with all these findings as of late, who is right? the newer studies contradict what doc g has been saying and researching for years, BUT within the newer studies how do they compare with the doctor's studies? ie example:

duration of studies, age of people in them, amounts used, health of each individual?

it has been shown a few times where studies have come out, only to find out the men involved already had previous heart attacks and so on....

I believe Dr. G's studies were done with a much smaller number of individuals than the latest one. I don't have time right now to research it right now, but maybe someone can and report back on that. Coincidentally, Dr. G. was one the researchers on the latest one which makes no sense.
 

J2048b

Member
I believe Dr. G's studies were done with a much smaller number of individuals than the latest one. I don't have time right now to research it right now, but maybe someone can and report back on that. Coincidentally, Dr. G. was one the researchers on the latest one which makes no sense.

wow yeah that makes no sense because he is contradicting what he reported before then correct?
 

J2048b

Member
also how much would one put stoc into a 23andme report? ive done mine and it said something about me having 2 genomes that are bad in regards to having dvt's etc... \

but its all based upon saliva and not blood testing, where as saliva, to my knowledge, especially in regards to long term issues, can change from day to day,

where as blood work,
allthough some markers change, if u have something more than likely u have something and it wont show up differently the next blood test...
 
also how much would one put stoc into a 23andme report? ive done mine and it said something about me having 2 genomes that are bad in regards to having dvt's etc... \

but its all based upon saliva and not blood testing, where as saliva, to my knowledge, especially in regards to long term issues, can change from day to day,

where as blood work,
allthough some markers change, if u have something more than likely u have something and it wont show up differently the next blood test...

The 23andme DNA saliva test is accurate. It's not like other saliva testing (e.g. for hormones) some of which are totally useless. The SNPs (mutations) in your genome is what it is. But just having a +/+ or +/- SNP does NOT always equate to whether they are expressed or not. There are way too many many variables to say and it is highly complex (as some SNPs cancel out others) + genetic testing is still very much in its infancy. There are very few specialists that can even interpret what these SNPs mean. Nonetheless, I found it a very useful tool to see what predispositions I have and can act accordingly. One of the most prolific is the MTHFR C677T gene mutation which can contribute to thrombophilia, especially if the homocysteine in elevated (>8). More than just having mutations, the comprehensive blood work I posted upthread needs to be done to rule out actual acquired or heretic coagulopathies.
 

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