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

[Marco N Cognito]

Marco - I am on 20mg. Started out on 15 twice a day. Now I would very much like to move to 15 for a few months and then down to 10mg.

Am I reading correctly that Dr. G only sees testosterone as an issue for those with a genetic factor that tilts towards clotting?

If one is dehydrated that alone can predispose an individual to high clotting risk. There is at least one study that shows that staying hydrated can cut the risk of a heart attack in half. In a nutshell low blood viscosity (thinner blood) is extremely protective for both arteries and veins.

One additional risk factor I may have the fact I have been low-carb for years. There are quite a few studies that show low-carb increase the blood viscosity where true wheat free vegetarians enjoy very low viscosity.
Short history - This June on Father's Day (Sunday) I was doing sprints on steps midday with the temperature around 90 degrees. On the sixth set I passed out briefly; probably because of not eating first and dehydration. I was at a resort hotel on the Gulf Coast so plenty of people responded. Within 10 or 15 minutes of that event I was fine and went home. Spent the next few days working and sitting for long hours, something I normally do. By Wednesday my left leg started swelling quickly and was painful. I also developed a mild cough which may have been about the time the pulmonary embolism happened. By Thursday I was in the hospital. I would never have known I had a pulmonary embolism if not for the CT in the hospital.

Five days later I was discharged on Coumadin with an INR of 1.3 and self administered Lovenox. The doctor raised my Coumadin to 15mg at which point my INR jumped to 4.2. His nurse called and told me to get off Coumadin and Lovenox for the next 3 or 4 days. Within 24 hours I was in unbelievable pain.

Found a new doctor that let me start Xarelto. The pain was gone within 2 days.

My take was that Dr. G seems pretty staunch anti-TRT regardless, as is the case with most mainstream old school docs. That's not to say he isn't brilliant insofar as hematology and cardiology, but definitely from the old school of thinking. Myself, I would only be concerned if my clotting disorder were of genetic etiology and not caused by factors such as diet, meds (like too much thyroid hormone), and other environmental factors that are within a person's control.

Please post the studies that show that LC diets increase viscosity or hypercoagulation or is linked to hydration or lack thereof. But, then again, those are two different issues.

 

[stcrim]

Here is the reverse of that search: https://www.google.com/?gws_rd=ssl#q=vegetarian+and+blood+viscosity+site:www.ncbi.nlm.nih.gov I'll dig up the low carb links ASAP

 

[Nelson Vergel]

The Atkins diet is well known for causing a large decrease in weight initially which is mostly water related. I guess this could cause dehydration in some men. Dehydration increases blood viscosity. However, I doubt that low carb diets increase chances for blood clots.

 

[Kiwi81]

What an interesting thread! I had a clot in 2006 (I was only 25 at the time) that travelled to the lungs and I was in ICU for 3 days... Cause was that I had a really bad flu and was lying in bed for about a week, not moving much and dehydrated.

After they fixed me up in the hospital I was put on Warfarin for about a year or so. No problems since. I am about to start TRT next week. Should I take the risk or just accept that I will have low energy for the rest of my life?

 

[Marco N Cognito]

What an interesting thread! I had a clot in 2006 (I was only 25 at the time) that travelled to the lungs and I was in ICU for 3 days... Cause was that I had a really bad flu and was lying in bed for about a week, not moving much and dehydrated.

After they fixed me up in the hospital I was put on Warfarin for about a year or so. No problems since. I am about to start TRT next week. Should I take the risk or just accept that I will have low energy for the rest of my life?

In my experience, immobility can exacerbate an underlying clotting disorder, but rarely itself causes one as severe as you've mentioned. What you've mentioned sounds like a DVT that caused a PE (pulmonary embolism). To be on the safe side, I would do as many of the tests I listed upthread to make sure you don't have acquired or familial thrombophilia prior to starting TRT.

 

[Nelson Vergel]

Kiwi81, please read the first post on this thread (page 1) to find Dr Glueck's email address. He can run tests for you before you start TRT.

 

[Kiwi81]

Hi guys, ok. I will try and do those tests before I start TRT. Only problem is that I am in New Zealand and I don't think Dr Glueck can help me from the States? But I will email him anyway, to see if he has got any suggestions.

 

[Nelson Vergel]

Freedman J, Glueck CJ, Prince M, Riaz R, Wang P. Testosterone, thrombophilia, thrombosis. Transl Res. http://www.sciencedirect.com/science/article/pii/S1931524414004678


We screened previously undiagnosed thrombophilia (V Leiden-prothrombin mutations, Factors VIII and XI, homocysteine, and antiphospholipid antibody [APL] syndrome) in 15 men and 2 women with venous thromboembolism (VTE) or osteonecrosis 7 months (median) after starting testosterone therapy (TT), gel (30-50 mg/d), intramuscular (100-400 mg/wk), or HCG (6000 IU/wk).


Thrombophilia was studied in 2 healthy control groups without thrombosis (97 normal controls, 31 subjects on TT) and in a third control group (n = 22) with VTE, not on TT.


Of the 17 cases, 76% had >/=1 thrombophilia vs 19% of 97 normal controls (P < 0.0001), vs 29% of 31 TT controls (P = 0.002).


Cases differed from normal controls by Factor V Leiden (12% vs 0%, P = 0.021), by high Factor VIII (>150%) (24% vs 7%, P = 0.058), by high homocysteine (29% vs 5%, P = 0.007), and from both normal and TT controls for APL syndrome (18% vs 2%, P = 0.023, vs 0%, P = 0.04).


Despite adequate anticoagulation with TT continued after the first deep venous thrombosis-pulmonary embolus (DVT-PE), 1 man sustained 3 DVT-PEs 5, 8, and 11 months later and a second man had 2 DVT-PEs 1 and 2 months later.


Of the 10 cases with serum T measured on TT, 6 (60%) had supranormal T (>800 ng/dL) and of 9 with estradiol measured on TT, 7 (78%) had supranormal levels (>42.6 pg/mL).


TT interacts with thrombophilia leading to thrombosis. TT continuation in thrombophilic men is contraindicated because of recurrent thrombi despite anticoagulation.



Screening for thrombophilia before starting TT should identify subjects at high risk for VTE with an adverse risk/benefit ratio for TT.

 

[Nelson Vergel]

Finally, a promising study.


Risk for venous thrombotic events no higher in men with hypogonadism on testosterone therapy

March 11, 2015


SAN DIEGO — Men with hypogonadism do not appear to have any increased risk for venous thrombotic events with exogenous testosterone replacement therapy, according to research presented at The Endocrine Society annual meeting.


“After carefully designing and evaluating real-world evidence data, we failed to find a positive relationship between testosterone replacement therapy and idiopathic venous thrombotic events,” Hu Li, MBBS, PhD, of Eli Lilly and Company, Indianapolis, Indiana, told Endocrine Today.

“Although the study is observational in nature with its own limitation, it provides valuable information to physicians and patients in addition to spontaneously reported cases,” he said.

In a retrospective cohort and nested-case-control analyses, Li and colleagues investigated the relationships between testosterone replacement therapy (TRT) and venous thrombotic events (VTE) among adult men with hypogonadism aged at least 18 years.

The investigators searched Truven Databases to obtain data on men with a hypogonadal condition, defined as being treated with an approved TRT product or untreated but having a hypogonadal diagnosis per International Classification of Diseases criteria. Patients had been enrolled in a health care plan for at least 12 months and had no VTE diagnosis at baseline.

After propensity score matching in a 1:1 ratio to ensure comparability, 102,650 patients treated with TRT and 102,650 untreated patients with idiopathic VTE were included.

Treated and untreated patients were then matched in a 1:4 ratio based on age and calendar year.

Index date among treated men (n = 2,785) was defined as the first TRT prescription and among untreated men (n = 11,119) was assigned at random according to the distribution for those treated. Incident VTE, and primarily idiopathic VTE, was the main outcome sought. The researchers assessed exposure as any TRT use and different administration methods.

Cox regression and conditional logistic regression models were used in the cohort and nested analyses to assess, respectively, HRs and ORs for relationships between TRT and VTE. Sensitivity analyses were performed with varied TRT exposure and VTE parameters.

In the retrospective cohort analysis, the HR for patients treated with any TRT was 1.08 (95% CI, 0.91-1.27), with topical/gel TRT was 1.07 (95% CI, 0.88-1.29) and with injectable TRT was 1.32 (95% CI, 0.89-1.96). The results were not significant when men were stratified by age.

Nested analyses of treated and untreated groups revealed similar, but not significant findings. The likelihood of having VTE with current TRT use was slightly higher than past TRT use (OR = 1.02; 95% CI, 0.92-1.13 vs. OR = 0.92; 95% CI, 0.82-1.03). When patients were stratified by age and TRT administration, results were similar but nonsignificant.

“Future studies are warranted to confirm the study findings,” Li said. “Regardless of this study finding, Lilly has updated the Axiron U.S. product label and the Medication Guide to reflect the additional language requested by FDA related to thromboembolic risk.” &#8211; by Allegra Tiver

Reference:

Li H. Abstract OR34-2. Presented at: The Endocrine Society Annual Meeting; March 5-8, 2015, San Diego.

Disclosure: Li reports being an employee at Eli Lilly & Company.

 

[Nelson Vergel]

The Effect of Androgen Replacement Therapy on Platelet Aggregation in Male Patients with Isolated Hypogonadotropic Hypogonadism

http://www.endocrine-abstracts.org/ea/0037/ea0037ep177.htm


Aim: To evaluate the effect of androgen replacement therapy on lipid profile and platelet aggregation in in male patients with isolated hypogonadotropic hypogonadism (IHH).


Material and methods: 36 male patient, mean age 32.2 (18&#8211;54)with IHH, admitted to the outpatient clinic of Endocrinology and Metabolism were included to the study. Patients in the study were divided into two groups as Testosterone (n=18) and human chorionic gonadotropin (HCG) therapy (n=18) groups. Total testosterone, fasting plasma glucose (FPG), alanine aminotransferase (ALT), lipid profile, mean platelet volume (MPV), platelet distribution width (PDW) and platelet count were evaluated before and after 6 months of the treatment in all patients.


Results: There was no statistically significant difference according to FPG, triglyceride levels, MPV and platelet counts when all patients (n=36) were evaluated due to pre-treatment and post-treatment (P>0.05). However, ALT and LDL levels were detected statistically significantly lower after treatment (P>0.05), HDL, PDW and testosterone levels were significantly higher after treatment (P<0.05). There was no significant difference due to testosterone, FPG, ALT, lipid profile, MPV, PDW and platelet levels compared according to treatment (HCG (n=18), and testosterone replacement (n=18)) (P>0.05). While there was negative correlation with testosterone and ALT levels (r=&#8722;0.25, P=0.03), positive correlation was detected between testosterone and PDW (r=0.31, P=0.007).


Conclusion: Platelets are involved in homeostatic process and have an important role in atherosclerosis and arterial thrombosis. MPV and PDW are two markers of platelet activation, and have recently been recognised as risk predictors of cardiovascular diseases. Our study revealed that androgen replacement therapy may have beneficial effects on lipid profile and ALT and negative effects on platelet aggregation. Therefore, we think that this situation should be taken into consideration when androgen replacement therapy is planned.

 

[Nelson Vergel]

Testosterone and Blood Clots: Study Finds No Link

 

[midlifealpha]

Nelson I really appreciate your willingness to share potential downside effects. In this case of the 1-2% that could be affected even on this very forum we have one very concerned participant.

Arimedex popped up again and I've been assigned 3 per week. I don't want to change the subject but I think there was a thread on here that suggested those of us splitting our T-injections to Monday morning/Thursday evening might not need to be taking it all. Then it shows up again here in this thread. I'm thinking of getting rid of it.

I've never had Deep Vein Thrombosis but twice now I've had superficial clots for which I was approved to receive laser therapy in about 10 sittings. None were of the life threatening variety. Incidentally my doc here in Orlando was ripped with serious vascularity and I couldn't believe he was 68. I'd love to talk to him again knowing what I know about TRT and NO now. My Nurse Practiioner didn't like the idea of NO stack because she felt my veins were so large anyway (in the legs) but I cannot deny the benefits from using Gene's stack.

Anyway to shorten this Nelson I'd like your take on Arimedix. If your opinion has nothing to do with this thread then no need to discuss here as this thread doesn't need hijacked.

 

[Nelson Vergel]

Strength training helps prevent thrombosis



Study

The researchers answered this question by setting up an experiment in which they got ten people with a sedentary lifestyle and ten well-trained strength athletes to perform six sets of squats using a weight with which they could just manage 10 reps. The researchers took blood samples from the subjects before and after the weight-training session.

Results

When the researchers analysed the blood they noticed that in both the inactive people and the strength athletes the activity of PAI-1 decreased and that of t-PA increased.








Strength training, it would seem, causes a shift in clotting balance in a favourable direction for people who are at risk from thrombosis. The effect is stronger in the experienced athletes.

The strength training had no effect on the blood-clot forming fibrinogen, but did boost the concentration of prothrombin fragment 1 + 2 and thrombin-antithrombin complexes. These are blood-clotting markers.

The researchers also measured the activated partial Thromboplastin time. This is the result of a test that says something about the balance between clotting and anti-clotting factors. The researchers discovered that the workout shifted the balance in the direction of the anti-clotting factors.

Conclusion

"Our findings suggest that habitual resistance training may limit the inhibitory activity of PAI-1 and enhance tPA activity, thereby allowing a favorable fibrinolytic state", the researchers conclude.

Source:
Thromb Res. 2013 Jun;131(6):e227-34.

 

[Nelson Vergel]

No Heart or Clotting Issues in Diabetic Men Using Testosterone after 3.5 years

 

[Nelson Vergel]

A new paper from Dr Glueck.

[h=2]Testosterone Therapy Can Interact With Thrombophilia, Leading to Osteonecrosis.[/b]Glueck CJ, et al. Orthopedics. 2015.

Although this effect is not widely recognized, testosterone therapy can interact with thrombophilia, causing osteonecrosis. In 12 men and 4 women who had idiopathic osteonecrosis a median of 6 months after the onset of testosterone therapy, the authors examined the interaction between testosterone therapy and previously undiagnosed thrombophilia. The authors hypothesized that patients who had osteonecrosis after starting testosterone therapy were more likely than 110 normal control subjects or 48 patients who had osteonecrosis and were not receiving testosterone therapy to have thrombophilia. Measures of thrombophilia included Factor V Leiden, prothrombin, PAI-1 gene mutations, Factor VIII, Factor XI, anticardiolipin antibody immunoglobulin G or immunoglobulin M, and homocysteine values. In 10 cases, osteonecrosis occurred 6 months or less after the onset of testosterone therapy, and in all 16 cases, it occurred after a median of 6 months of testosterone therapy. Of the 16 cases, 5 (31%) were Factor V Leiden heterozygotes vs 2 of 109 (2%) healthy control subjects (P=.0003) and 4 of 48 patients who had osteonecrosis and were not receiving testosterone therapy (P=.04). Of the 16 cases, 4 (25%) had high (>150%) Factor VIII levels vs 7 of 103 (7%) healthy control subjects (P=.04), and 3 (19%) had high (>150%) Factor XI levels vs 3 of 101 (3%) healthy control subjects (P=.03). Of the 16 patients with osteonecrosis, 14 (88%) had at least 1 abnormal procoagulant value (of the 8 measured) vs 47 of 110 (43%) healthy control subjects (P=.0009). Of the 5 men whose serum estradiol level was measured while they were receiving testosterone therapy, this level was high (&#8805;42.6 pg/mL) in 4. When testosterone therapy is given to patients with thrombophilia, they are at increased risk for osteonecrosis

 

[Dr Justin Saya MD]

A new paper from Dr Glueck.

[h=2]Testosterone Therapy Can Interact With Thrombophilia, Leading to Osteonecrosis.[/b]Glueck CJ, et al. Orthopedics. 2015.

Although this effect is not widely recognized, testosterone therapy can interact with thrombophilia, causing osteonecrosis. In 12 men and 4 women who had idiopathic osteonecrosis a median of 6 months after the onset of testosterone therapy, the authors examined the interaction between testosterone therapy and previously undiagnosed thrombophilia. The authors hypothesized that patients who had osteonecrosis after starting testosterone therapy were more likely than 110 normal control subjects or 48 patients who had osteonecrosis and were not receiving testosterone therapy to have thrombophilia. Measures of thrombophilia included Factor V Leiden, prothrombin, PAI-1 gene mutations, Factor VIII, Factor XI, anticardiolipin antibody immunoglobulin G or immunoglobulin M, and homocysteine values. In 10 cases, osteonecrosis occurred 6 months or less after the onset of testosterone therapy, and in all 16 cases, it occurred after a median of 6 months of testosterone therapy. Of the 16 cases, 5 (31%) were Factor V Leiden heterozygotes vs 2 of 109 (2%) healthy control subjects (P=.0003) and 4 of 48 patients who had osteonecrosis and were not receiving testosterone therapy (P=.04). Of the 16 cases, 4 (25%) had high (>150%) Factor VIII levels vs 7 of 103 (7%) healthy control subjects (P=.04), and 3 (19%) had high (>150%) Factor XI levels vs 3 of 101 (3%) healthy control subjects (P=.03). Of the 16 patients with osteonecrosis, 14 (88%) had at least 1 abnormal procoagulant value (of the 8 measured) vs 47 of 110 (43%) healthy control subjects (P=.0009). Of the 5 men whose serum estradiol level was measured while they were receiving testosterone therapy, this level was high (&#8805;42.6 pg/mL) in 4. When testosterone therapy is given to patients with thrombophilia, they are at increased risk for osteonecrosis

"Of the 5 men whose serum estradiol level was measured while they were receiving testosterone therapy, this level was high (&#8805;42.6 pg/mL) in 4."

Just absolutely amazing that estradiol levels were ONLY monitored in 5 of the patients. This data (as well as so much other data) is rendered essentially useless by lack of proper monitoring of KEY lab parameters.

 

[Nelson Vergel]

"Of the 5 men whose serum estradiol level was measured while they were receiving testosterone therapy, this level was high (&#8805;42.6 pg/mL) in 4."

Just absolutely amazing that estradiol levels were ONLY monitored in 5 of the patients. This data (as well as so much other data) is rendered essentially useless by lack of proper monitoring of KEY lab parameters.

I also see no mention of hematocrit

 

[Nelson Vergel]

J Investig Med High Impact Case Rep. 2016 Aug 1;4(3):2324709616661833. doi: 10.1177/2324709616661833

Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant.

Glueck CJ1, Lee K1, Prince M1, Jetty V1, Shah P1, Wang P1.

Author information
1Jewish Hospital of Cincinnati, Cincinnati, OH, USA.

Abstract


When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued.

CASE PRESENTATION:

A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis. In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism. Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin). Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux). One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE. Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months.

CONCLUSION:

When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation.

 

[Tommy Wall]

Nelson, in simple english once you have had a thrombose you should stop with both TT and HCG correct?
In this case could TT and HCG had provoked the thrombose?

 

[Nelson Vergel]

That is what Dr Glueck believes. Some other docs think that being on anticoagulants should be protective, but I guess we would need more data.