Article: Second Interview with Dr Charles Glueck About Testosterone and DVT

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Nelson Vergel

Second Interview with Dr Charles Glueck about Testosterone and DVT

It has been a while since I first interviewed Dr. Glueck about TRT and clotting issues. You can read the first interview here:

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

DVT testosterone TRT.jpg

I wanted to update readers about Dr. Glueck's continuing research on this controversial area. Several cohort reviews have found no association between testosterone replacement and DVT. But Dr. Glueck is concerned about the minority of men who may have a genetic predisposition to clotting issues while on TRT and how to manage these patients.

I sent him a few questions that he kindly answered for us.

1- Dr. Glueck, can you update us on what you have found after our last interview?

In late 2017 [1], we reported thrombotic events after starting testosterone therapy (TT) in 21 men who sustained 23 venous thromboembolisms (VTE). These 21 patients were referred to us and were studied sequentially after our first 67 patients [2]. None of the 21 patients had sustained thrombotic events before starting TT. Of the 21 patients, 8 had deep venous thrombosis (DVT) alone, 5 had DVT and pulmonary emboli (PE), 2 had ischemic stroke, 1 had idiopathic osteonecrosis, and 1 had central retinal artery thrombosis [1].

The density of thrombotic events was greatest at 3 months after starting TT, with a rapid decline in events by 10 months. Finding a peak of VTE events at 3 months was entirely congruent with the population study by Martinez et al [3]. This is a very important new finding since it suggests that after starting TT, the greatest likelihood of having a blood clot is 3 months later, and the likelihood of blood clotting, although still present, is much lower by 10 to 12 months after starting TT.

2- Are there any data on men with DVT history who remain on blood thinners and choose to stay on TRT?.

After a first thrombotic event and continuing testosterone therapy (TT) [2], 11 patients had a second thrombotic event despite adequate anticoagulation, 6 of whom, still anticoagulated, had a third thrombosis. Recurrent renal infarctions from blood clots have been reported in a patient taking both testosterone and anabolic steroids despite anticoagulation with apixaban [4]. After a thrombotic event, if TT is continued in thrombophilic patients, concomitant and adequate anticoagulation does not appear to prevent recurrent thrombotic events [2, 5, 6].

3- How much do the blood tests you recommend cost and do insurance companies cover it for men with no DVT history who want to learn if they are at risk?

The major tests include the following: PCR assays for Factor V Leiden and Prothrombin G20210A mutations. Coagulation tests include the Lupus Anticoagulant, Factors VIII and XI, anticardiolipin (ACLA) IgG and IgM, and homocysteine. It is very important to double check that these tests are covered by insurance, otherwise the “street, non insured cost” would be well over $1500.

Usually insurance companies will not cover these tests for men with no DVT history, and no family history of DVT, who want to learn if they are at risk. However, a positive family history is usually enough to get them to cover the tests, if it is well documented.

4- How many of the men you have reviewed have DVT with no known genetic factors?

Seventy-three percent of men with DVT-VTE have genetic factors (Factor V Leiden, Factors VIII and XI most commonly), and 23% have the acquired lupus anticoagulant. Thus, most men with DVT-VTE have either inherited thrombophilia or acquired thrombophilia.

5- What are the best lifestyle suggestions you have for aging men to prevent DVT?

Avoid long airplane or automobile trips (4 hours or more) get up to move around about once per hour. If unavoidably seated for long periods of time, flex legs and feet for 5-10 minutes every hour.

Avoid high red blood cell and hemoglobin counts if taking TT.

Exercise at least 3 times per week, for 30 or more minutes, at a pace where it is easy to have a conventional conversation. If unavoidably immobile (bedridden), consult with MD about prophylactic anticoagulation.

6- Are the men you have reviewed who had DVT while on TRT older? What is the age range? Any cofactors or comorbidities?

The majority of men are middle age, with very few age 75 or older. The median age of the 88 cases with DVT on TRT was 53 years, mean (standard deviation) 52 ± 14 years. Obesity and cigarette smoking are substantial comorbidities for DVT in men receiving TT. Men who develop high serum estradiol while on TT are at especially high risk for DVT.

7- What kind of work up should doctors do in older men who are starting TRT?

This is a controversial area. Many family doctors will decline to do any coagulation workup. Our suggestions are as follows: if there is any family history of DVT, PE, VTE, or retinal vein or retinal artery thrombosis, or greater or equal than 3 unexplained first trimester miscarriages in a first degree relative, then an optimal minimal workup should include PCR for the Factor V Leiden mutation, Factors VIII and XI, homocysteine, and the lupus anticoagulant. In the absence of family history or recurrent miscarriage, then screening for the Factor V Leiden mutation and for the lupus anticoagulant would be warranted.

8- What is your next research focus going to be?

We are focusing on whether men (or women) who develop blood clots within 3 months of starting TT have different patterns of thrombophilia than those with clots 3-6, 6-12, and >12 months after starting TT.

9- How can anyone having DVT issues contact you?

s before, if any of your readership has questions about TT and DVT, PE, VTE, and osteonecrosis they can contact me free of charge with questions, and I will review their status, make suggestions for coagulation testing, and advise, once I have received their data. They can contact me at [email protected]


[1]. Glueck CJ, Goldenberg N, Wang P. Thromboembolismpeaking 3 months after starting testosterone therapy: testosterone-thrombophilia interactions. J Investig Med.2017.
[2]. Glueck CJ, Prince M, Patel N, Patel J, Shah P, Mehta N, Wang P. Thrombophilia in 67 Patients With Thrombotic Events After Starting Testosterone Therapy. Clin Appl Thromb Hemost.2016;22:548-53.
[3]. Martinez C, Suissa S, Rietbrock S, Katholing A, Freedman B, Cohen AT, Handelsman DJ. Testosterone treatment and risk of venous thromboembolism: population based case-control study. BMJ.2016;355:i5968.
[4]. Colburn S, Childers WK, Chacon A, Swailes A, Ahmed FM, Sahi R. The cost of seeking an edge: Recurrent renal infarction in setting of recreational use of anabolic steroids. Ann Med Surg (Lond).2017;14:25-8.
[5]. Glueck CJ, Wang P. Testosterone therapy, thrombosis, thrombophilia, cardiovascular events. Metabolism.2014;63:989-94.
[6]. Freedman J, Glueck CJ, Prince M, Riaz R, Wang P. Testosterone, thrombophilia, thrombosis. Transl Res.2015;165:537-48.
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Nelson Vergel

This was a review looking at the effect of our body's own hormone levels (no supplementation)

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Thromb Haemost. 2018 Oct 8. doi: 10.1055/s-0038-1673613. [Epub ahead of print] Prospective Study of Endogenous Hormones and Incidence of Venous Thromboembolism: The Atherosclerosis Risk in Communities Study.

Exogenous hormone treatments in women (oral contraceptives and hormone replacement therapy [HRT]) are established risk factors for venous thromboembolism (VTE), but less is known about associations between plasma levels of endogenous hormones and VTE risk. We examined the association of baseline dehydroepiandrosterone sulphate (DHEAS), testosterone and sex hormone-binding globulin (SHBG) with risk of future VTE in men and post-menopausal women in the Atherosclerosis Risk in Communities Study. Testosterone, DHEAS and SHBG were measured in plasma samples collected in 1996 to 1998. Cox proportional hazards models were used to estimate hazard ratios for incident VTE adjusting for age, race/ethnicity, body mass index, height, smoking, estimated glomerular filtration rate and C-reactive protein. All analyses were stratified by sex and by current HRT use in women. Among 3,051 non-HRT-using women, 1,414 HRT-using women and 3,925 men at risk at baseline, 184, 62 and 206 experienced incident VTE after a median follow-up of 17.6 years. Plasma hormones were not associated with incidence of VTE among men and non-HRT-using women, although lower plasma DHEAS, when modelled using quartiles or restricted cubic splines, was associated with higher risk of VTE among HRT-using women. This study does not support the existence of an important association between plasma concentrations of endogenous testosterone, DHEAS or SHBG with risk of VTE in middle-aged to older men or post-menopausal women not using HRT.

Nelson Vergel

Urology. 2019 Feb;124:127-130. doi: 10.1016/j.urology.2018.11.009. Epub 2018 Nov 15.

Medical Treatments for Hypogonadism do not Significantly Increase the Risk of Deep Vein Thrombosis Over General Population Risk.

Kavoussi PK1, Machen GL2, Wenzel JL3, Ellis AM4, Kavoussi M5, Kavoussi KM6, Kavoussi SK6.

To evaluate the risk of deep vein thrombosis (DVT) in men treated with testosterone replacement therapy (TRT) or Clomiphene Citrate (CC) and assess other etiologies for DVT as contributing factors.

Retrospective chart review of 1180 consecutive hypogonadal men who were treated with either TRT or CC. Sixty-four percent had mixed, 16% had primary, and 20% had secondary hypogonadism.

Of the 1180 men with hypogonadism, 694 were treated with TRT, while 486 were treated with CC. Overall, 10 of 1180 (0.8%) men were diagnosed with a DVT during the treatment, 9 of whom were on TRT and 1 on CC. Of the 10 men diagnosed with DVT while on treatment, 7 (70%) had potential identifiable etiologies for DVT other than treatment for hypogonadism. None of the men were found to be polycythemic at the time of DVT diagnosis. There was a higher incidence of DVT in men treated with TRT than CC, however; the overall percentages of DVT in both treatment groups were relatively low. There was no difference in the percentages of men found to have other identifiable etiologies for DVT besides being on treatment between the TRT and CC groups. There was not a difference in testosterone levels between the TRT and CC groups.

The overall rates of DVT for TRT and CC treated patients are relatively low, and the majority of patients with DVT had other identifiable etiologies for DVT. Polycythemia was not found to be a risk factor in the patients diagnosed with DVTs.

Nelson Vergel

Eur J Epidemiol. 2019 Aug 1. doi: 10.1007/s10654-019-00544-z. [Epub ahead of print]
Sauna bathing reduces the risk of venous thromboembolism: a prospective cohort study.
Kunutsor SK1,2, Mäkikallio TH3, Khan H4, Laukkanen T5, Kauhanen J5, Laukkanen JA5,6,7.

National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK. \
Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Learning and Research Building (Level 1), Southmead Hospital, Bristol, BS10 5NB, UK. \
Division of Cardiology, Department of Internal Medicine, Oulu University Hospital, Oulu, Finland.
Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA.
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyvaskyla, Finland.
Central Finland Health Care District Hospital District, Jyvaskyla, Finland.

Emerging evidence suggests there is an inverse and independent association between sauna bathing and arterial thrombotic disease. However, the potential association between sauna bathing and venous thromboembolism (VTE) has not yet been investigated. We aimed to assess the prospective association between frequency of sauna bathing and the risk of VTE. Baseline sauna bathing habits were assessed in 2242 men aged 42-61 years without a history of VTE in the Kuopio Ischemic Heart Disease prospective cohort. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE. During a median follow-up of 24.9 years, 146 (6.5%) incident VTE events were recorded. In age-adjusted analyses, the HRs 95% (CIs) of VTE were 0.67 (0.47-0.96) and 0.95 (0.53-1.70) for participants who had 2-3 and ≥ 4 sauna sessions per week respectively compared with participants who had ≤ 1 sauna session per week. After further adjustment for several established risk factors including lifestyle factors, the corresponding HRs (95% CIs) were 0.67 (0.46-0.96) and 0.92 (0.51-1.68) respectively. Having sauna baths was associated with a reduced risk of VTE in a middle-aged male Caucasian population. Further studies in other populations and age groups are required to confirm these findings.
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