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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
I wanted to update ExcelMale.com 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. In the previous interview, he mentioned that less than 2% of men on TRT may have DVT.
I sent him a few questions that he kindly answered for us.
A- 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.
B- 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].
C- 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.
D- 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.
E- 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.
F- 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.
G- 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 ³3 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.
H- 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.
I- How can anyone having DVT issues contact you?
As 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]
Reference
[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.
