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

[Kushman42]

That is very interesting information.

 

[JPB]

Age 58, I am not on TRT. My therapy for hormones the last several years consisted of Clomid and growth hormone peptides. Approx. 1 year ago I had injured my leg and subsequently developed a clot (popliteal vein). I was put on Xarelto, three months later the clot was gone and I got off the Xarelto. I had got off the Clomid when clot was diagnosed. When the clot cleared at some point I resumed Clomid and growth peptides. This past week I rapidly developed symptoms in the same spot and was diagnosed again with a DVT in the popliteal vein and was started on Eliquis, since I did not want the Xarelto again. Will be talking to my doc about more detailed testing. At this point I am blaming things on the original injury and the Clomid. I'm not telling my doc about the Clomid since he told me to stay off it. But I do think the estrogens it produces are probably partly at blame. Hopefully can get the tests recommended by Dr. Glueck to help figure this out.

 

[easternpromise]

Looking at studies post 2014 shows no correlation between trt use and thrombosis. Texas study in 2015, u.s. chest physicians study, etc etc. I feel like one study showing it's true is not enough to warrant such anxiety and fear. Technically there are more studies showing no correlation then there are showing correlation. Reminds me of the studies on weather trt induces heart attacks, there were one or two which led to fear in the media, later those studies were shown to be inconclusive.

 

[Nelson Vergel]

I agree with you, easternpromise.

 

[easternpromise]

I agree with you, easternpromise.

I enjoy reading all the debate and the studies. I'm fascinated by medical science, and how much work it takes to conclusively correlate something. I think in some cases it may be impossible

 

[vood13]

I agree with you, easternpromise.

So, would it make sense that my trt doc suggests stopping TRT based on having FVL, but, with NO thrombosis event ever occurring?

 

[Nelson Vergel]

Aging (Albany NY). 2018 May 2;10(5):902-929. doi: 10.18632/aging.101438.

Testosterone and dihydrotestosterone reduce platelet activation and reactivity in older men and women.

Karolczak K1, Konieczna L2, Kostka T3, Witas PJ1, Soltysik B3, Baczek T2, Watala C1.

Author information
1
Department of Haemostatic Disorders, Medical University, Lodz, Poland.
2
Department of Pharmaceutical Chemistry, Medical University of Gdansk, Gdansk, Poland.
3
Department of Geriatrics, Healthy Ageing Research Centre (HARC), Medical University, Lodz, Poland.

Abstract

The cardiovascular effects of testosterone and dihydrotestosterone are generally attributed to their modulatory action on lipid and glucose metabolism. However, no ex vivo studies suggest that circulating androgen levels influence the activation and reactivity of blood platelets - one of the main components of the haemostasis system directly involved in atherosclerosis. The levels of testosterone, dihydrotestosterone and oestradiol in plasma from men and women aged from 60 to 65 years were measured by LC-MS; the aim was to identify any potential relationships between sex steroid levels and the markers of platelet activation (surface membrane expression of GPII/IIIa complex and P-selectin) and platelet reactivity in response to arachidonate, collagen or ADP, monitored with whole blood aggregometry and flow cytometry. The results of the ex vivo part of the study indicate that the concentrations of testosterone and its reduced form, dihydrotestosterone are significantly negatively associated with platelet activation and reactivity. These observations were confirmed in an in vitro model: testosterone and dihydrotestosterone significantly inhibited platelet aggregation triggered by arachidonate or collagen. Our findings indicate that testosterone and dihydrotestosterone are significant haemostatic steroids with inhibitory action on blood platelets in older people.

 

[Nelson Vergel]

More from Glueck

J Investig Med. 2018 Apr;66(4):733-738. doi: 10.1136/jim-2017-000637. Epub 2017 Dec 15.


Thromboembolism peaking 3 months after starting testosterone therapy: testosterone-thrombophilia interactions.

Glueck CJ1, Goldenberg N1, Wang P1.

Abstract

We assessed time of thrombotic events (venous thromboembolism (VTE)) after starting testosterone therapy (TT) in 21 men who sustained 23 VTE. The density of thrombotic events was greatest at 3 months after starting TT, with a rapid decline in events by 10 months. The 21 cases with VTE on TT differed from 110 patient controls with unprovoked VTE, not taking TT (VTE-no TT) for Factor V Leiden heterozygosity (FVL) (33 per cent vs 13 per cent, P=0.037), for high lipoprotein (a) (Lp(a)) (55 per cent vs 17 per cent, P=0.012), and for the lupus anticoagulant (33 per cent vs 4 per cent, P=0.003). These differences between cases and VTE-no TT controls were independent of age and gender. TT can interact with underlying thrombophilia-hypofibrinolysis promoting VTE. We suggest that TT should not be started in subjects with known thrombophilia. Coagulation screening, particularly for the FVL , Lp(a), and the lupus anticoagulant should be considered before starting TT, to identify men at high VTE risk who have an adverse risk/benefit ratio for TT.



KEYWORDS:
pulmonary embolism; testosterone; thromboembolism; thrombophilia; thrombosis

 

[Marco N Cognito]

More from Glueck

J Investig Med. 2018 Apr;66(4):733-738. doi: 10.1136/jim-2017-000637. Epub 2017 Dec 15.


Thromboembolism peaking 3 months after starting testosterone therapy: testosterone-thrombophilia interactions.

Glueck CJ1, Goldenberg N1, Wang P1.

Abstract

We assessed time of thrombotic events (venous thromboembolism (VTE)) after starting testosterone therapy (TT) in 21 men who sustained 23 VTE. The density of thrombotic events was greatest at 3 months after starting TT, with a rapid decline in events by 10 months. The 21 cases with VTE on TT differed from 110 patient controls with unprovoked VTE, not taking TT (VTE-no TT) for Factor V Leiden heterozygosity (FVL) (33 per cent vs 13 per cent, P=0.037), for high lipoprotein (a) (Lp(a)) (55 per cent vs 17 per cent, P=0.012), and for the lupus anticoagulant (33 per cent vs 4 per cent, P=0.003). These differences between cases and VTE-no TT controls were independent of age and gender. TT can interact with underlying thrombophilia-hypofibrinolysis promoting VTE. We suggest that TT should not be started in subjects with known thrombophilia. Coagulation screening, particularly for the FVL , Lp(a), and the lupus anticoagulant should be considered before starting TT, to identify men at high VTE risk who have an adverse risk/benefit ratio for TT.



KEYWORDS:
pulmonary embolism; testosterone; thromboembolism; thrombophilia; thrombosis

I can't believe that after 5 years, his assessments remain a one-way ticket to another dead end: staying hypogonadal which is no better option. Also, T reduces Lp(a): Testosterone-induced suppression of lipoprotein(a) in normal men; relation to basal lipoprotein(a) level. - PubMed - NCBI
To the contrary:
https://www.sciencedirect.com/science/article/pii/S0090429518312007

 

[Nelson Vergel]

Testosterone replacement therapy and the risk of venous thromboembolism: A systematic review and meta-analysis of randomized controlled trials - PubMed

Our systematic review suggests that TRT is not associated with an increased risk of VTE. However, estimates were accompanied by a wide 95% CIs, and a clinically important increased risk cannot be ruled out.

pubmed.ncbi.nlm.nih.gov

 

[Nelson Vergel]

Testosterone therapy increases the anticoagulant potential in men with opioid-induced hypogonadism: a randomized, placebo-controlled study

INTRODUCTION
Hypogonadism is prevalent during opioid treatment and low testosterone concentrations are associated with cardiovascular disease. The effect of testosterone replacement therapy (TRT) on the coagulation system in men with hypogonadism is not clarified. We investigate effects of TRT on the tissue factor (TF) and contact activation pathways of coagulation in opioid treated men.


MATERIALS AND METHODS
Double-blinded, placebo-controlled study in 37 men with total testosterone < 12 nmol/l randomized to 24 weeks of testosterone injections (n = 17) or placebo (n = 20). Variables of the coagulation system were analysed at baseline and after 24 weeks. Measurements included the TF pathway (endogenous thrombin potential (ETP), peak thrombin), the contact activation pathway (endogenous kallikrein potential (EKP), peak kallikrein), coagulation factors (FVII, FX, prothrombin, FXII), and inhibitors (tissue factor pathway inhibitor (TFPI), protein C, protein S, antithrombin, C1 esterase inhibitor (C1inh)). Between-group differences at 24 weeks were determined with analysis of covariance. Within-group changes in TRT and placebo were analysed with paired t-test.


RESULTS
Between-group differences at 24 weeks were observed for ETP (p = 0.036), FVII (p = 0.044), FX (p = 0.015), prothrombin (p = 0.003), protein C (p = 0.004), and protein S (p = 0.038). Within the TRT group, ETP, peak thrombin, FVII, FX, prothrombin, TFPI, protein C, FXII, and C1inh decreased and protein S increased (all p < 0.05). Within the placebo group, coagulation outcomes were unchanged.


CONCLUSION
TRT affects the coagulation system in an anticoagulant direction through suppressed TF pathway in men with opioid-induced hypogonadism.

Source: Testosterone therapy increases the anticoagulant potential in men with opioid-induced hypogonadism: a randomized, placebo-controlled study - PubMed

 

[J2048b]

I do believe the good doc has since retired? If so who took over for him? Last i heard it was his daughter, perhaps?

I tried emailing him but never received a reply….

 

[Nelson Vergel]

I do believe the good doc has since retired? If so who took over for him? Last i heard it was his daughter, perhaps?

I did not know. Some believe he created an irrational fear that made the FDA add a black box warning on every testosterone product package insert.

 

[Nelson Vergel]

According to the provided web search results, the FDA has issued multiple black box warnings for testosterone products. Here are the details on when each warning was added:

1. Cardiovascular Risk: The FDA issued a safety communication about the cardiovascular risk associated with testosterone products on March 3, 2015. [1]
2. Abuse and Dependence: The FDA approved class-wide labeling changes for all prescription testosterone products, adding a new warning and updating the abuse and dependence information on October 25, 2016. [2]
3. Prostate Cancer: None of the provided search results mentioned a black box warning specifically related to prostate cancer for testosterone products.
4. Blood Clots: In response to studies showing the risk of blood clots, stroke, heart attack, and death associated with testosterone therapy, Public Citizen filed a petition to the FDA on February 25, 2014, demanding the agency immediately require a black-box warning for cardiovascular risks on all testosterone therapy drugs. However, it is not clear from the provided search results whether the FDA ever issued a black box warning specifically related to blood clots for testosterone products. [3, 4]
5. Children's Risk: The FDA ordered a black box warning for the risk that testosterone gel products pose to children inadvertently exposed to those products by adults on May 7, 2009. [5]

 

[J2048b]

I did not know. Some believe he created an irrational fear that made the FDA add a black box warning on every testosterone product package insert.

So i have some questions in regards to that statement and the doc

Do u believe he did this? If he did why??

So Now im confused… was he saying u have less risk of blood clots and cardiovascular risks on testosterone OR was he saying its highly likely it can lead to these issues??

 

[Nelson Vergel]

TO YOUR GOOD HEATLH: Men with factor V Leiden can still receive testosterone therapy

DEAR DR. ROACH: I have factor V Leiden, but I have been wanting to do testosterone replacement therapy. I have heard that testosterone causes blood clots. Obviously, with FVL, that

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