Testosterone supplementation associated with development of DVT-PE-osteonecrosis

[cjg]

We have published two new original data manuscripts which focus on deep venous thrombosis-pulmonary emboli-osteonecrosis which occur when testosterone is given to men or women with previously undiagnosed thrombophilia. We have provided new data which shows that when testosterone is continued in men with thrombophilia, despite adequate anticoagulation, recurrent deep venous thrombosis-pulmonary emboli occur. We are glad to provide free consultation to any man or woman who has sustained DVT-PE-osteonecrosis after testosterone therapy or HCG therapy to increase endogenous testosterone. Contact us at Cholesterol Center, Jewish Hospital, Cincinnati OH (CJ Glueck MD)


Thrombophilia in 67 Patients With
Thrombotic Events After Starting
Testosterone Therapy

Charles J. Glueck, MD1, Marloe Prince, MD1,
Niravkumar Patel, MD1, Jaykumar Patel, MD1, Parth Shah, MD1,
Nishi Mehta, MD1, and Ping Wang, PhD1

Clinical and Applied Thrombosis/Hemostasis, 2015, pages 1-6
DOI: 10.1177/1076029615619486 Abstract

We compared thrombophilia in 67 cases (59 men and 8 women) with thrombotic events after starting testosterone therapy (TT) versus 111 patient controls having unprovoked venous thrombotic events without TT. In the 67 patients, thrombosis (47 deepvenous thrombosis–pulmonary embolism, 16 osteonecrosis, and 4 ocular thrombosis) occurred 6 months (median) after starting TT. Cases differed from controls for factor V Leiden heterozygosity (16 of the 67 [24%] vs 13 [12%] of the 111, P . .038) and forlupus anticoagulant (9 [14%] of the 64 vs 4 [4%] of the 106, P . .019). After a first thrombotic event and continuing TT, 11 caseshad a second thrombotic event, despite adequate anticoagulation, 6 of whom, still anticoagulated, had a third thrombosis.Screening for thrombophilia before starting TT should identify men and women at high risk for thrombotic events with an adverserisk–benefit ratio for TT. When TT is given to patients with familial and acquired thrombophilia, thrombosis may occur and recur
in thrombophilic men despite anticoagulation.


Testosterone Therapy Can Interact With Thrombophilia, Leading to Osteonecrosis
Charles J. Glueck, MD; RashidRiaz, MD; Marloe Prince, MD; RichardA. Freiberg, MD; PingWang, PhD
The authors are from the Cholesterol, Metabolism, and Thrombosis Center (CJG, PW), Jewish Hospital of Cincinnati, Cincinnati; and the Internal Medicine Resident Training Program (RR, MP) and the Department of Orthopedics (RAF), VA Hospital, Cincinnati, Ohio.
The authors have no relevant financial relationships to disclose.
This study was supported by the Lipoprotein Research Fund, Jewish Hospital of Cincinnati.
Correspondence should be addressed to: Charles J. Glueck, MD, Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati, Ste 430, 2135 Dana Ave, Cincinnati, OH 45207
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 (≥42.6 pg/mL) in 4. When testosterone therapy is given to patients with thrombophilia, they are at increased risk for osteonecrosis. [Orthopedics. 2015; 38(12):e1073-e1078.]

 

[Vince]

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

 

[Nelson Vergel]

Dr Glueck

What do you think about this report?

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.” – 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.

 

[cjg]

Epidemiologic studies of VTE in TRT users and non users

So far, epidemiologic studies of TRT users vs non users have not shown a statistically significant increase in VTE in users. Other studies are underway, particularly in Klinefelter's patients. Ultimately, we need a controlled clinical trial for men with TRT like the estrogen-progestin trial (Women's Health Initiative) to solve two pressing questions: On a population wide basis, does TRT increase VTE and Myocardial infarction. Until we have such a trial, it will be difficult to answer these pressing questions, and the history of estrogen-progestin studies before WHI is telling, in that there was no unanimity whether e-p was good, bad, or indifferent. CJ Glueck MD

 

[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]

I wonder if statins would help prevent DVT in men with genetic predisposition to DVT on TRT

Statins may lower vein blood clot risk among women on hormone therapy

Researchers from the University of Texas Medical Branch have found that adding statin therapy may help lower venous thromboembolism risk in women taking menopausal hormone therapy.

www.medicalnewstoday.com