Testosterone, Thrombophilia, Thrombosis

[Michael Scally MD]

[OA] Testosterone and Dihydrotestosterone Reduce Platelet Activation and Reactivity

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.

Karolczak K, Konieczna L, Kostka T, et al. Testosterone and dihydrotestosterone reduce platelet activation and reactivity in older men and women. Aging 2018. Aging

 

[Michael Scally MD]

Houghton DE, Alsawas M, Barrioneuvo P, et al. Testosterone therapy and venous thromboembolism: A systematic review and meta-analysis. Thrombosis Research. Redirecting

Highlights
· The Food and Drug Administration warns against VTE in testosterone users.
· 6 RCTs and 5 observational studies examining testosterone and VTE are reviewed.
· No significant association was found between testosterone and VTE.
· Limited data from RCTs and heterogeneity in observational studies limit conclusions.
· We conclude our review with 8 summarizing clinical management considerations.

Background - Testosterone prescribing for men has dramatically increased, and there have been concerns about inappropriate use and adverse events. While regulatory bodies have warned about increased risk of venous thromboembolism (VTE), published clinical data supporting an increased risk for VTE are limited.

Objective - To conduct a systematic review of studies examining the association between testosterone therapy in men and VTE.

Methods - Comprehensive searches of multiple databases were performed from inception through October 3rd, 2018. Randomized control trials (RCTs) and observational studies examining the association between exogenous testosterone (any route) and VTE. Study selection and data extraction were performed by two independent investigators. Random-effect model meta-analyses were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CIs). Heterogeneity among studies was evaluated using the I2 statistic. Risk of bias was assessed using the Cochrane and Newcastle-Ottawa tools.

Results - Six RCTs (n = 2236) and 5 observational studies (n = 1,249,640) were included. Five RCTs were performed in men with documented hypogonadism. The observational studies included: 2 case-control studies, 2 retrospective cohorts, and 1 retrospective cohort with a nested case-control study. There was no evidence of a statistically significant association between VTE and testosterone (OR 1.41, 95%CI 0.96–2.07). Heterogeneity was high (I-squared = 84.4%). The association remained nonsignificant when the analysis was stratified by study design: RCTs (2.05, 95% CI 0.78–5.39); cohort (1.06, 95% CI 0.85–1.33); and case-control (1.34, 95% CI 0.78–2.28). The overall risk of bias was moderate.

Conclusions - The current evidence is of low certainty but does not support an association between testosterone use and VTE in men.

 

[Michael Scally MD]

Anabolic Androgenic Steroid Abuse: The Effects on Thrombosis Risk, Coagulation, and Fibrinolysis

Anabolic androgenic steroid (AAS) abuse surged during the 1980s and is seen in approximately 1 in 20 of all males today. A wide spectrum of AAS compounds and abuse regimens are applied and AAS abuse has been associated with an unfavorable cardiovascular profile.

The aim of this review is to critique the collected data concerning effects of AAS abuse on thrombosis risk through presentation of condensed evidence from studies investigating AAS-induced changes in coagulation, fibrinolysis, and cardiovascular risk markers.

AAS abuse inflicts a procoagulant distribution of cardiovascular risk markers including dyslipidemia and atherosclerosis proneness. AAS abuse overall stimulates synthesis of coagulation factors, inhibitors, and fibrinolytic proteins resulting in both increased global coagulation and stimulation of fibrinolysis.

Overall, supported by many case reports and some epidemiological studies, AAS abuse is associated with an increased risk of thrombosis. However, to provide clear evidence for a causal relationship between AAS abuse and thrombosis risk, future studies need to address a range of potential biases, insufficient methodology, and other shortcomings of the current literature as highlighted in this review.

Chang S, Münster A-MB, Gram J, Sidelmann JJ. Anabolic Androgenic Steroid Abuse: The Effects on Thrombosis Risk, Coagulation, and Fibrinolysis. Semin Thromb Hemost 2018;44:734-46. Thieme E-Journals - Seminars in Thrombosis and Hemostasis / Abstract

 

[Michael Scally MD]

[OA] Medical Treatments for Hypogonadism Do Not Significantly Increase the Risk Of Deep Vein Thrombosis

OBJECTIVE: 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.

METHODS: Retrospective chart review of 1,180 consecutive hypogonadal men who were treated with either TRT or CC. Sixty-four percent had mixed, 16% had primary, and 20% had secondary hypogonadism.

RESULTS: Of the 1,180 men with hypogonadism, 694 were treated with TRT, while 486 were treated with CC. Overall, 10/1180 (0.8%) men were diagnosed with a DVT during the treatment, nine of whom were on TRT and one on CC. Of the 10 men diagnosed with DVT while on treatment, seven (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.

CONCLUSIONS: The overall of 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.

Kavoussi PK, Machen GL, Wenzel JL, et al. Medical treatments for hypogonadism do not significantly increase the risk of deep vein thrombosis over general population risk. Urology 2018. https://www.goldjournal.net/article/S0090-4295(18)31200-7/fulltext

 

[Michael Scally MD]

[OA] Testosterone Therapy, Thrombophilia, Venous Thromboembolism, and Thrombotic Events

In our sequential studies of 67 and 21 patients, testosterone therapy (TT) interacted with thrombophilia–hypofibrinolysis, leading to venous thromboembolism (VTE). Compared to 111 VTE controls not taking TT (VTE-no TT), the 67 and 21 cases were more likely (p < 0.05 for all) to have Factor V Leiden (FVL) heterogeneity (24% and 33% vs. 12%), the lupus anticoagulant (14% and 33% vs. 4%), and high lipoprotein(a) (33% vs. 13%, n = 21). After a first VTE and continuing TT, 11 thrombophilic cases had a second VTE despite adequate anticoagulation, 6 of whom, still anticoagulated, had a third VTE.

The greatest density of thrombotic events was at three months after starting TT, with a rapid decline by 10 months. From <1 to 8 months after starting TT, 65% of VTE occurred, which may reflect TT-induced depletion of susceptible thrombophilic patients, leaving a winnowed residual group with fewer VTE events despite the continuation of TT. Before starting TT, we suggest screening for FVL, lipoprotein(a), and the lupus anticoagulant to identify patients at increased VTE risk, with an adverse risk-to-benefit ratio for TT.

We suggest that TT should not be started in patients with known thrombophilia–hypofibrinolysis, and should not be continued after a first VTE. When TT is given to patients with thrombophilia–hypofibrinolysis, VTE may occur and then recur despite adequate anticoagulation.

Glueck CJ, Goldenberg N, Wang P. Testosterone Therapy, Thrombophilia, Venous Thromboembolism, and Thrombotic Events. Journal of Clinical Medicine. 2019; 8(1):11. Testosterone Therapy, Thrombophilia, Venous Thromboembolism, and Thrombotic Events

 

[Michael Scally MD]

Testosterone Therapy and Risk of Venous Thromboembolism Among Men Without Hypogonadism

Introduction: Testosterone therapy (TT) prescriptions among men increased over 300% from 2001 to 2013 because of relaxed TT prescription guidelines for common symptoms (such as low libido and fat redistribution) associated with natural declines in testosterone as age increases.

After concern about possible adverse cardiovascular effects from TT prompted a FDA warning in 2014, prescriptions of TT initially decreased and then plateaued. TT is often prescribed without clear clinical indication of a true hypogonadism diagnosis.

TT may increase VTE risk through hematocrit levels which affect blood viscosity and platelet accumulation for up to 6 months. Previous studies regarding the association between TT and VTE are both limited and unclear.

Objective: Using a case-crossover design, we assessed whether TT exposure increases the short-term risk of VTE. We also evaluated whether the association differed by age group.

Methods: The case-crossover study included men diagnosed with VTE identified using validated algorithms from 2012 to 2016 in the U.S. MarketScan Commercial and Medicare Supplemental administrative database.

After excluding participants with cancer and those with hypogonadism (for which TT is clinically indicated), we identified 36,251 male VTE patients with at least 1 year of follow-up prior to their diagnosis and evaluated whether they had a prescription for TT preceding their first VTE (0-6 months, ‘case period’ and 6-12 months ‘control period’).

Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) of TT in the case period relative to the control period, after adjusting for number of hospitalizations per period. Associations were also evaluated separately in VTE patients <65 vs. 65+ years old.

Results: Overall, 754 out of the 36,251 patients (2.1%) had at least 1 TT prescription during the 12 months prior to their VTE event. Of these, 588 were aged less than 65 years (78.0%) and 166 were aged 65+ years. Overall, use of TT did not vary substantially in the case period compared to the control period (OR: 1.19; 95% CI: 0.86, 1.64). However, the point estimate was slightly elevated for TT use (vs. no TT use) among men under 65 years old (OR: 1.31; 0.91, 1.89). For men aged 65+ the OR was 0.85 (95% CI: 0.42, 1.69).

Conclusions: Overall TT was not associated with greater risk of VTE among this population of men without hypogonadism. However, when stratified by age sub-group there was some suggestion of a higher association of TT in younger men.

This analysis suggests that TT overall is not a strong risk factor for VTE; however further studies are needed to determine if supraphysiologic TT doses especially those associated with polycythemia could increase VTE risk.

Walker Rob F, Zakai Neil A, MacLehose Richard F, Cowan Logan T, Alonso A, Lutsey Pamela L. Abstract P311: Testosterone Therapy and Risk of Venous Thromboembolism Among Men Without Hypogonadism. Circulation 2019;139:AP311-AP. https://doi.org/10.1161/circ.139.suppl_1.P311

 

[Michael Scally MD]

Association of Testosterone Therapy with Risk of Venous Thromboembolism Among Men With and Without Hypogonadism

Key Points

Question - Is clinical prescription of testosterone therapy associated with short-term risk of venous thromboembolism in men with and without hypogonadism?

Findings - In this case-crossover study comparing 6-month testosterone use for 39 622 men who had a venous thromboembolism with testosterone use 6 to 12 months before the venous thromboembolism, use of testosterone therapy in the 6-month case period was associated with an increased risk of venous thromboembolism among men with and without hypogonadism.

Meaning - The findings suggest that testosterone therapy is associated with increased short-term risk of venous thromboembolism among all men prescribed the therapy.

Walker RF, Zakai NA, MacLehose RF, et al. Association of Testosterone Therapy With Risk of Venous Thromboembolism Among Men With and Without Hypogonadism. JAMA Intern Med. Published online November 11, 2019. Testosterone Therapy and Venous Thromboembolism Risk in Men With and Without Hypogonadism

Importance - Testosterone therapy is increasingly prescribed in patients without a diagnosis of hypogonadism. This therapy may be associated with increased risk of venous thromboembolism (VTE) through several mechanisms, including elevated hematocrit levels, which increase blood viscosity.

Objective - To assess whether short-term testosterone therapy exposure is associated with increased short-term risk of VTE in men with and without evidence of hypogonadism.

Design, Setting, and Participants - This case-crossover study analyzed data on 39 622 men from the IBM MarketScan Commercial Claims and Encounter Database and the Medicare Supplemental Database from January 1, 2011, to December 31, 2017, with 12 months of follow-up. Men with VTE cases who were free of cancer at baseline and had 12 months of continuous enrollment before the VTE event were identified by International Classification of Diseases codes. Men in the case period were matched with themselves in the control period. Case periods of 6 months, 3 months, and 1 month before the VTE events were defined, with equivalent control periods (6 months, 3 months, and 1 month) in the 6 months before the case period.

Exposures - National drug codes were used to identify billed testosterone therapy prescriptions in the case period (0-6 months before the VTE) and the control period (6-12 months before the VTE).

Main Outcomes and Measures - The main outcome in this case-only experiment was first VTE event stratified by the presence or absence of hypogonadism.

Results - A total of 39 622 men (mean [SD] age, 57.4 [14.2] years) were enrolled in the study, and 3110 men (7.8%) had evidence of hypogonadism. In age-adjusted models, testosterone therapy use in all case periods was associated with a higher risk of VTE in men with (odds ratio [OR], 2.32; 95% CI, 1.97-2.74) and without (OR, 2.02; 95% CI, 1.47-2.77) hypogonadism.

Among men without hypogonadism, the point estimate for testosterone therapy and VTE risk in the 3-month case period was higher for men younger than 65 years (OR, 2.99; 95% CI, 1.91-4.68) than for older men (OR, 1.68; 95% CI, 0.90-3.14), although this interaction was not statistically significant (P = .14).

Conclusions and Relevance - Testosterone therapy was associated with an increase in short-term risk for VTE among men with and without hypogonadism, with some evidence that the association was more pronounced among younger men. These findings suggest that caution should be used when prescribing testosterone therapy.

 

[Michael Scally MD]

[OA] Metabolic Syndrome Increases Risk of Venous Thromboembolism Recurrence After Acute Deep Vein Thrombosis

An improved understanding of which patients are at higher risk of recurrent venous thromboembolism (VTE) is important to designing interventions to reduce degraded quality of life after VTE. Although metabolic syndrome (MetS), the clustering of hypertension, hyperlipidemia, diabetes mellitus, and obesity has been associated with a hypofibrinolytic state, data linking VTE recurrence with MetS remain limited.

The purpose of this study was to measure the prevalence of MetS in patients with deep vein thrombosis (DVT) across a large population and determine its effect on VTE recurrence. This was a retrospective analysis of a large statewide database from 2004 to 2017. We measured the frequency with which patients with DVT carried a comorbid International Coding of Diseases diagnosis of MetS components. Association of MetS with VTE recurrence was tested with a multiple logistic regression model and VTE recurrence as the dependent variable. Risk of VTE recurrence conferred by each MetS component was assessed by Kaplan-Meier curves with the log-rank statistic.

A total of 151 054 patients with DVT were included in this analysis. Recurrence of VTE occurred in 17% overall and increased stepwise with each criterion for MetS. All 4 components of MetS had significant adjusted odds ratios (OR) for VTE recurrence, with hyperlipidemia having the largest (OR, 1.8), representing the 4 largest ORs of all possible explanatory variables. All 4 MetS variables were significant on Kaplan-Meier analysis for recurrence of VTE. These data imply a role for appropriate therapies to reduce the effects of MetS as a way to reduce risk of VTE recurrence.

Stewart LK, Kline JA. Metabolic syndrome increases risk of venous thromboembolism recurrence after acute deep vein thrombosis. Blood Adv. 2020;4(1):127-135. https://ashpublications.org/bloodadvances/article-lookup/doi/10.1182/bloodadvances.2019000561

 

[Michael Scally MD]

The Effect of Anabolic-Androgenic Steroid Abuse on The Contact Activation System

The effect of anabolic-androgenic steroid (AAS) abuse on the contact activation system (CAS) is not known in detail. We hypothesized that current AAS abuse reduces the kallikrein generating capacity of CAS significantly and investigated the impact of AAS on the proteins and capacity of CAS in current and former AAS abusers and healthy age matched controls.

Men 18 to 50 years of age were included as current AAS abusers, former AAS abusers or controls. Blood samples were collected after overnight fasting. Kallikrein generation (lag time, peak height, and endogenous kallikrein potential (EKP)), coagulation factor XII (FXII), prekallikrein, high molecular weight kininogen (HK), and C1 esterase inhibitor (C1inh) were assessed.

Groups were compared by ANOVA or Kruskal-Wallis test and probabilities were corrected for multiple comparisons. Associations were evaluated by linear regression models.

The EKP was significantly reduced in current (n=37) AAS abusers (984 ± 328 nmol/L x min) compared to former (n=33) abusers (1543 ± 481 nmol/L x min) and controls (n=30) (1521 ± 339 nmol/L x min), p<0.001. Current abusers had higher levels of FXII and C1inh and lower levels of prekallikrein and HK than controls, p ≤ 0.025. Stepwise regression analysis showed that EKP was associated with C1inh and prekallikrein in current AAS abusers, R2 = 0.70, p<0.001.

We conclude that current AAS abuse reduces the kallikrein generating capacity of CAS by increasing the concentration of C1inh and reducing the concentration of prekallikrein. These changes may contribute to the anti-inflammatory effect of testosterone.

Sidelmann JJ, Gram JB, Palarasah Y, Rasmussen JJ, Kistorp C. The effect of anabolic-androgenic steroid abuse on the contact activation system. Thromb Haemost. 2021 Jan 5. doi: 10.1055/a-1346-3384. Epub ahead of print. PMID: 33401331. https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1346-3384

 

[Michael Scally MD]

[OA] Effects of Exogenous Androgens on Platelet Activity and Their Thrombogenic Potential in Supraphysiological Administration

Anabolic androgenic steroids (AAS), simply called "androgens", represent the most widespread drugs used to enhance performance and appearance in a sporting environment. High-dosage and/or long-term AAS administration has been associated frequently with significant alterations in the cardiovascular system, some of these with severe endpoints.

The induction of a prothrombotic state is probably the most life-threatening consequence, suggested by numerous case reports in AAS-abusing athletes, and by a considerable number of human and animal studies assessing the influence of exogenous androgens on hemostasis.

Despite over fifty years of research, data regarding the thrombogenic potential of exogenous androgens are still scarce. The main reason is the limited possibility of conducting human prospective studies.

However, human observational studies conducted in athletes or patients, in vitro human studies, and animal experiments have pointed out that androgens in supraphysiological doses induce enhanced platelet activity and thrombopoiesis, leading to increased platelet aggregation. If this tendency overlaps previously existing coagulation and/or fibrinolysis dysfunctions, it may lead to a thrombotic diathesis, which could explain the multitude of thromboembolic events reported in the AAS-abusing population.

The influence of androgen excess on the platelet activity and fluid-coagulant balance remains a subject of debate, urging for supplementary studies in order to clarify the effects on hemostasis, and to provide new compelling evidence for their claimed thrombogenic potential.

Roşca AE, Vlădăreanu AM, Mititelu A, Popescu BO, Badiu C, Căruntu C, Voiculescu SE, Onisâi M, Gologan Ş, Mirica R, Zăgrean L. Effects of Exogenous Androgens on Platelet Activity and Their Thrombogenic Potential in Supraphysiological Administration: A Literature Review. J Clin Med. 2021 Jan 4;10(1):E147. doi: 10.3390/jcm10010147. PMID: 33406783. Effects of Exogenous Androgens on Platelet Activity and Their Thrombogenic Potential in Supraphysiological Administration: A Literature Review

 

[Michael Scally MD]

Testosterone Replacement Therapy and The Risk of Venous Thromboembolism

Highlights

In the last 3 decades, testosterone use has increased 10-fold in North America.

However, the cardiovascular safety of testosterone use has remained controversial.

Our meta-analysis of randomized trials examined the VTE risk of testosterone use.

We found no evidence of an increased risk of VTE with testosterone use.

Given the low quality of evidence, there is a need for further studies in this area.

Introduction: The cardiovascular safety of testosterone replacement therapy (TRT) is controversial. While several studies have investigated the association between TRT and the risk of arterial thrombosis, limited information is available regarding its risk of venous thromboembolism (VTE). We aimed to compare the risk of VTE in men randomized to TRT versus placebo or active-comparator in a systematic review.

Methods: We searched Medline, EMBASE, CINAHL, CENTRAL, and clinical trial registries to identify randomized controlled trials (RCTs) comparing TRT to placebo in men aged ≥18 years. We assessed study quality using the Cochrane Risk of Bias assessment tool and the overall quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Data were pooled across RCTs using random-effects models.

Results: A total of 13 RCTs (n = 5050) were included in our meta-analysis. In all, 2636 men were randomized to testosterone, and 2414 men to placebo. Sample sizes ranged from 101 to 790 men, and TRT duration from 3 to 36 months. Five studies had a high risk of bias, largely driven by unclear randomization and outcome assessment.

When data were pooled across RCTs, testosterone therapy was not associated with VTE compared with placebo (RR: 1.03, 95% CI: 0.49-2.14; I2: 0%; low-quality evidence). Similar estimates were obtained for deep vein thrombosis and pulmonary embolism outcomes.

Conclusions: 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.

Ayele HT, Brunetti VC, Renoux C, Tagalakis V, Filion KB. Testosterone replacement therapy and the risk of venous thromboembolism: A systematic review and meta-analysis of randomized controlled trials. Thromb Res. 2021 Jan 6;199:123-131. doi: 10.1016/j.thromres.2020.12.029. Epub ahead of print. PMID: 33486321. Testosterone replacement therapy and the risk of venous thromboembolism: A systematic review and meta-analysis of randomized controlled trials

 

[Michael Scally MD]

Testosterone Replacement Therapy Causing Extensive Portal and Mesenteric Vein Thrombosis

A 62-year-old man presented to our emergency department reporting a 1 week history of diffuse abdominal pain. His initial vital signs were unremarkable. His past medical history was significant for panhypopituitarism secondary to a remote head trauma. His home medications included intramuscular testosterone cypionate 120 mg weekly.

His initial laboratory values were only remarkable for polycythemia (hemoglobin of 177 g/L) ( Table 1).

A contrast-enhanced abdominal computerized tomography showed extensive venous thrombosis of the portal vein, the superior mesenteric vein and most of the splenic vein, causing mesenteric ischemia (Figure 1). He underwent an urgent laparotomy and was started on intravenous unfractionated heparin.

Poirier-Blanchette L, Koolian M, Schwartz BC. Testosterone Replacement Therapy Causing Extensive Portal and Mesenteric Vein Thrombosis. Am J Med. 2021 Jan 11:S0002-9343(21)00010-3. doi: 10.1016/j.amjmed.2020.12.018. Epub ahead of print. PMID: 33444584. https://www.amjmed.com/article/S0002-9343(21)00010-3/fulltext


Contrast-enhanced abdominal computerized tomography – coronal plane showing the absence of contrast in the portal vein thrombosis.

 

[Avies48]

Testosterone Replacement Therapy Causing Extensive Portal and Mesenteric Vein Thrombosis

A 62-year-old man presented to our emergency department reporting a 1 week history of diffuse abdominal pain. His initial vital signs were unremarkable. His past medical history was significant for panhypopituitarism secondary to a remote head trauma. His home medications included intramuscular testosterone cypionate 120 mg weekly.

His initial laboratory values were only remarkable for polycythemia (hemoglobin of 177 g/L) ( Table 1).

A contrast-enhanced abdominal computerized tomography showed extensive venous thrombosis of the portal vein, the superior mesenteric vein and most of the splenic vein, causing mesenteric ischemia (Figure 1). He underwent an urgent laparotomy and was started on intravenous unfractionated heparin.

Poirier-Blanchette L, Koolian M, Schwartz BC. Testosterone Replacement Therapy Causing Extensive Portal and Mesenteric Vein Thrombosis. Am J Med. 2021 Jan 11:S0002-9343(21)00010-3. doi: 10.1016/j.amjmed.2020.12.018. Epub ahead of print. PMID: 33444584. https://www.amjmed.com/article/S0002-9343(21)00010-3/fulltext


Contrast-enhanced abdominal computerized tomography – coronal plane showing the absence of contrast in the portal vein thrombosis.

View attachment 141538

Wow thats pretty scarry,

Ive had a lot of stomach pains since ive been on trt, wonder if i can get one of these done and show my doc this to assist in getting 9ne done

 

[Michael Scally MD]

Wow thats pretty scarry,

Ive had a lot of stomach pains since ive been on trt, wonder if i can get one of these done and show my doc this to assist in getting 9ne done

Not worth worrying ... anecdotal.

 

[Michael Scally MD]

[OA] Association of Genetically Predicted Serum Estradiol with Risk of Thromboembolism

Context: An association was recently reported between genetic markers related to high testosterone and increased risk of thromboembolism in men but a possible causal role of estradiol for risk of thromboembolism in men remains unknown.

Objective: To determine whether endogenous estradiol has a causal role in thromboembolism in men.

Design: Two-sample mendelian randomization study using gene-based genetic instruments.

Setting: UK Biobank.

Participants: We assessed the association between endogenous estradiol genetically predicted by 22 variants in the CYP19A1 gene region and risk of thromboembolism (5815 cases) in 170,593 unrelated men of white ancestry in the UK Biobank.

Main outcome measure: Thromboembolism based on self-reports, hospital episodes, and death.

Results: Endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with risk of thromboembolism (odds ratio per SD increase in estradiol 0.74, 95% confidence interval 0.62-0.90). In contrast, genetic variants in the JMJD1C gene, used as a predictor of high endogenous testosterone, were associated with an increased risk of thromboembolism (odds ratio per SD increase in testosterone 1.39, 1.12-1.72).

Subsequent explorative analyses evaluating potential repercussions of thromboembolism revealed that endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with risk of ischemic stroke (0.68, 0.49-0.95) but not myocardial infarction (0.97, 0.84-1.13).

Conclusions: Genetically predicted estradiol was inversely associated with risk of thromboembolism and ischemic stroke in men. The ratio between testosterone and estradiol, determined by aromatase (CYP19A1) activity, may contribute to the overall impact of sex steroids on thromboembolism in men.

Nethander M, Quester J, Vandenput L, Ohlsson C. Association of genetically predicted serum estradiol with risk of thromboembolism in men: A mendelian randomization study. J Clin Endocrinol Metab. 2021 Mar 11:dgab164. doi: 10.1210/clinem/dgab164. Epub ahead of print. PMID: 33705547. Association of genetically predicted serum estradiol with risk of thromboembolism in men: A mendelian randomization study