Testosterone, Thrombophilia, Thrombosis

[Kinikuman]

Blood Coagulation & Fibrinolysis
Issue: Volume 25(7), October 2014, p 683–687
Copyright: © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

Testosterone, thrombophilia, thrombosis
Glueck, Charles J.a; Friedman, Joelb; Hafeez, Ahsanb; Hassan, Atifb; Wang, Pinga


Abstract
We assessed previously undiagnosed thrombophilia–hypofibrinolysis in 11 testosterone (T)-taking men, five of whom developed deep venous thrombosis (DVT), four pulmonary embolism, one spinal cord infarction, and one osteonecrosis 3.5 months (median) after starting T gel (50–160 mg/day) or T intramuscular (50–250 mg/week). In the order of referral because of thrombosis after starting T, thrombophilia–hypofibrinolysis was studied in 11 men, and, separately, in two control groups without thrombosis – 44 healthy normal male controls and 39 healthy men taking T. Nine men had DVT or DVT–pulmonary embolism after 3.5 months (median) on T, one spinal cord infarction after 5 days on T, and one had osteonecrosis (knee and then hip osteonecrosis after 6 and 18 months on T). Four of the 11 men (36%) had high factor VIII (>=150%) vs. one of 42 (2%) controls (P = 0.005), and vs. one of 25 (4%) T-controls, (P = 0.023). Of the 11 men, two (18%) had factor V Leiden heterozygosity vs. none of 44 controls, (P = 0.04) and vs. none of 39 T-controls(P = 0.045). Of the 11 men, three had 4G4G plasminogen activator inhibitor-1 homozygosity, one prothrombin G20210A heterozygosity, one low protein S, and one high factor XI. When T was continued, second DVT–pulmonary embolism recurred in three of 11 men despite adequate anticoagulation. T interacts with thrombophilia–hypofibrinolysis leading to thrombosis. Men sustaining DVT–pulmonary embolism–osteonecrosis on T should be studied for thrombophilia. Continuation of T in thrombophilic men appears to be contraindicated because of recurrent thrombosis despite adequate anticoagulation. Before starting T, to prevent T-associated thrombosis, we recommend measures of factor V Leiden, factor VIII, and the prothrombin gene.

 

[Michael Scally MD]

Renukanthan A, Quinton R, Turner B, MacCallum P, Seal L, et al. Kallmann syndrome patient with gender dysphoria, multiple sclerosis, and thrombophilia. Endocrine. http://link.springer.com/article/10.1007/s12020-015-0562-5

One of the challenging issues in patients with complex problems is that the various diseases and their treatment can influence each other and present unusual hurdles in management.

We investigated one such complex case. A 34-year-old XY male presented with azoospermia, detected on semen analysis for pre-orchidectomy sperm banking. He had a 20-year history of gender dysphoria and bilateral breast swelling. The patient suffered a deep vein thrombosis at the age of 19 years.

Examination confirmed clinical features of Kallmann syndrome including unilateral cryptorchidism, micropenis, congenital anosmia, and bimanual synkinesis (mirror movements), with reduced serum testosterone and normal gonadotropin levels demonstrating hypogonadotropic hypogonadism. MRI showed missing olfactory bulbs.

Osteopenia and reduced vitamin D levels of 21 nmol/L were identified. He was found to harbor a heterozygous factor-V-Leiden mutation.

The genetic basis of Kallmann syndrome remains unknown: his screening tests were negative for mutations in CHD7, FGF8, FGFR1, GNRH1, GNRHR, HS6ST1, KAL1, KISS1R, KISS1, NELF, PROK2, PROKR2, TAC3, and TACR3. The patient initially declined testosterone therapy with a view to undergo gender reassignment.

Over the next 2 years, the patient experienced recurrent episodes of weakness and paresthesia, associated with classical MRI appearances of multiple sclerosis-related demyelination in the spinal cord and brain.

Although it was difficult to elucidate an association between the patient's gender dysphoria and untreated congenital hypogonadism, his desire to become female together with his co-existing thrombophilia, presented challenges to the administration of hormone treatment.

Furthermore, we have considered an association between multiple sclerosis and hypogonadotropic hypogonadism.

 

[Michael Scally MD]

The Effect of Androgen Replacement Therapy on Platelet Aggregation in Male Patients with Isolated Hypogonadotropic Hypogonadism
http://www.endocrine-abstracts.org/ea/0037/ea0037ep177.htm

Aim: To evaluate the effect of androgen replacement therapy on lipid profile and platelet aggregation in in male patients with isolated hypogonadotropic hypogonadism (IHH).

Material and methods: 36 male patient, mean age 32.2 (18–54)with IHH, admitted to the outpatient clinic of Endocrinology and Metabolism were included to the study. Patients in the study were divided into two groups as Testosterone (n=18) and human chorionic gonadotropin (HCG) therapy (n=18) groups. Total testosterone, fasting plasma glucose (FPG), alanine aminotransferase (ALT), lipid profile, mean platelet volume (MPV), platelet distribution width (PDW) and platelet count were evaluated before and after 6 months of the treatment in all patients.

Results: There was no statistically significant difference according to FPG, triglyceride levels, MPV and platelet counts when all patients (n=36) were evaluated due to pre-treatment and post-treatment (P>0.05). However, ALT and LDL levels were detected statistically significantly lower after treatment (P>0.05), HDL, PDW and testosterone levels were significantly higher after treatment (P<0.05). There was no significant difference due to testosterone, FPG, ALT, lipid profile, MPV, PDW and platelet levels compared according to treatment (HCG (n=18), and testosterone replacement (n=18)) (P>0.05). While there was negative correlation with testosterone and ALT levels (r=−0.25, P=0.03), positive correlation was detected between testosterone and PDW (r=0.31, P=0.007).

Conclusion: Platelets are involved in homeostatic process and have an important role in atherosclerosis and arterial thrombosis. MPV and PDW are two markers of platelet activation, and have recently been recognised as risk predictors of cardiovascular diseases. Our study revealed that androgen replacement therapy may have beneficial effects on lipid profile and ALT and negative effects on platelet aggregation. Therefore, we think that this situation should be taken into consideration when androgen replacement therapy is planned.

 

[Michael Scally MD]

Baillargeon J, Urban RJ, Morgentaler A, Glueck CJ, Baillargeon G, et al. Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy. Mayo Clinic Proceedings. http://www.mayoclinicproceedings.org/article/S0025-6196(15)00428-0/abstract

Objective - To examine the risk of venous thromboembolism (VTE) associated with exposure to testosterone therapy in middle-aged and older men.

Patients and Methods - We conducted a case-control study of 30,572 men 40 years and older who were enrolled in one of the nation’s largest commercial insurance programs between January 1, 2007, and December 31, 2012. Cases were defined as men who had a primary diagnosis of VTE and received an anticoagulant drug in the 60 days after their diagnoses. Cases were matched with 3 controls on event/index month, age, geographic region, diagnosis of hypogonadism, and diagnosis of any underlying prothrombotic condition. Conditional logistic regression analysis was used to calculate adjusted odds ratios (aORs) and 95% CIs for the risk of VTE associated with previous exposure to testosterone therapy.

Results - Exposure to testosterone therapy in the 15 days before the event/index date was not associated with an increased risk of VTE (aOR, 0.90; 95% CI, 0.73-1.12). None of the specific routes of administration examined were associated with an increased risk of VTE (topical [aOR, 0.80; 95% CI, 0.61-10.41], transdermal [aOR, 0.91; 95% CI, 0.38-2.16], and intramuscular [aOR, 1.15; 95% CI, 0.80-1.64]). These findings persisted using exposure windows that extended to 30 and 60 days before the event/index date.

Conclusion - Having filled a prescription for testosterone therapy was not associated with an increased risk of VTE in commercially insured middle-aged and older men. These findings may provide clinically relevant information about the benefit-risk assessment for men with testosterone deficiency considering treatment.

 

[Michael Scally MD]

Li H, Benoit K, Wang W, Motsko S. Association between use of exogenous testosterone therapy (eTT) and risk of venous-thrombotic-events among eTT-treated and untreated men with hypogonadism. The Journal of Urology. https://www.sciencedirect.com/science/article/pii/S0022534715051575

Purpose Limited information exists about whether exogenous testosterone therapy (eTT) is associated with risk of venous thrombotic events (VTE). Here, we investigate via cohort and nested-case-control analyses whether eTT administration is associated with risk of VTE in men with hypogonadism.

Materials and Methods Databases were reviewed to identify men prescribed eTT and/or men with a hypogonadism diagnosis. Propensity-score 1:1 matching was used to select patients for the cohort analysis. Cases (men with VTE) were matched 1:4 with controls (men without VTE) for the nested-case-control analysis.

Primary outcome was defined as incident idiopathic VTE; Cox regression and conditional-logistic regression were used to assess hazard ratios (HRs) and odds ratios (ORs), respectively. Sensitivity analyses were also performed.

Results 102,650 eTT-treated patients and 102,650 untreated patients were included in the cohort analysis after matching; 2785 cases and 11,119 controls were included in the case-control analysis.

Cohort analysis revealed an HR of 1.08 for all eTT-treated patients (95% CI: 0.91, 1.27; p=0.378). Case-control analysis resulted in OR=1.02 (95% CI: 0.92, 1.13; p=0.702) for current eTT exposure and 0.92 (95% CI: 0.82, 1.03; p=0.145) for past eTT exposure.

These results remained non statistically significant after stratifying by eTT-administration-route and age category. Results from most of the sensitivity analyses yielded results that were consistent.

Conclusions NO SIGNIFICANT ASSOCIATION WAS FOUND BETWEEN eTT AND INCIDENTS OF IDIOPATHIC VTE, AS WELL AS OVERALL VTE IN MEN WITH HYPOGONADISM; HOWEVER, SOME DISCREPANT FINDINGS EXIST FOR THE ASSOCIATION BETWEEN INJECTABLE FORMULATIONS AND OVERALL VTE RISK.

 

[Michael Scally MD]

Inherited Antithrombin Deficiency and Anabolic Steroids: A Risky Combination

A 20-year-old male with asymptomatic inherited type 1 antithrombin deficiency and a family history of thrombosis started injecting himself with testosterone 250 mg intramuscularly twice weekly for 5 weeks.

He presented to the hospital with progressive dyspnea on exertion, chest pain and hemoptysis.

Workup revealed bilateral submassive pulmonary embolism and proximal right lower extremity deep vein thrombosis.

He was treated with intravenous (IV) unfractionated heparin and underwent catheter-directed thrombolysis with alteplase to the main pulmonary arteries.

Postprocedure, he remained on IV alteplase infusion for 24 h and unfractionated heparin in the intensive care unit.

Concomitantly he received plasma-derived antithrombin concentrate.

He was transitioned to subcutaneous enoxaparin twice daily and discharged from the hospital on oral rivaroxaban 15 mg twice a day.

This case highlights the heightened thrombogenic effect of anabolic steroids in the setting of underlying thrombophilia especially in younger subjects.

Choe H, Elfil M, DeSancho MT. Inherited antithrombin deficiency and anabolic steroids: a risky combination. Blood Coagul Fibrinolysis. http://www.ncbi.nlm.nih.gov/pubmed/26588446

 

[Michael Scally MD]

Glueck CJ, Prince M, Patel N, et al. Thrombophilia in 67 Patients With Thrombotic Events After Starting Testosterone Therapy. Clin Appl Thromb Hemost. http://cat.sagepub.com/content/early/2015/11/27/1076029615619486.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 deep venous 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 for lupus anticoagulant (9 [14%] of the 64 vs 4 [4%] of the 106, P = .019). After a first thrombotic event and continuing TT, 11 cases had 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 adverse risk-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.

 

[Michael Scally MD]

Editorial Comment – Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy

The Food and Drug Administration has added a warning to testosterone replacement therapy package inserts regarding the possibility that use of these agents may increase the risk of venous thromboembolism (VTE).

This important study appears to help refute that claim. The authors conducted a case-control study of 30,572 men 40 years or older who were enrolled in one of the largest national commercial insurance programs between January 1, 2007 and December 31, 2012.

Cases were defined as individuals who had a primary diagnosis of VTE and received an anticoagulant drug in the 60 days after their diagnoses. Cases were matched with 3 controls on event/index month, age, geographic region, diagnosis of hypogonadism and diagnosis of any underlying prothrombotic condition. Conditional logistic regression analysis was used to calculate adjusted ORs and 95% CIs for the risk of VTE associated with previous exposure to testosterone therapy.

Exposure to testosterone therapy in the 15 days before the event/index date was not associated with an increased risk of VTE (adjusted OR 0.90, 95% CI 0.73–1.12). These data are reassuring and provide guidance to the clinician.

Seftel AD. Re: Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy. J Urol 2016;195(2):441-2. https://www.sciencedirect.com/science/article/pii/S0022534715051277

 

[Michael Scally MD]

Prince M, Glueck CJ, Shah P, et al. Hospitalization for pulmonary embolism associated with antecedent testosterone or estrogen therapy in patients found to have familial and acquired thrombophilia. BMC Hematol 2016;16:6. BMC Hematology

BACKGROUND: In patients hospitalized over a 4 year period for pulmonary embolism (PE), we assessed relationships of testosterone (TT) and estrogen therapy (ET) anteceding PE in patients found to have familial-acquired thrombophilia.

METHODS: From 2011 through 2014, 347 patients were hospitalized in Cincinnati Mercy Hospitals with PE. Retrospective chart review was used to identify patients receiving TT or ET before PE; coagulation studies were done prospectively if necessary.

RESULTS: Preceding hospitalization for PE, 8 of 154 men (5 %) used TT, and 24 of 193 women (12 %) used ET. The median number of months from the initiation of TT or ET to development of PE was 7 months in men and 18 months in women.

Of the 6 men having coagulation measures, all had >/= 1 thrombophilia, and of the 18 women having measures of coagulation, 16 had >/= 1 thrombophilia. The sensitivity of a previous history of thrombosis to predict PE was low, 25 % (2/8 men), 4 % (1/24 women).

CONCLUSIONS: Of 154 men hospitalized for PE, 8 (5 %) used TT, and of 193 women, 24 (12 %) used ET. Our data suggests that PE is an important complication of TT in men and ET in women, in part reflecting an interaction between familial and acquired thrombophilia and exogenous hormone use.

 

[Michael Scally MD]

[No] Association between Testosterone Replacement Therapy and the Incidence of Deep Vein Thrombosis and Pulmonary Embolism

BACKGROUND: Testosterone Replacement Therapy (TRT) prescriptions have increased several-fold in the last decade. There have been concerns regarding a possible increased incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) with TRT. There is a paucity of data to support the association between TRT and DVT/ PE. We evaluated the incidence of DVT and PE in men who were prescribed TRT for low serum total testosterone levels (sTT).

METHODS: This is a retrospective cohort study, conducted using data obtained from the Veterans Administrations Informatics and Computing Infrastructure (VINCI). We compared the incidence of DVT/PE between those who received TRT and subsequently had normal on-treatment sTT levels (Gp1), those who received TRT but continued to have low on-treatment sTT (Gp2), and those who did not receive TRT (Gp3). Those with prior history of DVT/PE, cancer, hypercoagulable state and chronic anticoagulation were excluded.

RESULTS: The final cohort consisted of 71,407 subjects with low baseline sTT. Of these, 10,854 did not receive TRT (Gp3) and 60,553 received TRT. Of those who received TRT, 38362 achieved normal sTT (Gp1) while 22191 continued to have low sTT (Gp2). The incidence of DVT/PE was 0.5%, 0.4% and 0.4% in Gp1, Gp2 and Gp3 respectively. Univariate, Multivariate, and Stabilized inverse probability of treatment weights (SIPTW) analyses showed no statistically significant difference in DVT/PE free survival between different groups.

CONCLUSION: This study did not detect a significant association between testosterone replacement therapy and risk of DVT/PE in adult men with low sTT who were at low-moderate baseline risk of DVT/PE.

Sharma R, Oni OA, Chen G, et al. Association between Testosterone Replacement Therapy and the Incidence of Deep Vein Thrombosis and Pulmonary Embolism: A Retrospective Cohort Study of the Veterans Administration Database. Chest. https://www.sciencedirect.com/science/article/pii/S0012369216490008

 

[Michael Scally MD]

Mumoli N, Cei M, Giorgi Pierfranceschi M, Brondi B, Vitale J, Dentali F. Endogenous sex hormone levels in men with unprovoked deep-vein thrombosis. Thromb Haemost 2016;114(2):438-9. https://th.schattauer.de/en/contents/archive/issue/2238/manuscript/24279.html (Archive)

A potential thrombogenic effect in men for testosterone and estradiol has been reported by several laboratory studies.

However, according to the results of our study, sex hormones did not seem to have a role in the pathogenesis of unprovoked DVT in male patients.

Our findings are in agreement with results of two previous prospective cohort studies conducted in general population.

In these studies altered concentrations of testosterone and estradiol measured at the time of enrollment did not appear to predict future VTEs. As a step further, in our study, these hormones did not appear to be altered even during the acute phase of unprovoked DVT reinforcing the results of previous studies.

Thus, from the practical point of view, sex hormones should not be tested in male patients presenting with an episode of unprovoked VTE. To date, no information is available on their potential role on the risk of VTE recurrence in these patients and other studies are necessary to clarify this issue.

 

[Michael Scally MD]

[OA] Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant

BACKGROUND: When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued.

CASE PRESENTATION: A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis.

In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism.

Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin).

Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux).

One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE.

Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months.

CONCLUSION: When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation.

Glueck CJ, Lee K, Prince M, Jetty V, Shah P, Wang P. Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant. J Investig Med High Impact Case Rep 2016;4(3):2324709616661833. Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant

 

[Michael Scally MD]

[OA] Successful Penile Reconstruction Following Prior Arteriovenous Loop Thrombosis Due to Undiagnosed Protein-S Deficiency and Exogenous Testosterone

Flap failure from microvascular thrombotic occlusion is a rare but significant cause for unsuccessful reconstructive surgery.

We encountered thrombosis of arteriovenous loop in a patient undergoing phallus reconstruction. Further investigations revealed underlying previously asymptomatic hypercoagulable state due to protein-S deficiency in addition to long-term exogenous testosterone administration.

Role of thrombophilia testing, thrombogenic potential of testosterone and the need for therapeutic perioperative anti-coagulation in such situations are described here.

Anoop P, Malmande V, Prakash Kumar MN, Rao N. Successful penile reconstruction following prior arteriovenous loop thrombosis due to undiagnosed protein-S deficiency and exogenous testosterone. Indian J Plast Surg 2016;49(2):268-70. Successful penile reconstruction following prior arteriovenous loop thrombosis due to undiagnosed protein-S deficiency and exogenous testosterone Anoop P, Malmande V, Prakash Kumar M N, Rao N - Indian J Plast Surg

 

[Michael Scally MD]

[OA] Martinez C, Suissa S, Rietbrock S, et al. Testosterone treatment and risk of venous thromboembolism: population based case-control study. BMJ 2016;355. Testosterone treatment and risk of venous thromboembolism: population based case-control study | The BMJ

Objective To determine the risk of venous thromboembolism associated with use of testosterone treatment in men, focusing particularly on the timing of the risk.

Design Population based case-control study

Setting 370 general practices in UK primary care with linked hospital discharge diagnoses and in-hospital procedures and information on all cause mortality.

Participants 19 215 patients with confirmed venous thromboembolism (comprising deep venous thrombosis and pulmonary embolism) and 909 530 age matched controls from source population including more than 2.22 million men between January 2001 and May 2013.

Exposure of interest Three mutually exclusive testosterone exposure groups were identified: current treatment, recent (but not current) treatment, and no treatment in the previous two years. Current treatment was subdivided into duration of more or less than six months.

Main outcome measure Rate ratios of venous thromboembolism in association with current testosterone treatment compared with no treatment were estimated using conditional logistic regression and adjusted for comorbidities and all matching factors.

Results The adjusted rate ratio of venous thromboembolism was 1.25 (95% confidence interval 0.94 to 1.66) for current versus no testosterone treatment. In the first six months of testosterone treatment, the rate ratio of venous thromboembolism was 1.63 (1.12 to 2.37), corresponding to 10.0 (1.9 to 21.6) additional venous thromboembolisms above the base rate of 15.8 per 10 000 person years.

The rate ratio after more than six months’ treatment was 1.00 (0.68 to 1.47), and after treatment cessation it was 0.68 (0.43 to 1.07).

Increased rate ratios within the first six months of treatment were observed in all strata: the rate ratio was 1.52 (0.94 to 2.46) for patients with pathological hypogonadism and 1.88 (1.02 to 3.45) for those without it, and 1.41 (0.82 to 2.41) for those with a known risk factor for venous thromboembolism and 1.91 (1.13 to 3.23) for those without one.

Conclusions Starting testosterone treatment was associated with an increased risk of venous thromboembolism, which peaked within six months and declined thereafter.

 

[thrombus]

I was mysteriously attracted to this thread, but have nothing to offer.

 

[Michael Scally MD]

Greater Saphenous Vein Thrombosis and Testosterone Replacement Therapy: An Occasional Association?

We describe a case of greater saphenous vein thrombosis in a 50-year-old previously healthy man, occurred only 3 weeks after starting testosterone (T) replacement therapy (20 mg/day, gel) for hypergonadotropic hypogonadism.

There were no clinical known risk factors for thrombosis. Laboratory assessment of thrombophilia, performed later, revealed only methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism.

On the basis of other recently reported cases, we suppose a relationship between androgenic therapy and venous thrombosis.

We suggest the same caution before starting T replacement therapy in male as in female administration of estrogens.

Bertola G, Bianchi R, Giambona S, Sada S, Berra SA. [Greater saphenous vein thrombosis and testosterone replacement therapy: an occasional association?]. Recenti Prog Med 2017;108(5):239-41. Recenti Progressi in Medicina | Trombosi della grande safena e terapia sostitutiva con testosterone: un’associazione casuale?

 

[Michael Scally MD]

Relationship of Testosterone Therapy and Blood Clot Organization in Elderly Men in Different Type of Stroke

Background: The main aim to determine the prevalence of thrombotic events and all-cause mortality in men older than 65 years with hypogonadism treated with testosterone therapy (TST).

Objective: TIA/CVA

Patients and Methods/Material and Methods: We retrospectively reviewed the charts of 197 hypogonadal men N65 years. We compared men who received TST (n = 143) to hypogonadal men (n = 54) who did not receive TST. We evaluated all-cause mortality, prevalence of myocardial infarction (MI), transient ischemic attack (TIA), cerebrovascular accident (CVA or "stroke"), and deep vein thrombosis/pulmonary embolism (DVT/PE). All events were verified by contacting patients. We excluded men with previous thrombotic events, men previously on androgen deprivation therapy, and men who had used TST before 65 years.

Results: Median age and Charlson Comorbidity Index of men on TST (74y; 5.1) was similar to hypogonadal men not TST (73y, P = .48; 5.3, P =.36). Median follow-up was 3.8 vs 3.5 years (TST vs no TST). No man on TST died, whereas 5 hypogonadal men who did not receive TST died (P = .007). There were 4 thrombotic events (1 MI, 2 CVA/TIA, and 1 PE) in men who received TST and 1 event (CVA/TIA) among men who did not receive TST (P = .8). All events (1 death, 6-month follow-up) occurred least after 2 years of followup.

Conclusion: There was increased all-cause mortality in hypogonadal men not treated with testosterone compared to men who received TST. There was no difference in prevalence of MI, TIA/CVA, or PE between patients treated with testosterone and hypogonadal men not treated with testosterone.

Rakhimov F, Musaeva Y. Relationship of testosterone therapy and blood clot organization in elderly men in different type of stroke. Journal of the Neurological Sciences 2017;381:983-4. Redirecting

 

[Kinikuman]

Opinions seem to be going back and forth on this. We may be at risk of thrombosis or trt reduces your chances of dying. There at least seems to be enough interest in the subject to see continued research.

Relationship of Testosterone Therapy and Blood Clot Organization in Elderly Men in Different Type of Stroke

Background: The main aim to determine the prevalence of thrombotic events and all-cause mortality in men older than 65 years with hypogonadism treated with testosterone therapy (TST).

Objective: TIA/CVA

Patients and Methods/Material and Methods: We retrospectively reviewed the charts of 197 hypogonadal men N65 years. We compared men who received TST (n = 143) to hypogonadal men (n = 54) who did not receive TST. We evaluated all-cause mortality, prevalence of myocardial infarction (MI), transient ischemic attack (TIA), cerebrovascular accident (CVA or "stroke"), and deep vein thrombosis/pulmonary embolism (DVT/PE). All events were verified by contacting patients. We excluded men with previous thrombotic events, men previously on androgen deprivation therapy, and men who had used TST before 65 years.

Results: Median age and Charlson Comorbidity Index of men on TST (74y; 5.1) was similar to hypogonadal men not TST (73y, P = .48; 5.3, P =.36). Median follow-up was 3.8 vs 3.5 years (TST vs no TST). No man on TST died, whereas 5 hypogonadal men who did not receive TST died (P = .007). There were 4 thrombotic events (1 MI, 2 CVA/TIA, and 1 PE) in men who received TST and 1 event (CVA/TIA) among men who did not receive TST (P = .8). All events (1 death, 6-month follow-up) occurred least after 2 years of followup.

Conclusion: There was increased all-cause mortality in hypogonadal men not treated with testosterone compared to men who received TST. There was no difference in prevalence of MI, TIA/CVA, or PE between patients treated with testosterone and hypogonadal men not treated with testosterone.

Rakhimov F, Musaeva Y. Relationship of testosterone therapy and blood clot organization in elderly men in different type of stroke. Journal of the Neurological Sciences 2017;381:983-4. Redirecting

 

[Michael Scally MD]

Glueck CJ, Goldenberg N, Wang P. Thromboembolism peaking 3 months after starting testosterone therapy: testosterone–thrombophilia interactions. Journal of Investigative Medicine 2017. Thromboembolismpeaking 3 months after starting testosterone therapy: testosterone–thrombophilia interactions

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.

 

[Michael Scally MD]

Cole AP, Hanske J, Jiang W, et al. Impact of testosterone replacement therapy on thromboembolism, heart disease and obstructive sleep apnoea in men. BJU international. Impact of testosterone replacement therapy on thromboembolism, heart disease and obstructive sleep apnoea in men

Objectives: To assess the association of testosterone replacement therapy (TRT) with thromboembolism, cardiovascular disease (stroke, coronary artery disease and heart failure) and obstructive sleep apnoea (OSA).

Methods: A cohort of 3 422 male US military service members, retirees and their dependents, aged 40–64 years, was identified, who were prescribed TRT between 2006 and 2010 for low testosterone levels. The men in this cohort were matched on a 1:1 basis for age and comorbidities to men without a prescription for TRT. Event-free survival and rates of thromboembolism, cardiovascular events and OSA were compared between men using TRT and the control group, with a median follow-up of 17 months.

Results: There was no difference in event-free survival with regard to thromboembolism (P = 0.239). Relative to controls, men using TRT had improved cardiovascular event-free survival (P = 0.004), mainly as a result of lower incidence of coronary artery disease (P = 0.008). The risk of OSA was higher in TRT users (2-year risk 16.5% [95% confidence interval 15.1–18.1] in the TRT group vs 12.7% [11.4–14.1] in the control group.

Conclusions: This study adds to growing evidence that the cardiovascular risk associated with TRT may be lower than once feared. The elevated risk of OSA in men using TRT is noteworthy.