Testosterone therapy and venous thromboembolism: A systematic review and meta-analysis

Damon E. Houghton, Mouaz Alsawas, Patricia Barrioneuvo, Mouaffaa Tello, Wigdan Farah, Brad Beuschel, Larry J. Prokop, J. Bradley Layton, Mohammad H Murad, Stephan Moll

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)94-103
Number of pages10
JournalThrombosis Research
Volume172
DOIs
StatePublished - Dec 1 2018

Fingerprint

Venous Thromboembolism
Testosterone
Meta-Analysis
Confidence Intervals
Observational Studies
Case-Control Studies
Therapeutics
Odds Ratio
Hypogonadism
Research Personnel
Databases

Keywords

  • Hypercoagulability
  • Testosterone
  • Thrombosis
  • Venous thromboembolism

ASJC Scopus subject areas

  • Hematology

Cite this

Houghton, D. E., Alsawas, M., Barrioneuvo, P., Tello, M., Farah, W., Beuschel, B., ... Moll, S. (2018). Testosterone therapy and venous thromboembolism: A systematic review and meta-analysis. Thrombosis Research, 172, 94-103. https://doi.org/10.1016/j.thromres.2018.10.023

Testosterone therapy and venous thromboembolism : A systematic review and meta-analysis. / Houghton, Damon E.; Alsawas, Mouaz; Barrioneuvo, Patricia; Tello, Mouaffaa; Farah, Wigdan; Beuschel, Brad; Prokop, Larry J.; Layton, J. Bradley; Murad, Mohammad H; Moll, Stephan.

In: Thrombosis Research, Vol. 172, 01.12.2018, p. 94-103.

Research output: Contribution to journalReview article

Houghton, DE, Alsawas, M, Barrioneuvo, P, Tello, M, Farah, W, Beuschel, B, Prokop, LJ, Layton, JB, Murad, MH & Moll, S 2018, 'Testosterone therapy and venous thromboembolism: A systematic review and meta-analysis', Thrombosis Research, vol. 172, pp. 94-103. https://doi.org/10.1016/j.thromres.2018.10.023
Houghton DE, Alsawas M, Barrioneuvo P, Tello M, Farah W, Beuschel B et al. Testosterone therapy and venous thromboembolism: A systematic review and meta-analysis. Thrombosis Research. 2018 Dec 1;172:94-103. https://doi.org/10.1016/j.thromres.2018.10.023
Houghton, Damon E. ; Alsawas, Mouaz ; Barrioneuvo, Patricia ; Tello, Mouaffaa ; Farah, Wigdan ; Beuschel, Brad ; Prokop, Larry J. ; Layton, J. Bradley ; Murad, Mohammad H ; Moll, Stephan. / Testosterone therapy and venous thromboembolism : A systematic review and meta-analysis. In: Thrombosis Research. 2018 ; Vol. 172. pp. 94-103.
@article{d1fc07d739cf458bb1cdc2b605afafed,
title = "Testosterone therapy and venous thromboembolism: A systematic review and meta-analysis",
abstract = "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.",
keywords = "Hypercoagulability, Testosterone, Thrombosis, Venous thromboembolism",
author = "Houghton, {Damon E.} and Mouaz Alsawas and Patricia Barrioneuvo and Mouaffaa Tello and Wigdan Farah and Brad Beuschel and Prokop, {Larry J.} and Layton, {J. Bradley} and Murad, {Mohammad H} and Stephan Moll",
year = "2018",
month = "12",
day = "1",
doi = "10.1016/j.thromres.2018.10.023",
language = "English (US)",
volume = "172",
pages = "94--103",
journal = "Thrombosis Research",
issn = "0049-3848",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Testosterone therapy and venous thromboembolism

T2 - A systematic review and meta-analysis

AU - Houghton, Damon E.

AU - Alsawas, Mouaz

AU - Barrioneuvo, Patricia

AU - Tello, Mouaffaa

AU - Farah, Wigdan

AU - Beuschel, Brad

AU - Prokop, Larry J.

AU - Layton, J. Bradley

AU - Murad, Mohammad H

AU - Moll, Stephan

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

KW - Hypercoagulability

KW - Testosterone

KW - Thrombosis

KW - Venous thromboembolism

UR - http://www.scopus.com/inward/record.url?scp=85055913958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055913958&partnerID=8YFLogxK

U2 - 10.1016/j.thromres.2018.10.023

DO - 10.1016/j.thromres.2018.10.023

M3 - Review article

C2 - 30396049

AN - SCOPUS:85055913958

VL - 172

SP - 94

EP - 103

JO - Thrombosis Research

JF - Thrombosis Research

SN - 0049-3848

ER -