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, M. Hassan; Moll, Stephan

doi:10.1016/j.thromres.2018.10.023

Cited by 65 publications

(43 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2e4 Meta-analyses from 2017 and 2018 demonstrated no increased risk for venous thromboembolism in men taking testosterone therapy. 2,3 However, the investigators from the 2018 study concluded that the analysis would not be able to reveal significant differences because of the limited number of study populations analyzed. 3 A 2019 analysis of a larger study population, of men with and without hypogonadism (n ¼ 39,622), concluded that testosterone use (6-month case period) increased the risk of venous thromboembolism events.…”

Section: Discussionmentioning

confidence: 99%

“…2,3 However, the investigators from the 2018 study concluded that the analysis would not be able to reveal significant differences because of the limited number of study populations analyzed. 3 A 2019 analysis of a larger study population, of men with and without hypogonadism (n ¼ 39,622), concluded that testosterone use (6-month case period) increased the risk of venous thromboembolism events. 4 In contrast to venous thromboembolism, POME is an acute (<60-minute duration) adverse event associated with injection of an oil-based compound such as testosterone.…”

Section: Discussionmentioning

confidence: 99%

“…1 Some meta-analyses have supported that testosterone treatment is generally safe and does not increase cardiovascular or venous thromboembolism risk in patients diagnosed with late-onset hypogonadism. 2,3 However, a 2019 case-crossover study (6-month case period) reported that testosterone therapy increased the risk of venous thromboembolism in men with or without hypogonadism (n ¼ 39,622). 4 In contrast to venous thromboembolism, pulmonary oil microembolism (POME) is an acute (eg, <60 minute onset) reaction to injection of an oil-based compound and has been reported as an adverse event related to testosterone preparations formulated in oil, including castor oil (eg, testosterone undecanoate), to provide a longer half-life than noneoil-based preparations.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Occurrence of Pulmonary Oil Microembolism After Testosterone Undecanoate Injection: A Postmarketing Safety Analysis

Pastuszak

Freid

2020

Sexual Medicine

View full text Add to dashboard Cite

Background: The Aveed Risk Evaluation and Mitigation Strategy program was instituted because of potential risk of pulmonary oil microembolism (POME) and/or anaphylaxis after intramuscular injection of Aveed (testosterone undecanoate), indicated for treatment of adult male patients with congenital or acquired primary hypogonadism or hypogonadotropic hypogonadism. Aim: To analyze the reporting rate of POME associated with testosterone undecanoate administration (750 mg/ 3 mL) during postmarketing surveillance. Methods: The Endo Pharmaceuticals Inc database was searched for POME reports occurring from testosterone undecanoate approval on March 5, 2014, through June 30, 2018. Each case was reviewed and adjudicated by a drug safety physician to confirm the reported event had predefined clinical characteristics consistent with POME. Outcomes: Annual rate and clinical features of spontaneously reported POME cases were characterized. Results: During the 4.3-year period, 90,092 doses of intramuscular testosterone undecanoate were distributed via an Aveed Risk Evaluation and Mitigation Strategy program to health-care professionals for patient treatment. Of 633 individual case safety reports in the Endo Pharmaceuticals Inc safety database, 28 spontaneously reported adverse events were classified as POME, for a yearly spontaneously reported adverse event per-injection rate of <0.1%. Most (21/22) events resolved, and of those with a resolution time reported, most (13/17) resolved in 30 minutes. More than 60% (13/21) of patients required no medical intervention (ie, the POME event resolved spontaneously). One fatality was reported 18 months after a documented POME event and appeared unrelated to the reported testosterone undecanoate injection or subsequent injections after the POME event. In 3 out of 4 POME cases with symptoms serious enough to require an emergency room visit, issues with injection technique or dosing were identified as a potential contributing factor. Clinical Implications: Injection technique and proper product usage are key elements in the prevention of POME events. Strengths & Limitations: The reported rate of POME events was determined from a real-world clinical practice patient population; however, postmarketing safety data typically are underreported and retrospective in nature. Conclusion: POME events appear to be rare, with resolution occurring quickly without medical intervention in most cases.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Occurrence of Pulmonary Oil Microembolism After Testosterone Undecanoate Injection: A Postmarketing Safety Analysis

Pastuszak

Freid

2020

Sexual Medicine

View full text Add to dashboard Cite

show abstract

“…44 Testosterone supplementation has been linked with venous thromboembolism and pulmonary embolism. 45 On the other hand, male hypogonadism is a prothrombotic state and testosterone supplementation might have a protective role. 46 Endothelial nitric oxide production, a potent inhibitor of platelet activation, is enhanced by testosterone and might safeguard against thrombotic tendency.…”

Section: Testosterone As a Friendmentioning

confidence: 99%

Testosterone in COVID-19 – Foe, Friend or Fatal Victim?

Kalra¹,

Bhattacharya²,

Kalhan³

2020

European Endocrinology

View full text Add to dashboard Cite

“…Baillargeon et al 42 reviewed a health care database of 30,572 men and found no association between incident VTE and testosterone medication in the previous 14 days. Two meta-analyses 43,44 reported no association between VTE and TRT and Salter and Mulhall 45 analyzed the recommendations of six leading medical societies and all concluded that there was no association between TRT and VTE. Rather than considering an increase in hematocrit to be a cause for concern, the T trial 46 also found no increase in VTE but found that 126 of 788 men were anemic at baseline and 58% were normalized with TRT by 12 months.…”

Section: Introductionmentioning

confidence: 99%

COVID-19, Type 2 Diabetes, and Hypogonadism: Lessons for Acute Management and Long-Term Prevention

Hackett

Kirby

2020

Androgens: Clinical Research and Therapeutics

View full text Add to dashboard Cite

Despite similar infection rates due to COVID-19 (SARS CoV-2) between men and women, male patients have twice the mortality rate across older age groups compared with women. Studies from China, Germany, and Italy suggest that there is a severe primary hypogonadism associated with acute infection and that the more severe the drop in testosterone, the higher the mortality. The co-morbidities associated with increased mortality, namely age, obesity, type 2 diabetes, chronic obstructive pulmonary disease, and chronic kidney disease are all associated with lower rates of testosterone in the general population. Longitudinal studies of testosterone therapy in these conditions have shown reduced all cause mortality. These findings suggest that screening for low testosterone and treating low levels might reduce all-cause mortality including COVID-19. Paradoxically, some observational studies in prostate cancer patients have reported lower mortality rates in those receiving androgen deprivation therapy (ADT). This has led to studies of ADT to reduce mortality associated with COVID-19 infection and suggestions that testosterone replacement therapy (TRT) should be stopped. This seems ill advised as recent publications suggest that TRT can reverse progression to type 2 diabetes and even lead to complete regression, as well as reducing all-cause mortality. In contrast, ADT has been repeatedly shown to have adverse cardio-metabolic effects with increased rates of depression, suicide and reduced quality of life. We also suggest a potentially important role for daily PDE5 inhibitors based on their established beneficial effect on endothelial dysfunction, pulmonary hypertension, insulin resistance, inflammation and cellular apoptosis.

show abstract

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

Cited by 65 publications

References 44 publications

Occurrence of Pulmonary Oil Microembolism After Testosterone Undecanoate Injection: A Postmarketing Safety Analysis

Occurrence of Pulmonary Oil Microembolism After Testosterone Undecanoate Injection: A Postmarketing Safety Analysis

Testosterone in COVID-19 – Foe, Friend or Fatal Victim?

COVID-19, Type 2 Diabetes, and Hypogonadism: Lessons for Acute Management and Long-Term Prevention

Contact Info

Product

Resources

About