Is testosterone therapy safe in patients with a history of pulmonary embolism (PE)?

From the Guidelines

Testosterone therapy is not absolutely contraindicated in patients with a history of pulmonary embolism, but it should be used with caution and under close medical supervision, as the current evidence does not show a significant increased risk of venous thromboembolic events with testosterone therapy, according to the most recent and highest quality study 1. When considering testosterone therapy in patients with a history of pulmonary embolism, it is essential to weigh the potential benefits against the risks. The evidence from observational studies with a mean follow-up ranging from 0.73 to 10.3 years showed no increased risk for mortality, cardiovascular events, prostate cancer, or pulmonary embolism or deep venous thrombosis 1. However, it is crucial to note that most studies excluded men with recent cardiovascular disease, and evidence for long-term safety is lacking. Some key points to consider when making a decision about testosterone therapy in patients with a history of pulmonary embolism include:

• The potential benefits of testosterone therapy, such as improved energy, strength, and endurance, and enhanced overall quality of life
• The risks associated with testosterone therapy, including the potential for increased red blood cell production and altered coagulation factors, which may promote clot formation
• The importance of close medical supervision and regular monitoring of both hormone levels and clotting factors
• The potential use of anticoagulation therapy (blood thinners like warfarin, apixaban, or rivaroxaban) in conjunction with testosterone therapy to mitigate the risk of recurrent blood clots. It is also worth noting that some formulations, such as transdermal gels, may pose slightly lower risks than injectable forms, but all carry some degree of risk 1. Ultimately, the decision to use testosterone therapy in patients with a history of pulmonary embolism should be made on a case-by-case basis, taking into account the individual patient's unique medical history, risk factors, and potential benefits.

From the FDA Drug Label

There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as testosterone enanthate injection. If a venous thromboembolic event is suspected, discontinue treatment with testosterone enanthate injection and initiate appropriate workup and management.

Testosterone therapy may not be safe in patients with a history of pulmonary embolism (PE) due to the risk of venous thromboembolic events. The drug label recommends discontinuing treatment if a venous thromboembolic event is suspected, which suggests a potential risk for patients with a history of PE.

• Key points: + Postmarketing reports of venous thromboembolic events, including PE, have been associated with testosterone products. + Discontinue treatment if a venous thromboembolic event is suspected. 2

From the Research

Testosterone Therapy Safety in Patients with a History of Pulmonary Embolism (PE)

• The safety of testosterone therapy in patients with a history of pulmonary embolism (PE) is a concern due to the potential risk of thrombotic events 3, 4, 5, 6.
• Studies have shown that testosterone therapy can increase the risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), especially in patients with underlying thrombophilia 3, 5, 6.
• A case report found that a patient with lupus anticoagulant developed multiple thrombotic events, including two pulmonary emboli, while on testosterone therapy despite concurrent anticoagulation 3.
• Another case report found that a patient developed a large volume pulmonary embolism while on clomiphene citrate therapy, a medication used to treat hypogonadism 4.
• A systematic review and meta-analysis found that testosterone replacement therapy (TRT) did not significantly increase the risk of arterial thrombosis, stroke, myocardial infarction, or mortality, but the risk of venous thromboembolism (VTE) and pulmonary embolism remains uncertain due to limited data 7.
• Screening for thrombophilia, including factor V Leiden, lipoprotein(a), and the lupus anticoagulant, is recommended before starting testosterone therapy to identify patients at increased risk of VTE 6.
• Testosterone therapy should not be started in patients with known thrombophilia-hypofibrinolysis, and should not be continued after a first VTE 6.