What are the implications of testosterone therapy in patients with panhypopituitarism (hypopituitarism) and a history of thrombosis (blood clot)?

From the Guidelines

Testosterone therapy in patients with pan hypothyroidism and blood clot risk should be approached with caution, prioritizing optimization of thyroid function with levothyroxine before initiating testosterone therapy, and closely monitoring for clotting risks, as supported by recent evidence from the American College of Physicians 1.

Key Considerations

• Patients should optimize thyroid function first with levothyroxine, typically starting at 25-50 mcg daily, gradually increasing to achieve TSH within normal range, before initiating testosterone therapy.
• When starting testosterone, lower doses are recommended initially, such as 50 mg testosterone cypionate weekly or 5 g of 1% testosterone gel daily, with gradual titration based on symptoms and blood levels.
• Regular monitoring is essential, including complete blood count, lipid panel, and hematocrit levels every 3-6 months, as testosterone can increase red blood cell production and potentially elevate clotting risk.
• If hematocrit exceeds 54%, testosterone dose reduction or temporary discontinuation may be necessary.
• Patients should stay well-hydrated, maintain physical activity, and avoid prolonged immobility to reduce clot risk.
• Those with additional risk factors for blood clots (obesity, smoking, prior clot history) may benefit from prophylactic measures like low-dose aspirin, though this requires individualized assessment.

Evidence Base

The American College of Physicians' evidence report on testosterone treatment in men found that intramuscular or transdermal testosterone therapy resulted in small improvements in sexual functioning and quality of life, but had little to no effect on physical functioning, depressive symptoms, energy and vitality, and cognition 1. Additionally, the report found that testosterone was not associated with increased risk for pulmonary embolism or deep venous thrombosis in the few observational studies that reported that outcome 1. However, the evidence for most outcomes was of low or moderate certainty, and none of the trials had adequate power to assess risk for adverse cardiovascular events, prostate cancer, thromboembolic disease, or death.

Clinical Implications

Given the potential risks and benefits of testosterone therapy in patients with pan hypothyroidism and blood clot risk, a careful and individualized approach is necessary. Patients should be closely monitored for clotting risks, and testosterone dose adjustments should be made as needed to minimize these risks. Overall, the decision to initiate testosterone therapy in these patients should be based on a thorough assessment of the potential benefits and risks, and should be made in consultation with a healthcare provider.

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. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE If a venous thromboembolic event is suspected, discontinue treatment with testosterone enanthate injection and initiate appropriate workup and management.

The use of testosterone therapy, such as testosterone enanthate injection, may increase the risk of blood clots, including deep vein thrombosis (DVT) and pulmonary embolism (PE).

• Patients with pan hypothyroidism who are considering testosterone therapy should be aware of this potential risk.
• It is essential to monitor patients for symptoms of blood clots, such as pain, edema, warmth, and erythema in the lower extremity, and to discontinue treatment if a venous thromboembolic event is suspected 2.

From the Research

Testosterone Therapy in Pan Hypothyroidism and Blood Clot

• There is no direct evidence on the use of testosterone therapy in pan hypothyroidism and its effects on blood clotting.
• However, studies have investigated the relationship between hypothyroidism, coagulation, and fibrinolysis 3, 4.
• A study published in 2005 found that levothyroxine replacement therapy can correct coagulation factor abnormalities and hyperfibrinolytic status in severe hypothyroid patients 3.
• Another study published in 2011 reported that patients with overt hypothyroidism have a bleeding tendency, while those with hyperthyroidism or subclinical hypothyroidism have a hypercoagulative state 4.
• A nationwide cohort study published in 2020 found that hypothyroidism is significantly associated with an increased risk of venous thromboembolism (VTE), and thyroxine replacement therapy may have a non-significant trend of lower VTE risk 5.
• The current treatment for hypothyroidism is levothyroxine monotherapy, which is safe and effective in restoring thyroid function tests to within the reference range and improving symptoms in most patients 6.
• However, some patients may experience persistent symptoms despite normalisation of thyroid function tests, leading to debates around treatment thresholds and strategies for hypothyroidism 6.