What is the workup for a 33-year-old male on testosterone (hormone replacement therapy) injections for two years, presenting with intermittent palpitations, shortness of breath, and increased emotional stress?

From the Guidelines

The workup for a 33-year-old male on testosterone replacement therapy experiencing palpitations and shortness of breath should begin with a comprehensive history and physical examination, focusing on cardiovascular symptoms and testosterone usage patterns. Initial laboratory tests should include complete blood count, comprehensive metabolic panel, thyroid function tests, and most importantly, testosterone levels (both total and free) to assess for potential supraphysiologic levels 1. A lipid panel is essential as testosterone can affect cholesterol levels. Hematocrit and hemoglobin should be checked since testosterone therapy commonly causes erythrocytosis, which can increase cardiovascular risk, as noted in a study published in the New England Journal of Medicine 1. Electrocardiogram (ECG) should be performed to evaluate for arrhythmias or structural abnormalities, and an echocardiogram may be warranted to assess cardiac function and structure. Consider 24-hour Holter monitoring if symptoms are intermittent to capture potential arrhythmias during symptomatic periods. Stress testing might be appropriate to evaluate for exercise-induced symptoms. Testosterone therapy can increase risk of cardiovascular events through multiple mechanisms including increased hematocrit, adverse lipid changes, and direct effects on cardiac tissue, as highlighted in a guideline by the American College of Physicians 1. The emotional stress reported by the patient may also contribute to his symptoms, so assessment for anxiety disorders should be included. Depending on findings, testosterone dosage adjustment or administration frequency changes may be necessary to maintain therapeutic levels while minimizing side effects, as recommended in a study published in the Annals of Internal Medicine 1. It is crucial to weigh the benefits and risks of testosterone therapy, considering the patient's age, symptoms, and underlying medical conditions, to ensure the best possible outcome in terms of morbidity, mortality, and quality of life. Key considerations include monitoring hematocrit levels, as injectable testosterone is associated with a greater risk of erythrocytosis compared to topical preparations 1. Regular follow-up and adjustments to the treatment plan as needed are vital to mitigate potential adverse effects while maximizing the therapeutic benefits of testosterone replacement therapy.

From the FDA Drug Label

Abuse-Related Adverse Reactions Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression.

The workup for a 33-year-old male on hormone replacement therapy with testosterone injection experiencing heart palpitations and shortness of breath should include:

• Cardiovascular evaluation: to assess for potential cardiac complications such as cardiac arrest, myocardial infarction, or congestive heart failure
• Psychiatric evaluation: to assess for potential psychiatric manifestations such as major depression, mania, or anxiety
• Hepatic function tests: to assess for potential hepatotoxicity
• Testosterone level checks: to assess for potential supratherapeutic doses of testosterone
• Abuse screening: to assess for potential abuse of anabolic androgenic steroids 2

From the Research

Initial Evaluation

The patient presents with complaints of heart palpitations, shortness of breath, and increased emotional stress while on hormone replacement therapy with testosterone injections. The initial evaluation should include:

• A detailed history to identify potential causes of palpitations and shortness of breath, as well as to assess the patient's response to testosterone replacement therapy 3, 4
• A physical examination to look for signs of cardiovascular disease or other underlying conditions that may be contributing to the patient's symptoms 3, 4
• An electrocardiogram (ECG) to evaluate the patient's heart rhythm and identify any potential cardiac causes of palpitations 3, 5, 4

Consideration of Testosterone Replacement Therapy

The patient's use of testosterone replacement therapy should be considered in the evaluation, as it may be contributing to the patient's symptoms. Studies have shown that testosterone replacement therapy can have both positive and negative effects on the cardiovascular system 6, 7. While some studies suggest that testosterone replacement therapy may improve cardiovascular risk factors and reduce mortality in men with low testosterone levels 7, others have raised concerns about the potential risks of testosterone replacement therapy, particularly in older men with a history of heart failure 6.

Further Diagnostic Testing

Based on the initial evaluation, further diagnostic testing may be indicated to rule out underlying cardiac or other conditions that may be contributing to the patient's symptoms. This may include:

• Ambulatory ECG monitoring to evaluate the patient's heart rhythm over a longer period of time 3, 4
• Laboratory testing to evaluate the patient's cardiovascular risk factors and rule out other potential causes of palpitations and shortness of breath 4
• Imaging studies, such as echocardiography or cardiac MRI, to assess for functional and structural heart disease 4
• Referral to a cardiologist for further evaluation and management, particularly if the patient has a history of cardiovascular disease or if the initial evaluation suggests a cardiac cause of the patient's symptoms 3, 4