Is it advisable to administer testosterone to a female-to-male (FTM) patient with obesity, hypercholesterolemia, and impaired glucose regulation (prediabetes)?

From the Guidelines

Testosterone therapy can be considered for a transgender male patient with obesity, high cholesterol, and prediabetes, but requires careful medical supervision and risk management. According to the most recent study 1, testosterone regimens consist of gels, patches, injectable esters, and testosterone undecanoate, and the goal is to bring testosterone levels into the typical physiological range for cisgender men (300–1,000 ng/dL). Before initiating testosterone, the patient should undergo comprehensive baseline testing including complete metabolic panel, lipid profile, hemoglobin/hematocrit, and hemoglobin A1c.

The patient's obesity, high cholesterol, and prediabetes should be managed concurrently with lifestyle modifications (diet, exercise) and possibly medications for diabetes prevention or cholesterol management. Testosterone therapy may worsen metabolic parameters, potentially increasing insulin resistance, worsening lipid profiles, and contributing to further weight gain, as reported by T'Sjoen et al. 1. Regular monitoring every 3 months initially is essential, with particular attention to glucose levels, lipid profiles, blood pressure, and hematocrit.

Key considerations for testosterone therapy in this patient include:

• The potential benefits of gender-affirming hormone therapy for the patient's gender dysphoria
• The potential risks of testosterone therapy, including erythrocytosis, bone health, fertility, and pregnancy risks
• The importance of careful medical supervision and risk management to minimize potential adverse effects
• The need for concurrent management of the patient's metabolic conditions to optimize overall health outcomes

As noted in the study by T'Sjoen et al. 1, the data on cardiovascular outcomes in trans men are contradictory, with no significant difference in cardiovascular mortality outcomes when studies are viewed together, relative to the general population. However, the patient should be counseled about the potential risks and benefits of testosterone therapy, and treatment decisions should be made collaboratively between the patient and healthcare provider after thorough discussion of potential risks and benefits.

From the FDA Drug Label

INDICATIONS AND USAGE Testosterone cypionate injection is indicated for replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone. DOSAGE AND ADMINISTRATION Testosterone cypionate injection is for intramuscular use only.

The patient in question is a female wanting to transition to male, with pre-existing conditions of obesity, high cholesterol, and prediabetes. Testosterone therapy is not explicitly indicated for female-to-male transition in the provided drug labels.

• The labels only discuss replacement therapy in males with conditions associated with symptoms of deficiency or absence of endogenous testosterone.
• There is no direct information regarding the safety and efficacy of testosterone in females, particularly those with obesity, high cholesterol, and prediabetes. Given the lack of direct information, no conclusion can be drawn about the suitability of testosterone therapy for this patient 2, 2.

From the Research

Testosterone Therapy for Female-to-Male Transgender Patients with Obesity, High Cholesterol, and Prediabetes

• The decision to administer testosterone therapy to a female-to-male transgender patient with obesity, high cholesterol, and prediabetes requires careful consideration of the potential benefits and risks 3.
• Testosterone therapy may be used to produce physical male sex characteristics in female-to-male transgender patients, but it is essential to weigh the potential benefits against the risks, particularly in patients with pre-existing medical conditions 3.
• Obesity and prediabetes are associated with lower testosterone levels, and testosterone treatment may help reduce fat mass and insulin resistance, potentially decreasing the risk of developing type 2 diabetes 4, 5.
• However, testosterone therapy may also increase the risk of cardiovascular complications, and patients with high cholesterol and prediabetes may be at higher risk for these complications 3, 5.
• It is crucial to monitor patients receiving testosterone therapy closely to ensure that testosterone levels rise appropriately, clinical improvement occurs, and no complications develop 6, 3.
• The potential benefits of testosterone therapy for this patient population include increased libido, improved sexual function, improved mood and well-being, and increased muscle mass and bone density, but these benefits must be balanced against the potential risks 3, 7.