How should prolactin levels be managed in individuals undergoing testosterone replacement therapy (TRT)?

From the Guidelines

Prolactin levels should be measured in patients undergoing testosterone replacement therapy (TRT) who have low total testosterone and low or low/normal LH levels to screen for hyperprolactinemia, as recommended by the American Urological Association guideline 1. When managing prolactin levels in individuals on TRT, it is essential to follow a step-wise approach:

• Measure serum prolactin in patients with low total testosterone and low or low/normal LH levels to screen for hyperprolactinemia 1.
• If prolactin levels are elevated, repeat the measurement to ensure the initial elevation was not spurious.
• Persistently elevated prolactin levels may indicate pituitary tumors, such as prolactinomas, and patients should be referred to an endocrinologist for further evaluation 1.
• Men with total testosterone levels of <150 ng/dL in combination with a low or low/normal LH should undergo a pituitary MRI regardless of prolactin levels, as non-secreting adenomas may be identified 1. Key considerations in managing prolactin levels on TRT include:
• Monitoring prolactin levels regularly, with baseline measurements taken before starting treatment and follow-up testing as needed.
• Investigating the underlying cause of elevated prolactin, particularly ruling out pituitary adenomas through MRI imaging.
• Considering observation for mild elevations without symptoms, while continuing TRT.
• Using dopamine agonists like cabergoline or bromocriptine for significant elevations or symptomatic cases. It is crucial to note that TRT itself rarely causes prolactin elevation, and testosterone typically has a mild suppressive effect on prolactin 1. If prolactin levels remain persistently elevated despite treatment, consultation with an endocrinologist is recommended to adjust medication dosing or explore alternative approaches while maintaining effective testosterone replacement.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Testosterone cypionate injection, USP is for intramuscular use only. The FDA drug label does not answer the question.

From the Research

Prolactin Management on Testosterone Replacement Therapy

• Prolactin levels can be affected by testosterone replacement therapy (TRT) in individuals with prolactinomas 2
• Hyperprolactinemia is associated with suppression of the hypothalamic-pituitary-gonadal axis, leading to hypogonadism, loss of libido, infertility, and osteoporosis 3
• Treatment options for microprolactinomas include observation, dopamine agonist therapy, and gonadal steroid hormone replacement, such as testosterone replacement therapy in males 3
• Cabergoline treatment has been shown to be effective in normalizing prolactin levels, reducing tumor mass, and restoring pituitary function in men with prolactinoma 4
• Testosterone replacement therapy may induce hyperprolactinemia in some individuals, possibly due to the aromatization of testosterone to estrogen, which stimulates the release of prolactin 2

Monitoring and Treatment

• Regular monitoring of serum prolactin levels is recommended for individuals undergoing TRT, especially those with a history of hyperprolactinemia or prolactinoma 3, 2
• Dopamine agonists may not suppress the hyperprolactinemia induced by testosterone replacement therapy 2
• The use of aromatase inhibitors or non-aromatizable androgens may be considered in individuals with testosterone-replacement-induced hyperprolactinemia 2
• The risk of inducing prolactinomas through testosterone replacement therapy is likely to be small, but regular monitoring and follow-up are still necessary 5