How does hyperprolactinemia (elevated prolactin levels) affect testosterone levels and what is the recommended treatment approach?

From the Guidelines

Hyperprolactinemia is known to decrease testosterone levels by inhibiting gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus, which reduces luteinizing hormone (LH) production by the pituitary gland, ultimately lowering testosterone production in the testes, as supported by the most recent evidence from 2024 1. The recommended treatment approach focuses on addressing the underlying cause of elevated prolactin. For prolactinomas (pituitary tumors), dopamine agonists like cabergoline (starting at 0.25mg twice weekly, gradually increasing to 0.5-1mg twice weekly as needed) or bromocriptine (starting at 1.25-2.5mg daily, increasing to 2.5-10mg daily) are first-line treatments, with cabergoline being generally preferred due to better efficacy and fewer side effects, as indicated in a study from 2024 1. Some key points to consider in the treatment of hyperprolactinemia include:

• Treatment should continue until prolactin normalizes and tumor shrinks, which may take several months to years.
• For medication-induced hyperprolactinemia, the causative drug should be discontinued if possible or switched to an alternative, with common culprits including antipsychotics, certain antidepressants, and metoclopramide.
• In cases of idiopathic hyperprolactinemia, dopamine agonists may still be used if symptoms warrant treatment.
• Regular monitoring of prolactin levels, testosterone levels, and tumor size (if present) is essential to assess treatment efficacy, as suggested by a guideline from 2024 1.
• Testosterone levels typically normalize once prolactin returns to normal range, but temporary testosterone replacement therapy might be considered in cases of significant hypogonadism symptoms while waiting for prolactin normalization, although the use of testosterone treatment in adult men with age-related low testosterone is conditional and based on low-certainty evidence, as stated in a clinical guideline from 2020 1.

It's also important to note that the correlation between prolactin levels and testosterone is well-established, and managing hyperprolactinemia is crucial for maintaining normal testosterone levels and overall hormonal balance, as discussed in various studies, including those from 2009 1.

In terms of specific treatment recommendations, cabergoline is the preferred dopamine agonist for treating prolactinomas due to its better efficacy and fewer side effects, as supported by a study from 2024 1. The treatment approach should be individualized based on the underlying cause of hyperprolactinemia, the presence of symptoms, and the patient's overall health status.

From the FDA Drug Label

In 72 healthy volunteers, single or multiple doses (up to 2 mg) of cabergoline resulted in selective inhibition of prolactin with no apparent effect on other anterior pituitary hormones (GH, FSH, LH, ACTH, and TSH) or cortisol.

The effect of hyperprolactinemia on testosterone levels is not directly addressed in the provided drug label. However, it is known that hyperprolactinemia can suppress gonadotropin-releasing hormone (GnRH), leading to decreased luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, which in turn can decrease testosterone production.

• The label does mention that cabergoline has no apparent effect on LH (a key hormone in regulating testosterone production) in healthy volunteers.
• Cabergoline is used to treat hyperprolactinemia, and by reducing prolactin levels, it may help alleviate the suppressive effect of hyperprolactinemia on the hypothalamic-pituitary-gonadal axis, potentially leading to an increase in testosterone levels.
• The recommended treatment approach for hyperprolactinemia-related testosterone deficiency would likely involve treating the underlying hyperprolactinemia with a medication like cabergoline 2.

From the Research

Correlation between Prolactin Levels and Testosterone

• Hyperprolactinemia, or elevated prolactin levels, can lead to hypogonadism in men by inhibiting gonadotropin-releasing hormone pulsatile secretion, resulting in decreased follicle-stimulating hormone, luteinizing hormone, and testosterone levels 3.
• This decrease in testosterone levels can cause symptoms such as impaired libido, erectile dysfunction, diminished ejaculate volume, and oligospermia 3.
• Treatment with dopamine agonists, such as bromocriptine or cabergoline, can effectively reduce prolactin levels and improve testosterone levels in men with prolactinomas 3, 4.

Treatment Approach for Hyperprolactinemia

• The primary treatment for hyperprolactinemia is dopamine agonist therapy, which can effectively reduce prolactin levels and improve gonadal function 5, 6.
• Cabergoline is often considered the first-line treatment due to its efficacy and tolerability 5, 6.
• In cases where dopamine agonist therapy is not effective, surgical or radiological management may be necessary, particularly for pituitary macroadenomas 6, 7.
• Clomiphene can also be used to treat persistent hypogonadism in men with prolactinomas, as it can increase testosterone levels and improve sperm motility 4.

Important Considerations

• It is essential to investigate the underlying cause of hyperprolactinemia, particularly to rule out pituitary tumors 7.
• The presence of macroprolactinemia, a biologically inactive form of prolactin, can lead to falsely elevated prolactin levels and does not require treatment 7.
• Regular follow-up with serial prolactin measurements and pituitary imaging is necessary to monitor the effectiveness of treatment and potential tumor growth 5, 6.