What are the implications of elevated prolactin (PRL) levels?

From the Guidelines

Elevated prolactin levels should be treated with cabergoline as the first-line therapy, as it has been shown to be effective in normalizing prolactin levels, reducing tumor size, and improving symptoms, with a strong recommendation based on low-quality evidence 1. When managing elevated prolactin levels, it is crucial to first identify and treat the underlying cause. The symptoms of hyperprolactinemia can vary and include delayed puberty, galactorrhoea, visual field loss, growth or pubertal arrest, and menstrual disturbances in girls 1.

Key Considerations

• Before starting treatment, it's essential to rule out physiological causes like pregnancy, breastfeeding, stress, and sleep disturbances, as well as medication effects from antipsychotics, antidepressants, or certain antihypertensives.
• Patients should undergo MRI imaging to check for pituitary tumors (prolactinomas), which are a common cause of elevated prolactin levels.
• Dopamine agonists, such as cabergoline, reduce pituitary-origin hyperprolactinaemia of any cause and are effective in inducing normalization of prolactin levels, tumour shrinkage, resolution of visual field defects, normalization of menses, fertility, and sexual function, and resolution of galactorrhoea 1.

Treatment Options

• Cabergoline is the dopamine agonist of choice due to its longer half-life and greater affinity for the dopamine receptor, as well as its superior efficacy and fewer side effects compared to bromocriptine 1.
• The recommended dosage of cabergoline is 0.25-1 mg twice weekly, which can be adjusted based on the patient's response to treatment.

Monitoring and Follow-up

• Patients with prolactinoma should be carefully monitored for any deterioration in vision, pituitary function, or general status while on treatment with cabergoline 1.
• Regular follow-up appointments and prolactin level checks are necessary to assess the effectiveness of treatment and make any necessary adjustments.

From the FDA Drug Label

Hyperprolactinemic States Effective treatment with bromocriptine mesylate leads to a reduction in hyperprolactinemia and often to a resolution of the visual impairment In some patients, however, a secondary deterioration of visual fields may subsequently develop despite normalized prolactin levels and tumor shrinkage, which may result from traction on the optic chiasm which is pulled down into the now partially empty sella In these cases, the visual field defect may improve on reduction of bromocriptine dosage while there is some elevation of prolactin and some tumor re-expansion.

The medication bromocriptine mesylate is used to treat hyperprolactinemia, which is characterized by an elevated prolactin level. The treatment leads to a reduction in hyperprolactinemia. However, in some cases, despite normalized prolactin levels, secondary deterioration of visual fields may develop.

• The goal of treatment with bromocriptine mesylate is to reduce prolactin levels.
• Monitoring of visual fields is recommended for early recognition of secondary field loss due to chiasmal herniation and adaptation of drug dosage 2.

From the Research

Elevated Prolactin Level Treatment

• The primary therapy for prolactinomas is based on the use of dopamine-receptor agonists, such as bromocriptine and cabergoline 3.
• Cabergoline is very effective and well tolerated in more than 90% of patients with either microprolactinomas or macroprolactinomas, and it induces tumor shrinkage in the majority of patients with macroprolactinomas 3.
• Bromocriptine induces normalization of prolactin levels in 80-90% of patients with microprolactinomas and approximately 70% of those with macroprolactinomas, but it often causes side effects 3.

Comparison of Cabergoline and Bromocriptine

• Cabergoline was found to be more effective than bromocriptine in normalizing serum prolactin levels, shrinking prolactinomas, and relieving symptoms associated with hormone excess 4, 5.
• Cabergoline also has a better tolerability profile than bromocriptine, with fewer side effects reported 4, 5.
• The prolactin normalization rate and tumor volume shrinkage were significantly higher in patients treated with cabergoline compared to those treated with bromocriptine 4.

Evaluation and Treatment of Elevated Serum Prolactin

• Patients with unexplained elevations of serum prolactin or with a level above 200 ng/mL should undergo imaging of the sella turcica 6.
• Dopamine agonists, such as cabergoline, are effective for patients requiring drug treatment, and cabergoline is more effective and better tolerated than bromocriptine 6.
• Surgery is reserved for symptomatic patients not controlled medically 6.

Metabolic and Cardiovascular Risk Factors

• Cabergoline was found to have a more favorable effect on metabolic and cardiovascular risk factors, including plasma lipids, glucose homeostasis markers, and cardiovascular risk factors, compared to bromocriptine 7.
• Cabergoline reduced triglycerides, 2-hr post-challenge plasma glucose, and circulating levels of IGF-1, FFA, uric acid, hsCRP, homocysteine, and fibrinogen, and increased HDL cholesterol and 25-hydroxyvitamin D 7.