What is the treatment for hyperprolactinemia (elevated prolactin)?

Treatment of Hyperprolactinemia

Treat the underlying condition first—exclude hypothyroidism, renal/hepatic disease, and medication-induced causes before initiating dopamine agonist therapy. 1, 2

Initial Management Approach

First, identify and address reversible causes:

• Review all medications for dopamine antagonists (antipsychotics, antiemetics like prochlorperazine), as these are among the most common causes of hyperprolactinemia 1, 2
• Screen for hypothyroidism with TSH testing, as primary hypothyroidism causes hyperprolactinemia in 43% of women and 40% of men with frank hypothyroidism 1, 2
• Assess renal function (chronic kidney disease causes hyperprolactinemia in 30-65% of adult patients) and liver function (severe liver disease is associated with hyperprolactinemia) 2
• Exclude macroprolactinemia using polyethylene glycol (PEG) precipitation testing when prolactin is mildly or incidentally elevated, as it accounts for 10-40% of all hyperprolactinemia cases and represents biologically inactive prolactin 1, 3

When to Treat with Dopamine Agonists

Treatment is indicated only after excluding confounding conditions and when:

• Macroprolactinemia has been ruled out 1
• Patient develops symptomatic hyperprolactinemia (menstrual irregularities, galactorrhea, hypogonadism, visual disturbances) 1
• Prolactin levels rise significantly on serial measurements 1
• A prolactinoma is confirmed on MRI 1

Do not start dopamine agonist therapy for mild, asymptomatic hyperprolactinemia 1

First-Line Pharmacologic Treatment

Cabergoline is the preferred first-line dopamine agonist due to superior effectiveness and better tolerability compared to bromocriptine 1, 3, 4, 5, 6

Cabergoline Dosing and Monitoring

• Starting dose: Typically initiated at low doses and titrated to the lowest effective dose 7
• Frequency: Once or twice weekly due to long duration of action 5
• Efficacy: Normalizes prolactin levels, shrinks tumors, and restores menstrual/gonadal function in over 80% of cases 1, 8, 9

Critical Safety Monitoring for Cabergoline

Cardiac surveillance is mandatory:

• Baseline cardiovascular evaluation including echocardiogram to assess for valvular disease before initiating therapy 7
• Echocardiographic monitoring every 6-12 months for patients on standard doses (≤2 mg/week) to monitor for cardiac valvulopathy 3, 7
• Discontinue immediately if echocardiogram reveals new valvular regurgitation, valvular restriction, or valve leaflet thickening 7

Important caveat: The increased risk of cardiac valvulopathy is primarily associated with high doses (>2 mg/day) used in Parkinson's disease; studies of dopamine agonist-treated hyperprolactinemia showed no elevated risk of cardiac valvular regurgitation at lower doses 7, 4

Monitor for extracardiac fibrotic complications:

• Watch for pleural/pericardial effusions, pulmonary fibrosis, retroperitoneal fibrosis 7
• Clinical signs include dyspnea, persistent cough, chest pain, back pain, lower limb edema 7
• Perform baseline and periodic monitoring with chest x-ray, erythrocyte sedimentation rate, serum creatinine 7

Bromocriptine as Alternative

Use bromocriptine when:

• Patient is intolerant to cabergoline 3, 9
• Pregnancy is desired (bromocriptine has more safety data during early pregnancy) 8, 6

Bromocriptine characteristics:

• Given once or twice daily (shorter half-life than cabergoline) 5
• Less well-tolerated than cabergoline with more side effects 8, 9, 5
• Requires blood pressure monitoring, particularly during first weeks of therapy 10
• Contraindicated in pregnancy-induced hypertension (preeclampsia, eclampsia) unless potential benefit outweighs risk 10

Treatment Monitoring

Prolactin level monitoring:

• Measure prolactin 1-3 months after initiating dopamine agonist therapy 3
• Continue every 3-6 months until levels stabilize 3

MRI monitoring for macroprolactinomas:

• Perform MRI after 3 months to verify tumor size reduction 9
• Then after 1 year, yearly for 5 years, then every 5 years if stable 9

For microprolactinomas: MRI after 1 year, then after 5 years 9

Special Considerations

Hook effect awareness: In patients with large pituitary masses but paradoxically normal or mildly elevated prolactin, request manual serial dilutions to rule out the "high-dose hook effect," which occurs in approximately 5% of macroprolactinomas 1, 2

Pregnancy management:

• Withdraw dopamine agonists when pregnancy is diagnosed in patients with hyperprolactinemia 10
• Exception: May reinitiate if rapidly expanding macroadenoma threatens vision 10
• Visual field defects from macroadenomas resolve in 67% of patients treated with dopamine agonists 2

Treatment withdrawal: After prolonged treatment with normal prolactin levels, gradual dose reduction or discontinuation may be attempted, as only 20-30% of patients experience recurrence, particularly when no residual adenoma exists 8, 9, 4

Surgical Intervention

Transsphenoidal surgery is reserved for:

• Patients who refuse long-term dopamine agonist therapy 8, 6
• Dopamine agonist resistance or intolerance 8, 6
• Persistent mass effects despite medical therapy 5
• Emergency situations with acute visual compromise 10