What is the treatment for hyperprolactinemia?

Treatment of Hyperprolactinemia

Cabergoline is the first-line treatment for hyperprolactinemia, with superior effectiveness and tolerability compared to bromocriptine, but only after excluding and treating secondary causes such as medications, hypothyroidism, renal disease, and macroprolactinemia. 1

Initial Management: Treat Underlying Causes First

Before initiating dopamine agonist therapy, you must systematically exclude and address reversible causes 2, 1:

• Discontinue causative medications if possible, particularly dopamine antagonists (antipsychotics, antiemetics like prochlorperazine), as drug-induced hyperprolactinemia is one of the most common causes 3, 1
• Treat primary hypothyroidism if present, as it causes hyperprolactinemia in 43% of women and 40% of men with frank hypothyroidism through compensatory TRH hypersecretion 2, 3, 1
• Manage chronic kidney disease, which causes hyperprolactinemia in 30-65% of patients due to increased secretion and reduced renal clearance 3, 1
• Address severe liver disease if identified 3, 1

Critical pitfall to avoid: Do not start dopamine agonist therapy for mild, asymptomatic hyperprolactinemia without first excluding macroprolactinemia, which accounts for 10-40% of cases and represents biologically inactive prolactin complexes that generally do not require treatment 2, 1

When to Initiate Dopamine Agonist Therapy

Treatment with dopamine agonists is indicated when 2, 1:

• Macroprolactinemia has been excluded (via PEG precipitation testing)
• Secondary causes have been ruled out or treated
• Patient develops symptomatic hyperprolactinemia (amenorrhea, galactorrhea, infertility, hypogonadism, visual disturbances)
• Prolactinoma is confirmed on MRI
• Prolactin levels rise significantly despite addressing secondary causes

Pharmacologic Treatment Algorithm

First-Line: Cabergoline

Cabergoline is the preferred dopamine agonist due to superior effectiveness in normalizing prolactin levels, restoring gonadal function, and better tolerability compared to bromocriptine 2, 1, 4, 5, 6:

• Dosing: Administered once or twice weekly due to long duration of action 4
• Efficacy: Normalizes prolactin and restores ovulatory cycles in over 80% of cases 7
• Tumor reduction: Effectively shrinks prolactinomas, including macroadenomas 2

Second-Line: Bromocriptine

Bromocriptine is an alternative when 8, 4, 6:

• Cabergoline is not tolerated
• Patient is planning pregnancy (more safety data available during pregnancy) 6
• Dosing: Given once or twice daily 4
• Tolerability: Less well-tolerated than cabergoline, with more frequent nausea, hallucinations, confusion, and hypotension 8, 7

If one dopamine agonist is poorly tolerated, switch to another, as tolerance varies between agents 7

Monitoring During Treatment

Prolactin Level Monitoring

• Measure prolactin 1-3 months after initiating treatment 1
• Continue every 3-6 months until levels stabilize 1
• After discontinuation, continue monitoring as prolactin may rise again after months or years 7

Cardiac Surveillance (Critical Safety Concern)

For patients on standard cabergoline doses (≤2 mg/week), perform echocardiographic surveillance every 6-12 months to monitor for cardiac valvulopathy 1, 9:

• Postmarketing cases of cardiac valvulopathy have been reported, particularly with high doses (>2 mg/day) used in Parkinson's disease 9
• Discontinue cabergoline if echocardiogram reveals new valvular regurgitation, restriction, or leaflet thickening 9
• Monitor for signs of fibrotic complications including dyspnea, persistent cough, chest pain, or cardiac failure 9

Imaging Surveillance

For macroadenomas 7:

• MRI at 3 months to verify tumor size reduction
• MRI at 1 year, then yearly for 5 years
• Once every 5 years if adenoma size remains stable

For microadenomas 7:

• MRI may be performed after 1 year, then after 5 years
• Control imaging during treatment is often unnecessary

Special Considerations

Prolactinomas

• Prolactin levels typically correlate with tumor size, generally exceeding 4,000 mU/L (approximately 200 ng/mL) in children and adolescents with prolactinomas 1
• Hook effect warning: In large pituitary masses with paradoxically normal or mildly elevated prolactin, request serial dilutions to detect falsely low measurements, which occur in approximately 5% of macroprolactinomas 2, 3, 1
• Visual field testing should be performed if macroadenoma is present due to potential optic chiasm compression 2

Treatment Discontinuation

• After achieving normal prolactin levels, treatment discontinuation can be attempted 7
• Only 20-30% of patients experience return of hyperprolactinemia after prolonged treatment, particularly when no residual adenoma exists 7
• Alternative approach: reduce dose or frequency to lowest effective level maintaining normal prolactin and stable adenoma size 7

Drug-Induced Hyperprolactinemia

• When the causative medication cannot be withdrawn, dopamine agonist therapy is often unnecessary and possibly dangerous 7
• Confirm absence of pituitary adenoma on MRI 7
• Consider sex steroid replacement to ensure adequate hormonal impregnation and prevent osteoporosis 7