What is the treatment for hyperprolactinemia?

Treatment of Hyperprolactinemia

Cabergoline is the first-line treatment for hyperprolactinemia, offering superior efficacy and tolerability compared to other dopamine agonists, with normalization of prolactin levels in over 80% of patients. 1, 2, 3

Initial Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm the diagnosis and exclude secondary causes:

• Repeat prolactin measurement in a fasting morning sample to exclude stress-related elevation, as stress alone can elevate prolactin up to five times the upper limit of normal 2, 4
• Screen for macroprolactinemia using polyethylene glycol (PEG) precipitation when prolactin is mildly or incidentally elevated, as this benign condition accounts for 10-40% of all hyperprolactinemia cases and represents biologically inactive prolactin that may not require treatment 5, 2
• Exclude secondary causes: pregnancy, primary hypothyroidism (causes hyperprolactinemia in 43% of women and 40% of men), chronic kidney disease (30-65% prevalence), severe liver disease, and medication-induced hyperprolactinemia 5, 2
• Review all medications, particularly dopamine antagonists (antipsychotics, antiemetics, antidepressants), as drug-induced hyperprolactinemia is one of the most common causes 5, 2
• Obtain pituitary MRI for all patients with confirmed hyperprolactinemia after excluding secondary causes, as prolactin levels directly correlate with tumor size and generally exceed 4,000 mU/L in prolactinomas 2
• Perform serial dilutions of serum prolactin when large pituitary lesions show paradoxically normal or mildly elevated prolactin levels, as the "high-dose hook effect" occurs in approximately 5% of macroprolactinomas 1, 5, 2

First-Line Pharmacologic Treatment

Cabergoline: Preferred Dopamine Agonist

Cabergoline is the dopamine agonist of choice due to superior effectiveness and lower adverse effect profile compared to bromocriptine. 1, 2

• Efficacy: Normalizes prolactin in 83% of patients (versus 59% with bromocriptine), induces tumor shrinkage in 62% of cases, and resolves visual field defects in 67% of patients 1, 6
• Dosing: Start with low doses and titrate upward; typical maintenance doses are up to 2 mg/week 1, 2
• Tolerability: Adverse events occur in 52% of cabergoline-treated patients versus 72% with bromocriptine 1
• Monitoring: Measure prolactin levels 1-3 months after initiating treatment, then every 3-6 months until stabilized 2

Bromocriptine: Alternative Option

Bromocriptine remains an alternative when cabergoline is unavailable or in specific circumstances:

• Pregnancy planning: Bromocriptine has more safety data during pregnancy and remains the treatment of choice in hyperprolactinemic women wishing to conceive 7, 8
• Efficacy: Normalizes prolactin in over 80% of cases but with inferior tolerability compared to cabergoline 6, 9
• Dosing: Usually given once or twice daily (versus once or twice weekly for cabergoline) 9

Special Clinical Situations

Prolactinomas with Visual Disturbance or Pituitary Apoplexy

Offer cabergoline as first-line therapy even in the presence of visual disturbance and pituitary apoplexy, while carefully monitoring for any deterioration in vision, pituitary function, or general status. 1

• Dopamine agonists improve visual deficits in the majority of patients and induce rapid tumor shrinkage 1
• Surgery is reserved for patients intolerant of or resistant to dopamine agonists 8, 10

Medication-Induced Hyperprolactinemia

For patients on dopamine antagonists (e.g., risperidone) with symptomatic hyperprolactinemia:

• First option: Coordinate with the treating psychiatrist to switch to a prolactin-sparing antipsychotic (quetiapine, clozapine, or aripiprazole) 4
• Second option: Add aripiprazole 5-10 mg daily as adjunctive therapy, which normalizes prolactin in 93% of risperidone-treated patients 4
• If medication cannot be withdrawn: Check for absence of pituitary adenoma and consider sex steroid replacement to prevent osteoporosis 6

Macroprolactinemia

• Most patients with isolated macroprolactinemia are asymptomatic and do not require treatment 5, 2
• However, 20% have coexisting pituitary adenomas, so obtain MRI if symptomatic 2

Cardiac Monitoring Requirements

Critical safety consideration: Cabergoline carries a risk of cardiac valvulopathy, particularly at higher doses.

• Baseline evaluation: All patients should undergo cardiovascular evaluation including echocardiogram before starting cabergoline 3
• Contraindication: Do not use cabergoline if valvular disease is detected at baseline 3
• Routine monitoring: Perform echocardiographic surveillance every 6-12 months for patients on standard doses (≤2 mg/week) 2, 3
• Discontinuation: Stop cabergoline if echocardiogram reveals new valvular regurgitation, valvular restriction, or valve leaflet thickening 3
• Fibrotic complications: Monitor for pleural, pericardial, and retroperitoneal fibrosis with clinical assessment and investigations (chest x-ray, serum creatinine, erythrocyte sedimentation rate) 3

Treatment Duration and Discontinuation

• Microprolactinomas: Once normal prolactin levels are achieved, attempt treatment discontinuation; only 20-30% experience return of hyperprolactinemia, particularly when no residual adenoma exists 6
• Macroadenomas: Continue monitoring with MRI after 3 months to verify tumor size reduction, then yearly for 5 years, then every 5 years if stable 6
• Alternative to discontinuation: Reduce dose or dosing frequency stepwise to the lowest effective dose that maintains normal prolactin levels and stable adenoma size 6
• Post-discontinuation monitoring: Continue monitoring prolactin levels as they may rise again after months or years 6

Common Pitfalls to Avoid

• Do not dismiss macroprolactinemia without evaluating for coexisting monomeric hyperprolactinemia or pituitary adenomas (20% have concurrent adenomas) 2
• Do not miss the hook effect: Always perform serial dilutions when large pituitary masses have disproportionately low prolactin levels 1, 5, 2
• Do not overlook stress-related elevation: Obtain serial measurements for modestly elevated levels 2, 4
• Do not forget pregnancy testing in women of reproductive age before attributing hyperprolactinemia to other causes 2
• Do not use dopamine agonists for drug-induced hyperprolactinemia when the causative medication cannot be withdrawn, as this may be dangerous; instead, ensure absence of pituitary adenoma and consider sex steroid replacement 6