What is the treatment for hyperprolactinemia (high prolactin levels)?

Treatment of Hyperprolactinemia

Dopamine agonists are the first-line treatment for hyperprolactinemia, with cabergoline preferred over bromocriptine due to superior effectiveness and better tolerability. 1

Initial Diagnostic Steps Before Treatment

Before initiating therapy, you must exclude secondary causes that require different management:

• Rule out pregnancy - a common physiologic cause that requires no treatment 2
• Check thyroid function - primary hypothyroidism causes hyperprolactinemia in 43% of women and 40% of men with frank hypothyroidism 2
• Review all medications - antipsychotics and dopamine antagonists are among the most common causes 2, 1
• Assess for chronic kidney disease (30-65% have hyperprolactinemia) and severe liver disease 2
• Test for macroprolactinemia when prolactin is mildly or incidentally elevated, as this accounts for 10-40% of hyperprolactinemia cases and may not require treatment 1, 3
• Perform serial dilutions in patients with large pituitary lesions but only modestly elevated prolactin to rule out the "hook effect" (falsely low readings from assay saturation) 2, 1

Pituitary Imaging

• Obtain pituitary MRI when prolactin levels are significantly elevated (typically >4,000 mU/L or 188 μg/L in pediatric patients, though lower in microprolactinomas) suggesting a prolactinoma 2, 1
• Consider MRI even with modest elevations if symptoms of hyperprolactinemia, hypopituitarism, or mass effects are present 2

Medical Treatment: Dopamine Agonists

First-Line Agent: Cabergoline

Cabergoline is the preferred dopamine agonist because it demonstrates superior efficacy in normalizing prolactin levels, restoring gonadal function, and better tolerability compared to bromocriptine 1, 4, 5

Dosing advantages:

• Long duration of action allows once or twice weekly dosing (versus daily for bromocriptine) 4
• More effective at reducing prolactin levels and shrinking tumor size 1

Critical monitoring for cabergoline:

• Echocardiographic surveillance every 6-12 months is required to monitor for cardiac valvulopathy, particularly at doses >2 mg/week 6
• Cardiac valvulopathy risk is increased in Parkinson's disease patients on high doses but not elevated in hyperprolactinemia patients at standard doses 6
• All patients should undergo baseline cardiovascular evaluation including echocardiogram before starting treatment 6
• Discontinue immediately if echocardiogram reveals new valvular regurgitation, restriction, or leaflet thickening 6

Additional cabergoline warnings:

• Monitor for extracardiac fibrotic reactions (pleural, pericardial, retroperitoneal fibrosis) with clinical and diagnostic monitoring 6
• Watch for signs of pleuro-pulmonary disease (dyspnea, persistent cough, chest pain) 6
• Use lowest effective dose and periodically reassess need for continuing therapy 6

Alternative Agent: Bromocriptine

Bromocriptine remains an option when:

• Cabergoline is not tolerated or contraindicated 1
• Pregnancy is desired - bromocriptine has more extensive safety data during pregnancy and can be used safely 7, 5

Dosing:

• Usually given once or twice daily 4
• Should be taken with food due to high incidence of vomiting under fasting conditions 8

Bromocriptine warnings:

• Withdraw when pregnancy is diagnosed in hyperprolactinemic patients 8
• Monitor blood pressure, particularly during first weeks of therapy 8
• Discontinue immediately if hypertension, severe progressive headache, visual disturbances, or CNS toxicity develops 8
• Postmarketing reports of serious cardiovascular events (hypertension, MI, seizures, stroke) in postpartum women, though causal relationship not established 8
• Long-term high-dose use associated with pleural/pericardial effusions, pulmonary fibrosis, and retroperitoneal fibrosis 8
• Produces somnolence and sudden sleep onset - patients must be warned not to drive or operate machinery 8

Treatment Monitoring

For macroprolactinomas:

• Repeat MRI 3-6 months after starting treatment to verify tumor size reduction 1
• Continue imaging yearly for 5 years, then every 5 years if stable 9

For microprolactinomas:

• Re-imaging depends on clinical and biochemical follow-up 1
• MRI may be performed after 1 year, then after 5 years 9

Biochemical monitoring:

• Measure prolactin levels to assess treatment response 1
• In 80-90% of cases, dopamine agonists normalize prolactin levels and restore ovulatory cycles 9, 10

Treatment Duration and Discontinuation

• Attempt treatment discontinuation once normal prolactin levels have been achieved 9
• After prolonged treatment with cabergoline, only 20-30% of patients experience return of hyperprolactinemia symptoms, particularly when residual adenoma exists 9
• Alternative approach: reduce dose or dosing frequency stepwise to lowest effective dose maintaining normal prolactin and stable tumor size 9
• Continue monitoring prolactin after discontinuation, as levels may rise again after months or years 9

Resistant Cases

• Change to a different dopamine agonist if resistance occurs (>80% respond to dopamine agonists overall) 9, 10
• Transsphenoidal surgery is indicated for patients intolerant of or resistant to dopamine agonists 10, 5
• Radiotherapy is rarely used due to side effects and low efficacy 10
• Temozolomide has shown efficacy for aggressive and resistant prolactinomas 10

Special Situations

Drug-induced hyperprolactinemia:

• When causative medication cannot be withdrawn, administering a dopamine agonist is often pointless and possibly dangerous 9
• Check for absence of pituitary adenoma 9
• Begin sex steroid treatment to ensure adequate hormonal impregnation and prevent osteoporosis 9

Pregnancy:

• Bromocriptine is preferred due to more extensive safety data 7, 5
• No increased risk of abortion, malformations, or multiple births with bromocriptine 7
• Pregnancy itself can be beneficial, inducing decreased prolactin levels 7

Critical Pitfalls to Avoid

• Don't miss the hook effect - extremely high prolactin saturates immunoassays producing falsely low measurements in ~5% of macroprolactinomas 1, 11
• Don't overlook macroprolactinemia - present in 10-40% of hyperprolactinemia cases, has low biological activity, and may not require treatment 1, 3
• Don't ignore cardiac monitoring - echocardiographic surveillance is mandatory for patients on cabergoline 6
• Don't continue dopamine agonists in pregnancy-induced hypertension unless potential benefit outweighs risk 6