Treatment of Elevated Prolactin Levels
Cabergoline is the preferred first-line treatment for hyperprolactinemia requiring therapy, given at doses ≤2 mg/week, due to superior effectiveness and tolerability compared to bromocriptine. 1
Initial Diagnostic Workup Before Treatment
Before initiating treatment, confirm true hyperprolactinemia and exclude secondary causes:
Confirm hyperprolactinemia with a single serum prolactin measurement at any time of day; for modest elevations, obtain serial measurements to exclude stress-related elevation (stress can raise prolactin up to 5 times the upper limit of normal). 1
Review all medications immediately, as drug-induced hyperprolactinemia is among the most common causes through dopamine antagonism or direct prolactin stimulation. 2, 3
Exclude primary hypothyroidism, which causes hyperprolactinemia in 43% of women and 40% of men with frank hypothyroidism, and 36% of women and 32% of men with subclinical hypothyroidism. 2, 1
Assess for chronic kidney disease (causes hyperprolactinemia in 30-65% of patients) and severe liver disease. 2, 1
Rule out pregnancy in all women of reproductive age, as this is a physiologic cause. 1
Screen for macroprolactinemia using polyethylene glycol (PEG) precipitation when prolactin is mildly or incidentally elevated, especially in asymptomatic patients, as this accounts for 10-40% of all hyperprolactinemia cases and represents biologically inactive prolactin. 1
Obtain pituitary MRI for all patients with confirmed hyperprolactinemia after excluding secondary causes. 1
Check for the "hook effect" by performing serial dilutions when large pituitary lesions show paradoxically normal or mildly elevated prolactin (occurs in ~5% of macroprolactinomas). 2, 1
Indications for Treatment
Treatment is indicated for patients with:
- Macroprolactinoma (tumor >1 cm) 4
- Hypogonadism with risk of osteoporosis 4
- Infertility 4
- Bothersome galactorrhea 4, 5
- Visual field defects from optic chiasm compression 2
- Symptomatic amenorrhea/oligomenorrhea 5
Microprolactinomas without these indications may be followed conservatively, as growth is uncommon. 5
First-Line Medical Treatment
Cabergoline is the preferred dopamine agonist:
Dosing: Start cabergoline at low doses and titrate; standard dosing is ≤2 mg/week given once or twice weekly due to its long duration of action. 1, 5
Superiority over bromocriptine: Cabergoline demonstrates superior effectiveness in normalizing prolactin levels and restoring gonadal function, with significantly better tolerability. 1, 4, 5
Monitoring prolactin levels: Measure prolactin 1-3 months after initiating treatment, then every 3-6 months until stabilized. 1
Cardiac surveillance: Perform echocardiography every 6-12 months for patients on standard cabergoline doses (≤2 mg/week) to monitor for cardiac valvulopathy. 1, 6
Clinical monitoring: Conduct chest x-ray, CT scan, and cardiac echocardiogram at baseline and periodically to assess for fibrotic complications (pleural, pericardial, retroperitoneal fibrosis). 6
Alternative: Bromocriptine
Bromocriptine remains the treatment of choice for women actively seeking pregnancy due to more extensive safety data during pregnancy, despite inferior tolerability. 7
Dosing: Typically given once or twice daily with food (to reduce nausea/vomiting). 8, 5
Monitoring: Blood pressure should be monitored periodically, particularly during the first weeks of therapy, as symptomatic hypotension occurs in almost 30% of patients. 8
Pregnancy considerations: Withdraw bromocriptine when pregnancy is diagnosed in patients being treated for hyperprolactinemia. 8
Special Clinical Situations
For macroprolactinomas:
- Medical therapy with dopamine agonists is first-line treatment. 9, 5
- MRI monitoring should occur after 3 months to verify tumor size reduction, then yearly for 5 years, then every 5 years if stable. 9
- Visual field defects resolve in 67% of patients treated with dopamine agonists. 2
- Transsphenoidal surgery is reserved for patients intolerant of or resistant to dopamine agonists, or when mass effect persists despite medical therapy. 7, 5
For microprolactinomas:
- MRI monitoring may be performed after 1 year, then after 5 years; routine imaging under treatment is unnecessary. 9
For drug-induced hyperprolactinemia:
- Where the causative medication cannot be withdrawn, confirm absence of pituitary adenoma and consider sex steroid replacement to prevent osteoporosis rather than adding a dopamine agonist. 10, 9
For pregnancy:
- Dopamine agonists should not be used in patients with pregnancy-induced hypertension (preeclampsia, eclampsia, postpartum hypertension) unless potential benefit outweighs risk. 6
- If a rapidly expanding macroadenoma requires reinitiation of therapy during pregnancy, weigh benefits against risks, particularly in hypertensive disorders of pregnancy. 8
Treatment Discontinuation
- After achieving normal prolactin levels, attempt treatment discontinuation or dose reduction to the lowest effective dose. 1, 9
- With cabergoline, only 20-30% of patients experience return of hyperprolactinemia after prolonged treatment discontinuation, particularly when no residual adenoma exists. 9
- Continue monitoring prolactin levels after discontinuation, as levels may rise again after months or years. 9
Critical Pitfalls to Avoid
Do not dismiss macroprolactinemia patients without evaluating for coexisting monomeric hyperprolactinemia or pituitary adenomas (20% have coexisting adenomas). 2, 1
Do not miss the hook effect: Always perform serial dilutions when large pituitary masses have disproportionately low prolactin levels. 2, 1
Discontinue cabergoline immediately if echocardiogram reveals new valvular regurgitation, valvular restriction, or valve leaflet thickening. 6
Monitor for fibrotic complications: Watch for dyspnea, persistent cough, chest pain (pleuro-pulmonary), renal insufficiency, lower limb edema (retroperitoneal), or cardiac failure signs. 6
Do not use cabergoline in patients with history of cardiac or extracardiac fibrotic disorders. 6