What is the first line treatment for hyperprolactemia?

Treatment of Hyperprolactinemia

Cabergoline is the first-line treatment for hyperprolactinemia due to its superior effectiveness in normalizing prolactin levels and better adverse effect profile compared to other dopamine agonists. 1

Initial Assessment and Diagnosis

• Before initiating treatment, exclude other causes of hyperprolactinemia such as pregnancy, primary hypothyroidism, and medication effects 1
• Assess baseline macroprolactin levels when serum prolactin is mildly or incidentally elevated to rule out macroprolactinemia 1
• For patients with large pituitary lesions but normal or mildly elevated prolactin levels, perform serial dilutions to detect the "high-dose hook effect" which can cause artificially low measurements 1

First-Line Treatment

• Cabergoline is superior to bromocriptine in normalizing prolactin levels (83% vs 59%) with fewer adverse events (52% vs 72%) 2, 3
• Standard initial dosing of cabergoline is 0.25 mg twice weekly, with gradual increases up to 2 mg/week for most patients 2
• Clinical benefits of cabergoline include:
  • Normalization of prolactin levels in 60-70% of patients 1
  • Tumor shrinkage in 80-88% of cases 1
  • Improvement of visual deficits and resolution of symptoms like headache 1

Dosage and Administration

• Start with low doses (0.25 mg twice weekly) and gradually increase to minimize side effects 2
• For patients with smaller prolactinomas (<13.5 mm), standard doses up to 2 mg/week are typically effective 1, 2
• For resistant cases, graduated dose increments up to 3.5 mg/week may be offered 1, 2
• In exceptional cases, doses up to 7 mg/week may be considered, though some studies report little additional benefit above 3.5 mg/week 2

Monitoring During Treatment

• All patients should undergo a baseline cardiovascular evaluation, including echocardiogram to assess for valvular disease 4
• For patients on standard doses (≤2 mg/week), echocardiographic surveillance every 5 years is recommended 1, 2
• For patients on higher doses (>2 mg/week), annual echocardiography with cardiac auscultation is required 5, 1, 2
• Monitor prolactin levels 1-3 months after initiating treatment and every 3-6 months until stabilized 6
• For macroprolactinomas, repeat MRI 3-6 months after starting treatment to verify tumor shrinkage 1

Managing Side Effects

• Common side effects include gastrointestinal intolerance, postural hypotension, and psychological effects 2
• Small nocturnal dose increments can reduce gastrointestinal intolerance and postural hypotension 2
• Be vigilant for rhinorrhea after initiating treatment, which may indicate cerebrospinal fluid leak due to medication-induced tumor shrinkage requiring urgent intervention 1
• Psychological side effects (mood changes, depression, aggression, hypersexuality, impulse control disorders) are dose-independent and may require dose adjustment or medication change 2

Treatment Duration and Discontinuation

• If prolactin levels have been normalized for at least 2 years on medical therapy and there is no visible residual prolactinoma on MRI, consider gradual cabergoline dose reduction 5
• Eventual treatment discontinuation may be attempted with continued prolactin monitoring for at least 2 more years 5
• Relapse rates after discontinuation vary (26-89%), with most recurrences occurring within the first 2 years 5
• Tapering doses prior to withdrawal reduces the risk of relapse 5

Second-Line Options

• Surgical intervention (transsphenoidal surgery) should be considered when a patient is unable to tolerate or is resistant to high-dose cabergoline 1
• Dopamine agonist resistance is defined as failure to achieve normal prolactin levels and/or less than 50% reduction in tumor area after 3-6 months of maximally tolerated doses 2
• Radiotherapy is reserved for exceptional cases with growing prolactinoma where other treatments have failed 1

Special Considerations

• Cabergoline should not be used in patients with a history of cardiac or extracardiac fibrotic disorders 4
• Bromocriptine may be preferred for women wishing to conceive due to more extensive safety data during pregnancy 7
• For medication-induced hyperprolactinemia where the causative drug cannot be withdrawn, it may be unnecessary to administer a dopamine agonist 8

Cardiac Safety Monitoring

• Cardiac valvulopathy risk increases with higher doses of cabergoline, particularly above 2 mg/week 4
• Following treatment initiation, clinical and diagnostic monitoring should be conducted to assess the risk of cardiac valvulopathy 4
• Cabergoline should be discontinued if an echocardiogram reveals new valvular regurgitation, valvular restriction, or valve leaflet thickening 4