How can high prolactin (hyperprolactinemia) levels be reduced?

Reducing High Prolactin (Hyperprolactinemia)

Cabergoline is the first-line treatment to reduce high prolactin levels, started at doses up to 2 mg/week, with superior efficacy (83% normalization rate) and better tolerability compared to other dopamine agonists. 1

Before Starting Treatment: Essential Diagnostic Steps

Before initiating any treatment, you must exclude secondary causes and confirm true hyperprolactinemia:

• Repeat the prolactin measurement in the morning while fasting to exclude stress-induced or pulsatile elevation, as a single elevated value may be spurious 2, 3
• For modestly elevated levels, obtain serial measurements 20-60 minutes apart using an indwelling cannula to differentiate stress-related hyperprolactinemia from organic disease 4, 2
• Review all medications immediately - antipsychotics, antidepressants, antihypertensive agents, and drugs that increase bowel motility are the most common causes of hyperprolactinemia 3, 5
• Screen for pregnancy, primary hypothyroidism, chronic kidney disease, and liver disease - these conditions commonly cause hyperprolactinemia 4, 2
• Assess for macroprolactinemia when prolactin is mildly or incidentally elevated, especially if the patient is asymptomatic - this is present in 10-40% of cases and does not require treatment 1, 2, 3
• Measure serum luteinizing hormone (LH) levels in all patients with confirmed hyperprolactinemia to establish whether this is central (hypothalamic-pituitary) versus peripheral 2, 3

Critical Pitfall to Avoid

• For patients with large pituitary lesions but only modestly elevated prolactin levels, perform serial dilutions of serum prolactin measurement to detect the "high-dose hook effect" which causes falsely low measurements 1, 2

First-Line Pharmacologic Treatment: Cabergoline

Cabergoline is recommended by the Endocrine Society as the preferred dopamine agonist due to its superior effectiveness and tolerability profile 1, 6:

Dosing Strategy

• Start with doses up to 2 mg/week for smaller prolactinomas (<13.5 mm) 1
• Use small nocturnal dose increments to reduce gastrointestinal intolerance and postural hypotension 1, 3
• Cabergoline has a prolonged half-life of 63-69 hours, allowing for once or twice weekly dosing 7
• Take with food to minimize gastrointestinal side effects 7

Expected Outcomes

• Normalization of prolactin levels in 60-70% of patients 1
• Tumor shrinkage in 80-88% of cases 1
• Improvement of visual deficits, resolution of pubertal delay, and headache relief 1
• Cabergoline achieves 83% normalization rate compared to 59% for bromocriptine 1

Monitoring Requirements

• Monitor prolactin levels 1-3 months after initiating treatment and every 3-6 months until stabilized 3
• For patients on standard doses (≤2 mg/week), echocardiographic surveillance every 5 years is recommended 1
• For patients on higher doses (>2 mg/week), perform baseline echocardiogram at treatment initiation and annual echocardiography to monitor for cardiac valvulopathy 1, 3
• Watch for cerebrospinal fluid leak (rhinorrhea) due to medication-induced tumor shrinkage, particularly in tumors that have invaded sphenoid bone - this requires urgent intervention 1

Dose Escalation for Resistant Cases

• For patients resistant to standard cabergoline doses, offer graduated dose increments up to 3.5 mg/week 1
• In exceptional cases, doses up to 7 mg/week may be considered 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 1

Important Side Effects to Monitor

• Psychological side effects (mood changes, depression, aggression, hypersexuality, impulse control disorders) are dose-independent and may be more common in children and adolescents 1
• These require appropriate patient counseling and monitoring 1

Alternative Dopamine Agonist: Bromocriptine

If cabergoline is unavailable or not tolerated:

• Bromocriptine is a well-established alternative with a longer history of use 8
• Requires multiple daily dosing (compared to weekly for cabergoline) 8
• Less effective than cabergoline with normalization rates of 59% versus 83% 1
• More poorly tolerated than cabergoline, particularly regarding gastrointestinal side effects 9, 8
• Bromocriptine undergoes extensive first-pass metabolism with 90-96% protein binding 10
• Take with food due to high percentage of subjects who vomit under fasting conditions 10

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 1
• Tapering doses prior to withdrawal reduces the risk of relapse 1
• Eventual treatment discontinuation may be attempted with continued prolactin monitoring for at least 2 more years 1
• Relapse rates after discontinuation vary (26-89%), with most recurrences occurring within the first 2 years 1

Second-Line Options When Medical Therapy Fails

Surgical Intervention

• Transsphenoidal surgery should be considered after multidisciplinary discussion when a patient is unable to tolerate or is resistant to high-dose cabergoline, or when a patient develops deteriorating vision on cabergoline 1
• Surgical remission rates are lower in pediatric patients compared to adults 1

Radiotherapy

• Reserved for exceptional cases with growing prolactinoma where other treatments have failed 1
• The main indication is control of tumor growth rather than normalization of prolactin levels 1

Special Consideration: Medication-Induced Hyperprolactinemia

• When the causative medication cannot be withdrawn, it is often pointless and possibly even dangerous to administer a dopamine agonist 9
• Check for absence of pituitary adenoma 9
• Where necessary, begin treatment with sex steroids to ensure satisfactory hormonal impregnation and avoid osteoporosis 9

Imaging Follow-Up

• For macroprolactinomas, repeat MRI 3-6 months after starting treatment to verify tumor size reduction 2, 9
• For microprolactinomas, re-imaging depends on clinical and biochemical follow-up 2
• After initial response, perform MRI after 1 year, then yearly for the next 5 years, and once every 5 years if adenoma size is stable 9