What are the symptoms and treatment options for hyperprolactinemia?

Symptoms and Treatment of Hyperprolactinemia

The primary symptoms of hyperprolactinemia include galactorrhea, menstrual irregularities (particularly oligomenorrhea) in women, and erectile dysfunction and infertility in men, with cabergoline being the first-line treatment option at an initial dose of 0.25 mg twice weekly. 1, 2

Clinical Presentation

Symptoms in Women

• Oligomenorrhea (35% of cases) 2
• Amenorrhea (with or without galactorrhea)
• Galactorrhea (spontaneous milk production)
• Infertility
• Decreased libido
• Vaginal dryness

Symptoms in Men

• Erectile dysfunction (44.7% of cases) 2
• Infertility (50% of cases) 2
• Decreased libido
• Gynecomastia
• Rarely galactorrhea

Both Sexes

• Osteopenia/osteoporosis (due to hypogonadism)
• Headaches (if caused by pituitary tumor)
• Visual field defects (with large macroadenomas)

Etiology

1. Prolactinomas (27.5% of cases) 2

   • Micro (<10mm) or macroadenomas (≥10mm)

2. Idiopathic (36.6% of cases - most common) 2

3. Medication-induced 3

   • Antipsychotics (especially typical antipsychotics)
   • Antidepressants
   • Antihypertensive agents
   • GI motility drugs

4. Physiologic causes

   • Pregnancy
   • Breastfeeding
   • Stress
   • Sleep
   • Nipple stimulation

5. Other pathologic causes

   • Primary hypothyroidism
   • Chronic renal failure
   • Cirrhosis
   • Chest wall lesions

Diagnosis

1. Laboratory confirmation

   • Serum prolactin levels:
     • Non-pregnant females: 3.0-30.0 ng/mL
     • Pregnant females: 10.0-209.0 ng/mL
     • Postmenopausal females: 2.0-20.0 ng/mL 1

2. Exclude other causes

   • Medication review
   • Thyroid function tests
   • Pregnancy test (in women of childbearing age)
   • Renal function tests

3. Imaging

   • MRI of the pituitary if prolactin >100 ng/mL or if symptoms of mass effect

Treatment

First-Line Treatment: Dopamine Agonists

1. Cabergoline (preferred) 1, 4

   • Initial dose: 0.25 mg twice weekly
   • Titration: Increase by 0.25 mg twice weekly at 4-week intervals
   • Maximum dose: Typically up to 1 mg twice weekly
   • Advantages: Better efficacy and tolerability than bromocriptine, once or twice weekly dosing

2. Bromocriptine 5, 6

   • Alternative option, especially in women planning pregnancy
   • Usually given once or twice daily
   • Common side effects: nausea, dizziness, headache (in about 13% of patients) 1

Monitoring During Treatment

• Prolactin levels should be checked regularly
• For patients with prolactinomas, MRI follow-up to assess tumor size
• Cardiac monitoring:
  • Baseline echocardiogram before starting treatment
  • Yearly echocardiography if dose >2 mg/week
  • Every 5 years if dose ≤2 mg/week 1, 7

Treatment Duration and Discontinuation

• Consider dose reduction if prolactin levels remain normal for ≥6 months 1

• Tapering approach:

  1. Reduce to 0.25 mg once weekly for 4-8 weeks
  2. If prolactin remains normal, further reduce to 0.25 mg every 2 weeks for 8 weeks
  3. Then discontinue completely 1

• After discontinuation, monitor prolactin:

  • Every 3 months for the first year
  • Every 6 months for the second year 1

Surgical Treatment Indications

Consider surgical referral for:

• Resistance to dopamine agonist therapy
• Intolerance to medical therapy
• Patient preference for definitive treatment
• Deteriorating vision despite cabergoline therapy 1

Special Considerations

Pregnancy

• Dopamine agonists should be discontinued once pregnancy is confirmed unless there's risk of tumor expansion 1, 7
• Bromocriptine has more safety data in pregnancy than cabergoline 8

Medication-Induced Hyperprolactinemia

• Consider stopping the causative medication temporarily (if possible)
• Switch to an alternative medication in the same class that doesn't cause hyperprolactinemia
• If medication cannot be changed and symptoms are bothersome, consider dopamine agonist therapy 3

Cardiac Risk

• Cabergoline at doses >2 mg/week has been associated with cardiac valvulopathy
• Patients with hyperprolactinemia typically require lower doses and have not shown increased risk of cardiac valvulopathy 7
• Avoid cabergoline in patients with history of cardiac or extracardiac fibrotic disorders 7

Potential Pitfalls

• Abrupt discontinuation may lead to rapid recurrence of hyperprolactinemia 1
• Inadequate follow-up may miss early signs of recurrence after discontinuation 1
• Dopamine agonist resistance (failure to normalize prolactin levels after 3-6 months of maximally tolerated doses) may require dose increase or surgical intervention 1
• Side effects of cabergoline occur in about 13% of patients - starting with lower doses and titrating slowly can help minimize these 1