What are the symptoms and treatment options for hyperprolactinemia?

Symptoms of Hyperprolactinemia

The primary symptoms of hyperprolactinemia include delayed or arrested puberty, galactorrhea, menstrual disturbances (amenorrhea/oligomenorrhea), infertility, sexual dysfunction, and in cases of larger prolactinomas, headaches and visual field defects. 1, 2

Clinical Presentation by Sex

In Women:

• Menstrual abnormalities:
  • Oligomenorrhea (irregular periods)
  • Amenorrhea (absence of periods)
  • Primary amenorrhea in adolescents
• Galactorrhea (milk discharge from breasts)
• Infertility
• Sexual dysfunction including decreased libido
• Osteopenia/osteoporosis (long-term consequence)

In Men:

• Sexual dysfunction:
  • Decreased libido
  • Erectile dysfunction
  • Infertility
• Gynecomastia (breast enlargement)
• Galactorrhea (less common than in women)
• Decreased facial/body hair

In Both Sexes (particularly with larger tumors):

• Headaches
• Visual field defects (especially bitemporal hemianopsia)
• Growth failure or short stature (in children/adolescents)
• Weight gain (reported in 23% of patients with macroprolactinomas) 1

Diagnostic Approach

1. Prolactin measurement:

   • Single blood sample at any time of day is sufficient 1, 2
   • For mildly elevated levels, consider serial measurements to rule out stress-induced elevation 1, 2
   • Use age-specific and sex-specific reference ranges 1

2. Rule out other causes:

   • Medication review (antipsychotics, antidepressants, opiates, etc.)
   • Thyroid function tests (hypothyroidism)
   • Renal and liver function tests
   • Pregnancy test in women of childbearing age 2

3. Imaging:

   • MRI of the pituitary for confirmed hyperprolactinemia

Treatment Options

First-Line Treatment: Dopamine Agonists

1. Cabergoline:

   • Preferred due to better efficacy and tolerability 2, 3
   • Starting dose: 0.25-0.5 mg/week 2
   • Monitor for cardiac valvulopathy with echocardiogram at baseline and periodically during treatment 2, 4

2. Bromocriptine:

   • Alternative option, especially for women planning pregnancy 2, 5
   • Less well-tolerated than cabergoline 6
   • Can cause hypotension, especially during initial treatment 5

Monitoring During Treatment

• Check prolactin levels 1 month after starting treatment 2
• Adjust dose based on prolactin response and side effects
• For macroprolactinomas: MRI after 3 months, then yearly for 5 years 6
• For microprolactinomas: MRI after 1 year and then after 5 years 6

Special Considerations

• Pregnancy: Dopamine agonists typically discontinued unless risk of tumor expansion 2
• Drug-induced hyperprolactinemia: Consider sex hormone replacement rather than dopamine agonists if causative medication cannot be withdrawn 6
• Resistant cases: Consider switching to another dopamine agonist or surgical intervention 2, 3

Important Caveats

1. Stress-induced elevation: Mild elevations may be due to stress during blood collection and should be confirmed with repeat testing 2

2. "High-dose hook effect": In patients with large pituitary lesions but only mildly elevated prolactin, consider serial dilutions of serum for accurate measurement 2

3. Antipsychotic medications: Common cause of hyperprolactinemia, with conventional antipsychotics and some atypicals (risperidone, amisulpride) more likely to cause elevation than others (aripiprazole, clozapine, olanzapine, quetiapine) 7

4. Long-term consequences: Untreated hyperprolactinemia can lead to bone density loss and increased fracture risk due to hypogonadism 2, 8

5. Microprolactinomas: Over 90% do not enlarge when followed for 10 years, allowing for observation in some cases 8