Hyperprolactinemia Treatment

• Goal is to decrease prolactin (PRL) levels and to alleviate symptoms
• If possible, discontinue offending medication

• Titrate dose to achieve maximum prolactin (PRL) suppression and to restore reproductive function
• Therapy recommended to lower prolactin levels, decrease tumor size and restore gonadal function in patients with microadenomas or macroadenomas

Bromocriptine

• Initial drug of choice
• Actions: Ergot alkaloid that binds to and stimulates D₂ dopamine-receptors on lactotroph cells
• Effects: Lowers serum prolactin (PRL) levels in 70-100% of patients
  
  • Decreases tumor size and restores gonadal function
  • Macroadenomas shrinkage of ≥50% is observed in 40% of patients
  • Headaches and visual disturbances improve rapidly within days of commencing therapy
  • Resumption of menses and ovulation in 80-90% of hyperprolactinemic women

• Discontinuation results in recurrent hyperprolactinemia and tumor regrowth along with the risk of visual disturbances
  
  • ~5% of patients do not have recurrence with discontinuation of Bromocriptine

• May be administered intravaginally if oral dose is not tolerated
• Pregnancy: Bromocriptine has been used to restore fertility in hyperprolactinemic women
  
  • Attempt to reduce neonatal exposure to the drug
  • Woman desiring to become pregnant should use barrier contraception and Bromocriptine until 3 regular menstrual cycles have occurred (to allow for conception timing)
  • Bromocriptine can be safely discontinued in women with microadenomas or intrasellar macroadenomas without significant suprasellar or parasellar extension
  • In women with larger macroadenomas, 2 options are recommended:
    
    • Discontinue Bromocriptine
    • Give Bromocriptine continuously throughout gestation, however with theoretical fetal risk

• 5% of microadenomas and 15-30% of macroadenomas may grow during pregnancy
• Prolactin (PRL) levels rise progressively in pregnancy and monitoring of prolactin (PRL) levels is not useful
• Regular visual field exam throughout pregnancy is recommended
• Visual field testing is recommended in patients with macroadenomas
• Restart Bromocriptine if tumor growth occurs and explain to patient the risks and benefits of treatment
• Surgical decompression may be used if vision is threatened

Cabergoline

• Useful in patients who are resistant or intolerant to Bromocriptine
  
  • Fewer side effects than Bromocriptine and can be given 2x/week
  • Higher efficacy in normalizing prolactin levels and higher frequency of pituitary tumor shrinkage

• Actions: Ergot derivative which is a long-acting dopamine agonist with high affinity for D₂ receptors on lactotroph cells
• Effects: Suppresses prolactin (PRL) secretion for >14 days after a single oral dose
  
  • Lowers serum prolactin (PRL) levels and restores gonadal function in ~80% of patients with microadenomas
  • Normalizes prolactin (PRL) and shrinks tumor in ~70% of macroadenomas

Quinagolide

• May be useful in patients who are intolerant of ergot derivatives
• Actions: Non-ergot Dopamine agonist
• Effects: ~50% of patients who are resistant to Bromocriptine respond to Quinagolide
  
  • Efficacy is similar to other Dopamine agonists

Pergolide

• Effects: Several studies have shown that Pergolide is as efficacious as Bromocriptine
  
  • Tolerance is similar to Bromocriptine
• Discontinued in other countries due to increased risk of valvular heart disease

Metergoline

• Actions: Ergot derivative which is both a dopamine agonist and a serotonin antagonist
• Indicated for use in hyperprolactinemic amenorrhea

Watchful Observation

• Appropriate in patients who present with microadenomas, are not concerned with fertility, and have minimal symptoms
• Effects: Studies have shown that 93% of microadenomas do not grow over a 4-6 year period
• Close observation of the adenoma is necessary to determine if it is growing
  
  • Serial prolactin (PRL) levels should be done regularly
  • Magnetic resonance imaging (MRI) should be performed if a significant rise in prolactin (PRL) is noticed
  • Imaging studies at yearly intervals

Formal Visual Field Testing

• Performed prior to dopamine agonist treatment and every 6-12 months thereafter
• More frequent monitoring initially in those with visual field deficit

Hypothyroidism

• Levothyroxine (T₄) replacement
  
  • Resolution of hyperprolactinemia usually occurs after adequate thyroid replacement
•  Please see Hypothyroidism disease management chart for further information
  

Drug-Induced Hyperprolactinemia

• If possible, discontinue offending medication for 3 days or substitute an alternative drug
  
  • Then, repeat measurement of serum prolactin

Psychiatric patients who cannot stop medication:

• If possible, slowly decrease dose of offending antipsychotic medications or substitute an alternative drug
• Dopamine agonist may be added to restore normoprolactinemia and alleviate symptoms
  
  • Use with caution as it may worsen underlying psychiatric condition

Renal Failure

• Treat underlying cause
• Renal transplant may help restore prolactin levels to normal

Hypothalamic-Pituitary Stalk Damage

Granulomatous Infiltrates

• Glucocorticoids (rarely effective)

Hypothalamic or Sellar Mass Lesions

• Surgical resection may reverse hyperprolactinemia

Irreversible Hypothalamic Damage

• No treatment may be necessary