Description

• Milky nipple discharge not associated with gestation or present >1 year after weaning. Galactorrhea does not include serous, purulent, or bloody nipple discharge.
• System(s) affected: endocrine/metabolic, nervous, reproductive

Pregnancy Considerations

• Most cases of galactorrhea during pregnancy are physiologic.
• Pregnancy stimulates lactotroph cells, so pituitary prolactin-secreting macroadenomas may increase by 21% (1)[A].

Epidemiology

• Predominant age: 15 to 50 years (reproductive age)
• Predominant sex: female > male (rare, e.g., in patients with multiple endocrine neoplasia type 1 [MEN1], the most common anterior pituitary tumors are prolactinomas)

Incidence
Prolactinomas, as a cause of galactorrhea, have a 44.4 persons per 100,000 incidence in adults (2).

Prevalence
6.8% of women referred to physicians with a breast complaint have nipple discharge. Another source defines nipple discharge as the chief complaint in 2–5% of women visiting health care providers (3). 20–25% of women experience galactorrhea in their lifetime (4)[C].

Etiology and Pathophysiology

• Lactation is stimulated by prolactin, which is secreted in pulses by the anterior pituitary, and inhibited by dopamine produced in the hypothalamus.
• Galactorrhea results either from prolactin overproduction or loss of inhibitory regulation by dopamine.
  • Afferent neural stimulation
    • Chest wall trauma
    • Chiari-Frommel, del Castillo, and Forbes-Albright syndromes
    • Herpes zoster
    • Nipple stimulation
    • Spinal cord injury
  • Organic hyperprolactinemia
    • Craniopharyngiomas
    • Irradiation
    • Meningiomas or other tumors
    • Multiple sclerosis (MS) (with hypothalamic lesion)
    • Pituitary stalk compression
    • Post-breast augmentation surgery (1%)
    • Prolactinoma
    • Sarcoid
    • Traumatic injury
    • Vascular malformations (aneurysms)
  • Functional hyperprolactinemia
    • Adrenal insufficiency
    • Breast tissue with increased sensitivity to prolactin and/or increased prolactin receptors
    • Chronic kidney disease
    • Cirrhosis
    • Hypothyroidism
    • Lung cancer
    • Renal cell cancer
  • Medications/substances:
    • Cardiology
      • α-Methyldopa
      • Reserpine
      • Verapamil
    • GI
      • Domperidone
      • H₂ blockers
      • Metoclopramide
      • Proton pump inhibitors (5)[C]
    • Herbal
      • Anise
      • Barley
      • Blessed thistle
      • Fenugreek seed
      • Fennel
    • Illicit
      • Cocaine
      • Marijuana (4)[C]
    • Infectious disease
      • Isoniazid
      • Protease inhibitors
      • Typical and atypical antipsychotics
    • Pain
      • Opioids
    • Psych/neuro
      • Neuroleptics
      • Stimulants
      • Selective serotonin reuptake inhibitors (SSRIs) (prolactin not always elevated)
      • Tricyclic antidepressants
    • Reproductive
      • Estrogens
      • Copper intrauterine device
  • Postoperative condition, especially oophorectomy
  • Idiopathic
    • Normal prolactin levels

Genetics
No known genetic component

Risk Factors

Female. Certain medications and supplements—see below.

General Prevention

• Frequent nipple stimulation can cause galactorrhea.
• Avoid medications that can suppress dopamine.

Commonly Associated Conditions

See “Etiology and Pathophysiology.”