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Am Fam Physician. 2022;106(6):695-700

Patient information: See related handout on galactorrhea (milk discharge), written by the authors of this article.

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Galactorrhea is the production of breast milk that is not the result of physiologic lactation. Milky nipple discharge within one year of pregnancy and the cessation of breastfeeding is usually physiologic. Galactorrhea is more often the result of hyperprolactinemia caused by medication use or pituitary microadenomas, and less often hypothyroidism, chronic renal failure, cirrhosis, pituitary macroadenomas, hypothalamic lesions, or unidentifiable causes. A pregnancy test should be obtained for premenopausal women who present with galactorrhea. In addition to prolactin and thyroid-stimulating hormone levels, renal function should also be assessed. Medications contributing to hyperprolactinemia should be discontinued if possible. Treatment of galactorrhea is not needed if prolactin and thyroid-stimulating hormone levels are normal and the discharge is not troublesome to the patient. Magnetic resonance imaging of the pituitary gland should be performed if the cause of hyperprolactinemia is unclear after a medication review and laboratory evaluation. Cabergoline is the preferred medication for treatment of hyperprolactinemia. Transsphenoidal surgery may be necessary if prolactin levels do not improve and symptoms persist despite high doses of cabergoline and in patients who cannot tolerate dopamine agonist therapy.

Galactorrhea is the production of breast milk that is not the result of physiologic lactation. The typical milky nipple discharge associated with galactorrhea can result from a variety of causes, including physical stimulation, endocrinopathies, and pituitary disorders. The decision to treat galactorrhea depends on the underlying cause and whether the discharge is troublesome to the patient.

Epidemiology

  • Discharge from galactorrhea presents one year or more after pregnancy and the cessation of breastfeeding.1

  • Galactorrhea can occur in postmenopausal women and in men.2

  • The prevalence of galactorrhea is unknown, but the condition is estimated to occur in about 20% to 25% of women.3

  • Nipple discharge is the third most common breast-related medical issue after masses and pain.4

  • Hyperprolactinemia may cause galactorrhea and is more common in women than men. The prevalence of hyperprolactinemia in women varies (0.4% of an unselected population, 5% of patients from a family planning clinic, 9% of women being evaluated for amenorrhea, and 17% of women with polycystic ovary syndrome).5,6

Diagnosis

  • Galactorrhea is milk production not related to pregnancy or breastfeeding within the past year or a breast abnormality.7

  • The differential diagnosis of galactorrhea and hyperprolactinemia includes physiologic causes, pharmacologic adverse effects, pituitary and hypothalamic conditions (e.g., prolactinoma), and systemic disease (Table 1).3,5,826

  • Antipsychotics and antidepressants are the medications most commonly associated with galactorrhea. Selective serotonin reuptake inhibitors account for 95% of cases.18,19

  • Prolactinomas are classified as microadenomas (less than 1 cm in diameter) or macroadenomas (1 cm or greater in diameter), with a symptomatic prevalence of 40 per 100,000 people and 10 per 100,000 people, respectively.11,21

  • Microadenomas are more common in premenopausal women, whereas macroadenomas are more common in men and older women.21

  • Prolactinomas are more common in women 20 to 50 years of age compared with men, at a ratio of 10:1. After 50 years of age, women and men are equally affected.22

Physiologic
Pregnancy
Breastfeeding within the past year
Breast/nipple stimulation
Sexual activity
Exercise
Chest trauma (e.g., from herpes zoster, nipple rings, burns, or breast surgery) or lesions
Seizure (within one to two hours)
Pharmacologic
Antipsychotics
 First-generation: phenothiazines, haloperidol
 Second-generation: amisulpride, risperidone (Risperdal), olanzapine (Zyprexa), quetiapine
Antidepressants
 Serotonergic: paroxetine, fluoxetine, sertraline, fluvoxamine, escitalopram
 Tricyclic: clomipramine
 Monoamine oxidase inhibitors: clorgiline, pargyline (not available in the United States)
Antihypertensives: verapamil, methyldopa, reserpine
Narcotics: opioids, cocaine
Antiemetics: metoclopramide, domperidone
Protease inhibitors: ritonavir, saquinavir
Pathologic
Pituitary: prolactinoma, acromegaly, Cushing disease, compressive effect (non–prolactin-secreting macroadenoma, Rathke cyst)
Hypothalamic
 Tumors: craniopharyngiomas, meningioma, germinoma, gliomas, metastatic disease
 Infiltrative diseases: sarcoidosis, Langerhans cell histiocytosis, tuberculosis
 Neuroaxis irradiation
Systemic diseases: primary hypothyroidism, chronic renal failure, cirrhosis, adrenal insufficiency

SIGNS AND SYMPTOMS

  • Galactorrhea typically presents as bilateral, nonbloody, milk white nipple discharge involving multiple ducts.7 The discharge may be clear or greenish.

  • Symptoms of galactorrhea are a result of hyperprolactinemia and may include changes in menstruation (amenorrhea, hypo- or hypermenorrhea, irregular cycles, oligomenorrhea), decreased libido, infertility, erectile dysfunction, or gynecomastia.10,16

  • Pituitary or hypothalamic lesions may present as headaches or vision changes due to compression of the optic chiasm and surrounding structures.24

  • Galactorrhea may also be associated with signs and symptoms of underlying hypothyroidism, chronic renal failure, or cirrhosis.5

DIAGNOSTIC TESTING

  • A suggested approach to the evaluation of galactorrhea is summarized in Figure 1.5,1114

  • The first step in the evaluation of premenopausal women is to rule out physiologic lactation by asking about breastfeeding and pregnancy within the past year and obtaining a urine pregnancy test. During a normal pregnancy, serum prolactin rises to 200 to 500 ng per mL (200 to 500 mcg per L).5

  • All patients should receive an ophthalmologic examination, including visual acuity, pupil, fundus, and ocular motor assessment, evaluation for ptosis, and visual field assessment to check for compression of the optic chiasm by pituitary or hypothalamic lesions.25

  • If galactorrhea is confirmed, serum prolactin measurement and medication history should be completed.17

  • Because exercise and nipple stimulation can elevate serum prolactin levels, they should be avoided for at least 30 minutes before the measurement.17

  • According to one laboratory, prolactin levels are elevated if greater than 30 ng per mL (30 mcg per L) in nonpregnant premenopausal females, greater than 20 ng per mL (20 mcg per L) in postmenopausal women, and greater than 18 ng per mL (18 mcg per L) in males.26 These values may differ depending on the laboratory.

  • The degree of prolactin elevation can indicate possible etiologies, although there can be exceptions. A prolactin level less than 100 ng per mL (100 mcg per L) is associated with drug-induced hyperprolactinemia, systemic disease, or microadenoma, whereas a prolactin level greater than 250 ng per mL (250 mcg per L) is highly suggestive of a macroadenoma.17

  • If prolactin is elevated, further testing should be performed to rule out systemic etiologies, including thyroid-stimulating hormone with free thyroxine for primary hypothyroidism; liver function testing (complete blood count, hepatic function panel, and prothrombin time) for cirrhosis; and basic metabolic panel for chronic renal failure.5,16

  • If the cause of hyperprolactinemia is unclear after laboratory evaluation and review of medications, pituitary imaging is recommended to assess for pituitary and hypothalamic lesions.15,16

  • Pituitary imaging should include magnetic resonance imaging (MRI) of the brain with and without contrast (contrast-enhanced MRI has 90% sensitivity), or computed tomography of the brain with contrast if MRI is unavailable.22,27

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