Causes of Galactorrhea
Galactorrhea is most commonly caused by medication-induced hyperprolactinemia or pituitary prolactinomas, with hypothyroidism, chronic renal failure, and idiopathic causes representing important secondary etiologies that must be systematically excluded. 1, 2, 3
Medication-Induced Causes
Medications are the most frequent cause of galactorrhea after infancy, working through direct prolactin stimulation or by antagonizing dopamine's inhibitory effect on prolactin release. 1, 4, 5
- Dopamine antagonists including antipsychotics (typical and atypical), antiemetics (metoclopramide, domperidone), and some antihypertensives are the primary culprits. 1, 4
- Other medications that can induce hyperprolactinemia include antidepressants, H2-receptor antagonists, opioids, and estrogen-containing compounds. 2, 6
- A thorough medication review is essential before pursuing extensive workup, as discontinuation or substitution may resolve the galactorrhea. 1, 3
Pituitary and Hypothalamic Causes
Prolactinomas are the most common pathologic cause of galactorrhea, with microadenomas (<10 mm) being more frequent than macroadenomas. 7, 2, 5
- Microprolactinomas typically present in premenopausal women with amenorrhea and galactorrhea, while men often remain asymptomatic until visual symptoms develop from larger tumors. 7
- Macroadenomas and other sellar/suprasellar lesions can cause hyperprolactinemia through mass effect on the pituitary stalk, disrupting dopamine delivery ("stalk effect"). 2, 6
- Hypothalamic lesions that disrupt dopamine transport to the pituitary can result in disinhibition of prolactin secretion. 3, 5
Endocrine Disorders
Primary hypothyroidism is a critical reversible cause that must be excluded in all patients with galactorrhea, as elevated TRH stimulates prolactin release. 1, 4, 2
- Hypothyroidism can cause galactorrhea even with normal or mildly elevated prolactin levels. 1
- Polycystic ovary syndrome (PCOS) may be associated with hyperprolactinemia and galactorrhea, though the relationship is complex and bidirectional. 7, 8
Renal and Hepatic Causes
Chronic renal failure causes hyperprolactinemia through decreased prolactin clearance and should be assessed with renal function testing. 4, 2, 3
- Severe liver disease/cirrhosis can also impair prolactin metabolism, leading to elevated levels. 3
Physiologic and Idiopathic Causes
Physiologic galactorrhea can occur from chest wall stimulation, nipple stimulation, stress, sleep, or sexual intercourse through neurogenic pathways. 2, 6, 5
- Pregnancy and recent lactation (within one year of cessation) are normal physiologic causes that must be excluded. 6, 3
- Idiopathic galactorrhea with normal prolactin levels occurs in 20-25% of women and represents a diagnosis of exclusion. 6, 5
Neurologic Causes
Epilepsy and seizure disorders are associated with reproductive endocrine disorders including functional hyperprolactinemia and galactorrhea. 7
- Antiepileptic drugs, particularly valproate, may contribute to endocrine dysfunction independent of seizure activity. 7
Common Pitfalls to Avoid
- Do not measure prolactin immediately post-seizure or during acute stress, as transient elevations will confound interpretation; wait for a resting morning sample. 7, 9
- Do not miss the "hook effect" in patients with large pituitary masses but unexpectedly normal/low prolactin—request serial dilutions when clinical suspicion is high. 1, 4, 9
- Do not forget to assess for macroprolactin (biologically inactive prolactin-antibody complexes) in cases of mild hyperprolactinemia without clinical symptoms, as it accounts for 10-40% of hyperprolactinemia cases. 4, 9
- Do not overlook hypothyroidism as a reversible cause—always include TSH testing in the initial workup. 1, 4, 3