What causes spontaneous lactation in the absence of pregnancy or childbirth?

Causes of Spontaneous Lactation Without Pregnancy or Childbirth

Spontaneous lactation (galactorrhea) without pregnancy or childbirth is most commonly caused by hyperprolactinemia, which can result from medication use or pituitary microadenomas. 1, 2

Definition and Prevalence

• Galactorrhea is the production of breast milk that is not associated with physiologic lactation (pregnancy or recent childbirth) 1
• It occurs in approximately 20-25% of women 2
• Note that milky nipple discharge within one year of pregnancy and cessation of breastfeeding is usually considered physiologic rather than pathologic 1

Primary Causes of Spontaneous Lactation

Hormonal Causes

• Hyperprolactinemia - elevated prolactin levels are the most common cause of galactorrhea 1, 3
• Pituitary adenomas - particularly prolactinomas (prolactin-secreting tumors):
  • Microadenomas (<10mm) are more common than macroadenomas 2, 4
  • These tumors secrete excess prolactin, triggering milk production 3
• Hypothyroidism - can cause secondary hyperprolactinemia by increasing thyrotropin-releasing hormone, which stimulates prolactin release 1, 3

Medication-Induced Causes

• Antipsychotics (especially typical antipsychotics) - block dopamine receptors, leading to increased prolactin 1, 3
• Antidepressants (particularly SSRIs) - can elevate prolactin levels 3
• Antihypertensives (methyldopa, verapamil, reserpine) 3
• Opioids - can cause hyperprolactinemia 3
• Metoclopramide and domperidone - dopamine antagonists used for GI disorders 3

Other Medical Conditions

• Chronic renal failure - decreased clearance of prolactin 1, 3
• Cirrhosis - impaired hepatic metabolism of estrogen 1
• Hypothalamic disorders - lesions affecting the dopamine pathway 1
• Chest wall stimulation or irritation - can trigger prolactin release through neural pathways 2, 3
• Chronic nipple stimulation - can increase prolactin levels 2

Idiopathic Causes

• In some cases (approximately 40%), no clear cause can be identified despite thorough evaluation 3, 4
• Some patients have normal prolactin levels despite galactorrhea (normoprolactinemic galactorrhea) 3

Diagnostic Approach

Initial Evaluation

• Pregnancy test - must be performed first in premenopausal women 1
• Prolactin level - the most important initial test 1, 3
• Thyroid-stimulating hormone (TSH) - to rule out hypothyroidism 1, 3
• Renal function tests - to assess for chronic kidney disease 1, 3
• Medication review - identify and potentially discontinue medications that can cause hyperprolactinemia 1, 3

Advanced Imaging

• MRI of the pituitary gland - indicated when:
  • Prolactin levels are elevated without other explanation
  • Prolactin levels are significantly elevated (>100 ng/mL)
  • Neurological symptoms are present
  • To evaluate for pituitary or hypothalamic lesions 1, 3

Treatment Approach

For Medication-Induced Galactorrhea

• Discontinue or replace the offending medication if possible 1, 3
• If medication cannot be discontinued, consider dopamine agonist therapy 3

For Prolactinomas

• Dopamine agonists are first-line treatment:
  • Cabergoline (preferred due to better efficacy and fewer side effects) 1
  • Bromocriptine (alternative option) 2, 3
• Surgical intervention (transsphenoidal surgery) may be necessary if:
  • Patient does not respond to or cannot tolerate dopamine agonists
  • Tumor is large with compression of surrounding structures
  • Visual field defects are present 1, 3

For Idiopathic Galactorrhea

• If prolactin levels are normal and discharge is not bothersome, reassurance is sufficient 1, 3
• For bothersome normoprolactinemic galactorrhea, a short course of low-dose dopamine agonist may be effective 3

Prognosis

• Most prolactinomas remain stable or regress over time 2, 4
• Long-term follow-up of women with hyperprolactinemia shows that many experience spontaneous resolution of symptoms, including galactorrhea 4
• The clinical course is generally benign, with minimal risk of progression of microadenomas to macroadenomas 4