Domperidone and Prolactin: Mechanism and Clinical Role
Domperidone Increases Prolactin Levels and Should Not Be Used to Treat Hyperprolactinemia
Domperidone is a dopamine D2 receptor antagonist that blocks dopamine's inhibitory effect on prolactin secretion, thereby causing prolactin levels to rise—it is contraindicated in patients with hyperprolactinemia. 1, 2
Pharmacologic Mechanism
- Domperidone acts as a D2 dopamine receptor antagonist that blocks dopamine's normal inhibitory control over prolactin release from the pituitary lactotroph cells 1
- Unlike other dopamine antagonists, domperidone does not readily cross the blood-brain barrier, exerting its effects primarily at the pituitary level and median eminence 1, 3
- The drug undergoes rapid hepatic metabolism with an average terminal plasma half-life of approximately 6 hours and very low systemic bioavailability 1
Effect on Prolactin Secretion
- In normoprolactinemic women, intravenous domperidone (4 mg) induces a clear-cut and sustained rise in plasma prolactin, with peak levels occurring 15-30 minutes post-injection 2
- The prolactin-releasing effect is evident even at doses as low as 0.25 mg intravenously in normal subjects 2
- In puerperal women with physiologic hyperprolactinemia, domperidone administration causes further increases in plasma prolactin levels (51-517% above baseline) 2
Response in Pathologic Hyperprolactinemia
- In patients with pathologic hyperprolactinemia from pituitary tumors, domperidone typically fails to further increase prolactin levels—88% of patients with proven or suspected prolactinomas are "domperidone-nonresponders" (maximum increase <48% above baseline) 2
- This blunted response occurs because prolactinomas already have autonomous, maximal prolactin secretion that cannot be further stimulated by dopamine receptor blockade 2, 4
- The domperidone stimulation test can help differentiate macroprolactinemia (biologically inactive prolactin) from true microprolactinomas: patients with macroprolactinemia show normal TSH and prolactin responses, while microprolactinoma patients show exaggerated TSH responses and reduced prolactin responses 5
Correct Treatment for Hyperprolactinemia
- Cabergoline is the first-line treatment for hyperprolactinemia, not domperidone 6, 7, 8
- Cabergoline normalizes prolactin levels in 60-83% of patients and achieves tumor shrinkage in 80-88% of cases 6, 7
- Standard initial dosing is 0.25 mg twice weekly, titrating up to 2 mg/week for most patients 6, 8
- For resistant cases, doses can be increased to 3.5 mg/week, or up to 7 mg/week in exceptional circumstances 6, 8
Clinical Pitfall to Avoid
- Never use domperidone (or other dopamine antagonists like metoclopramide) in patients with hyperprolactinemia, as these medications will worsen the condition by further elevating prolactin levels 1, 2
- Always review medication lists to identify and discontinue drugs that can cause or exacerbate hyperprolactinemia before initiating treatment with dopamine agonists 6