PharmacologyTier 1Medical Sciences concept

Drug-induced hyperprolactinaemia (dopamine antagonists)

Core concept

Prolactin secretion is tonically inhibited by dopamine (D2 receptors on lactotrophs) -- any dopamine antagonist or dopamine-depleting drug disinhibits prolactin release
Antipsychotics (D2 antagonists) are the commonest cause: risperidone and first-generation (typical) antipsychotics cause the most marked rises; aripiprazole (partial D2 agonist) and clozapine, quetiapine are prolactin-sparing
Metoclopramide, domperidone (D2 antagonist antiemetics) also cause hyperprolactinaemia -- domperidone less so centrally (poor BBB penetration) but still raises prolactin (acts on pituitary, which lies outside the BBB)

Clinical effects: galactorrhoea, amenorrhoea/oligomenorrhoea, infertility, reduced libido; men -- gynaecomastia, erectile dysfunction, reduced libido
Chronic hyperprolactinaemia -> suppressed GnRH pulsatility -> hypogonadotropic hypogonadism -> long-term reduced bone density
Domperidone raises prolactin without significant CNS dopaminergic side effects because the pituitary is outside the blood-brain barrier (area postrema/pituitary stalk are circumventricular)

Trap: attributing hyperprolactinaemia in a patient on antipsychotics to a prolactinoma and proceeding straight to pituitary MRI -- first exclude/adjust the causative drug when feasible
Switching to a prolactin-sparing agent (aripiprazole, quetiapine, clozapine) is preferred over adding a dopamine agonist (which can destabilise psychiatric control)
Markedly elevated levels (>~200-250 depending on assay) or failure to fall after stopping/switching the drug raises suspicion of a genuine prolactinoma and warrants MRI

Contrast with prolactinoma (pituitary tumour, dopamine agonist e.g. cabergoline is treatment) -- drug-induced hyperprolactinaemia resolves with cessation/switch, no tumour
Same dopamine-antagonism principle explains why metoclopramide/domperidone are avoided long-term or in high dose
Physiological causes (pregnancy, breastfeeding, stress, nipple stimulation) and other pathological causes (hypothyroidism via TRH stimulation, renal failure via reduced clearance) sit in the same differential

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