Hyperprolactinaemia in Women
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Direct answer
Hyperprolactinaemia means raised serum prolactin, most often from dopamine-blocking drugs, hypothyroidism or a prolactinoma, and it suppresses GnRH pulsatility to cause oligo-amenorrhoea, galactorrhoea and infertility. The first steps are to exclude pregnancy, measure TSH, review drugs and confirm that the value is not caused by macroprolactin. Pituitary imaging follows only when the level is markedly raised or a mass is suspected.
What you must remember
- Normal range: raised prolactin is assay-dependent, roughly above 25 ng/mL in non-pregnant women; the physiological rise in pregnancy and breastfeeding is expected.
- Macroprolactin: a large, biologically inactive complex that gives falsely high readings; polyethylene glycol precipitation confirms it.
- Drug causes: dopamine antagonists such as antipsychotics, metoclopramide and domperidone are the commonest, with oestrogens, methyldopa and verapamil also implicated.
- Hypothyroidism: raised TRH stimulates prolactin release, so TSH is checked in every case and hypothyroidism is treated first.
- Prolactinoma: the commonest functional pituitary adenoma; microadenomas present with oligomenorrhoea and galactorrhoea, while macroadenomas cause headache and bitemporal field loss.
- Galactorrhoea work-up: exclude pregnancy, measure prolactin and TSH, review drugs and nipple stimulation before any pituitary imaging.
- Cabergoline: the first-line dopamine agonist for prolactinoma, given twice weekly, with better tolerance and generally greater efficacy than bromocriptine.
- Surgery: transsphenoidal resection is reserved for dopamine agonist intolerance, resistance, or visual compromise from a large tumour.
Dopamine agonists compared
Dopamine agonists are the medical treatment of choice for prolactinoma, and drug-induced cases are usually handled by changing the offending drug where possible. Both agents act on the same dopamine receptors, so the choice between them rests mainly on dosing frequency and tolerability.
| Feature | Cabergoline | Bromocriptine |
|---|---|---|
| Usual schedule | Twice weekly | Daily, in divided doses |
| Side effects | Less nausea, better tolerated | More nausea and postural hypotension |
| Current role | Preferred first-line agent | Alternative when cabergoline is unsuitable |
Cabergoline is the usual choice for a new prolactinoma, while bromocriptine remains useful when the first agent is not tolerated.
Dose is titrated against prolactin levels and symptoms, and the lowest effective dose is preferred. Response is judged on both the prolactin level and the return of menstrual cycles or regression of galactorrhoea. Dopamine agonists are usually stopped once pregnancy is confirmed, with visual and clinical monitoring for tumour growth, especially in macroadenomas. Headache or visual change needs urgent review, because a macroadenoma can compress the optic chiasm.
Where the exam tests prolactin
Prolactin questions usually reward the step that comes before imaging or treatment, namely checking the value and its cause.
- Trap: Treating a single high prolactin without repeating it Correct: Stress, recent nipple stimulation and macroprolactin all raise values, so repeat the test and check for macroprolactin before starting therapy.
- Trap: Ordering MRI for every mild rise Correct: Imaging is directed by markedly raised levels, a mass, headache or visual field loss; drug-induced and functional cases do not need it.
- Trap: Calling every galactorrhoea a prolactinoma Correct: Drugs, nipple stimulation and hypothyroidism are common causes, so review medicines and TSH before imaging the pituitary.
- Trap: Continuing dopamine agonists unchanged after pregnancy is confirmed Correct: They are usually stopped once pregnancy is confirmed, with monitoring for tumour growth.
Frequently asked questions
Which laboratory artefact can falsely raise serum prolactin?
Macroprolactin, a large, biologically inactive complex of prolactin with immunoglobulin, is detected by many assays and produces a falsely high reading. Polyethylene glycol precipitation separates it from monomeric prolactin, which avoids unnecessary treatment or imaging.
Why does hyperprolactinaemia cause amenorrhoea?
Raised prolactin suppresses the pulsatile release of GnRH from the hypothalamus, which lowers LH and FSH and blocks ovulation. The result is oligo-amenorrhoea, and cycles often return once prolactin is normalised.
Which drugs most commonly cause raised prolactin in women?
Dopamine antagonists cause it most often, including antipsychotics such as risperidone and haloperidol, and metoclopramide and domperidone. Oestrogens, methyldopa and verapamil can also raise prolactin, so the drug history is reviewed in every case.
Why are dopamine agonists withdrawn when pregnancy is confirmed?
Dopamine agonists are usually withdrawn once pregnancy is confirmed, because most prolactinomas do not need drug treatment during pregnancy. The tumour is monitored instead for growth, with particular attention to visual fields in macroadenomas.