Prolactin
Differential diagnosis in the PCOS workup
What it is
Prolactin is a hormone produced by the anterior pituitary gland, best known for its role in lactation after childbirth. Outside of pregnancy and breastfeeding, levels are normally low in women.
When prolactin is abnormally elevated — a condition called hyperprolactinaemia — it inhibits GnRH (gonadotrophin-releasing hormone) secretion, disrupting the menstrual cycle and ovulation. This can produce symptoms very similar to those of PCOS: menstrual irregularities, anovulation, and difficulty conceiving.
Why it matters in PCOS
Prolactin is routinely measured in the initial PCOS workup to exclude hyperprolactinaemia as the cause of menstrual irregularity. It is not that prolactin is elevated in PCOS — generally it is not — but because undiagnosed hyperprolactinaemia can closely mimic PCOS and requires its own specific treatment.
Causes of hyperprolactinaemia are varied: prolactinoma (a benign pituitary adenoma secreting prolactin), medications (antipsychotics, metoclopramide, some antiemetics), hypothyroidism, renal or hepatic insufficiency, and venepuncture stress. A moderately elevated result is therefore sometimes repeated under optimal conditions before further investigation.
Macroprolactin is a form of prolactin bound to immunoglobulins, biologically largely inactive but detected by standard assays. It can falsely elevate the reported level without any real clinical impact. A polyethylene glycol (PEG) precipitation test can distinguish macroprolactin from biologically active monomeric prolactin.
Normal values and action thresholds
- Normal (non-pregnant, non-breastfeeding women): < 25 ng/mL (< 500 mIU/L)
- Moderate elevation: 25–100 ng/mL → recheck, investigate medication causes
- Marked elevation (> 100 ng/mL): pituitary MRI recommended
- Macroprolactinoma: sometimes > 200–500 ng/mL
When is it measured?
Prolactin is measured in the baseline hormone panel, preferably in the morning, fasting, at rest, at least one hour after waking (stress and physical activity can transiently raise prolactin). If the level is elevated, a repeat test under optimal conditions is often requested before considering imaging.
Key takeaways
- Measured to exclude hyperprolactinaemia — not to confirm PCOS
- Hyperprolactinaemia: a distinct diagnosis from PCOS with its own treatment
- Normal < 25 ng/mL; pituitary MRI if > 100 ng/mL
- Macroprolactin: biologically inactive form — PEG test to distinguish
- Treatment: dopamine agonists (bromocriptine, cabergoline) when indicated