Prolactin in Men

Prolactin secretion is tonically inhibited by hypothalamic dopamine (via the tuberoinfundibular dopaminergic pathway). Any disruption to this inhibitory tone — whether by a pituitary tumour, dopamine-blocking medications, or the stalk effect of other sellar masses — elevates prolactin.

Prolactin is secreted in a pulsatile manner with a strong circadian component: levels peak during sleep and are lowest in the afternoon. A single borderline-elevated result should always be repeated; physiological stress, nipple stimulation, recent food intake, and vigorous exercise can transiently raise prolactin by 2-3 times.

Unlike many anterior pituitary hormones, prolactin does not have a peripheral hormonal feedback loop — the primary regulator is hypothalamic dopamine, not prolactin itself.

Prolactin in men: 2-18 ng/mL (42-374 mIU/L). Values above 25 ng/mL (520 mIU/L) warrant investigation. Values above 200 ng/mL (4,200 mIU/L) are highly indicative of a macroprolactinoma.

Macroprolactin (biologically inactive immunoglobulin-bound prolactin) can falsely elevate immunoassay results without causing clinical symptoms. When hyperprolactinaemia is detected without symptoms, laboratories can test for macroprolactinaemia by polyethylene glycol (PEG) precipitation.

Mildly elevated prolactin (18-40 ng/mL) should be confirmed with a repeat fasted, unstressed morning draw before initiating further investigation.

Physiological: pregnancy and lactation (not applicable to men), nipple stimulation, stress, sleep.

Pharmacological (the most common cause of significant hyperprolactinaemia in clinical practice): antipsychotics (haloperidol, risperidone, amisulpride), metoclopramide, domperidone, verapamil, opioids, and some antidepressants.

Pathological — pituitary: prolactinoma (microadenoma <10 mm or macroadenoma ≥10 mm); stalk compression from any sellar mass reducing dopamine delivery; empty sella syndrome.

Other pathological: primary hypothyroidism (elevated TRH stimulates prolactin), chronic kidney disease (reduced clearance), cirrhosis.

In men, sustained hyperprolactinaemia causes secondary hypogonadism: testosterone falls, LH and FSH are suppressed, and sexual function deteriorates. Men may also develop gynaecomastia. Galactorrhoea (nipple discharge) is less common in men than in women due to lower baseline oestrogen.

Macroprolactinomas in men are more often macroadenomas at diagnosis than in women (partly due to delayed presentation), and may cause mass effects including headache, visual field defects (bitemporal hemianopia from optic chiasm compression), and hypopituitarism.

Treatment: dopamine agonists (cabergoline or bromocriptine) are first-line for prolactinomas, normalising prolactin in >80% of cases and reducing tumour size. Surgery is reserved for resistant or rapidly growing adenomas.

Screening for prolactin is recommended in all men with hypogonadism, erectile dysfunction of unclear cause, or infertility — as hyperprolactinaemia is a reversible cause that is easily identified with a single blood test.