Prolactin hormone , reference range, interpretation

Prolactin hormone is synthesized in anterior pituitary gland. prolactin promotes development of mammary gland and support lactation.  High concentrations of prolactin have an inhibiting action on steroidogenesis of the ovaries and secretion of gonadotropins .  Hyperprolactinemia in men and women is cause of fertility disorders.

Clinical uses:

Determination of Prolactin is done in following conditions


Anovular cycles


Galactorrhea(milk production in non-lactating women)


Pituitary tumors



Reference range:

Adult male4.04 – 15.2 ng/ml
Adult female4.79 -23.3 ng/ml
pregnant female20 -400 ng/ml

prolactin levels are increased in: Prolactin secreting pituitary adenoma,  acromegaly, stress, anorexia nervosa medications- antipsychotics drugs, Amoxapine,  verampil , cimetidine, opiates, Metoclopramide .

prolactin levels are decreased in: Pituitary infarction, pituitary destruction from drugs like bromocriptine,  Ergotamines.

Note: prolactin is secreted pulsatile manner and is also influenced by physiological variation ,it is recommended to test pooled prolactin.

A pooled prolactin test is a blood test that measures the average prolactin level over a period of time. It is typically performed by collecting three blood samples at 20-minute intervals and pooling them together before testing

prolactin physiology

The hormone is made up of 198 amino acids and has a molecular weight of approximately 22‑23 kDa

The secretion is mainly under inhibitory control by hypothalamic dopamine and regulated in a negative feedback manner, with prolactin itself providing the afferent signal: short-loop feedback1.

Prolactin appears in serum in three different forms. The biologically and immunologically active monomeric form predominates, followed by the biologically inactive dimeric form and the tetrameric form having low biological activity.

During pregnancy the concentration of prolactin rises under the influence of elevated estrogen and progesterone production. The stimulating action of prolactin on the mammary gland leads postpartum to lactation.

Limitations in prolactin testing :

In rare cases heterophile antibodies in serum can react with reagent immunoglobulin and cause interference in results, particularly seen in persons exposed to animals and animal serum products .

Immunoassays may encounter interference from a high molecular mass complex known as macroprolactin, which consists of prolactin bound to IgG autoantibodies. Although macroprolactin can show reactivity in most prolactin immunoassays, it generally lacks significant biological activity in vivo. As a result, its clinical relevance is considered minimal.

What is macroprolactinemia?

Macroprolactinaemia, defined as hyperprolactinaemia due to excess macroprolactin with normal concentrations of bioactive monomeric prolactin, which may lead to misdiagnosis and mismanagement of hyperprolactinemic patients if not recognised. Macroprolactin has a variable composition and structure, but is most frequently a complex of PRL and IgG, with a molecular mass of 150-170 kDa 2

In case of implausible high prolactin values a precipitation by polyethyleneglycol (PEG) is recommended in order to estimate the amount of the biological active monomeric prolactin.3

Healthcare professionals should remain vigilant regarding this possible diagnostic challenge and advocate for the implementation of PEG screening.


1.Saleem M, Martin H, Coates P. Prolactin Biology and Laboratory Measurement: An Update on Physiology and Current Analytical Issues. Clin Biochem Rev. 2018 Feb;39(1):3-16. PubMed 30072818

2.Fahie-Wilson MN, John R, Ellis AR. Macroprolactin; high molecular mass forms of circulating prolactin. Annals of Clinical Biochemistry. 2005 May;42(Pt 3):175-192. DOI: 10.1258/0004563053857969.

3.Fahie-Wilson M, Smith TP. Determination of prolactin: The macroprolactin problem. Best Pract Res Clin Endocrinol Metab2013;27:725-742

Henry’s clinical diagnosis and management by laboratory methods,23rd edition.

Mosby’s Diagnostic and Laboratory Test Reference, 15th Edition

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