Prolactin is synthesized and secreted from the lactotroph cells in the anterior pituitary gland. PRL secretion is pulsatile and serum levels vary depending on time of day. Peak serum levels are usually in the early morning hours of sleep. Secretion is regulated by an inhibitory mechanism via a dopamine-mediated suppression. Dopamine type 2 (D2) receptors in the pituitary mediate PRL inhibition. The hypothalamic thyrotropin releasing hormone (TRH) increases secretion of PRL.

An important physiologic role of prolactin is to induce and maintain lactation. It also suppresses reproduction so that physiologic maternal lactation is not interrupted. PRL levels rise during pregnancy and then decrease at the end of pregnancy and after delivery with intermittent elevations during breastfeeding. PRL inhibits reproductive function at multiple levels from the hypothalamus to the ovaries and testicles. Changes caused by PRL reduce libido and fertility in both men and women.

PRL also has other metabolic effects that are geared to sustain lactation. It acts on centers in the brain involved in parenting behaviors and appetite stimulation. It also stimulates gastrointestinal absorption of calcium and mobilization of calcium from bone.

The main effect of a sustained elevation in PRL is reduction of fertility in both men and women. Elevated PRL for many years may affect calcium homeostasis and bone health.

See table for causes of hyperprolactinemia. The major physiologic causes of PRL elevation are pregnancy and lactation. Both physical and psychological stress can also increase PRL levels. Chronic renal and liver failure can result in decreased peripheral clearance of PRL.

Prolactinomas are prolactin-secreting adenomas in the pituitary. They are classified as microadenomas if the size is <1 cm or macroadenomas if size is >1 cm. Less commonly, other pituitary tumors and hypothalamic lesions cause some PRL elevation.

Many antipsychotics and antidepressants cause hyperprolactinemia. Other medications that cause PRL elevation also act by inhibiting dopamine synthesis or release. Oral contraceptives may cause a slight elevation in PRL levels.

Any medication with activity against dopamine receptors can cause PRL elevation by inhibiting the normal dopamine-mediated suppression of PRL. The estimated incidence of dopamine antagonist-treated hyperprolactinemia for women is 8.7/100,000 person-years and for men 1.4/100,000 person-years [1]. For patients who use high-potency dopamine-2 receptor blocking agents, incidence as high as 70% has been reported [2].