Prolactin Regulation

lactation regulationProlactin is the hormone that stimulates milk production in the breast. During pregnancy, prolactin secretion increases and stimulates growth of the breast, but high estrogen and progesterone secretion prevent milk production. After delivery, estrogen and progesterone levels drop, and prolactin stimulates the production of milk by alveolar cells in the breast.

Figure 1 illustrates how bursts of prolactin secretion are stimulated so as to maintain milk production during lactation. Suckling by the infant stimulates nipple mechanoreceptors that are connected by neural circuits to two types of neurosecretory cells in the hypothalamus.

Hyperprolactinemia: Causes and Treatments

Hyperprolactinemia is most often caused by a prolactinoma, a common type of pituitary tumor that hypersecretes prolactin. Hyperprolactinemia (high prolactin secretion) causes infertility because prolactin inhibits GnRH secretion.

As shown in Figure 2, GnRH is required to stimulate secretion of the gonadotropins, FSH and LH.  When GnRH secretion is low, FSH and LH secretion are low and so do not stimulate gamete production and gonadal steroid synthesis. Thus, hyperprolactinemia is an example of the type of infertility called hypogonadotropic hypogonadism, where low gonadal function results from low gonadotropin secretion. In females this causes anovulation (lack of ovulation). Typically, females with hyperprolactinemia will present with amenorrhea (lack of menstruation) and sometimes galactorrhea (abnormal milk production). Prolactinomas seem to be less common in males, but in males hyperprolactinemia also causes hypogonadism, which causes infertility and loss of libido. Another concern with hyperprolactinemia is that decreased gonadal steroid secretion will lead to osteoporosis.

Drugs that are dopamine antagonists are another cause of hyperprolactinemia. Dopamine antagonists are used to treat schizophrenia. Drug-induced hyperprolactinemia may be treated by stopping use of the drug, or if that is not possible, by treating the hypogonadism with gonadal steroid hormone replacement.

Pituitary surgery to remove a prolactinoma can successfully cure hyperprolactinemia, however it is expensive and difficult. Instead, the first line of treatment for hyperprolactinemia is usually medical treatment with a dopamine agonist. Dopamine agonists reduce prolactin secretion and often cause tumors to shrink so that treatment does not need to go on indefinitely. Dopamine agonists that are approved for the treatment of hyperprolactinemia are bromocriptine and cabergoline.

Note that cabergoline has been associated with an increased risk for the development of heart valve defects in patients using it as a treatment for Parkinsonís disease. The mechanism is thought to involve the action of cabergoline at a certain type of serotonin receptor that stimulates abnormal growth of heart valves. Much lower doses of the drug are needed in the treatment of hyperprolactinemia, 0.5mg twice a week vs. greater than 3mg/day for treating Parkinsonís disease.  So far, several prospective studies have shown no increase of heart valve disorders in patients being treated for hyperprolactinemia with cabergoline.