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Hyperprolactinemia

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Hyperprolactinemia

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Hyperprolactinemia

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Which of the following is the most likely mechanism of the therapeutic effect of Bromocriptine in female patients with hyperprolactinemia to help increase fertility?

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Content Reviewers:

Rishi Desai, MD, MPH

With hyperprolactinemia, hyper- means above, -prolactin refers to the hormone produced by the pituitary gland, and -emia refers to the blood, so hyperprolactinemia means higher than normal prolactin levels in the blood.

Normally, at the base of the brain, there’s a small pea-sized gland called the pituitary gland.

The anterior pituitary - the front of the pituitary gland - has a number of different cells, each of which secretes a different hormone.

One group, the lactotroph cells, secrete prolactin. In men, excess prolactin decreases testosterone production.

In women, during pregnancy, elevated levels of estrogen stimulate the lactotrophs to produce large amounts of prolactin which stimulates alveolar cells in the breasts.

In response to prolactin, the alveolar cells divide and enlarge - and once a baby is born, lactogenesis begins - which means that milk is produced.

Apart from milk production, high levels of prolactin also inhibit the release of gonadotropin releasing hormone from the hypothalamus, which results in decreased luteinizing and follicle stimulating hormone levels, which in turn, decreases estrogen levels.

In women, this can stop ovulation and menstruation, which is why women typically don’t have a menstrual period while breastfeeding. In women that are not pregnant or breastfeeding, and in men, prolactin levels are usually kept in check by the hypothalamus in two ways.

The first way is the most important, and it’s when the hypothalamus secretes a constant stream of dopamine which is also called prolactin inhibiting factor.

Dopamine binds to specific receptors on the lactotrophs and inhibits the release of prolactin. The second way is when the hypothalamus secretes thyrotropin releasing hormone, also called prolactin releasing hormone, which can stimulate prolactin release.

If the level of prolactin rises for any reason, then it signals the hypothalamus to release more dopamine, eventually decreasing its own production, a process called negative feedback or feedback inhibition.

Hyperprolactinemia can develop a few different ways. The first is physiologic hyperprolactinemia, which is what happens during pregnancy and lactation - and levels of prolactin typically return back to normal afterwards.

Another cause is a prolactinoma, a type of pituitary adenoma, a benign tumor of lactotroph cells which grow uncontrollably and make excess amounts of prolactin. There are also systemic causes of hyperprolactinemia like hypothyroidism.

In hypothyroidism, the hypothalamus tries to boost the production of thyroid hormones by releasing more thyrotropin releasing hormone. That leads to higher levels of prolactin.

Sources
  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "Harrison's Endocrinology, 4E" McGraw-Hill Education / Medical (2016)
  5. "Laboratory and clinical significance of macroprolactinemia in women with hyperprolactinemia" Taiwanese Journal of Obstetrics and Gynecology (2017)
  6. "Pitfalls in the Diagnostic Evaluation of Hyperprolactinemia" Neuroendocrinology (2019)