Hyperprolactinaemia

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Hyperprolactinaemia
Other names	Hyperprolactinemia, Chiari–Frommel syndrome
Prolactin
Specialty	Endocrinology

Hyperprolactinaemia also known as Hyperprolactinemia is a condition characterized by abnormally high levels of prolactin in the blood. In women, normal prolactin levels average to about 13 ng/mL, while in men, they average 5 ng/mL. The upper normal limit of serum prolactin is typically between 15 to 25 ng/mL for both genders.^[1] Levels exceeding this range indicate hyperprolactinemia.

Prolactin (PRL) is a peptide hormone produced by lactotroph cells in the anterior pituitary gland.^[1] It plays a vital role in lactation and breast development.^[1] Hyperprolactinemia, characterized by abnormally high levels of prolactin, may cause galactorrhea (production and spontaneous flow of breast milk), infertility, and menstrual disruptions in women. In men, it can lead to hypogonadism, infertility and erectile dysfunction.

Prolactin is crucial for milk production during pregnancy and lactation. Together with estrogen, progesterone, insulin-like growth factor-1 (IGF-1), and hormones from the placenta, prolactin stimulates the proliferation of breast alveolar elements during pregnancy. However, lactation is inhibited during pregnancy due to elevated estrogen levels.^[1] After childbirth, the rapid decline in estrogen and progesterone levels allows lactation to begin.

Unlike most tropic hormones released by the anterior pituitary gland, prolactin secretion is primarily regulated by hypothalamic inhibition rather than by negative feedback from peripheral hormones. Prolactin also self-regulates through a counter-current flow in the hypophyseal pituitary portal system, which triggers the release of hypothalamic dopamine. This process also inhibits the pulsatile secretion of gonadotropin-releasing hormone (GnRH), thereby negatively influencing the secretion of pituitary hormones that regulate gonadal function.^[2]

Estrogen promotes the growth of pituitary lactotroph cells, particularly during pregnancy. However, lactation is hindered by the elevated levels of estrogen and progesterone during this period. The rapid decline in estrogen and progesterone after childbirth enables lactation to begin. While breastfeeding, prolactin suppresses gonadotropin secretion, potentially delaying ovulation. Ovulation may resume before the return of menstruation during this time.^[2] Although hyperprolactinemia can result from normal physiological changes during pregnancy and breastfeeding, it can also be caused by other etiologies. For example, high prolactin levels could result from diseases affecting the hypothalamus and pituitary gland.^[2] Other organs, such as the liver and kidneys, could affect prolactin clearance and consequently, prolactin levels in the serum.^[2] The disruption of prolactin regulation could also be attributed to external sources such as medications.^[2]

In the general population, the prevalence of hyperprolactinemia is 0.4%.^[2] The prevalence increases to as high as 17% in women with reproductive diseases, such as polycystic ovary syndrome.^[2] In cases of tumor-related hyperprolactinemia, prolactinoma is the most common culprit of consistently high levels of prolactin as well as the most common type of pituitary tumor.^[2] For non-tumor related hyperprolactinemia, the most common cause is medication-induced prolactin secretion.^[3] Particularly, antipsychotics have been linked to a majority of non-tumor related hyperprolactinemia cases due to their prolactin-rising and prolactin-sparing mechanisms.^[4] Typical antipsychotics have been shown to induce significant, dose-dependent increases in prolactin levels up to 10-fold the normal limit. Atypical antipsychotics vary in their ability to elevate prolactin levels, however, medications in this class such as risperidone and paliperidone carry the highest potential to induce hyperprolactinemia in a dose-dependent manner similar to typical antipsychotics.^[5]