inhibits the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which in turn inhibits the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland and results in diminished gonadal sex hormone production (termed hypogonadism). This is the cause of many of the symptoms described below. In many people, elevated prolactin levels remain unexplained and may represent a form of hypothalamic–pituitary–adrenal axis dysregulation. Physiological causes Physiological (i.e., non-pathological) causes include: ovulation, pregnancy, breastfeeding, chest wall injury, stress, stress-associated REM sleep, and exercise. During pregnancy, prolactin levels can range up to 600 ng/mL, depending on estrogen concentration. At 6 weeks post-birth (postpartum), estradiol concentrations decrease, and prolactin concentrations return to normal even during breastfeeding. Stress-related factors include physical, exercise, hypoglycemia, myocardial infarction, and surgery. Coitus and sleep can also contribute to an increased prolactin release. Medications Prolactin secretion in the pituitary is normally suppressed by the brain chemical dopamine, which binds to dopamine receptors. Drugs that block the effects of dopamine at the pituitary or deplete dopamine stores in the brain may cause the pituitary to secrete prolactin without an inhibitory effect. These drugs include the typical antipsychotics: phenothiazines such as chlorpromazine (Thorazine), and butyrophenones such as haloperidol (Haldol); atypical antipsychotics such as risperidone (Risperdal) and paliperidone (Invega); gastroprokinetic drugs used to treat gastro-esophageal reflux and medication-induced nausea (such as that from chemotherapy): metoclopramide (Reglan) and domperidone; less often, alpha-methyldopa and reserpine, used to control hypertension; and TRH. The use of estrogen-containing oral contraceptives are also known to increase prolactin levels when taken in high doses >35 μg. The sleep drug ramelteon (Rozerem) also increases the risk of hyperprolactinaemia. Particularly, the dopamine antagonists metoclopramide and domperidone are both powerful prolactin stimulators and have been used to stimulate breast milk secretion for decades. However, since prolactin is antagonized by dopamine and the body depends on the two being in balance, the risk of prolactin stimulation is generally present with all drugs that deplete dopamine, either directly or as a rebound effect. Specific diseases Prolactinoma or other tumors arising in or near the pituitary — such as those that cause acromegaly may block the flow of dopamine from the brain to the prolactin-secreting cells, likewise, division of the pituitary stalk or hypothalamic disease. Other causes include chronic kidney failure, hypothyroidism, bronchogenic carcinoma and sarcoidosis. Some women with polycystic ovary syndrome may have mildly-elevated prolactin levels. Nonpuerperal mastitis may induce transient