Hyperprolactinemia: It is a common clinical reproductive endocrine disorder in which the serum prolactin (PRL) level is higher than 1.14 nmol/L (25 μg/L). Clinical symptoms such as amenorrhea, lactation, frequent menstruation, scanty menstruation, infertility, hypogonadism, headache, and obesity are common. The etiological diagnosis of patients with hyper-PRLemia should distinguish between functional and organic causes such as pituitary tumors. Imaging tests can help to clarify the diagnosis of pituitary lesions. For mild hyper-PRL (PRL > 4.55 nmol/L) without a clear etiology, cranial/ptrachnoid imaging (MRI or CT) is recommended; if serum prolactin levels are persistently elevated > 9.1 nmol/L, a pituitary prolactinoma is highly likely and cranial/ptrachnoid imaging (MRI or CT) should be performed promptly to exclude or determine the presence of compression of the pituitary stalk or The presence of intracranial tumors that compress the pituitary stalk or secrete prolactin and empty saddle syndrome should be ruled out or determined. Pathologic hyperprolactinemia Hypothalamic lesions that block the entry of dopamine (DA) from the portal system of the pituitary stalk into the anterior pituitary cells can lead to elevated serum PRL, including craniopharyngioma, glioma, nodular disease, and tuberculosis, which can compress the pituitary stalk and decrease DA transmission to the pituitary gland. Impaired hypothalamic function after cranial radiation therapy can also affect DA synthesis. Pituitary disorders Pituitary tumors: About 40% of pituitary microadenomas are prolactinomas, which are the most common cause of hyper-PRLemia in young women. Other tumors include growth hormone tumors and adrenocorticotropic hormone tumors that can cause increased TRH and stimulate increased PRL secretion. In addition, other diseases that block the portal system of the pituitary stalk, such as empty saddle syndrome, nodular disease, sarcoidosis, and inflammatory lesions, can squeeze the normal pituitary gland and affect portal blood flow, thereby reducing anterior pituitary DA concentrations and causing elevated PRL. about 30% of patients with PCOS have high PRL, which is associated with prolonged and sustained stimulation of estrogen levels. Transient hyper-PRLemia is associated with luteal insufficiency and infertility and is characterized by elevated basal PRL and nocturnal transient PRL levels. Hyper-PRLemia is associated with decreased renal metabolic clearance of PRL and excessive PRL production in 20-30% of patients with chronic renal failure. In renal failure, the hormone is not properly metabolized and inactivated, and hyperazotemia also alters the sensitivity of pituitary prolactin cells to DA, resulting in reduced inhibition of PRL secretion. Severe liver disease and cirrhosis may also affect the metabolism of DA and cause an increase in serum PRL. Some tumors, such as adrenal adenoma, bronchial carcinoma, and ovarian cystic teratoma, can cause the activation of PRL gene transcription and secretion of large amounts of PRL, resulting in hyperprolactinemia. Idiopathic hyperprolactinemia refers to elevated serum PRL (usually 4.55 nmol/L) with negative pituitary, central nervous system, and systemic tests, accompanied by symptoms such as lactation, menorrhagia, and amenorrhea. The onset of the disease may be related to the presence of heterotypic structures in the PRL molecule. Physiologic hyperprolactin Physiologic PRL is a stress hormone that is secreted in a pulsatile manner with sleep-wake cyclic changes and higher secretion at night than during the day. PRL secretion peaks during the luteal phase of the menstrual cycle and is low during the follicular phase. The secretion level increases 10-fold at full term of pregnancy, decreases before delivery, and increases again after delivery, reaching a peak about 2 hours after delivery. PRL secretion increases significantly under stressful conditions. High protein diet, exercise, stress and sexual activity, breastfeeding, nipple stimulation and sleep disturbances can all lead to increased serum PRL levels. Pharmacological hyperprolactin Estrogen In long-term estrogen users, the drug acts directly on pituitary prolactin cells to promote PRL synthesis and release, resulting in elevated PRL. However, it is generally believed that oral contraceptives are low in estrogen and do not affect PRL levels. DA receptor or H2 receptor blocking agents antipsychotic drugs, gastric motility drugs morpholine, metoclopramide and cimetidine and other H2 receptor blocking agents can block the DA receptors of pituitary prolactin cells, resulting in the weakening of DA inhibition of PRL release and thus promoting PRL secretion; sedatives, anti-hypertensive drugs rifampin, monoamine oxidase inhibitors (such as phenelzine), α-methyldopa and other drugs cause the central nervous system DA levels, leading to increased secretion and release of PRL. Opioids Opioids stimulate hypothalamic opioid receptors and inhibit DA metabolism. Treatment principles for hyperprolactinemia In addition to the factors of physiological and pharmacological hyperprolactinemia, selection is based on the serum PRL level of pathological hyperprolactinemia, clinical symptoms and the presence or absence of fertility requirements. For ectopic prolactin secretion caused by ectopic pregnancy, malignant tumor, hypothyroidism, renal failure, etc., treatment should be directed at the primary cause; if PRL is mildly elevated, menstruation is regular and no fertility is desired, temporary observation can be performed; for amenorrhea, low estrogen status, infertility and pituitary microadenoma, or with headache, drug treatment should be preferred. In cases of pituitary macroadenoma with pressure symptoms, visual field loss, headache and vomiting, or if drug therapy is not effective or not tolerated, surgery may be considered; in cases not suitable for surgery, radiotherapy may be used. The goals of treatment are to suppress prolactin secretion, restore normal menstruation and ovulation or conception, reduce lactation, and improve visual impairment. Pharmacological treatment of hyperprolactinemia Bromocriptine (BCT) is still the most effective drug in clinical practice and is mainly used for the treatment of hyperprolactinemia in addition to the initial dose of 2.5 mg once daily or 2.5 mg twice daily orally. If the PRL level cannot be reduced to normal, the dose can be increased to 7.5-10mg per day. Because the half-life of BCT is 3-4 hours, high doses should be given in 2-3 doses per day. ……BCT induced pregnancy is similar to the natural pregnancy process, with no significant increase in the abortion rate, fetal malformation rate and twin pregnancy rate. In cases of combined pregnancy with high PRL levels, treatment with bromocriptine should be continued until the placenta establishes its role in replacing the gestational corpus luteum after pregnancy (approximately 12 weeks or more). BCT is also available as a long-acting intramuscular injection and as an oral extended-release agent (5-15 mg/day for the extended-release form), which have similar efficiency and side effects as the short-acting ones. There is now an injectable BCT (LAR), 50-100mg per dose, once a month, which has a rapid onset of action and can be used for the treatment of macroadenoma. It is important to note that symptoms and changes in serum PRL levels need to be monitored during administration. Blood PRL decreases significantly after 4 weeks of treatment, and ovulatory menstruation and lactation stops in about 70% to 90% of patients after 7 to 8 weeks of treatment (average 5 to 7 weeks). Usually 3 months of medication is a course of treatment. For patients who wish to become pregnant, BCT 2.5 mg/d until pregnancy and stop, or only during the follicular phase and stop after ovulation (ultrasound monitoring) to prevent overdose in early pregnancy. The oral administration of cartegolide has a long half-life and can be taken once or twice a week, which is more effective, less gastrointestinal and better tolerated. The efficacy of oral administration of Cabergoline 1~2mg/w and BCT 5~10mg/d in patients with hyperprolactinemia is comparable, and the PRL can be stabilized in the normal range for a longer period of time after discontinuation of the former. Cabergoline can also be administered vaginally to those who cannot tolerate it. Quinagoline (CV205-502) is a non-ergot alkaloid dopamine agonist, 75-300mg once a day at bedtime, its efficacy is similar to BCT, but not as effective as Cabergoline. and those who are resistant to BCT.