Hyperprolactinemia

　　First, etiology

　　1, Physiological hyperprolactinemia:In normal healthy women, plasma prolactin increases during the night and sleep (2-6 am), late follicular phase and luteal phase. Plasma prolactin increases 5-10 times during pregnancy. After the second trimester of pregnancy, the concentration of prolactin in amniotic fluid is higher than that in plasma. In lactating women, the concentration of plasma prolactin is 1 times higher than that in the non-pregnant period. The plasma prolactin level in fetuses and newborns (≥28 weeks of gestation to 2-3 weeks postpartum) is equivalent to that of the mother. Massaging the breasts and suckling the nipples reflexively promote the secretion of prolactin. Plasma prolactin still maintains a high level during the puerperium (within 4 weeks). The prolactin level in non-lactating women decreases to the level of the non-pregnant period within 3 months. Prolactin levels increase significantly during fasting, insulin-induced hypoglycemia, exercise, stress, and sexual intercourse.

　　2, Pathological hyperprolactinemia

　　(1) Hypothalamic-pituitary lesions:

　　① Hypothalamic nonfunctional tumors: including craniopharyngiomas, infiltrative hypothalamic sarcomatoid disease, histiocytosis, glioma, and leukemia.

　　②Pituitary functional tumors: including pituitary adenoma (80% secreting prolactin), prolactinoma, acromegaly (25% associated with hyperprolactinemia), Cushing's syndrome (adrenal ACTH adenoma, 10% associated with hyperprolactinemia), prolactin cell hyperplasia (80% associated with hyperprolactinemia).

　　③Functional hyperprolactinemia: caused by dopamine function inhibition, including primary empty sella syndrome (5% associated with amenorrheic galactorrhea) and secondary empty sella syndrome (10% associated with hyperprolactinemia).

　　④Inflammatory and destructive lesions: including meningitis, tuberculosis, syphilis, actinomycosis, injury, surgery, arteriovenous malformations, granulomatosis; pituitary stalk lesions, injury, or tumor compression.

　　⑤Psychological trauma, stress, and Parkinson's disease.

　　(2) Thyroid and adrenal diseases: including primary and secondary hypothyroidism, pseudothyroidism, Hashimoto's thyroiditis. Adrenal diseases, including chronic kidney disease, Addison's disease, and chronic renal failure may present with hyperprolactinemia.

　　(3) Ectopic prolactin secretion syndrome: including undifferentiated bronchogenic lung cancer, adrenal cancer, and embryonal cancer.

　　(4) Polycystic ovary syndrome.

　　(5) Gynecological and obstetric surgery and local stimulation: including induced abortion, postpartum abortion of hydatidiform mole or stillbirth, hysterectomy, tubal ligation, oophorectomy. Local stimulation of the breast, including mastitis, fissures, chest wall trauma, herpes zoster, tuberculosis, and chest wall surgery can also reflexively cause hyperprolactinemia.

　　(6) Drugs that promote prolactin secretion:

　　①Anesthetic drugs: including Morphine, Methadone, Methionine enkephalin.

　　②Psychiatric drugs: including Phenothiazines, including Haloperidol, Fluphenazine, Chlorpromazine, Tricyclic antidepressants, Apomorphine, Chlorodiazepines, Amphetamines, and Diazepam.

　　③Hormonal drugs: including Estrogens, oral contraceptives, Thyrotropin-releasing hormone (TSH-RH).

　　④Antihypertensive drugs: including Methyldopa, Reserpine, Verapamil (Isuprel).

　　⑤Drugs affecting dopamine metabolism and function: including: A. Dopamine receptor antagonists, including Phenothiazines, Haloperidol, Metoclopramide, Domperidone, Pimozide; B. Dopamine reuptake inhibitors: Nomifensine (Phenylquinazoline); C. Dopamine degradants, including Reserpine, Methyldopa; D. Dopamine conversion inhibitors: Apomorphine.

　　⑥Monoamine oxidase inhibitors.

　　⑦Benzodiazepine derivatives: including diphenylbutazepine derivatives, Carisoprodol, Amisulpride, Imipramine, Amitriptyline, Phenytoin, Diazepam, Clonazepam.

　　⑧Antihistamines and H1, H2 receptor antagonists: including Serotonin, Amphetamines, etc. H1 receptor antagonists include Chlorpheniramine, Pyrilamine. H2 receptor antagonists include Cimetidine.

　　⑨Antiemetic drugs: including Sultopride, Promazine (Promeazine), Fenfluramine.

　　⑩Other: Seganidine.

　　II. Pathogenesis

　　The secretion of pituitary prolactin (PRL) is strongly controlled by dopaminergic neurons at the hypothalamic结节-漏斗, so any damage to the hypothalamus, such as tumors, radiation injury, and inflammation, may cause an increase in pituitary PRL secretion, thus causing hyperprolactinemia. Some pituitary diseases (such as inflammation) can cause hyperprolactinemia if the pituitary stalk is damaged, as the dopamine transported from the hypothalamus to the pituitary PRL cells is reduced. Certain non-PRL pituitary tumors such as GH tumors, ACTH tumors, etc., can compress the pituitary stalk and cause hyperprolactinemia. TRH has a strong stimulatory effect on PRL secretion, while thyroid hormones can slightly inhibit the response of PRL cells to TRH, so hyperprolactinemia may occur in primary hypothyroidism. 30% to 80% of end-stage renal failure patients have mild to moderate hyperprolactinemia, the cause may be the accelerated metabolism of dopamine in these patients. Liver cirrhosis can cause hyperprolactinemia due to abnormal metabolism of neurotransmitters. Some chest and breast diseases such as chest surgery, chest herpes zoster, mastitis, etc., can also cause hyperprolactinemia. Some non-endocrine gland tumors such as bronchogenic carcinoma can also secrete PRL, causing hyperprolactinemia, but it is very rare.

　　Hyperprolactinemia (HP) is an endocrine disease caused by hypothalamic-pituitary dysfunction, the most common cause of which is the excessive secretion of prolactin (PRL) by pituitary prolactinoma. Due to the elevated serum PRL, it causes menstrual disorders, galactorrhea, and infertility in women, so HP is a difficult disease that obstetricians and gynecologists pay attention to. Hyperprolactinemia can also cause significant osteoporosis, the cause may be the decrease in estrogen levels, but some people believe that PRL itself has a negative impact on bone density. Some patients have hyperplasia of the lobules of the breast or macromastia.

　　I. General manifestations

　　1, Menstrual disorders:Primary amenorrhea accounts for 4%, secondary amenorrhea accounts for 89%, oligomenorrhea accounts for 7%, dysfunctional uterine bleeding and incomplete luteal function account for 23% to 77%.

　　2, Typical galactorrhea amenorrhea syndrome:The incidence rate is 20.84% in non-tumor hyperprolactinemia, 70.6% in tumor type, 63% to 83.5% in simple galactorrhea, galactorrhea appears when the breast is prominent or squeezed, it is watery, serous, or milk-like, and the breasts are mostly normal.

　　3, Infertility:The incidence is 70.7%, it can be primary or secondary infertility, and is related to anovulation, incomplete luteal function, or luteinized unruptured follicle syndrome (LUFS).

　　4, Estrogenemia and hyperandrogenemia:Estrogen decrease can cause flushing, palpitations, spontaneous sweating, vaginal dryness, sexual pain, decreased libido, etc., while androgen increase can cause moderate obesity, seborrhea, acne, and hirsutism.

　　5, Changes in vision and field of view:When pituitary tumors involve the optic nerve chiasm, they can cause vision loss, headache, dizziness, hemianopia, and blindness, as well as damage to cranial nerves II, III, IV, papilledema, and exudation.

　　6, Acromegaly:Seen in PRL-GH adenomas, myxedema seen in concurrent hypothyroidism, some patients have type 2 diabetes and osteoporosis.

　　Second, clinical classification

　　1, Tumor-type hyperprolactinemia:Accounts for 71.61% of hyperprolactinemia, among which prolactin adenomas account for 46%, microadenomas account for 66%, macroadenomas account for 34%, a few are prolactin-growth hormone adenomas and嫌染细胞瘤, most pituitary adenomas PRL≥200ng/ml, some pituitary adenomas can regress naturally.

　　2, Postpartum hyperprolactinemia:Accounts for 30% of hyperprolactinemia, occurring within 3 years of pregnancy, delivery, abortion, and postpartum, with slightly elevated plasma prolactin, menstrual oligomenorrhea, menstrual disorders, galactorrhea, and good treatment prognosis.

　　3, Idiopathic hyperprolactinemia:Rare, mostly related to mental trauma, stress factors, and some are extremely small adenomas.

　　4, Iatrogenic hyperprolactinemia:Caused by iatrogenic factors or drugs, mostly due to other diseases (such as hypothyroidism), which can recover naturally after removing the cause.

　　5, Potential hyperprolactinemia (OHP):Also known as occult hyperprolactinemia.

　　Pituitary PRL tumors are the most common cause of hyperprolactinemia. Foreign data show that the prevalence of PRL tumors with clinical symptoms is about 1 in 5000, and the onset age of most PRL tumors is between 30 and 50 years old. About 65% of PRL tumors are microadenomas, and they are almost only seen in women; another 35% are macroadenomas, and there is no difference in incidence between genders. Long-term follow-up of PRL microadenomas shows that about 7% of microadenomas will develop into macroadenomas without treatment. Etiology: The most common cause of hyperprolactinemia is pituitary PRL tumors. Like other pituitary adenomas, the etiology of PRL tumors includes both abnormality of PRL cells themselves and hypothalamic dysfunction. In terms of pituitary abnormalities, the mutation of Gsα gene is most concerned. It has been found that about 1/3 of PRL tumors are caused by the mutation of Gsα gene. The mutation of H-ras may play a certain role in malignant PRL tumors, but it has little significance in common PRL tumors. Some people have suspected that the decrease of hypothalamic dopaminergic activity is involved in the formation of PRL tumors, but it has not been confirmed. Since PRL microadenomas are almost only seen in women, it is believed that estrogen plays an important role in the formation of PRL tumors. Occasionally, PRL tumors can be one of the manifestations of type 1 multiple endocrine neoplasia (MEN1). Sometimes, hyperprolactinemia has no obvious cause and is called idiopathic hyperprolactinemia. Some people believe that idiopathic hyperprolactinemia is also caused by PRL microadenomas, but the tumor volume is very small, and it cannot be displayed by the existing imaging technology. Some people also believe that idiopathic hyperprolactinemia is caused by hypothalamic dysfunction. Some foreign researchers have followed up idiopathic hyperprolactinemia for a long time, and the results show that about half of the patients have no significant change in blood PRL levels, about 1/3 of the patients have blood PRL levels decreased to normal, and about 15% of the patients appear PRL microadenomas 2 to 6 years later.

　　Prognosis:

　　First, the prognosis of drug treatment:

　　1. Ovulation and pregnancy rates:Observations from the treatment of 1579 cases of hyperprolactinemia with bromocriptine (2.5 to 10mg/d, 1 to 12 months) in 54 Chinese hospitals show that the rate of menstrual reconstruction is 95% (range 72% to 100%), the ovulation rate is 73% (range 60% to 100%), the pregnancy rate is 70% (range 32% to 100%), and most occurred within 6 months after treatment.

　　Turkalj (1982) observed 1410 cases of pituitary microadenoma pregnancy, with an abortion rate of 11%, an ectopic pregnancy rate of 0.7%, a twin pregnancy rate of 1.8%, a minor malformation rate of 2.5%, and a major malformation rate of 1%, similar to normal pregnant women. Follow-up of 200 bromocriptine newborns did not show any adverse effects of bromocriptine on infantile development.

　　2. Effects on pregnancy and fetus:Since bromocriptine can cross the placenta and enter the fetal body to inhibit the secretion of prolactin by the fetal pituitary gland, bromocriptine should be discontinued after pituitary adenoma treatment during pregnancy. If tumor compression symptoms (changes in field of vision and headache) occur after delivery, bromocriptine treatment can be resumed. Ruiz-Velasco and Tolis (1984) observed 2000 patients with hyperprolactinemia and found that the term delivery rate after bromocriptine treatment was 85%, the abortion rate was 11%, the preterm birth rate was 2%, and the multiple pregnancy rate was 1.2%. After pregnancy, 85% of the patients returned to normal prolactin levels. The plasma prolactin level after delivery was 3% higher than before delivery, with 13% returning to normal prolactin levels, 84% showing no change in the tumor, 9% showing improvement, and 7% showing deterioration. Starting breastfeeding after delivery has no adverse effects on the tumor.

　　3. Outcome of pregnancy:Observations from 2648 cases in 82 Chinese hospitals show that the abortion rate is 10.9% (0% to 32%), the ectopic pregnancy rate is 0.3% (0% to 1.1%), the hydatid mole rate is 0.3% (0% to 4.9%), the preterm birth rate is 1.9% (0% to 11.8%), the term birth rate is 84.6% (0% to 100%), the congenital malformation rate is 0.9% (0% to 11.8%), and the multiple pregnancy rate is 1.2% (0.5% to 17.6%).

　　4, Changes during the postpartum period:Returning to the level before pregnancy was 83.3％ (72％～91.4％), returning to normal was 13.3％ (8.6％～20.0％), significantly higher than before pregnancy was 3.3％ (0％～8％), and symptom improvement after delivery was 68％， no change was 32％， no change in sella turcica after delivery was 84.1％ (44.4％～94.3％), symptom improvement was 9.1％ (2.8％～33.3％), and symptom deterioration was 6.8％ (2.8％～22.2％).

　　Second, the prognosis of surgical treatment:The prognosis of pituitary adenoma surgery is related to tumor size, pathological type, and the completeness of surgery. According to the follow-up of 3172 cases of pituitary tumor sphenoid sinus microsurgery by Ciric (1997), 1.94％ developed secondary hypopituitarism after surgery, 17.8％ had diabetes insipidus, 3.9％ had cerebrospinal fluid fistula, 1％ had optic nerve damage, and the mortality rate was 0.9％. The incidence rate of diabetes after surgery was 10％～40％, and the incidence rate of permanent diabetes and hypopituitarism was ≤2％. The rate of menstrual recovery and ovulation in microadenoma was 65％～85％, and that in macroadenoma was 20％～40％. 85％ of patients recovered normal visual field. 15％ still had visual or field defects. The cure rate of microadenoma surgery was 80％, and that of macroadenoma was 30％, with a recurrence rate of 20％ in the late stage.

　　After microsurgical resection of pituitary adenoma, prolactin levels decreased by 89.2％～96.4％. The decrease rate of prolactin in microadenoma and macroadenoma was 86％ and 64％ respectively, with 70％ and 69％ in females and males. The improvement rate of sexual function was 82％ and 57％ in females and males respectively. The shrinkage rate of giant adenoma in females and males was 45％±2％ and 52％±24％ respectively, and that of microadenoma was 44％±31％ and 38％±29％ respectively. The disappearance rate of field defects was 61％ and 71％ respectively, and the treatment success rate of both genders was similar.

　　Third, attention should be paid to long-term follow-up of hyperprolactinemia, and a small number of patients may even develop pituitary adenomas 10～20 years later.

　　For idiopathic hyperprolactinemia, mild prolactin elevation, regular menstrual cycle, unaffected ovarian function, no galactorrhea, and no impact on normal life, treatment is not necessary, but regular follow-up should be carried out to observe clinical manifestations and changes in PRL.

　　First, determination of reproductive hormones in the hypothalamus-pituitary-ovary axis:FSH, LH decreases, the ratio of LH/FSH increases, if PRL ≤ 100ng/ml, it is mostly functional elevation, if PRL ≥ 100ng/ml, it is mostly tumor elevation. The larger the tumor, the higher the PRL. For example, when the tumor diameter ≤ 5mm, PRL is (171±38) ng/ml; when the tumor diameter is 5～10mm, PRL is (206±29) ng/ml; when the tumor diameter ≥ 10mm, PRL is mostly (485±158) ng/ml. In the case of hemorrhage and necrosis of a giant adenoma, plasma PRL may not increase.

　　2. Thyroid, adrenal, and pancreatic function tests:When hyperprolactinemia is combined with hypothyroidism, TSH increases, T3, T4, and PBI decrease. When hyperprolactinemia is combined with Cushing's disease and virilization symptoms, testosterone (T), androstenedione (△4dione), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), 17-ketosteroids (17KS), and plasma cortisol increase. When hyperprolactinemia is combined with diabetes and acromegaly, plasma insulin, blood glucose, glucagon, and glucose tolerance test should be measured.

　　3. Prolactin stimulation test

　　1. Thyrotropin-releasing hormone (TRH) test:In normal women, a single intravenous injection of TRH 100 to 400pg, PRL increases 5 to 10 times compared to before injection within 15 to 30 minutes, and TSH increases 2 times, but not in pituitary tumors.

　　2. Chlorpromazine test:Chlorpromazine inhibits the reuptake of norepinephrine and dopamine function through receptor mechanisms, promotes PRL secretion. In normal women, after intramuscular injection of 25 to 50mg of chlorpromazine, the blood PRL level increases 1 to 2 times compared to before injection within 60 to 90 minutes, lasting for 3 hours, but not in pituitary tumors.

　　3. Metoclopramide test:Metoclopramide promotes PRL production and release. In normal women, after intravenous injection of 10mg for 30 to 60 minutes, PRL increases more than 3 times compared to before injection, but not in pituitary tumors.

　　4. Prolactin suppression test

　　1. L-Dopa test:L-Dopa is a dopamine precursor that is converted into dopamine by decarboxylation and inhibits PRL production and secretion. In normal women, after taking 500mg orally for 2 to 3 hours, PRL decreases significantly, but not in pituitary tumors.

　　2. Bromocriptine test:L-Dopa is a dopamine receptor agonist that inhibits PRL production and release. In normal women, after taking 2.5 to 5mg orally for 2 to 4 hours, PRL decreases by more than 50%, lasting for 20 to 30 hours. In cases of functional hyperprolactinemia and prolactinoma, the prolactin level decreases significantly after taking the medicine, while GH and ACTH decrease, but the decrease is not significant.

　　5. Sella turcica tomography (CT) examination:Anteroposterior diameter of the sella turcica in normal women

　　1. Bladder-like expansion.

　　2. Double sellar floor or double margin.

　　3. High/low density areas or heterogeneity inside the sella.

　　4. Plateau deformation.

　　5. Suprasellar calcification.

　　6. Osteoporosis of the anterior and posterior sellar processes.

　　7. Sphenoid sinus vacuolation.

　　8. Bone destruction.

　　6. Magnetic resonance (MRI), cavernous sinus angiography, pneumoencephalography, and cerebral angiography:Can determine the location and size of the tumor and help distinguish it from other intracranial lesions. Since the false positive and false negative rates of CT diagnosis are 20%, and the accuracy rate is only 61%, it is recommended to use MRI for diagnosis.

　　7. Ophthalmic examination:Including vision, field of vision, intraocular pressure, fundus examination, to determine the presence of signs of intracranial tumor compression (bitemporal hemianopia, decreased vision, blindness, nausea, vomiting, and headache, etc.).

　　First, dietary therapy for hyperprolactinemia

　　1, Peach Seed Cuttlefish Soup

　　Boil 1 cuttlefish with the internal organs removed and 6 grams of peach seeds in 400 milliliters of water until the fish is cooked. Eat the fish and drink the soup, once a day.

　　Function to activate blood and remove blood stasis. Mainly used for hyperprolactinemia with blood stasis; symptoms include irregular menstruation, or menstrual提前, or excessive menstruation, or metrorrhagia that does not stop, or amenorrhea, infertility, galactorrhea, chest and hypochondriac distension, irritability, breast or lower abdominal pain before menstruation that is difficult to press, lumbar pain, dark red menstrual blood with many blood clots.

　　2, Motherwort and Black Bean Decoction

　　Boil 30 grams of motherwort and 60 grams of black beans in 500 milliliters of water, and then add brown sugar and yellow wine. Take twice a day.

　　Function to promote blood circulation and invigorate the Qi. Mainly used for hyperprolactinemia with Qi stagnation and blood stasis; symptoms include irregular menstruation, menstrual提前, or excessive menstruation, or metrorrhagia that does not stop, or amenorrhea, infertility, galactorrhea, chest and hypochondriac distension, irritability, breast or lower abdominal pain before menstruation that is difficult to press, lumbar pain, dark red menstrual blood with many blood clots.

　　3, Deer Horn Glue Porridge

　　Boil 100 grams of glutinous rice in 600 milliliters of water, add 10 grams of deer horn glue and 3 slices of ginger when half-cooked, and cook into a thin gruel. Eat once a day.

　　Function to nourish kidney essence. Mainly used for hyperprolactinemia with kidney deficiency and essence deficiency; symptoms include scanty menstruation or oligomenorrhea, or amenorrhea, or infertility, lumbar pain and tinnitus, dizziness and forgetfulness, aversion to cold and cold limbs.

　　4, Black Bean and Su木 Drink

　　Boil 100 grams of black beans and 10 grams of su木 in adequate amount of water until the black beans are fully cooked, remove the su木 and dissolve some brown sugar. Take in two doses a day, eat the beans and drink the soup.

　　Function to tonify the kidney and activate blood circulation. Mainly used for hyperprolactinemia with kidney deficiency and blood stasis; symptoms include irregular menstruation, or menstrual提前, or excessive menstruation, or metrorrhagia that does not stop, or amenorrhea, infertility, galactorrhea, irritability, breast or lower abdominal pain before menstruation that is difficult to press, lumbar and knee pain, tinnitus and dizziness, dark red menstrual blood with many blood clots.

　　5, Turtle Shell Nourishing Kidney Soup

　　Boil 1 turtle (over 300 grams) in boiling water, remove the head, claws, turtle shell, and internal organs, and cut into small pieces. Add the turtle pieces back into the pot, add 30 grams of goji berries, 15 grams of prepared rehmannia, and 600 milliliters of water, and simmer until tender. Take once a day.

　　Function to nourish the liver and kidney and moisten the Yin. Mainly used for hyperprolactinemia with Yin deficiency of liver and kidney; symptoms include excessive menstruation, or vaginal bleeding that does not stop, lumbar and knee pain, irritability, insomnia and dreams, thick galactorrhea, or afternoon feverishness, hot palms and soles.

　　6, Hawthorn and Barley Tea

　　50 grams of raw hawthorn, 30 grams of roasted barley; or 60 grams of single roasted barley. Boil the ingredients in water to make tea, 1 dose a day.

　　Function to stop lactation. Mainly used for various galactorrhea, including hyperprolactinemia, postpartum lactation cessation, and lactation cessation after abortion.

　　7, Black Chicken Soup

　　Cut 500 grams of male black chicken into pieces, together with 3 grams of dried tangerine peel, 3 grams of high良姜, 6 grams of pepper, 2 apples, and cook in a pot with scallion, vinegar, soy sauce, and water to cover the chicken. Boil until tender. Take the soup and food, 1-2 times a day.

　　Function to nourish Qi and blood. Mainly used for hyperprolactinemia with Qi and blood deficiency; symptoms include scanty menstruation or amenorrhea, or infertility, thin and pale galactorrhea, pale complexion, weak speech, fatigue and lack of movement.

　　8, Rose flower wine

　　Dry rose flower 10 petals, burn to ash and take with moderate amount of yellow wine.

　　Function to promote blood circulation and invigorate the Qi. Mainly used for hyperprolactinemia with Qi stagnation and blood stasis; symptoms include irregular menstruation, menstrual提前, or excessive menstruation, or metrorrhagia that does not stop, or amenorrhea, infertility, galactorrhea, chest and hypochondriac distension, irritability, breast or lower abdominal pain before menstruation that is difficult to press, lumbar pain, dark red menstrual blood with many blood clots.

　　9. Angelica Sinensis and Astragalus Membranaceus Lean Pork Soup

　　250 grams of lean pork slices, 12 grams of Angelica sinensis, and 30 grams of Astragalus membranaceus are cooked together in a pot with an appropriate amount of water. Boil with strong fire and then switch to a low fire to cook for 2 hours, season and eat.

　　Functions: replenishing qi and invigorating the spleen, nourishing blood and regulating the menstrual cycle. Indications: Blood deficiency and qi weakness type hyperprolactinemia; symptoms include pale complexion, dizziness and palpitations, irregular menstruation, light red menstrual blood with scanty flow, leading to amenorrhea, fatigue and shortness of breath, decreased appetite.

　　10. Angelica Sinensis and Polygonatum Odoratum Beef Soup

　　250 grams of fresh and tender beef cubes, 12 grams of Angelica sinensis, 30 grams of Polygonatum odorum, and 3 grams of dried tangerine peel are cooked together in a pot with an appropriate amount of water. Boil with strong fire and then switch to a low fire to cook for 2-3 hours, season and eat.

　　Functions: nourishing blood and liver, invigorating the spleen and benefiting qi. Indications: Qi and blood deficiency type hyperprolactinemia; symptoms include scanty menstrual flow or amenorrhea, or infertility, thin and clear galactorrhea, weak speech, fatigue and inactivity, sallow complexion, fatigue and weakness, palpitations and dizziness.

　　11. Safflower and Hawthorn Wine

　　15 grams of safflower and 30 grams of hawthorn are soaked in 250 milliliters of white wine for one week. Drink 15-30 milliliters per time, 2 times a day. Depending on the amount of alcohol, drink to the point of not being drunk, and use it continuously for 3 months before menstruation.

　　Functions: activating blood circulation and removing blood stasis. Indications: Blood stasis type hyperprolactinemia; symptoms include irregular menstruation, or menstrual precocity, or menorrhagia, or metrorrhagia, or amenorrhea, infertility, galactorrhea, irritability, breast or lower abdominal pain before menstruation, pressing pain, soreness and weakness in the lower back and knees, dizziness and tinnitus, dark red menstrual blood with many clots.

　　12. Job's Tears and Hawthorn Porridge

　　30 grams of Job's tears, 15 grams of mung beans and hawthorn (with the seeds removed), and 400 milliliters of water are cooked into porridge. Add an appropriate amount of brown sugar and take it as a medicine. 1 time/day.

　　Functions: invigorating the spleen and resolving phlegm. Indications: Phlegm-damp obstruction type hyperprolactinemia; symptoms include oligomenorrhea or amenorrhea, or infertility, galactorrhea, obesity, increased phlegm in the morning, nausea and vomiting, decreased appetite, epigastric distension, mouth stickiness, and lack of thirst or thirst without desire to drink.

　　13. Codonopsis, Jujube, and Angelica Sinensis Beef Soup

　　250 grams of fresh and tender beef cubes, 20 grams of Angelica sinensis, 30 grams of Codonopsis pilosula, and 6 red dates (with the seeds removed) are cooked together in a pot with an appropriate amount of water. Boil with strong fire and then switch to a low fire to cook for 1-2 hours, season and eat.

　　Functions: nourishing blood and regulating the menstrual cycle, replenishing qi and invigorating the spleen. Indications: Qi and blood deficiency type hyperprolactinemia; symptoms include irregular menstruation, scanty menstrual flow, lower abdominal pain, or amenorrhea, fatigue, decreased appetite, dizziness and blurred vision, palpitations and insomnia. It can also be used to treat blood deficiency, dizziness and blurred vision, palpitations, etc.

　　(The above information is for reference only, please consult a doctor for details.)

　　II. What is good to eat for hyperprolactinemia

　　1. It is advisable to eat small and frequent meals:Eating small and frequent meals is beneficial for the body to regulate body temperature.

　　2. Drink more water:Drinking more water or juice can also effectively control body temperature

　　III. What to eat less for hyperprolactinemia

　　1. Reduce caffeine and alcohol:Drinks containing caffeine and alcohol will stimulate the secretion of certain hormones and trigger skin heat.

　　2. Dairy products should be avoided in the diet:Yogurt, dairy products, and sugar and meat are prone to cause skin heat, so dairy products should be avoided in the diet as much as possible.

　　I. Treatment

　　1. Antiprolactin drugs:Anti-prolactin agents include bromocriptine, long-acting bromocriptine, thioridazine, cabergoline, trametinib, methysergide, quinagolide (Nogalam), and ergometrine.

　　(1) Bromocriptine therapy: Bromocriptine is a semi-synthetic ergot alkaloid derivative and a dopamine receptor agonist. Bromocriptine enhances the function of dopamine receptors, promotes the generation and secretion of hypothalamic PRI-IH, inhibits the generation of pituitary PRI, and also directly inhibits the growth of pituitary tumors, inhibits the secretion of pituitary PRI, GH, TSH, and ACTH.

　　Bromocriptine therapy is suitable for all types of hyperprolactinemia and is the first-line drug for the treatment of pituitary adenomas. The oral dose is 2.5～5.0mg/d. After oral administration of bromocriptine, the blood concentration reaches its peak in 1～3h, and the inhibitory effect on prolactin secretion lasts for 14h. Approximately 90% of patients have a decrease in prolactin levels after taking 2.5mg of bromocriptine orally, and 1/3 of patients have prolactin levels return to normal. For those who cannot tolerate oral administration, vaginal administration can be used.

　　The aim of bromocriptine treatment is to inhibit galactorrhea, restore menstrual function, promote ovulation and pregnancy. The average treatment time for non-tumor-type hyperprolactinemia is 12 months, and for tumor-type hyperprolactinemia, the average treatment time with bromocriptine is 47 months. Univariate and multivariate analyses have found that the efficacy of treatment is correlated with age, gender, initial dose of bromocriptine, duration of treatment, tumor size, pregnancy during treatment, and previous radiotherapy.

　　After bromocriptine treatment for tumor-type hyperprolactinemia, 80%～90% of pituitary microadenomas shrink, and 10%～20% permanently regress, usually occurring in the first few weeks of treatment. The recurrence rate of tumors after discontinuing bromocriptine is 35%. Although there is no evidence to suggest that bromocriptine has teratogenic effects, nor does it affect the outcome of pregnancy, treatment should be discontinued if pregnancy occurs during treatment.

　　After 1 year of bromocriptine treatment, 11% of women with microadenomas have permanently restored prolactin and menstrual function. After 2 years of treatment, the permanent regression rate of pituitary tumors is 22%. Although bromocriptine at high doses (10mg/d) is more effective than at low doses, the rate of adverse reactions is high and difficult to tolerate. Bromocriptine (5～12.5mg/d) can cause 50% of pituitary macroadenomas to shrink, of which 2/3 occur within 6 weeks before treatment, and 1/3 after 6 months of treatment. The ovulation rate, pregnancy rate, dose, and efficacy of bromocriptine treatment are detailed in the section on anti-prolactin agents.

　　(2) Cabergoline: As a long-acting and highly effective dopamine agonist, it has good clinical efficacy and tolerability. Cabergoline has a high affinity for dopamine receptor D2, directly inhibits prolactin-secreting cells in the pituitary gland, reduces prolactin secretion, and the therapeutic dose range is 0.25～1.0mg/week. It is recommended to start with a low dose of 0.25mg, twice a week, and after 4 weeks, increase to 1mg, twice a week. After taking the medicine, the blood concentration reaches its peak in 2～3h, with a plasma half-life of 65h. After treatment with cabergoline, 80% of patients' prolactin levels return to normal, the ovulation rate is 72%, and the rate of galactorrhea cessation is 90%. The plasma prolactin level returns to normal after 6 months and the medicine can be gradually discontinued. Clinical observations show that cabergoline has better efficacy and tolerability than bromocriptine, and is the first-line choice for the treatment of hyperprolactinemia, a safe and effective new-generation drug.

　　Cabergoline significantly reduces pituitary tumors and even causes them to completely disappear, and can be used to treat pituitary macroadenomas that are resistant to bromocriptine. Clinical data indicate that although cabergoline has no adverse effects on pregnancy, treatment should be stopped one month before the desired pregnancy if ovulation resumes during the treatment process.

　　Quinagolide (Noglutide): It is a non-ergot alkaloid dopamine agonist, a new generation of specific, effective, and long-acting anti-PRL drug. The plasma half-life is 22 hours. CV205-502 acts as a potent dopamine receptor (D1, D2) agonist, at the level of PRL cells in the hypothalamus-pituitary axis, by enhancing dopamine receptor function, inhibiting PRL production, with strong and long-lasting effects, good tolerance, and mild side effects. Headache, dizziness, nausea, and vomiting may occur at high doses, but it has no adverse effects on heart, lung, liver, kidney, and blood functions. Patients have good tolerance to Quinagolide, with a drug discontinuation rate due to adverse reactions of 7%, which is better than bromocriptine.

　　Quinagolide is used to treat patients who cannot tolerate bromocriptine, those who have not responded to treatment, and those who have relapsed. The dose range is 0.04 to 0.1mg/d. The therapeutic effect is related to the dose, such as oral administration of 0.04mg/d, PRL reduction >50% for 8 hours; oral administration of 0.06mg/d, PRL reduction 66% for 24 hours, and still reduced by 47% at 36 hours, with the prolactin peak during sleep disappearing. Quinagolide inhibits TSH synthesis and release but does not affect FSH, LH, T, and adrenal axis function. Quinagolide increases GH-RH release while inhibiting GH-IH release, resulting in a temporary increase in plasma GH after administration, but GH levels remain normal at night.

　　Quinagolide treatment should start with a low dose, 0.025mg daily for the first 3 days, 0.050mg/d for the next 3 days, then increased to 0.075mg/d, and the dose should be adjusted according to the treatment response. The dose reached 0.1mg/d within 3 months. Most patients showed a decrease in prolactin levels after 1 month of treatment, and the tolerance was good.

　　After the treatment with Quinagolide, the average volume of pituitary macroadenomas was reduced by 324mm3 (46%), microadenomas by 73mm3 (57%), the average plasma prolactin level decreased by 163μg/L (65%) in macroadenomas, and by 113μg/L (73%) in microadenomas. In a study of 107 patients from 27 medical centers in France, significant clinical efficacy was observed more than 2 years after treatment. Schultz's (2000) treatment observation found (50 cases, dose of 100μg/d, average treatment duration of 31.6 months), the rate of prolactin normalization was 82% for non-tumorous hyperprolactinemia, 73% for microadenomas, and 67% for macroadenomas. The tumor volume reduction rate was 55% for microadenomas and 75% for macroadenomas. Vision improved or returned to normal in some cases, and the pregnancy rate was 26%. Nobels (2000) found that high-dose Quinagolide was not effective in inhibiting the growth of pituitary non-functional tumors, and its effect may be related to the expression of dopamine receptors in the tumors.

　　DiSarno (2000) first used quinagolide (0.075 to 0.6mg/d, 12 months), followed by cabergoline (0.5 to 1.5mg per dose, twice a week, 12 months), the rate of prolactin returning to normal was 100% for microadenoma and 87.5% for macroadenoma. The tumor volume shrinkage rate was more than 80% for microadenoma (21.7%) and macroadenoma (25%). All patients experienced hyperprolactinemia again from 15 to 60 days after discontinuing quinagolide. Both drugs have good tolerance. Some patients may experience nausea and orthostatic hypotension in the first week of quinagolide treatment, but these symptoms naturally disappear in the third week of treatment.

　　(4) Sulpiride: as a new generation of safe, inexpensive, and well-tolerated anti-prolactin drug, it is the first-line drug for the treatment of pituitary macroadenoma. The dose is 0.05 to 0.5mg/d, treated for 12 months (3 to 36 months), PRL decreased by 88%, 86% of patients with pituitary tumor shrinkage by 25%, 77% by more than 50%, and 45% by more than 75%. Most patients have their visual field restored (Orrego, 2000).

　　2. Ovulation induction therapy:Applicable to patients with hyperprolactinemia, anovulatory infertility, and those who cannot achieve ovulation and pregnancy with simple bromocriptine treatment. In such cases, a comprehensive therapy with bromocriptine as the main drug and other ovulation-inducing drugs is adopted:

　　(1) bromocriptine-CC-hCG.

　　(2) bromocriptine-hMG-hCG.

　　(3) GnRH, pulse therapy - bromocriptine, etc., comprehensive therapy can save anti-prolactin drugs, shorten the treatment cycle, and improve the ovulation rate and pregnancy rate.

　　3. Surgical treatment:Applicable to patients with intracranial compression symptoms due to macroadenoma, ineffective treatment with bromocriptine, giant adenoma,嫌染细胞瘤with multiple pituitary hormone secretion, the current transsphenoidal microsurgery is safe, convenient, and easy to perform, with efficacy similar to bromocriptine therapy. The use of bromocriptine before and after surgery can improve efficacy. The disadvantages of surgery are that the pituitary tumor has no obvious capsule, unclear boundaries, making it difficult to complete the surgery or cause damage, leading to cerebrospinal fluid nasal fistula and postoperative hypopituitarism. It is noteworthy that although the use of bromocriptine before surgery can shrink the tumor, it can also cause tumor fibrosis, hardening, and adhesion of surrounding tissues, which is not conducive to surgical separation and resection. Therefore, if surgery is determined, medication can be temporarily discontinued before surgery, and then supplemented with medication or radiotherapy after surgery.

　　The mortality rate of microsurgical resection of prolactinoma is less than 0.5%, the incidence of transient diabetes after surgery is 10% to 40%, the incidence of permanent diabetes and iatrogenic hypothyroidism is less than 2%, and the probability of prolactin and ovulation returning to normal after microadenoma surgery is 65% to 85%, while for macroadenoma it is 20% to 40%, and the proportion of patients with normal visual field is 85%.

　　4. Radiotherapy:Applicable to non-functional tumors of the hypothalamic-pituitary system, as well as those who are ineffective to drug and surgical treatment, currently advanced stereotactic radiosurgery methods are mostly used, including deep X-ray, gamma, 60Co, alpha particles and proton beams, radionuclide 90Y, 198Au pituitary implantation, and so on.

　　2. Prognosis

　　1. Prognosis of drug treatment

　　(1) Ovulation and pregnancy rates: Observations from 1579 cases of hyperprolactinemia treated with bromocriptine (2.5 to 10mg/d, 1 to 12 months) in 54 hospitals in China indicate that the rate of menstrual reconstruction is 95% (range 72% to 100%), the ovulation rate is 73% (range 60% to 100%), and the pregnancy rate is 70% (range 32% to 100%), which mostly occur within 6 months after treatment.

　　Turkalj (1982) observed 1410 cases of pituitary microadenoma after pregnancy, with an abortion rate of 11%, an ectopic pregnancy rate of 0.7%, a twin rate of 1.8%, a micro-malformation rate of 2.5%, and a macro-malformation rate of 1%. Similar to normal pregnant women, the follow-up of 200 bromocriptine newborns did not show any adverse effects on the development of infants and young children.

　　(2) Effects on pregnancy and the fetus: As bromocriptine can cross the placenta and enter the fetal body to inhibit the secretion of prolactin by the fetal pituitary, bromocriptine should be discontinued after the treatment of pituitary adenoma during pregnancy. If tumor compression symptoms (changes in field of vision and headache) appear after delivery, bromocriptine treatment can be resumed. Ruiz-Velasco and Tolis (1984) observed 2000 patients with hyperprolactinemia and found that the rate of full-term delivery after bromocriptine treatment was 85%, the abortion rate was 11%, the preterm birth rate was 2%, the multiple pregnancy rate was 1.2%, 85% of the patients returned to normal prolactin levels after pregnancy, 3% of the patients had higher plasma prolactin levels after delivery than before delivery, 13% of the patients returned to normal prolactin levels after delivery, 84% of the patients showed no change in the tumor after delivery, 9% showed improvement, 7% showed deterioration, and starting breastfeeding after delivery had no adverse effects on the tumor.

　　(3) Outcome of pregnancy: Observations from 2648 cases in 82 hospitals in China and abroad indicate that the abortion rate is 10.9% (0% to 32%), the ectopic pregnancy rate is 0.3% (0% to 1.1%), the hydatidiform mole rate is 0.3% (0% to 4.9%), the preterm birth rate is 1.9% (0% to 11.8%), the term birth rate is 84.6% (0% to 100%), the congenital malformation rate is 0.9% (0% to 11.8%), and the multiple pregnancy rate is 1.2% (0.5% to 17.6%).

　　(4) Changes during the puerperium: 83.3% (72% to 91.4%) recover to the pre-pregnancy level, 13.3% (8.6% to 20.0%) return to normal, 3.3% (0% to 8%) show significant increase compared to before pregnancy, 68% show improvement in postpartum symptoms, 32% show no change, 84.1% (44.4% to 94.3%) show no change in the pituitary saddle after delivery, 9.1% (2.8% to 33.3%) show improvement in symptoms, and 6.8% (2.8% to 22.2%) show deterioration in symptoms.

　　2. Prognosis of surgical treatment application:The prognosis of pituitary adenoma surgery is related to tumor size, pathological type, and the completeness of surgery. According to the follow-up of 3172 cases of pituitary tumor sphenoid sinus microsurgery by Ciric (1997), 1.94% developed secondary hypopituitarism after surgery, 17.8% developed diabetes insipidus, 3.9% developed cerebrospinal fluid fistula, 1% had optic nerve damage, the mortality rate was 0.9%, the incidence rate of diabetes after surgery was 10% to 40%, the incidence rate of permanent diabetes and hypopituitarism was ≤2%, the rate of menstrual recovery and ovulation in microadenomas was 65% to 85%, in macroadenomas was 20% to 40%, 85% of patients recovered visual fields, 15% still had visual or field defects, the cure rate of microadenoma surgery was 80%, in macroadenomas was 30%, and the recurrence rate in the late stage was 20%.

　　After microsurgical resection of pituitary adenomas, prolactin levels decreased by 89.2% to 96.4%, with microadenomas and macroadenomas showing prolactin reduction rates of 86% and 64%, respectively, and in females and males, respectively, 70% and 69%. The improvement rate of sexual function was 82% in females and 57% in males, and the reduction rate of giant adenomas in females and males was 45% ± 2% and 52% ± 24%, respectively, and in microadenomas, 44% ± 31% and 38% ± 29%, respectively. The rate of disappearance of field defects was 61% and 71%, respectively, and the success rate of treatment in both genders was similar.

　　3. Hyperprolactinemia should be followed up for a long time, and a small number of patients may even develop pituitary adenomas 10 to 20 years later.

　　4. For idiopathic hyperprolactinemia, mild prolactin increase, regular menstruation, unaffected ovarian function, no galactorrhea, and no impact on normal life, treatment may not be necessary, but regular follow-up should be carried out to observe clinical manifestations and changes in PRL.