Polycystic ovary syndrome

　　The etiology of polycystic ovary syndrome is not yet clear, and the involved pathogenic mechanisms are very complex. It is generally believed to be related to dysfunction of the hypothalamus-pituitary-ovary axis, adrenal gland dysfunction, genetics, metabolism, and other factors.

　　1, Genetic factors

　　PCOS is a disease caused by autosomal dominant inheritance, or X-linked (sex-linked) inheritance, or gene mutation. Most patients have a karyotype of 46, XX, and some patients show chromosomal abnormalities or mosaicism such as 46, XX/45, XO/46, XX/46, XXq and 46, XXq.

　　2, Adrenal primacy hypothesis

　　PCOS originates from adrenal disease before puberty, that is, when exposed to strong stress stimuli, the reticular zone secretes too much androgen, which is converted into estrone outside the gonads, and feedbackally causes HP axis GnRH-GnH release rhythm disorder, LH/FSH ratio increase, and secondary to cause increased androgen production in the ovary, that is, the adrenal gland and ovary secrete more androgen, leading to hyperandrogenemia. Hyperandrogenemia in the ovary causes capsule fibrosis thickening, inhibits follicle development, causing ovarian cystic enlargement and chronic anovulation.

　　Traditional Chinese medicine believes that the disease is mainly caused by kidney deficiency, phlegm dampness, Qi stasis and blood stasis, liver meridian dampness and heat, etc., leading to dysfunction of the kidney-Tian Gui-Chong Ren-Gong Gong axis, causing amenorrhea, infertility, and other symptoms.

　　1, Tumors with persistent, non-cyclic, relatively high estrogen levels and elevated E1 and E1/E2 ratios stimulate the endometrium, and there is no progesterone resistance, leading to an increased incidence of endometrial cancer and breast cancer.

　　2, Cardiovascular disease: Disordered lipid metabolism, prone to cause atherosclerosis, leading to coronary heart disease, hypertension, and other diseases.

　　3, Diabetes insulin resistance state and hyperinsulinemia, obesity, are prone to develop latent diabetes or diabetes.

　　4, Acne: Due to excessive facial sebum secretion caused by hirsutism.

　　5, Infertility: Caused by amenorrhea and anovulation.

　　Polycystic ovary syndrome can lead to anovulation or oligomenorrhea in patients, about 70% are accompanied by menstrual disorders, the main clinical manifestations are amenorrhea, oligomenorrhea, and functional uterine bleeding, accounting for 70-80% of menstrual abnormal women, 30% of secondary amenorrhea, and 85% of anovulatory functional uterine bleeding. Due to the排卵 dysfunction in PCOS patients, the lack of cyclic progesterone secretion, the endometrium is under the stimulation of simple high estrogen for a long time, and the continuous endometrial hyperplasia is prone to simple endometrial hyperplasia, atypical hyperplasia, and even endometrial atypical hyperplasia and endometrial cancer.

　　13. Abnormal menstruation: Menstruation is sparse, amenorrhea, and a few may manifest as functional uterine bleeding, most occurring in adolescence, as the continuation of irregular menstruation after menarche, and sometimes accompanied by dysmenorrhea.

　　12. Hirsutism: More common, the incidence rate can reach 69%, due to increased androgens, there is hair thickening and increase in the upper lip, chin, chest, back, middle part of the lower abdomen, upper part of the thighs on both sides, and perianal areas, but the degree of hirsutism is not proportional to the level of androgens (influenced by factors such as receptor number, estrogen, SHBG, and the sensitivity of hair follicles to androgens), and at the same time, acne, excessive facial sebum secretion, low and hoarse voice, clitoral hypertrophy, and the appearance of Adam's apple and other masculinization signs may occur.

　　11. Infertility: Due to long-term anovulation, most patients have infertility, and there may be occasional ovulation or miscarriage, with an incidence rate of up to 74%.

　　10. Obesity: More than 20% of the body weight, the body mass index ≥25 accounts for 30% to 60%, obesity is concentrated in the upper body, waist/hip ratio >0.85, mostly starting from adolescence and gradually worsening with age.

　　9. Ovarian enlargement: A few patients can feel the enlarged, hard ovaries through general gynecological examination, and most need auxiliary examination to determine.

　　8. Estrogen effect: All patients show good estrogen effect, during examination, it can be seen that the cervical mucus is abundant and persistent, and excessive estrogen effect can lead to rapid endometrial hyperplasia, atypical hyperplasia, and even canceration.

　　For polycystic ovary syndrome, the best preventive measure is to control diet and exercise scientifically.

　　1. Obese patients with polycystic ovary syndrome should lose weight scientifically

　　Obese patients with polycystic ovary syndrome (BMI>24) should lose weight in an effective and healthy way: including reducing calorie intake by about 500 calories per day, so that weight can be reduced safely at a rate of about 2 kilograms per month.

　　2. Optimize dietary treatment for polycystic ovary syndrome

　　Dietary adjustment is an important auxiliary treatment for polycystic ovary syndrome (PCOS), and in addition to total calories, for those who have reached the standard weight or those who are not overweight, food selection should be cautious. To avoid malabsorption caused by dietary control, 500 to 1500 milligrams (mg) of calcium tablets and one vitamin containing 400 micrograms (mcg) of folic acid should be supplemented daily, and the daily water intake should reach 8 cups; to avoid abnormal blood lipids, eat less food containing saturated fatty acids and hydrogenated fatty acids, such as pork, beef, mutton, lard, various poultry and livestock skins, butter, artificial butter, whole milk, fried foods, and Western and Chinese-style pastries; fish, protein, beans, and nuts are good sources of protein.

　　3, Engage in moderate exercise

　　Regular exercise can help control blood sugar, blood lipids, and blood pressure.

　　In 1935, Stein and Leventhal first reported this disease and it was named Stein-Leventhal syndrome (S-L syndrome). In 1960, due to the characteristic of bilateral ovarian cystic enlargement in patients, it was renamed polycystic ovary syndrome (PCOS). Since PCOS has high clinical heterogeneity, the etiology and pathogenesis are not yet clear. Up to 2003, the experts of the European Society of Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) held an international collaborative group expert meeting of PCOS to formulate the international diagnostic criteria for PCOS. The specific diagnostic criteria are as follows:

　　One, Hormone measurement

　　1, Gonadotropins: About 75% of patients have increased LH, with normal or decreased PSH, and LH/FSH≥3.

　　2, Steroid hormones

　　(1) Androgens, including testosterone, dihydrotestosterone, androstenedione, and 17-ketosteroids, are elevated due to decreased SHBG, leading to increased free androgen levels.

　　(2) The total estrogen level can reach 140pg/ml, with estradiol at the level of early follicular phase about 60pg/ml, and increased estrone production outside the gonads leads to E1/E2≥1.

　　(3) Increased DHEAS production in the adrenal glands, with plasma concentration ≥3.3μg/ml, and increased 17-hydroxyprogesterone as well. (Normal laparoscopy, to directly observe the ovarian morphology or perform biopsy, puncture, wedge resection, and electrocautery, etc., for treatment.)

　　Two, CT and magnetic resonance

　　To identify and exclude extrapelvic tumors.

　　Three, laparotomy

　　It is performed when there is a suspected ovarian tumor or when ovarian wedge resection is to be performed.

　　1, LH/FSH: The blood LH and FSH ratio and concentration are abnormal, showing non-cyclical secretion. Most patients have increased LH, while FSH is at the level of early follicular phase, with LH/FSH≥2.5～3. Many scholars believe that the increase in the LH/FSH ratio is a characteristic of PCOS.

　　2, Male steroids: Androgen levels can be increased, including testosterone, androstenedione, DHEA, and DHEAS.

　　3, Female steroids: Estrone and estrogen are abnormal, with a constant estrogen level, small fluctuations in E2 level, no normal menstrual cyclical changes, and increased E1 level, with E1/E2>1.

　　4, PRL: It can slightly increase in PCOS, but due to hyperprolactinemia, it can appear with symptoms similar to PCOS, and it should be differentiated.

　　5. Urine: The increase of 24-hour urine 17-OHCS and 17-KS reflects the increase of adrenal androgen secretion.

　　6. Dexamethasone suppression test: It can inhibit the secretion of adrenal androgen, take dexamethasone 0.5mg, once every 6 hours, for a total of 4 days, take blood samples after taking, if the serum dehydroepiandrosterone sulfate or urinary 17-ketosteroids are suppressed to normal levels, it can exclude the possibility of adrenal tumor or hyperplasia.

　　7. Chorionic gonadotropin (HCG) stimulation test: HCG can stimulate the ovary to synthesize androgens, and the injection of HCG can cause the level of androgens in plasma to increase.

　　8. Adrenocorticotropic hormone (ACTH) stimulation test: ACTH stimulation test can promote the increase of adrenal androgen DHEA and urinary 17-KS.

　　Through HCG stimulation test, dexamethasone suppression test, ACTH stimulation test can help differentiate the source of elevated androgens.

　　9. Vaginal squamous cell maturity index: It is a simple method to initially understand the condition of sex hormones in the body. The smear often shows a three-layer cell pattern when testosterone is excessive, and when it is significantly increased, the number of three layers of cells is almost equal, but it must be distinguished from inflammation. The level of estrogen can be estimated from the percentage of surface cells, but it cannot reflect the content of hormones in the blood.

　　10. Basal body temperature measurement: Determine whether there is ovulation, ovulating individuals show a biphasic pattern, and non-ovulating individuals are generally monophasic.

　　Four, factors affecting the examination

　　1. Pelvic ultrasound: The ovaries are enlarged, with at least 10 or more 2-6mm diameter follicles in each plane, mainly distributed around the ovarian cortex, a few scattered in the stroma, and the stroma is increased.

　　2. Pneumoperitoneal radiography: Both ovaries are increased by 2-3 times, if the main source of androgens is the adrenal glands, then the ovaries are relatively small.

　　3. Laparoscopy (or surgery): The ovarian morphology is full, the surface is pale and smooth, the capsule is thick, and sometimes a network of capillaries can be seen below. Because the surface color is pearl-like, it is commonly known as oyster ovaries, and multiple cystic follicles can be seen on the surface.

　　4. High-resolution transvaginal ultrasound examination of the ovary has broken through the diagnosis of PCOS, currently, experienced doctors have made this examination the basis of diagnosis, transvaginal 100% can detect polycystic ovaries, while transabdominal examination has a 30% missed diagnosis rate. For unmarried obese patients, anal ultrasound can be used to detect. In 1986, Adams first reported that the ultrasound characteristics of PCOS patients' ovaries are that there are more than 8 diameter ovules in both ovaries.

　　6. CT, MRI can also be used for the examination of ovarian morphology.

　　For patients with polycystic ovary syndrome, it is recommended to eat less high cholesterol and high-fat foods to avoid weight gain. Below are two diet therapy recipes for polycystic ovary syndrome for patients to refer to.

　　1. Diet therapy:

　　Danggui 30 grams, Huangqi 30 grams, ginger 65 grams, mutton 250 grams. Cut the mutton into pieces, slice the ginger, wrap Danggui and Huangqi in gauze, and put them in an earthen pot with an appropriate amount of water, cook until soft, remove the medicine residue, season and eat. Take once a day, for 3-5 days in a month.

　　2. Food Therapy Two:

　　50 grams of turtle shell, 1 pigeon. Clean the pigeon, crush the turtle shell, put it in the pigeon's belly, and put them together.

　　Currently, drug treatment has replaced surgical treatment as the first-line treatment for PCOS, and the purpose of treatment is mainly related to the patient's fertility requirements.

　　1. Drug Treatment

　　1. Obesity and Insulin Resistance Increase physical activity to reduce weight, correct endocrine and metabolic disorders exacerbated by obesity, reduce insulin resistance and hyperinsulinemia, lower IGF-1, increase IGfBP-1, and at the same time, increase SHBG to decrease the level of free androgens. Weight loss can restore ovulation in some obese PCOS patients and can prevent the occurrence of type 2 diabetes and cardiovascular diseases. Metformin 1.5 to 2.5g/d can be used for both diabetics and non-diabetics, and it can effectively reduce weight, improve insulin sensitivity, lower insulin levels, and even restore menstruation (25%) and ovulation. Since obesity and insulin resistance are the main causes of PCOS, any drug that can reduce weight and increase insulin sensitivity can be used to treat this syndrome. In recent years, there have been many reports on the treatment of insulin-sensitizing agents (insulinsensitizing agents). Thiazolidone is a class of oral insulin-sensitizing agents, mainly used for the treatment of diabetes, such as troglitazone (Troglitazone) can significantly reduce hyperinsulinemia and hyperandrogenemia in PCOS patients and help induce ovulation. Ciotta et al. reported that insulin-sensitizing agents can significantly reduce blood LH, androgen levels, inhibit insulin secretion, increase SHBG concentration, and can be treated for a long time. Insulin-sensitizing agents may be more suitable for PCOS patients with hyperinsulinemia.

　　2. Induced Ovulation by Medication

　　(1) Clomiphene: It is the first-line medication for PCOS, with an ovulation rate of 60% to 80% and a pregnancy rate of 30% to 50%. Clomiphene competes with endogenous estrogen receptors at the hypothalamic-pituitary level, inhibits estrogen negative feedback, increases the pulsatile frequency of GnRH secretion, thereby adjusting the secretion ratio of LH and FSH. Clomiphene also directly promotes the synthesis and secretion of estrogen by the ovary. Starting from the 5th day of the natural menstrual cycle or withdrawal uterine bleeding, 50mg is taken orally daily for 5 consecutive days as one course of treatment. Ovulation usually occurs between the 3rd to 10th day (average 7 days) after taking the medication, and most women become pregnant within 3 to 4 courses. If there is still no ovulation after 3 treatment cycles, the dose can be increased to 100 to 150mg daily, and for those with lower body weight, it may be considered to reduce the initial dose (25mg/d). After taking this drug, the ovary may enlarge due to overstimulation (13.6%), with symptoms such as vasodilation and intermittent heat (10.4%), abdominal discomfort (5.5%), blurred vision (1.5%), or skin rash and mild hair loss as side effects.

　　During treatment, the basal body temperature during the menstrual cycle should be recorded, ovulation should be monitored, or serum progesterone and estradiol levels should be measured to confirm the occurrence of ovulation, and to guide the adjustment of the next treatment dose. If there is still no ovulation or pregnancy after 6 to 12 months of clomiphene treatment, clomiphene plus HCG or glucocorticoids, bromocriptine, or treatment with HMG, FSH, GnRH, etc., can be given.

　　(2) Combination of Clomiphene and Chorionic Gonadotropin (HCG): Chorionic Gonadotropin (HCG) 2000 to 5000U is administered intramuscularly 7 days after the discontinuation of clomiphene.

　　(3) Combination of Glucocorticoids and Clomiphene: The action of adrenal cortical hormones is based on their ability to inhibit excessive androgens secreted from the ovary or adrenal glands. Dexamethasone or Prednisone are usually selected. The daily dose of Prednisone is 7.5 to 10mg, with an effective rate of 35.7% in 2 months, and the ovarian function of amenorrheic anovulatory patients is restored to some extent. When clomiphene fails to induce ovulation, 0.5mg of dexamethasone can be added to the treatment regimen, taken 2.0mg at bedtime for 10 days, to improve the response of clomiphene or the pituitary to gonadotropin therapy, and to increase the rate of ovulation and pregnancy.

　　(4) Human Menopausal Gonadotropin (HMG): Mainly used for patients with reduced endogenous pituitary gonadotropin and estrogen secretion. Human Menopausal Gonadotropin (HMG) is a purified extract from the urine of postmenopausal women, containing FSH and LH in a 1:1 ratio, with each vial containing 75U of FSH and LH. Human Menopausal Gonadotropin (HMG) is considered an alternative medication for triggering ovulation in cases of anovulatory infertility, due to its many side effects and the high risk of ovarian hyperstimulation syndrome (OHSS). Generally, HMG 1 vial is administered intramuscularly daily, and if the level of estradiol in serum gradually increases 3 to 4 days later, the medication is continued. If the level of estradiol does not rise, an additional 0.5 to 1 vial can be added, and the dosage is adjusted after 3 days. The medication should be discontinued when the level of urinary estrogen reaches 50 to 100?g/24h, or when the level of estradiol in serum is between 500 to 1000pg/ml, or when the ovary is significantly enlarged. The therapeutic dose of Chorionic Gonadotropin (HCG) should vary according to the individual and the treatment cycle, and strict monitoring of follicle maturation should be in place to prevent the occurrence of ovarian hyperstimulation syndrome (OHSS).

　　(5) Gonadotropin-releasing hormone (GnRH): GnRH can promote the release of FSH and LH from the pituitary, but long-term use makes the GnRH receptors of pituitary cells insensitive, leading to a decrease in gonadotropins, thus reducing the synthesis of ovarian sex hormones. Its effect is reversible, initially stimulating the FSH, LH, and sex hormones of the ovary, and after 14 days, it decreases to normal levels, and after 28 days, it reaches the castration level.

　　In clinical practice, GnRH-A 1500pg can be administered subcutaneously once a day, starting from the follicular phase or from the luteal phase of the previous cycle (day 21). After the sex hormones reach the castration level, human chorionic gonadotropin (HCG) is used to induce ovulation, with the same dose as before. This can avoid the early LH peak in the menstrual cycle causing follicular luteinization. However, due to the high cost and large dosage of GnRH-A, its clinical application is limited.

　　(6) FSH: There are two types of FSH: purified human FSH and recombinant human FSH (rhFSH). FSH is an ideal treatment for polycystic ovary syndrome, but it is expensive and may cause OHSS. During use, strict monitoring of ovarian changes is necessary. A dose of 75U is relatively safe. FSH can also be used in combination with GnRH-A to improve the success rate of ovulation. (7) Bromocriptine: It is suitable for patients with ICOS and high PRL levels. The initial dose is 1.25mg, twice a day, which can gradually increase to 2.5mg, 2 to 3 times a day, taken after meals.

　　3. Bilateral ovarian wedge resection: It is suitable for patients with elevated blood testosterone, enlarged ovaries, and normal DHEA and PRL levels (indicating that the main cause is in the ovaries). Partial ovarian resection can remove excess androgens produced by the ovaries, correct the regulatory disorder of the hypothalamus-pituitary-ovary axis, but the efficacy is related to the site and amount of tissue removed, with varying efficacy. The pregnancy rate is 50% to 60%. The recurrence rate after surgery is high, and if concurrent pelvic adhesions are present, it is not conducive to pregnancy. Laparoscopic ovarian cauterization or resection can also achieve certain effects.

　　4. Hirsutism treatment: Hair can be regularly trimmed or treated with 'hair removal agents', but not pulled out to prevent excessive growth of hair follicles. Electrosurgical treatment or the use of drugs that inhibit androgen production can also be considered.

　　(1) Oral contraceptives: Combination tablets containing estrogen and progesterone, mainly estrogen, are ideal, as they can inhibit LH secretion, reduce blood testosterone, androstenolone, and DHEAS, and increase the concentration of sex hormone-binding globulin.

　　(2) Progesterone: It has a weak anti-androgenic effect and mild suppression of gonadotropin secretion, which can reduce the levels of testosterone and 17-ketosteroids. Medroxyprogesterone acetate (Anagon) is commonly used. Generally, 6 to 8 mg per day is taken orally. In addition, cyproterone acetate (CPA) is a highly effective progesterone with strong anti-androgenic activity. It is often taken with ethinylestradiol.

　　(3) GnRH-A: It is used from the 1st to the 5th day of the menstrual cycle, and now there are various preparations available for choice, such as transdermal inhalation, subcutaneous, and intramuscular injection. At the same time, ethinylestradiol can be taken to avoid adverse reactions caused by estrogen after medication.

　　(4) Dexamethasone: It is suitable for hyperandrogenism from the adrenal gland, 0.25 to 0.5mg/d. Taken orally every night.

　　(5) Spironolactone (Aldactone): By blocking the binding of testosterone to the receptor of hair follicles, it can also interfere with the synthesis of androgens in the ovary by inhibiting 17α-hydroxylase. 50mg taken orally daily can reduce hair growth in patients and make hair finer. For patients with hyperandrogenism and anovulatory menstrual disorders, 20mg taken orally daily from the 5th to the 21st day of the menstrual cycle can restore the menstrual cycle and ovulation in some patients.

　　5. Artificial Menstrual Cycle: For patients without hirsutism and without fertility requirements, artificial cycle treatment with progesterone can be given to avoid excessive hyperplasia and cancer of the endometrium.

　　Second, Surgical Treatment

　　1. Ovarian Wedge Resection: The exact mechanism of OWR in the treatment of PCOS is not yet clear. Two groups of literature report that 3 to 4 days after OWR, serum To, Adione, E1, and E2 are significantly reduced, and then LH decreases while FSH remains unchanged. Two weeks after the operation, the LH/FSH ratio returns to normal, and follicle development and ovulation appear successively. The ovulation rate of OWR is 80%, the pregnancy rate is 50%, and the adhesion rate after the operation is 41% (Buttram 1975). The use of new microsurgical technology and new adhesive barrier method can effectively prevent postoperative adhesions.

　　2. Laparoscopic Ovarian Treatment: It is a new technology. It involves laparoscopic multiple punch biopsy resection (MPBR), ovarian electrocautery, and laser multiple ovarian vaporization and laser wedge resection.