I. Overview of PCOS
The prevalence of PCOS in women of reproductive age is 5-10% (no exact prevalence has been reported in China), accounting for 30%-60% of patients with anovulatory infertility. The exact cause of PCOS is not known, but some studies suggest that it may be caused by the interaction of certain genetic and environmental factors.
1, genetic factors: PCOS has a family aggregation phenomenon, is presumed to be a polygenic disease, the current candidate gene research involves insulin action-related genes, high androgen-related genes and chronic inflammatory factors.
2, environmental factors: intrauterine hyperandrogenic environment, antiepileptic drugs, geography, nutrition and lifestyle, etc., may be risk factors or predisposing factors for the development of PCOS, and epidemiological investigation is still needed to improve the understanding of the relationship between the environment and PCOS.
Second, the diagnosis of PCOS
At this stage, it is recommended that the criteria recommended by the European Society of Human Reproduction and Embryology and the American Society of Reproductive Medicine expert meeting in 2003 be used in China, and after the preliminary results of epidemiological surveys and related studies in China, we will consider whether to amend this diagnostic criteria.
1, PCOS diagnostic criteria.
(1) Sporadic ovulation or anovulation;
(2) Clinical manifestations of elevated androgen levels and/or hyperandrogenemia;
(3) polycystic ovarian changes;
(4) Two of the above three criteria are met, and other etiologies causing elevated androgen levels are excluded, including congenital adrenocortical hyperplasia, Cushing’s syndrome, androgen-secreting tumors, and other diseases causing ovulation disorders, such as hyperprolactinemia, premature ovarian failure and pituitary or hypothalamic amenorrhea, as well as abnormal thyroid function.
2. Judgment of criteria.
(1) Sporadic ovulation or anovulation.
① 2-3 years after menarche cannot establish regular menstruation; amenorrhea (menopause for more than 3 previous menstrual cycles or ≥ 6 months); sporadic menstruation, i.e., those with ≥ 35d cycles and ≥ 3 months per year without ovulation (WHO class II anovulation);
②Menstrual regularity cannot be used as evidence of ovulation;
(3) Basal body temperature (BBT), ultrasound monitoring of ovulation, and progesterone measurement in the second half of menstruation can help to determine whether ovulation is present;
(2) Clinical manifestations of elevated androgen levels: acne (recurrent acne, often located on the forehead, cheeks, nose and jaw), hirsutism (coarse and hard hair on the upper lip, jaw, around the areola, lower abdomen midline, etc.);
(3) Biochemical indicators of elevated androgen levels: total testosterone, free testosterone index or free testosterone levels higher than laboratory reference normal values;
(4) Diagnostic criteria for polycystic ovaries (PCO): ≥12 follicles of 2 to 9 Shan in diameter in one or both ovaries, and/or ovarian volume ≥10 ml.
3, PCOS diagnostic exclusion criteria: exclusion criteria are necessary to diagnose PCOS, such as prolactin levels are significantly elevated, should exclude pituitary tumors, 20%-35% of patients with PCOS can be accompanied by mildly elevated prolactin levels; such as the presence of sporadic ovulation or anovulation, follicle stimulating hormone (FSH) and estradiol levels should be measured to exclude premature ovarian failure and central amenorrhea; determination of thyroid function. To rule out sporadic menstruation due to hypothyroidism;
In case of hyperandrogenemia or obvious clinical manifestations of elevated androgen levels, atypical adrenocortical hyperplasia (NCAH), Cushing syndrome, and androgen-secreting ovarian tumors should be excluded.
4, adolescent PCOS diagnostic criteria: due to the difficulty of distinguishing the physiological state from the PCOS state, and the lack of evidence of evidence-based medicine, there is no unified diagnostic criteria for adolescent PCOS.
Third, PCOS comorbidities
PCOS is often associated with obesity, metabolic syndrome and insulin resistance.
Fourth, the treatment of PCOS
PCOS patients, regardless of whether they have childbearing requirements, should first of all carry out lifestyle adjustments, quit smoking, quit drinking. Obese patients through low-calorie diet and energy-consuming exercise, reduce all body warbler 5% or more, can change or reduce menstrual disorders, hairy, acne and other symptoms and conducive to the treatment of infertility. Reducing body weight to the normal range can improve insulin resistance and stop the long-term development of PCOS with adverse consequences such as diabetes, hypertension, hyperlipidemia and cardiovascular disease and other metabolic syndromes.
(I) Adjustment of menstrual cycle
Irregular menstruation in patients with PCOS can be manifested as irregular menstrual cycles, scanty menstruation, low volume or amenorrhea, and some vaginal bleeding that is unpredictable. Adjusting menstrual cycle can protect the endometrium and reduce the occurrence of endometrial cancer.
1. Oral contraceptives: Various short-acting oral contraceptives are available, among which, progesterone can convert the endometrium, thus reducing the occurrence of endometrial cancer. Conventional usage is to start taking it on the 5th day of natural menstruation or retreating bleeding, 1 tablet daily for 2ld, stopping about 5d to start retreating bleeding, restarting the pill on the 5th day of retreating bleeding, or repeating the activation after 7d of stopping the pill. Repeatable for at least 3-6 months.
Oral contraceptives can correct hyperandrogenemia and improve the clinical manifestations of elevated androgen levels; they can also provide effective contraception, and cyclic withdrawal bleeding can also improve the state of the endometrium and prevent the development of endometrial cancer.
However, special attention should be paid to the fact that PCOS patients are a special group of people who often have disorders of glucose and lipid metabolism, and changes in blood glucose and lipids should be monitored during the medication; full informed consent should be given before applying oral contraceptives to adolescent women; contraindications to oral contraceptives should be excluded before taking the medication.
2.Progestin: for anovulatory patients without obvious clinical and laboratory manifestations of elevated androgen levels and without obvious insulin resistance, regular progestin therapy can be used alone to improve the endometrial status with cyclic withdrawal bleeding. Commonly used progestins include medroxyprogesterone acetate, progesterone (other name: Kine), and detroxyprogesterone (other name: Duffetone).
Conventional usage is meprogesterone acetate 6mg/d, or progesterone 200mg/d, or dydrogesterone 10-20m/d in the second half of the menstrual cycle for 10d per month, with retreating bleeding at least once every two months; retreating bleeding can also be treated with intramuscular progesterone injections for 5-7d, and if applied for a long time still requires intramuscular injections for more than 10d to protect the endometrium.
The advantages of using progesterone are.
(1) Adjustment of menstrual cycle, protection of endometrium and prevention of endometrial cancer;
(2)May reduce androgen levels to some extent by slowing down the frequency of luteinizing hormone (LH) pulsatile secretion;
(3) It is suitable for patients without severe hyperandrogenemia and metabolic disorders.
(II) Treatment of hyperandrogenemia
Various short-acting oral contraceptives can be used for the treatment of hyperandrogenemia, with compound cyproterone acetate (other name: Daying I35) being preferred; it can inhibit the production of high levels of androgens in follicular membrane cells by suppressing hypothalamic and pituitary LH secretion. Usually, acne needs to be treated for 3 months and hirsutism needs to be treated for 6 months, but the symptoms of elevated androgen levels will return after stopping the drug.
(C) Treatment of insulin resistance
Metformin is indicated for the treatment of patients who are obese or have insulin resistance. Metformin improves insulin resistance and prevents metabolic syndrome by enhancing glucose uptake by peripheral tissues, inhibiting hepatic glycogen production, and enhancing insulin sensitivity at the post-receptor level and reducing postprandial insulin secretion. Routine usage is: 500mg 2-3 times a day. Treatment should be followed up every 3-6 months for recovery of menstruation and ovulation, any adverse effects, and rechecking of serum insulin levels.
If menstruation does not resume, additional progestin must still be used to regulate menstruation. Metformin is a class B drug, and the drug description does not include post-pregnancy women as an indication group. Whether to continue its use after pregnancy should be decided carefully according to the patient’s specific situation and the endocrinologist’s advice. The most common side effects of metformin are gastrointestinal reactions, such as bloating, nausea, vomiting and diarrhea, which are dose-dependent and can be reduced by gradually increasing the dosage to the full amount over 2-3 weeks and by taking the drug with meals. Serious side effects are possible renal impairment and lactic acidosis, and renal function must be reviewed regularly.