Polycystic ovary syndrome (PCOS) is a reproductive endocrine and metabolic disorder that affects women throughout their lives and can develop into diabetes mellitus, hypertension, cardiovascular disease, endometrial cancer and infertility in the long term. Although there are many studies on PCOS, we still know very little about PCOS. In the 2015 Congress of Obstetricians and Gynecologists of the Chinese Medical Association, Professor Yu Qi explained the characteristics, etiology, diagnostic criteria, consequences, typing, treatment, and controversies of adolescent polycystic ovaries, so that we can have a more comprehensive and in-depth understanding of PCOS.
I. Characteristics of PCOS
1. Heterogeneity: polycystic ovary syndrome has obvious heterogeneity, with different clinical manifestations in different patients and great differences in laboratory tests and ancillary examinations. As the name of polycystic ovary syndrome disease, more than 50% of patients with polycystic ovary syndrome do not have it, while more than 20% of the general population can be found to have ovarian polycystic changes, and more than half of them are not polycystic ovary syndrome.
2, incurable: polycystic ovary syndrome is a hereditary disease, which needs to be controlled by long-term medication, and the regulation of lifestyle is the most important control method.
3, progressive development: polycystic ovary syndrome without control can develop into metabolic diseases, such as diabetes, hypertension, cardiovascular disease, and may develop into endometrial cancer and infertility.
Etiology of PCOS
The exact cause of PCOS is still unclear, and many people have studied it from genetic and environmental perspectives, but it is now mostly encountering bottlenecks. In terms of genetic factors, researchers believe that PCOS has a family aggregation phenomenon, so it is presumed to be a polygenic disease, and the current candidate gene research involves insulin action-related genes, androgen-related genes and chronic inflammatory factors. Environmental factors, including intrauterine hyperandrogenism, birth weight, antiepileptic drugs, geography, nutrition, and lifestyle, all of which may be risk factors, predisposing factors, and high-risk factors for PCOS, require further epidemiological investigation to improve the understanding of the relationship between environment and PCOS. Genetic and environmental interactions are currently the cause of many diseases, and they are also the cause of PCOS.
Third, the diagnostic criteria of PCOS
The diagnostic criteria for PCOS have been controversial internationally, but basically include ovarian polycystic changes, ovulation disorders, hyperandrogenemia and/or hyperandrogenism, the 2003 Rotterdam Diagnostic Criteria consider that any two of the above three can be diagnosed, which has Kaohsiung and ovulation disorders for classic PCOS, included in all the diagnostic criteria for PCOS; ovarian In 2006, the diagnostic criteria of the Androgen Excess Society (AES) included only the regular and classic type of menstruation, but not the non-Kaohsiung type; in 2010, the diagnostic criteria of the Ministry of Health emphasized fertility and ovulation, so the diagnostic criteria did not include the regular type of menstruation. The Japanese diagnostic criteria are more specific and include abnormal menstruation (anomenorrhea, scanty menstruation, anovulatory cycles, etc.), increased LH, normal FSH values, increased LH/FSH values and polycystic changes in the ovaries as seen by ultrasound.
IV. Main consequences and features of PCOS
1, metabolic syndrome: central obese patients meet and TG elevation, HDL-ch decrease, blood pressure increase and fasting blood sugar increase in two of the four items can be diagnosed as metabolic syndrome. Metabolic syndrome includes sugar and lipid metabolism abnormalities, thus leading to susceptible to diabetes and various cardiovascular diseases; quite a number of other diseases will also lead to these problems, and the judgment of insulin resistance is extremely complex and not easy to grasp.
2. Hyperandrogenism: hyperandrogenemia leads to metabolic syndrome and affects the patient’s aesthetics and body mass distribution, and is also a direct cause of ovulation disorders and metabolic abnormalities; androgen measurements are also highly variable and do not match well with physical signs. Blood androgen levels are the most inaccurate for determining hyperandrogenism because we can only measure total testosterone, which plays an uncertain role in androgenic activity. The real androgenic activity is free testosterone, which accounts for only a very small portion of total testosterone and is influenced by albumin and sex hormone binding globulin. Therefore, the measurement of androgen level is the least important indicator for the diagnosis of hyperandrogenism, compared with the presence or absence of Kaohsiung signs, which is more important.
3.Signs and symptoms of hyperandrogenism: Clinical manifestations of hyperandrogenism include acne and hirsutism. Acne means more acne on the face, forehead and back for more than 3 consecutive months. It is a chronic inflammation of the sebaceous glands of hair follicles, caused by excessive secretion of sebaceous glands stimulated by DHT resulting in excessive free fatty acids and low linoleic acid in sebum. Hirsutism mainly refers to an increase in sexual hair. Sexual hair is hair that responds to sex hormones and grows mainly on the face, lower abdomen, anterior thighs, chest, breasts, pubic bone area and armpits. High androgenic symptoms can better respond to androgenic activity, but there are large racial differences.
4. Ovulation disorder: It can lead to irregular menstruation, infertility and endometrial lesions. Menorrhagia lasting longer than ≥6 months or 3 previous menstrual cycles is called amenorrhea, and those who do not ovulate for ≥35 days and ≥3 months per year become menstrually sporadic, both of which are essentially sporadic ovulation or anovulation. Patients with normal menstruation also have the possibility of anovulation. Therefore, patients with PCOS symptoms must undergo ovulation determination even if they have normal menstruation, such as BBT measurement, ultrasound monitoring of ovulation and progesterone measurement half a month after menstruation. Other causes of scanty menstruation such as hyperprolactinemia, hypogonadotropic hypogonadism and premature ovarian failure should also be excluded.
5, LH/FSH ratio: Although it is also more common, there are differences in different weights and kits used for the determination.
6, polycystic changes of the ovaries: i.e. PCO. PCO is only a description of ovarian morphology by ultrasonography and refers to the number of follicles ≥ 12 with diameters of 2 mm to 9 mm in one or both ovaries, or ovarian volume ≥ 10 cm3 (ovarian volume calculated as 0.5 × long diameter (cm) × transverse diameter (cm) × anterior-posterior diameter (cm)).
The various current diagnostic criteria are motivated by a combination of the above indicators. In addition, obesity is also a problem that we need to pay attention to. Obesity diagnosis standard BMI between 18.5-25 is normal weight standard, but 23-25 is already obese pre-state. In the standard formulated by the Chinese Academy of Preventive Medicine after a sample survey of more than 40,000 people in urban and rural areas of 11 provinces and cities, central obesity refers to hip circumference ratio (waist circumference cm/hip circumference cm, WHR) ≥ 0.9 for men and ≥ 0.8 for women; the survey of the Chinese Working Group on Obesity shows that central obesity has a waist circumference of ≥ 85 cm for men and ≥ 80 cm for women. Insulin resistance, insulin resistance has several diagnostic criteria, obstetricians and gynecologists mostly look at fasting insulin, but basic obese patients may have insulin resistance.
V. Diagnostic typing
According to the presence or absence of obesity and central obesity, the presence or absence of impaired glucose tolerance, diabetes mellitus, metabolic syndrome, and the presence or absence of Kaohsiung characteristics, there are 2 categories: one category is classical PCOS patients with abnormal menstruation and hyperandrogenism, with or without PCO, and the metabolic disorder may be heavily manifested. The second category is without hyperandrogenic PCO, mostly with only menstrual abnormalities and PCO, and the manifestation of metabolic disorders may be less severe.
VI. Controversies about the treatment of adolescent PCOS
Because the hypothalamic-pituitary-ovarian axis of adolescent girls is still developing and is a dynamic process of change, no international authoritative diagnostic criteria for adolescent PCOS have been published so far. In adolescent girls with a family history, a history of abnormal growth, and signs of obesity, pubertal PCOS may serve as an important comprehensive clue to identify potential PCOS patients. For adolescent girls at high risk of PCOS, the recommended treatment is still mainly appropriate weight loss and lifestyle modification, and natural progestin or low androgenic activity progestin reagents with withdrawal bleeding every 1-2 months for those with scanty menstruation.
VII. Treatment of PCOS
1.Treatment principles
The etiology of PCOS is not known and it is difficult to cure it. Standardized and individualized symptomatic treatment should be adopted to introduce patients to the long-term complications and make it clear that the disease requires long-term treatment. Because of the different age and treatment needs of PCOS patients, clinical treatment should be based on patients’ complaints, treatment needs, and metabolic changes.
2.Treatment goal
The treatment goals of PCOS are to control the cycle and maintain the regularity of menstruation; to relieve the symptoms of Kaohsiung and safeguard physical and mental health; to reduce obesity and insulin resistance and avoid metabolic abnormalities; to treat infertility and solve fertility problems. In the clinic, it is meaningless to be confused about the diagnosis, and treatment should be carried out for the symptoms and the patient’s claims.
3.The significance of weight reduction
Behavioral therapy is the basis of PCOS treatment, patients should be instructed to eat less and exercise more, and persist with confidence, perseverance and persistence. Lifestyle adjustment to exercise to reduce body fat can improve insulin sensitivity, metformin is a good choice, safe and effective. Weight control is a priority step for ovulation promotion in PCOS. Weight loss is the first treatment for patients with PCOS with obesity, and ideally weight loss should be at least 5%. Obesity affects oocyte quality and pregnancy outcome, in addition to other risks associated with it, such as coronary heart disease and diabetes. And the occurrence of clomiphene resistance is mostly attributed to elevated free testosterone, hyperinsulinemia, abnormal glucose tolerance, and obesity. Weight control improves ovarian response and ovulation well, and both descending and reducing weight improve live birth. Normal weight women with abdominal obesity need to be concerned in the clinic.
4, PCOS patients of fertility promotion treatment
In the treatment of fertility promotion, excluding other health and fertility problems and emphasizing the importance of improving lifestyle, the treatment needs to be divided into three levels, namely clomiphene citrate (CC) or aromatase inhibitors (letrozole), gonadotropin or surgical ovarian perforation therapy, and assisted reproductive technology, not all patients with PCOS have to do IVF. In theory, IVF is not necessary for patients with anovulatory infertility due to PCOS alone, but it is indicated for patients with other combined infertility factors (endometriosis, tubal obstruction, PGD, male factor infertility, etc.).
In accordance with the basic principle that medical interventions should be simple to complex, non-invasive to invasive, and low-cost to expensive, the preferred ovulation-promoting treatment is of course oral ovulation-promoting drugs, commonly used are clomiphene and aromatase inhibitors. Before implementing this program, weight loss and control of metabolic abnormalities remain key. A trial of 3-6 cycles of oral ovulation-promoting drugs may be used, and if ovulation-promoting fails, consideration may be given to moving to second-line ovulation-promoting therapy.
When ovulation with gonadotropins is required, safely promoting ovulation from a single follicle is a challenge. If no follicles develop after one week, the dose is increased. To further reduce the risk, the starting dose can be extended (7-14 days) and the incremental dose reduced (75 IU-37.5 IU). This regimen is similar to the low-dose incremental regimen in terms of single follicle development rate, but has a lower safety and ovulation rate and requires more experience and skill. Commonly used combinations of superovulatory drugs include CC+HMG/FSH; Gn alone, i.e. HMG or u-FSH/r-FSH.
Ovarian perforation, another second-line ovulation protocol, is no longer used as a routine treatment due to its invasive nature, the need for surgery, and the potential for ovarian function damage.
When all of these ovulation promotion options fail, in vitro fertilization (IVF), or in vitro fertilization treatment, is required. The most important and difficult step in IVF remains the safe ovulation protocol. The GnRH agonist long protocol, the modified extra-long protocol and the GnRH antagonist protocol are the commonly used ovulation protocols. Care should always be taken not to overstimulate during the ovulation process, which could lead to OHSS.
In conclusion, PCOS is a reproductive endocrine and metabolic disorder that affects women throughout their lives, with a high degree of heterogeneity and complex etiological mechanisms, influenced by environmental and genetic interactions. The diagnosis and treatment of PCOS in adolescence need to be cautious to prevent overtreatment and mishandling; according to the domestic and international consensus, the treatment of PCOS needs to pay attention to the improvement of lifestyle and weight control; in the treatment of fertility promotion, the complications of ovulation promotion need to be strictly controlled, and the ovulation promotion program that is safe and prevents multiple births and OHSS is the future development trend.