Polycystic ovary syndrome (PCOS) is the most important type of hyperandrogenic disease in women and is common in gynecological endocrine clinics, with an estimated prevalence of 4-12% among women of reproductive age [1,2]. According to the 2006 China Health Statistics Executive Summary, it is projected that the number of women with PCOS may be as high as 4.33 to 13 million nationwide between the ages of 25 and 34 years only. PCOS has four main features: 1) hyperandrogenism, 2) ovulation disorders and menstrual disorders, 3) clinical features of hyperandrogenism, and 4) polycystic ovary changes (PCO) [3]. PCOS is clinically heterogeneous: about 75% of patients diagnosed with PCOS have significant menstrual disorders, but about 20% have normal menstruation; about 60% to 80% have elevated circulating androgen levels; about 60% have hirsutism and 15-25% have acne; transvaginal ultrasonography reveals polycystic ovaries in about 75% of patients, but in 10% to 30% of patients, the ovaries do not show polycystic changes. PCOS may start in the uterus and stay with the woman long after birth [4], thus requiring long-term or even lifelong medical treatment and care. Over the decades, as attention to the evolution of PCOS has increased, the strategy for managing the disease has evolved from one that focused on a particular stage of treatment to one that addresses the entire spectrum of reproductive and health problems and prevention. However, not much research has been done on the evolution of PCOS, and it remains to be explored in depth and breadth. In this paper, we only summarize the limited literature and combine it with our long-term clinical practice to appreciate the evolution of the syndrome. I. Etiology, pathophysiology and clinical evolution of PCOS The first step in understanding the clinical evolution of the disease is to start with the etiology. To date, the exact etiology of PCOS is not clear, but there is a clear family aggregation phenomenon, and it is presumed from genetic studies that the syndrome is a polygenic disease with candidate genes involving hyperandrogenism-related genes, insulin action-related genes and chronic inflammatory factors. Environmental factors, including intrauterine hyperandrogenism, antiepileptic drugs, geography, nutrition and lifestyle, may have an association with the development of PCOS. The effects of embryonic androgens may predispose some individuals to the clinical manifestations of PCOS, which may result from a combination or interaction of certain genetic and environmental factors. There is no uniform explanation for the pathophysiology of PCOS, but all agree that hyperandrogenic activity is a key component. Elevated levels of total androgens, elevated levels of highly active androgens such as testosterone, elevated levels of biologically active androgens such as free testosterone, and increased sensitivity of target tissues and cells to androgens, i.e., abnormalities in the pre-, mid-, and post-binding links to androgen receptors, can all lead to increased androgen activity (see related topics in this issue). Through a series of associated links, the enhanced androgenic activity leads to impaired follicular development in the ovary, and the subcortex of the ovary is filled with mid-sinus follicles of grades 5 to 7 (2-10 mm in diameter). There is a relative excess of follicular membrane cells and stromal components, and the ovary continues to produce excess androgens, leaving the ovary in a persistently hyperandrogenic internal environment. The excess androgens are also converted to estrogens in the peripheral tissues, creating a relatively homeostatic, non-cyclically altered, moderate level of estrogen. These links form a loop that perpetuates the sign and allows for persistent anovulation of the ovaries. Women may have persistent menstrual disorders and signs of hyperandrogenic activity. Thus PCOS does not have a fundamental defect in one individual site, but is a functional disorder involving the entire hypothalamic-pituitary-ovarian axis system and peripheral metabolism. The link between insulin resistance and androgen excess in PCOS has not been clearly established, but it is an important link in the development of metabolic syndrome in PCOS [5].Patients with PCOS are prone to insulin resistance, but not all women with PCOS have abnormal insulin secretion. Studies have shown that insulin resistance can perpetuate abnormal changes in reproductive and metabolic physiology in PCOS patients. Although increased androgen synthesis by the adrenal glands is present in only about 50% of patients with PCOS, excessive androgen secretion by the adrenal glands at the time of initial presentation may play a role in the initiation of PCOS and may be a source of excess androgen secretion by the adrenal glands in a subset of PCOS that, together with other sources of androgens, perpetuates PCOS. II. Clinical evolution of PCOS in women during all stages of life (a) From fetal to childhood The development of the ovaries begins in mid-gestation when the ovaries are filled with primordial follicles. Thereafter, the follicles develop and mature rapidly, gradually forming primary follicles, secondary follicles and sinus follicles, but they cannot continue to develop to maturity. On histological examination, both healthy and atretic follicles can be seen. This pattern of follicular activity is maintained throughout the neonatal and childhood periods. In some children at this stage, the ovary may be occupied by numerous dilated cystic follicles that are distributed throughout the ovarian cortex, similar to the multifollicular ovaries seen on ultrasound in adult women. Some girls with polycystic ovarian changes may have clinical manifestations of PCOS, and there is no sufficient information on whether the polycystic ovarian changes in these girls appear before or simultaneously with or after the reproductive-metabolic abnormalities. A number of factors during the fetal period may increase the risk of developing PCOS later in life. For example, embryonic exposure to excess androgens may predispose some individuals to the clinical manifestations of PCOS in the future. Girls with fetal growth retardation (FGR) have increased levels of adrenal-derived androgens before puberty [6]; ovulation rates are much lower after puberty than in girls with normal fetal growth [7], and FGR affects follicular development in adolescent girls, with higher rates of sporadic ovulation and anovulation. Studies have also found that girls with FGR have relative hyperinsulinemia, hyperandrogenemia and increased FSH secretion (reduced ovarian responsiveness to FSH) during puberty. Fetal development affects the priming of adrenal function, and children with FGR have amplified priming of adrenal function and increased secretion of dehydroepiandrosterone sulfate in prepubertal or early adolescence, and the resulting enlarged androgen pool may be involved in initiating a range of physiological changes. The effect of excessive weight gain in childhood on the development of PCOS is similar to that of FGR. (ii) Prepubertal Prepubertal is the stage when PCOS patients begin to show their features. Early onset of sexual hair is the first clinical sign that can be detected. Prepubescence is the initiation of adrenocortical puberty with a subsequent increase in adrenal-derived androgens, including dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione, promoting pubic hair priming (pubarche). Premature pubarche is usually defined as the appearance of pubic hair before the age of 8 years and is a clinical manifestation of early onset of adrenal function. This is when androgens of adrenal origin are increased relative to biological age, but corresponding to height age and pubic hair staging. Girls with early pubic hair onset are typically not associated with precocious puberty, all events of puberty appear to be normal, and eventual height is not affected. Therefore, it was thought that the early appearance of pubic hair was not clinically significant and did not require special management. However, Ibanez et al [8] showed that about 45% of girls with precocious pubic hair had clinical features of PCOS and its hormonal features after puberty.Battaglia et al [9] studied 27 girls with precocious pubic hair and found that 41% of them had polycystic changes of the ovaries; those with PCO at the time of entry into the study had significantly larger ovaries compared to those without PCO after 2 years There was a significant increase in the number of small follicles. Girls with premature pubic hair and sporadic menstruation are more likely to have hyperandrogenemia and PCO than those with regular menstruation. (iii) Puberty Puberty is the phase in which the four features of PCOS develop more clearly. Mild hirsutism and anovulation can persist for several years during puberty and are often considered part of the normal developmental process. Most patients with PCOS clinically often trace the origin of their symptoms to early puberty, suggesting that PCOS may be associated with abnormal expression or response to those factors that initiate and regulate puberty. The evolution of PCOS in early puberty, involving abnormal activity of the HPO axis and specific morphological alterations of the ovaries, is not well understood to date [10]. 1. excess androgens or excessive activity The core of endocrine abnormalities in PCOS is the excessive production of androgens by the ovaries. Elevated free testosterone and reduced SHBG are common among adolescents with a proposed diagnosis of PCOS, and total testosterone may be normal. A national study showed that hyperandrogenemia in “adolescent PCOS” is similar in magnitude to that of adult PCOS patients [11]. In 2006, the Androgen Excess Society (AES) stated that the measurement of circulating androgen levels should only be used as an adjunct to the diagnosis of hyperandrogenism and should not be used as the sole criterion for diagnosis or as a substitute for clinical evaluation [3]. It is worth mentioning that, similar to adult patients, those with hyperandrogenism in adolescent PCOS may also exhibit an abnormal insulin response to glycemic load, and assessment of their 24-hour insulin secretion pattern shows a higher release than in normal adolescent girls. The lipid profile of these adolescent girls with hyperandrogenemia showed an increased ratio of LDL cholesterol to HDL cholesterol. These results suggest that these adolescent girls already have long-term health risk factors early in their reproductive activity. 2. Ovulation disorders and menstrual disorders Apter [12] reported that anovulatory cycles in 200 adolescent girls accounted for 80% in the first year after menarche, 50% in the third year, and 10% in the fifth year after menarche. It is unclear whether post-ovulatory anovulation has the same mechanism as the long-term anovulation in PCOS. However, it is clinically impossible to distinguish PCOS from irregular bleeding after menarche, and therefore it is not recommended to diagnose PCOS in young girls based on menstrual abnormalities alone. Most anovulatory menstrual disorders in PCOS begin at menarche, and the mean age at menarche is similar to that of normal controls. A retrospective study by Lin Shouqing et al [13] found that 75.9% of patients with PCOS had menstrual disorders starting at menarche, and another 1/4 had regular menstruation initially after menarche, with onset several years later. Jiang Yanhua et al [14] retrospectively analyzed the menstrual status of women with PCOS in their reproductive years at puberty, suggesting that those with sparse menstruation and amenorrhea at puberty have more severe endocrine metabolic disorders in their reproductive years, accompanied by lower pregnancy rates. Recent evidence suggests that sparse menstruation may actually be an early manifestation of PCOS in the first years after menarche [15]. Cohort surveys have shown that 45-57% of girls with sparse menses have PCO. which later may be diagnosed as PCOS, also with menstrual disorders, has been studied by many authors. About 50% of girls with irregular menses and no manifestations of hirsutism had elevated LH levels and circulating androgen levels with an increased frequency of LH pulses, consistent with the diagnosis of PCOS [16].In a study by Venturoli et al. on long-term follow-up of girls with sparse menses, it was found that those with normal LH levels eventually developed regular menses, while more than half of those with elevated LH levels had persistent gonadotropin abnormalities and hyperandrogenemia [17].Yoo et al. studied nine girls with persistent menstrual sparseness at puberty with obesity, no hirsutism, and no hyperandrogenemia [18] and found that eight of them had LH pulse frequencies similar to those with PCOS, all significantly higher than normal controls.Porcu et al [19] found that during puberty whether LH is normal or LH is elevated, both may evolve into a normal physiological state: with ovulation, normal LH values and loss of circadian rhythm, but a higher percentage of those with normal LH later experienced regular ovulation. The mechanism of why some of these girls with elevated LH remain elevated into adulthood and become PCOS, while others have normal LH, is not clear; whether abnormal LH secretion is a cause or a consequence of anovulation is not known. 3. Clinical features of hyperandrogenism The reasons for the occurrence of hirsutism in women are complex. Hirsutism is not only related to the type of androgen, metabolic clearance rate and SHBG content, but also related to the sensitivity of individual hair follicles to androgens and the length of time they are affected by androgens. Therefore, people with elevated androgen levels may not have hirsutism, and people with low androgen levels may also have hirsutism. Hirsutism is also related to race and genetic factors. Generally speaking, women in China have less body hair. Hairiness alone is not sufficient to diagnose PCOS, but it is the most significant clinical sign in women with PCOS. The incidence of hirsutism in the literature varies widely (17.8%-100%), with an average of about 60%, which may be related to ethnicity and inconsistent diagnostic criteria [3]. In a study by Lin Shouqing et al [13], hirsutism accounted for 86.2% of patients with PCOS. Usually facial hirsutism appears at the onset of puberty or shortly after the onset, and the growth rate is relatively slow. If the hair grows rapidly within a few months, androgen-secreting tumors should be alerted.Facial hirsutism in women with PCOS can occur on the cheeks, over the lips and in the area under the chin extending to the neck. This hypertrichosis is often combined with excessive growth of pubic hair toward the umbilicus, resembling a male shield-like distribution. A small upper lip whisker or mild hirsutism does not necessarily indicate hyperandrogenemia, but the persistence or progressive growth of hair should be considered an evidence of androgen overproduction. Acne vulgaris is a chronic inflammatory condition of the sebaceous glands of the hair follicles. Increased dihydrotestosterone stimulates overproduction of sebaceous glands, which leads to blockage of sebaceous duct openings and overgrowth of Propionibacterium acnes, a conditionally pathogenic bacteria in the sebaceous glands, leading to infection. The presence of multiple acne sites in Chinese women for 3 consecutive months reflects increased androgen levels. However, some authors [5] have argued that acne, as a separate symptom, is not considered as a sign of PCOS. Androgenetic alopecia is a well-recognized sign of PCOS, but its prevalence in PCOS is not known. Polycystic changes of the ovaries (PCO) Current data suggest that approximately 75% of women with a clinical diagnosis of PCOS have polycystic changes of the ovaries detected by transvaginal ultrasonography. It should be noted that about 10-30% of women with PCOS do not have PCO on transvaginal ultrasound, while on the other hand, ultrasound shows typical PCO changes in 8-25% of women with normal pregnancy and 14% of women on the pill. In addition, PCO can be present in a wide range of diseases that may cause elevated androgen activity, and PCO is a sign rather than a central or local specific disease. In addition to the four clinical features described above, obesity is a concern. approximately 20-50% of women with PCOS are obese. Compared to those who are also obese but do not have PCOS, those with PCOS have a more centripetal distribution of fat and an increased waist-to-hip ratio, i.e., a male-to-male distribution. Obesity may promote or amplify the functional abnormalities associated with PCOS. In adolescent girls, hyperandrogenemia is significantly more common in overweight than in normal weight individuals, and this phenomenon is more pronounced in early adolescence. Obese girls with a history of premature sexual hair and a family history of PCOS are at high risk for developing PCOS [20] and deserve close monitoring. (iv) Reproductive age In addition to the four characteristics mentioned above still persist, there are added problems with reproductive implications. 1. low fertility and high rates of spontaneous abortion. patients with PCOS have low fertility overall, but infertility in these patients is relatively easy to treat. One study [21] found that although 70% of patients with PCOS had been seen for infertility problems, only 24% of these patients ended up childless. Anovulation is the main reason for failure to conceive in women with PCOS, and the high rate of spontaneous abortions is also an important factor affecting fertility. The mechanism for the high rate of spontaneous abortion remains unclear and may be related to hyperinsulinemia and polycystic changes in the ovaries. 2. gestational diabetes mellitus (GDM) The effect of PCOS and GDM is twofold. Several studies have suggested a higher incidence of GDM in women with PCOS than in those without PCOS, and a population-based survey in North Carolinas between 2002 and 2004 found [22] that the incidence of GDM was 14.3% in women with PCOS and 5.9% in women without PCOS, with the former being 2.4 times higher than the latter. On the other hand, the study also found a high rate of PCOS in women with a history of GDM. At 3-5 years postpartum follow-up of 34 women with a history of GDM and 36 control women, ultrasound, clinical and endocrine changes consistent with PCOS features were found to be significantly more frequent in women with a history of GDM [23]. Women with a history of GDM and altered PCO were more likely to develop insulin resistance than women without PCO. a 2006 meta-analysis of pregnancy outcomes in PCOS [24] showed an increased incidence of GDM (OR2.94), increased gestational hypertension (OR3.67), increased preterm delivery (OR1.75), increased odds of neonatal monitoring ( OR2.31), and increased perinatal mortality (OR3.07). In conclusion, women with PCOS are at increased risk of pregnancy complications and neonatal complications and require increased monitoring before pregnancy, during prenatal and intrapartum to reduce these risks. (v) Perimenopause and postmenopause (decline in ovarian axis function) Studies on the clinical evolution of women with PCOS during the perimenopause and postmenopause are relatively scarce in the literature. A very valuable study was conducted in Sweden on the evolution of women with PCOS during this phase [21]: a retrospective analysis of patients with a definite diagnosis of PCOS who underwent ovarian wedge resection between 1956 and 1965, in 1987 (age 40-59 years in 1987), and local women selected as 1:4, age-matched who served as controls. Compared with controls, sporadic menstruation (cycles >35 days) was observed in 81% of PCOS patients when they were young and in 61% after ovarian wedge resection, but in only 28% during the last 10 years (referring to the period 1978-1987), i.e., many patients naturally approached normal menstrual cycles as they grew older. Of interest is that 90% of those who developed normal menstrual cycles were not associated with weight loss.Elting MW et al [25] (Netherlands) reported in 2000 a study of patients with PCOS who had not undergone surgery and found a negative correlation between age and menstrual cycle length in these women: by age group, regular ovulation was found in 40.6% of the 30-35 year olds and in more than 80% of the 42-52 year olds. -52 years of age group exceeded 80%; the effect of age on the menstrual cycle was not affected by weight, weight loss, or hirsutism. The paper also mentions that in 50 patients (more than 1/3) the change towards a normal menstrual cycle occurred after childbirth, in 2 cases after weight loss and in 90 cases without a clear cause. The two studies mentioned above suggest the same trend of natural evolution towards normal menstruation with age in the natural state and after surgical intervention. The epidemiology on PCOS in Jinan shows that Han Chinese PCOS patients in Jinan are mainly distributed in the group under 35 years of age, which also indirectly supports the above view.The reasons for the onset of regular ovulation in women with PCOS during the ageing process, especially in the late reproductive years, are not clear. A study [26] found that older women with PCOS who had regular menstrual cycles had smaller follicular clusters, higher blood FSH levels, and less FSH-induced inhibin release compared to age-matched persistent anovulators. Notably, serum androgen levels were also significantly lower in those with regular menstrual cycles than in the anovulatory group. Whether changes in follicular clusters or the ovarian endocrine milieu lead to a return to ovulation in older women with PCOS remains to be demonstrated. The Swedish study also found late menopause in women with PCOS: 27% of PCOS patients were menopausal and 60% of age-matched normal controls were menopausal. A similar evolution to the one described above has been found in our clinical practice. The Swedish study also measured hormone levels and found that in younger women with PCOS, the typical hormonal changes were still present in the perimenopausal and postmenopausal periods: testosterone (T), T/SHBG, androstenedione, estrone, and LH/FSH were elevated, but the differences between PCOS patients and normal controls were relatively small in the perimenopausal period and became significant in the postmenopausal period. It is possible to understand that after menopause, although the follicle count is almost depleted, the ovarian stroma may still retain the characteristics of the PCOS stroma and be able to secrete more androgens. During the perimenopausal period the differences between PCOS patients and normal controls are relatively small because of the relative increase in androgen levels that also exist in normal women [27]. Metabolic syndrome, diabetes mellitus, hypertension, and endometrial cancer are the distant complications of PCOS and their clinical course, see the description of the topic in this issue. III. SUMMARY AND PROSPECTS PCOS is characterized by persistent hyperandrogenism and prolonged ovulatory disturbances, caused by functional and peripheral metabolic abnormalities in all parts of the hypothalamus-pituitary-ovary-adrenal gland. All these factors can produce a clinical phenotype and increase long-term health risks. Most long-term reproductive abnormalities and overall health problems in PCOS are associated with hyperandrogenemia and hyperinsulinemia. It has been generally accepted that PCOS is a persistent loop lesion that is difficult to treat because of its unclear etiology. However, if either part of the pathogenesis of PCOS is interrupted, improvement is possible. For example, reducing body weight, even by a small amount or even just 5%, can significantly improve menstrual status and restore ovulation, while improving the morphology of the ovaries [28]. After bariatric surgery with biliopancreatic diversion or gastric bypass in morbidly obese patients with PCOS, with 7 to 26 months of follow-up, weight loss averaged 41 ± 9 kg, patients had decreased hirsutism scores, total and free testosterone, androstenedione, and dehydroepiandrosterone sulfate were decreased, insulin resistance was reduced, and normal menstruation and ovulation resumed in all patients [29]. This is an extreme case, but suggests that PCOS may remit under certain circumstances. In clinical practice, diagnosing a woman with PCOS implies that she may be at increased risk for infertility, dysfunctional uterine bleeding, endometrial cancer, obesity, type 2 diabetes, dyslipidemia, hypertension, and cardiovascular disease, and may require long-term treatment. Therefore, the diagnosis of PCOS should be made with caution, especially during adolescence when it is difficult to make a correct diagnosis quickly. There may be many women with features suggestive of PCOS who do not necessarily have PCOS, but these women and their symptoms should be treated regardless of whether PCOS has been diagnosed. Clinical management should be targeted at different stages to improve clinical symptoms and reduce long-term complications through menstrual adjustment, anti-hyperandrogenemia, treatment of infertility, and adjustment of metabolic abnormalities. Although PCOS may not be curable, it is a manageable disease, and long-term complications can be reduced by the above methods. Although the number of diseases is considerable, it is important not to expand or make it serious to avoid psychological stress and excessive medical treatment for patients. There are still many questions about PCOS that need to be addressed: the etiology is unclear, the diagnostic criteria are not yet uniform, and there is a lack of long-term, large sample studies to understand its clinical evolution, which need to be further investigated.