Prevalence of polycystic ovary syndrome under NIH criteria among the tenth-grade Chinese schoolgirls in Guangzhou area: a cross-sectional epidemiological survey

Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy, defined by the presence of chronic anovulation and hyperandrogenism after the exclusion of secondary causes, with an estimated prevalence of approximately 6% in premenopausal women [1]. In addition to reproductive and hyperandrogenic concerns, PCOS is also associated with a broad range of long-term adverse sequalae, including insulin resistance (IR), dyslipidemia, glucose intolerance and hypertension [2]. It was once thought to affect the appearance and fertility primarily of the adult women, but is currently recognized to have a peri-adolescence onset and continuously influence the patient’s whole life [3].

Since its original description in 1935, the definition of PCOS has undergone three major revisions, including the National Institues of Health (NIH) consensus conference held in 1990 [4], the Rotterdam European Society for ESHRE/ASRM- sponsored PCOS consensus workshop group held in 2003 [5], and the Androgen Excess and PCOS Society in 2006 [6]. These three criteria have established similar diagnostic points based on the specific pathophysiological changes of PCOS, but with different emphasis. In addition, none of the above groups has put forward the diagnostic criteria of PCOS specifically for adolescent population, probably due to the overlapping between pathophysiological feature in PCOS adolescents and normal pubertal physiology. The application of PCOS criteria for adult women among adolescent population would be probably not enough to reflect the speciality of adolescent PCOS. Some experts have ever raised their own opinions on the diagnosis of adolescent PCOS [7, 8], which were generally stricter than adult standard to avoid inappropriate premature diagnosis, while none has obtained the consent from any expert panel or society in this area. Accordingly, the absence of unified criteria leads to the scarcity of literature and reports over the epidemiological data either domestically or abroad.

Considering the various metabolic abnormalities related to PCOS and the early onset of PCOS during peri-adolescence, it is quite meaningful to make early diagnosis and take early measures on PCOS during puberty in order to guarantee the reproductive and physical health in the later life. Most of the reports on adolescent PCOS result from the patients in hospitals, while the materials from the general population are quite few. Therefore, according to the cross-sectional epidemiological survey design, we carried out a large-scale, cluster sampling study in Guangzhou area to explore the incidence and related clinical characteristics of PCOS in adolescent girls, and to collect experiences on clinical diagnosis of adolescent PCOS.

From January 2012 to April 2014, a total of 1294 tenth-grade schoolgirls in 5 senior high schools in Baiyun District, Haizhu District, Tianhe District, Liwan District and Yuexiu District of Guangzhou were investigated, in which 199 girls had a physical examination in the afternoon and were not fasting, so 1095 serum samples were kept for further tests. Their age ranged between 14 and 18 years with a mean age of 15.8 years, and mean body mass index was 20.72 ± 2.56 kg/m². Information about previous living habits, previous medical history and family conditions in this adolescent population was found to be similar to that in the adult counterpart from the previous survey we performed [10]. Figure 1 outlined the survey procedure and outcomes.

At present, the data about the incidence rate of PCOS throughout the world had been obtained intensively from reproductive-aged female population. Due to the differences in diagnostic criteria, sampling methods and the heterogeneity of PCOS itself, the prevalence rates, retrieved by domestic and foreign researchers in the epidemiological investigations on PCOS, vary greatly. The prevalence rate of PCOS among women of reproductive age in various countries was reported to be between 5 and 13% [16]. In a newly published meta-analysis in Chinese women, Wu et al. analyzed 69 studies with totally 154,599 participants enrolled from the regional population survey to understand the prevalence of PCOS in different regions and different population fully. In result, the overall prevalence of PCOS was 10.01% (95% CI 8.31–11.89%), and it varied with different regions, occupation/identity, age, time of publication, diagnostic criteria, survey time, which is coincidence with the current knowledge of PCOS [17].

Until now, large-sample epidemiological study on puberty PCOS was quite limited, which could be due to the absence of universally unified diagnostic criteria for adolescent PCOS. Nidhi et al. [18] prospectively investigated 460 girls aged 15–18 years from a residential college in India. By taking T > 2.85 nmol/L as the standard for biochemical hyperandrogenism, mFG ≥ 6 as the standard for clinical hyperandrogenism, and presence of > 10 follicles, 2–8 mm in diameter, or ovarian volume > 10m³ as the standard for ultrasonic PCO, the survey results showed that the incidence of adolescent PCOS was 9.13% under Rotterdam criteria and 2.61% under NIH criteria. Recently, Shama et al. [19] conducted systematic review and meta-analysis to estimate the pooled prevalence of PCOS among Indian girls aged 14–19 years, including 12 studies and totally 4473 participants. Approximately one in five Indian adolescent girls were diagnosed using NIH criteria, AES criteria or Rotterdam criteria. In a sub-study of comprehensive health and lifestyle studies of young Australian women (aged 16–29 years), Varanasi et al. [20] recruited the participants via Facebook advertising to complete questionnaires, physical examinations and blood tests. Therein, mFG ≥ 8 and T > 2.2 nmol/L were defined as clinical and biochemical hyperandrogenism respectively. According to NIH criteria, the prevalence of PCOS was 12% (31/254) in this study and 14.3% (7/63) in aged 16–20 subgroup. In Chinese scholar Wu’s meta-analysis report, with statistics from 1995 to 2020, the pooled prevalence rate of PCOS was 10.26% and 3.01% in individuals aged 10–20, and in school-based studies, respectively. Hence, diagnosing PCOS in adolescents is more challenging, because anovulatory cyclic bleeding and multi-follicular ovaries are common during puberty and considered as part of normal pubertal physiology, while the application of adult criteria results in a high prevalence and may lead to over-diagnosis and unnecessary anxiety among adolescents. According to the international evidence-based guideline for the assessment and management of PCOS in 2018, both oligo-anovulation and hyperandrogenism are required, with ultrasound not recommended for diagnosis of PCOS in adolescents, i.e., NIH criteria [21].

Until now, the definition of biochemical hyperandrogensim has not been universally unified yet. None of the well-konwn guidelines did specify which androgen indicator should be tested and which detection method should be used. Total testosterone was the most commonly used parameter. However, the sensitivity of the measuring method is not high, and the normal range and normal value corresponding to age are lacking, making it difficult to compare the data measured by different laboratories.FAI is recently considered as a more sensitive evaluation method, which can distinguish PCOS patients from healthy people. Hence, in this study, we took mFG ≥ 6 as the definition for clinical hyperandrogenism, and T > 2.28 nmol/L as one of the criteria for biochemical hypersandrogenism. At the same time, A2 and FAI were also used as reference indexes for diagnosing biochemical hyperandrogenism. According to NIH criteria, the prevalence of PCOS among the tenth-grade schoolgirls in Guangzhou is 3.86%, which is slightly higher than the result from Indian scholars under the similar research background (Asian population, NIH criteria, school-based). The slight discrepancy might be caused by that we tested three androgen indexes: T, A2 and FAI, which expanded the scope of androgen measurement, leading to detect more hyperandrogenemia individuals.

What’s more, we also noted that the incidence rate of PCOS in this survey increased slightly with age and gynecologic age, which was worthy of our vigilance. According to our study: (1) with the increase of age and gynecologic age, the menstrual cycle of adolescent girls gradually becomes regular, and the incidence of oligomenorrhea or amenorrhea is decreasing; (2) with the increase of age and gynecologic age, the incidence of hirsutism remained quite stable; (3) with the increase of gynecologic age, the serum androgen indexes increased significantly. The above results suggest that the transcending tendency of the incidence of adolescent PCOS with age and gynecologic age could be mainly due to the increase in the incidence of biochemical hyperandrogenism. Therefore, some scholars proposed that it could be better to diagnose adolescent PCOS according to hyperandrogenemia rather than the clinical manifestations of hyperandrogensim [8]. We also agreed with this view. However, due to the lack of the normal range of androgen indicators in adolescent population, researchers should formulate their own reference values according to the local population, otherwise the definition of adolescent biochemical hyperandrogenism would be arbitrary.

The present study also had certain limitations. Firstly, since the vast majority of girls in middle school were minors and under the double guardianship of the school and their parents, the actual implementation process was limited to questionnaires, physical examinations and serum collection for objective reasons, and no trans-abdominally or trans-rectally pelvic ultrasonography examination was performed. Secondly, considering that this study was a cross-sectional study without random sampling, and the age of the surveyed girls was quite limited, the incidence of adolescent PCOS in Guangzhou area could not be accurately obtained, so it is necessary to make further efforts to carry out standardized epidemiological investigation and research in the future.

This large scale epidemiological survey reveals that, based on the NIH criteria, the prevalence of PCOS among the tenth grade schoolgirls in Guangzhou area was 3.86%. Although it seems lower than that in other ethnic groups and regions, it is worthwhile to pay more attention on this specific age population. Meanwhile, the diagnosis of hyperandrogenism among adolescents should also be based on both clinical and biochemical parameters.