Diagnosis of PCOS: 3998 Chinese cases NIH, Rotterdam criteria or AES ？ NIH, Rotterdam criteria or AES ？ Zi-Jiang Chen M.D., Ph.D Center for Reproductive Medicine Jinan, China

Outline History of diagnostic criteria 1 Clinical study of Chinese PCOS 2 Conclusion 3

The history of the criteria 2006 AES 2003 Rotterdam 1990 NIH 1935 S -L PCOS

The history of the criteria oligo-/anovulation (AO), hyperandrogenism(HA) and polycystic ovaries (PCO) ROTTERDAM AO+PCO AES HA+ PCO NIH AO+HA

Comments on the criteria NIH Rotterdam AES Which is more proper ?

 Aim: to have a profound understanding of the features of Chinese PCOS  Time:  Cases: 3998 PCOS patients from China (13 infertility centers involved)  Screen criteria: Rotterdam criteria, then subgrouped by AES and NIH criteria respectively Clinical study of Chinese PCOS

PCOS database

Informed consents

The clinical phenotypes  3998 patients (Rotterdam criteria) 2798 (70%) cases diagnosed by AES （ 51.53% ） 2715 (67.9%) cases diagnosed by NIH  The clinical characters (Rotterdam criteria) : PCOS from clinical patients PCOS from epidemiological study mentrual dysfunction 97.0 ％ 89.4% polycystic ovaries 94.0% 72.94% hyperandrogenism 70.0% 57.65% hirsutism 16.5% 1.18% acne 18.1% 38.82% Constituent ratio of different phenotypes --- Unpulblished

The endocrine of AES and non-AES group (x±s) AES groupnon-AES group tp Age28.54± ± ＜ 0.01 ** BMI24.97± ± FSH6.81± ± ＜ 0.01 ** LH11.43± ± ＜ 0.01 ** LH/FSH1.74± ± ＜ 0.01 ** E255.31± ± ＜ 0.01 ** PRL18.82± ± Unpublished

Metabolic features of AES and non-AES group AES groupNon AES grouptp Waistline83.97± ± W/H0.864± ± * CHO4.66± ± TG1.26± ± HDL1.24± ± LDL2.56± ± FG5.10± ± G308.69± ± G608.59± ± G ± ± G ± ± F INS10.66± ± INS ± ± * INS ± ± * INS ± ± ** INS ± ± *

DiseasesAES group non-AES group X2X2 p Hypertension 10.6 ％ 11.4 ％ Insulin resistance （ HOMA ） 15.2 ％ 15.8 ％ Obesity 46.0 ％ 45.2 ％ Clinical study of Chinese PCOS --- Unpublished

Family history of AES and non-AES group Family historyAES group non-AES group X2X2 p Hypertension 29.8 ％ 29.4 ％ Diabetes 11.5 ％ 8.5 ％ * Cerebrovascular disease 4.9 ％ 4.5 ％ Cardiovascular disease 9.4 ％ 8.8 ％ Unpublished

Endocrine of NIH group and non-NIH group NIH groupnon-NIH group tp Age28.55± ± ＜ 0.01 ** BMI24.94± ± FSH6.81± ± ＜ 0.01 ** LH11.58± ± ＜ 0.01 ** LH/FSH1.76± ± ＜ 0.01 ** E255.67± ± ＜ 0.01 ** T77.48± ± ＜ 0.01 ** PRL18.79± ± Clinical study of Chinese PCOS --- Unpublished

NIH groupnon-NIH group tp Waistline ± ± W/H ± ± * CHO 4.66 ± ± TG 1.26 ± ± HDL 1.24 ± ± LDL 2.57 ± ± BG ± ± BG ± ± BG ± ± BG ± ± BG ± ± INS ± ± INS ± ± * INS ± ± * INS ± ± ** INS ± ± ** The difference was still statistical significant after excluding the effect of age. (P=0.044)

Metabolism results of NIH and non-NIH group DiseasesNIH group non-NIH group X2X2 p Hypertension 10.5 ％ 11.5 ％ Insulin resistance （ HOMA ） 15.3 ％ 15.5 ％ Obesity 45.8 ％ No difference was found between groups about their medical history. Clinical study of Chinese PCOS --- Unpublished

Family history of NIH and non-NIH group Family historyNIH group non-NIH group X2X2 p Hypertension 30.5 ％ 28.1 ％ Diabetes 11.6 ％ 8.7 ％ * Cerebrovascular disease 4.7 ％ 4.9 ％ Cardiovascular disease 9.5 ％ 8.6 ％ Clinical study of Chinese PCOS --- Unpublished

 In AES group and NIH group: Patients are younger, Besides higher T, higher FSH and LH level. LH/FSH ratio is also higher significantly  Similar in both groups: Insulin levels are higher than that of non- groups Prevalence of Diabetes family history is significantly higher More risk of long-term complications Clinical study of Chinese PCOS

 The increased level of FSH and hypersensitivity caused by hyperandrogenism can promote the development of mutiple pre-antral follicles. This may be the reason of the morphological change in PCOS.  Elevated LH level will stimulate the production of androgen and form the vicious cycle which will aggravate the ovulatory dysfunction. Sarma HN Discussion

 A strong association between hyperandrogenism and metabolic syndrome, independent of obesity and insulin resistance. Hyperandrogenism is the independent risk factor of CVD  NIH PCOS is associated with a more adverse metabolic profile. The prevalence of obesity and insulin resistance is higher in NIH group. The risk of CVD and DM was increased. Coviello AD 2006, Legro 2006, Shaw LJ 2008, Cussons 2008, Moran L 2009 Goverde AJ, 2009 Discussion

 Our present results: both NIH and AES PCOS are associated with a more adverse metabolic profile. The insulin level are higher than that of non- groups, the insulin sensitivity was impaired in these subgroups. Prevalence of Diabetes family history is significantly higher.  PCOS without polycystic ovaries (non-PCO ) had higher cholesterol and low-density lipoprotein, had a higher incidence of developing long-term complications. ZJ Chen, et al Discussion

IR Anovulation Hyperinsulinemia IGFBP-1Free IGF-1 Hypersensitivity to FSH Androgen excess Discussion Androgen excess plays an important role in the pathophysiological process and has crucial significance ， but in clinic, how to determine androgen excess ?

Serum total Testosterone level in PCOS in different ethnicities Studiesethnicityn T PCOS % increased over Ctl mean T Chang et al., 2005USA mixed % Hahn et al., 2005German % Legro et al., 2006USA Caucasian % Diamanti 2007Greek % T Iwasa, 2007Japanese49 86±48.00 ng/dl 29.4% D.Y ang 2008 S.Chinese ±0.30 nmol/l 88.22% Liou, et al 2008Chinese TW ±1.4nmol/l 57.88% ZJ Chen, 2010Chinese ±24.10 ng/dl 51.9% Orio et al., 2010Italians ±0.3nmol/l % M ASUNCIO´ N, 2010Spainish9 1.7 ±0.9 nmol/l 70%

Conclusions NIH and AES criteria are stricter than Rotterdam criteria In clinic, which is more practical for PCOS diagnosis? 4 We still need more evidence and studies in the future … 2 Which is more proper for Chinese patients with PCOS: AO + HA /+PCO ? (mentrual dysfunction should be necessary condition?)

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