Xiaomiao Zhao

Defining hirsutism in Chinese women: A cross-sectional study

OBJECTIVE To determine the normative cut-off score that defines hirsutism among Chinese women, and the effect of age, menstrual irregularities, and polycystic ovaries on the same. DESIGN Cross-sectional, population-based study. SETTING A multistage systematic cluster random sampling among 16 communities from two rural and two city regions. PATIENT(S) A representative sample of 2,988 women aged 20-45 years from the general population of Southern China. INTERVENTION(S) Subjects underwent physical and ultrasound evaluations. MAIN OUTCOME MEASURE(S) Terminal hair growth was assessed using the modified Ferriman-Gallwey (mFG) scoring system. RESULT(S) An mFG score ≥5 was observed in 10% and a score of ≥2 in 25% of the subjects. Cluster analysis identified an mFG score of 5 as the cut-off value that defines abnormal terminal facial and body hair growth in a male pattern (i.e., hirsutism) in the total population; scores of 6, 5, and 4 for women aged 20-25, 26-30, and >30 years, respectively. Defined by these cut-off values, the prevalence of hirsutism in our total population was 10.5%; and decreased with increasing age: 14.4%, 10.7%, 7.9%, 3.6%, and 1.5%, respectively, in women aged 20-25, 26-30, 31-35, 36-40, and 41-45 years. Furthermore, the incidence of acne, menses irregularities, polycystic ovaries, and acanthosis nigricans were significantly increased among the hirsute women. CONCLUSION(S) An mFG score of 5 or greater indicates hair growth above the norm among women in the general Southern Chinese population, a cut-off value that decreases with increasing age.

Association of biochemical hyperandrogenism with type 2 diabetes and obesity in Chinese women with polycystic ovary syndrome.

To evaluate the effect of hyperandrogenism on metabolic disorders among patients with polycystic ovary syndrome (PCOS) diagnosed using the Rotterdam criteria.

MicroRNA-93 Promotes Ovarian Granulosa Cells Proliferation Through Targeting CDKN1A in Polycystic Ovarian Syndrome

CONTEXT MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression post-transcriptionally. Whether differently expressed miRNAs contribute to promoting granulosa cell proliferation in polycystic ovarian syndrome disease (PCOS) remains unknown. OBJECTIVE We explored whether certain miRNAs are involved in the ovarian dysfunction of PCOS and the mechanism of increased granulosa cells proliferation. Patients and Cells: miRNA expression was analyzed in excised ovarian cortexes from 16 women with PCOS and 8 non-PCOS. An immortalized human granulosa (KGN) cell was used for the mechanism study. MAIN OUTCOME MEASURES Expressions of miRNAs in ovarian cortexes were measured using qRT-PCR and KGN granulosa cells were cultured for proliferation assays after overexpression or inhibition of miR-93 or after insulin treatment. Bioinformatics were used to identify the potential miRNA targets. Protein expression analysis, luciferase assays, and rescue assays were used to confirm the substrate of miR-93. RESULTS MiR-93 expression was higher in PCOS ovarian cortex and its identified target, CDKN1A, was downregulated. MiR-93 overexpression promoted cell proliferation and G1 to S transition. Knocking down CDKN1A promoted cell growth and cell cycle progression in granulosa cells, and CDKN1A re-introduction reversed the promotional role of miR-93. High concentrations of insulin induced upregulation of miR-93, stimulated KGN cells proliferation and reduced CDKN1A expression. CONCLUSIONS miR-93 was increased in PCOS granulosa cells and targeted CDKN1A to promote proliferation and cell cycle progression. Insulin could upregulate the expression of miR-93 and stimulate cell proliferation. This might provide a new insight into the dysfunction of granulosa cells in PCOS.

Clinical and metabolic features of polycystic ovary syndrome among Chinese adolescents.

OBJECTIVES To explore the clinical and metabolic features exhibited by Chinese adolescents with polycystic ovary syndrome (PCOS) and to determine the differences between nonobese and obese adolescent patients with PCOS. DESIGN Clinical cross-sectional study. SETTING Department of Gynecology and Reproductive Center. PARTICIPANTS 25 obese and 66 nonobese adolescents with PCOS and 26 age-matched controls. INTERVENTIONS Fasting venous blood samples and an oral glucose tolerance test using 75 g of glucose were obtained from PCOS patients and controls. MAIN OUTCOME MEASURES Clinical features were summarized. Serum levels of FSH, LH, E(2), TT, SHBG, fasting insulin, and fasting glucose were measured. RESULTS The prevalence of obesity in adolescents with PCOS was 27% (25/91). 99% of these patients presented with menstrual disorders, 84% presented with clinical and/or biochemical hyperandrogenism, and 90% exhibited an ultrasonographic appearance of polycystic ovaries. The prevalence of hirsutism and acanthosis nigricans were higher in the obese PCOS group than in the nonobese PCOS group (72% vs 41% and 44% vs 5%, respectively). A total of 5 of 20 obese (25%) and 5 of 36 nonobese patients (14%) demonstrated impaired glucose tolerance levels. CONCLUSIONS Chinese adolescents with PCOS manifest clinical and metabolic features similar to those of adult Chinese women with PCOS except for the increased prevalence of hyperandrogenism and insulin resistance. Adolescents with high risk factors, especially those with menstrual disorders and hyperandrogenism, may need careful clinical screening.

Prognostic significance of cyclooxygenase-2 in cervical cancer: a meta-analysis.

Published data on the prognostic value of cyclooxygenase‐2 (COX‐2) overexpression in cervical cancer are conflicting and heterogeneous. We performed a meta‐analysis to more precisely estimate its prognostic significance. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the effects. Twenty‐three studies with 1,477 cervical cancer patients were selected to evaluate the association between COX‐2 and overall survival (OS), disease‐free survival (DFS), response to chemoradiation (RC) and clinicopathological parameters. High COX‐2 expression predicted poor OS (HR: 2.53, 95% CI: 1.54–4.18), DFS (HR: 2.41, 95% CI: 1.58–3.69) and RC (OR: 3.03, 95% CI: 1.97–4.64). Subgroup analyses showed that COX‐2 overexpression was related significantly with poor OS in patients treated by chemoradiation or surgery, and in patients with squamous cell carcinoma, respectively. Besides, COX‐2 overexpression was related significantly with poor DFS in chemoradiation subgroup. Furthermore, COX‐2 overexpression was associated with poor RC in patients who received “FP” regimen or “P” regimen. Additionally, there were significant associations between COX‐2 expression and all clinicopathological parameters except tumor grade. The pooled ORs (95% CI) were as follows: 1.49 (1.09–2.04) for age, 1.77 (1.22–2.56) for lymph node metastasis, 1.04 (0.74–1.47) for tumor grade, 1.71 (1.12–2.64) for tumor size, 2.38 (1.28–4.45) for FIGO stage, 3.96 (2.32–6.77) for histological type, 2.45(1.10–5.42) for parametrical involvement. This meta‐analysis indicated that COX‐2 overexpression might be an unfavorable prognostic and a chemoradiation resistance predictive factor for cervical cancer; it could potentially help to stratify patients further in clinical treatment.

Risks for gestational diabetes mellitus and pregnancy-induced hypertension are increased in polycystic ovary syndrome.

Objectives. To evaluate pregnancy outcomes and its determinants in women with polycystic ovary syndrome (PCOS). Methods. Two-hundred and twenty pregnant PCOS and 594 healthy women were followed from early pregnancy. Incidences of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preterm birth, twinning, and fetal growth restriction (FGR) were determined. Results. The incidence of GDM was notably higher among all PCOS combined (54.9%; OR: 2.9, 95% CI: 2.0–4.1) and PCOS subgroups, whether they conceived spontaneously (51.5%; OR: 3.3, 95% CI: 2.0–5.4), or via IVF-ET or ovarian stimulation, compared with controls (14.3%; P < 0.001). The incidence of PIH was also higher among all PCOS (10.4%; OR: 2.2, 95% CI: 1.1–4.4) and the subgroup conceiving spontaneously (11.8%; OR: 2.6, 95% CI: 1.1–6.2; P < 0.001) but not for those conceiving with IVF-ET (9.1%) or ovarian stimulation (9.4%). Lean women with PCOS (BMI <24 kg/m2) had higher incidences of GDM (51.1% versus 14.5%; OR: 5.6, 95% CI: 3.4–9.0) and PIH (8.9% versus 3.2%; OR: 3.0, 95% CI: 1.3–7.1) than lean controls. PCOS woemn with normal glucose tolerance had higher risk for PIH than their comparable control group (OR: 4.0, 95% CI: 1.3–11.7). Conclusion. This study suggested that PCOS is an independent risk factor for the development of GDM and PIH. This trial is registered with ChiCTR-RCC-11001824.

Four polymorphisms of the CAPN 10 gene and their relationship to polycystic ovary syndrome susceptibility: a meta-analysis.

Objective  To investigate the association between CAPN 10 gene polymorphism and polycystic ovary syndrome (PCOS) susceptibility.

Determining the normal cut-off levels for hyperandrogenemia in Chinese women of reproductive age

OBJECTIVE To determine the normative cut-off levels of free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS) and total testosterone (TT) among reproductive age women in China. STUDY DESIGN A total of 450 reference subjects without known factors affecting androgen levels were selected from a total study population of 904 presumably healthy women undergoing annual check-ups. The upper limits of normal levels of biochemical androgens were computed by k-means cluster analysis, with the results categorized by age and expressed as both concentrations and percentiles. RESULTS The upper limits (cut-off levels) of normal FT, DHEAS and TT levels as determined by k-means cluster analysis are 26 pmol/L, 4.92 μmol/L and 2.39 nmol/L, respectively, in the selected reference subjects. The corresponding percentiles of the cut-off levels of FT (91.8th vs. 87.9th), DHEAS (69.8th vs. 67.6th) and TT (90.0 th vs. 83.8th) were all higher in the reference subjects than in the total study population, suggesting that there were fewer abnormal subjects with elevated androgens in the healthier reference population than in the total study population. The level of DHEAS significantly declined by age (P < 0.05), whereas there was no significant difference in the mean FT or TT levels between age groups among these women of reproductive age. CONCLUSIONS The normal hyperandrogenism cut-off values for FT, DHEAS and TT are 26.00 pmol/L, 4.92 μmol/L and 2.39 nmol/L, respectively, among women of reproductive age in China who are without factors that might affect androgen levels. The cut-off levels in percentiles are 91.8th for FT, 69.8th for DHEAS and 90.0 th for TT.

Prevalence of Metabolic Syndrome and Overweight/Obesity among Chinese Women of Childbearing Age: A Cross-Sectional Epidemic Study

Objects: Metabolic syndrome (MS) is an independent risk factor for chronic metabolic disorders (CMD). This study investigated the prevalence of MS and overweight/obesity among women of childbearing age in southern China. Methods: A nationally representative sample of 3200 southern Chinese women aged 20-45 years were randomly selected from 16 sampling units of two rural areas (Zhongshan and Xinhui) and two city regions (Guangzhou and Shenzhen) in Guangdong Province in China between June 2008 and July 2009. The prevalence of MS according to modified ATP III criteria and overweight/obesity (≥ 23.0 kg/m2) were analyzed. Results: Approximately 1.28 million women in Guangdong, China, were estimated to have MS, with an ageadjusted prevalence of 6.6% (95% CI 5.3%-7.5%), and 4.22 million [21.7% (95% CI 20.2%-23.2%)] were estimated to have overweight/obesity. In total, 39.5% women had one component of MS, 19.4% two components, 5.6% three components, and 0.9% at least four components. Compared to the 4.7% MS prevalence in women aged 20-25 years, the prevalence increased in women aged 31-35 years (1.3-fold) and increased more sharply in women aged 36-45 years (2.3-fold). The age-specific prevalence of overweight/obesity increased steadily by 1.3-1.8-fold beginning at 26-30 years of age (9.0%), and it reached a peak at 36-45 years of age (36.0%). The prevalence of MS and overweight/obesity increased in rural residents who preferred unhealthy diets and exercised less compared to urban residents. Conclusion: Some women of reproductive age in southern China had MS, and a significant, and perhaps growing, proportion of women were overweight. Less exercise contributes to the higher prevalence of MS and overweight/obesity among rural residents than urban residents.

Levonorgestrel Inhibits Human Endometrial Cell Proliferation through the Upregulation of Gap Junctional Intercellular Communication via the Nuclear Translocation of Ser255 Phosphorylated Cx43

Objects. To assess whether LNG exerts antiproliferation effects on human endometrial cells through changes of GJIC function and the phosphorylated Cx43. Methods. Cell proliferation and apoptosis of human endometrial stromal cells (HESCs) and glandular cells (HEGCs) treated with LNG in a dose- and time-dependent manner. GJIC change and further total Cx43 and serine 368 and 255 phosphorylated Cx43 were measured. Results. 5 × 10−5 mol/L LNG revealed a time-dependent inhibition of cell proliferation and an increase of apoptosis in both HESCs and HEGCs. Furthermore, these cells demonstrated a significant GJIC enhancement upon treatment with 5 × 10−5 mol/L for 48 hours. The effects of LNG were most noticeable in HESCs rather than in HEGCs. Associated with these changes, LNG induced a relative increase in total Cx43 in a time-dependent manner but not Ser368 phosphorylated Cx43. Moreover, laser scanning confocal microscope confirmed the increased expression of total Cx43 in the cytoplasm and, interestingly, the nuclear translocation of Ser255 phosphorylated Cx43. Conclusions. LNG likely inhibits the proliferation and promotes apoptosis in HESCs and HEGCs though an increase in gap junction permeability in vitro, which is achieved through the upregulation of Cx43 expression and the translocation of serine 255 phosphorylated Cx43 from the plasma to the nuclear compartment.