Soo Jin Chae

Clinical and biochemical characteristics of polycystic ovary syndrome in Korean women

BACKGROUND We investigated the differences in anthropometrical, hormonal and insulin resistance parameters according to the subtype of polycystic ovary syndrome (PCOS) in Korean women. METHODS We recruited 166 women with PCOS and retrospectively recruited 277 controls. PCOS was diagnosed by irregular menstruation (IM), polycystic ovary (PCO) and hyperandrogenism (HA). Subjects were divided into four subgroups: the IM/HA/PCO group (n = 87, 52.4%), the IM/PCO group (n = 52, 31.3%), the IM/HA group (n = 23, 13.9%) and the HA/PCO group (n = 4, 2.4%). Clinical and biochemical variables were compared among the PCOS subgroups. RESULTS The IM/HA/PCO and IM/HA groups showed higher body mass index (P < 0.001) and waist-to-hip ratio (P < 0.001) than the IM/PCO group. The IM/HA group had higher triglyceride levels than the other groups (P < 0.001). Higher fasting insulin (P < 0.001) and postprandial 2 h insulin (P < 0.01) were noted in the IM/HA/PCO group and the IM/HA group, compared with the IM/PCO group. Women with PCOS showed lower sex hormone-binding globulin (P < 0.001) and higher systolic blood pressure (BP) (P = 0.004), diastolic BP (P = 0.001), fasting insulin (P < 0.001), postprandial 2 h insulin (P < 0.001), homeostatic model for insulin resistance (P < 0.001) and clinical and biochemical parameters of metabolic syndrome (P < 0.05) compared with subjects without PCOS. CONCLUSIONS Women with PCOS without HA are common in Korea and are less likely to have metabolic dysfunction, insulin resistance and elevated BP. PCOS without HA may be a mild phenotype of PCOS. Therefore, women with PCOS in Korea could have a reduced likelihood of having metabolic syndrome compared with women of other ethnicities.

Assessment of hirsutism among Korean women: results of a randomly selected sample of women seeking pre-employment physical check-up

BACKGROUND The objectives of this study were to define the distribution of the modified Ferriman-Gallwey (mF-G) score in a random group of Korean women and to study any association(s) between hirsutism and endocrine/metabolic markers. METHODS A single investigator assessed the mF-G score prospectively in 1010 Korean women, who consulted a health-care center as part of a group check-up for employment. Logistic regression models were utilized to test the relationships between the presence of hirsutism and levels of endocrine/metabolic markers. RESULTS Subjects had mF-G scores ranging from 0 to 19, and 505 subjects (50.0%) had an mF-G score of zero. Of the 1010 subjects, 95.1% had a score at or below six; thus, a score of six or greater represented hirsute women in our population. The most frequently affected site was the upper back, but the most densely affected area was found to be the lower abdomen. Hirsutism was significantly and positively associated with serum levels of total testosterone (T) and hemoglobin A1(c), but negatively associated with those of sex hormone binding globulin (SHBG). In addition, the odds of a woman developing hirsutism were higher for increased total T and HbA1(c), and lower for decreased SHBG. Hirsutism and homeostatic model assessment for insulin resistance were positively associated, but the relationship was not significant after adjusting for age and BMI. CONCLUSIONS mF-G scores greater that six represent the appropriate diagnostic cutoff for the detection of hirsutism in Korean women. Increased serum total T and HbA1(c,) and decreased SHBG concentrations were associated with the presence of hirsutism.

ORIGINAL ARTICLE: Tumor Necrosis Factor (TNF)–TNF Receptor Gene Polymorphisms and Their Serum Levels in Korean Women with Endometriosis

Problem  The aim of this study was to investigate the relationship between the polymorphisms of the tumor necrosis factor‐α (TNF‐α) and TNF receptor (TNFR) genes and serum levels of TNF‐α and its soluble receptor (sTNFR) in Korean women with endometriosis.

An efficient and reliable DNA extraction method for preimplantation genetic diagnosis: a comparison of allele drop out and amplification rates using different single cell lysis methods.

OBJECTIVE To evaluate methods of DNA extraction from single cells for their suitability to amplify and provide a correct diagnosis of target disease genes. DESIGN Experimental study. SETTING University hospital laboratory. PATIENT(S) Two normal adult male and female blood donors. INTERVENTION(S) Exon 51 of the dystrophin gene and the ZFX/ZFY gene were amplified from single lymphocytes using nested PCR. Five different methods of DNA extraction were tested (lysis in distilled water with freezing and thawing using liquid nitrogen, lysis in distilled water, alkaline lysis buffer, Proteinase K/sodium dodecyl sulfate (SDS) buffer, and N-lauroylsarcosine salt solution). MAIN OUTCOME MEASURE(S) Allele drop out and amplification rate. RESULT(S) The amplification efficiency from single unaffected lymphocytes was 89.0% using the liquid nitrogen method, 88.1% with the distilled water lysis method, 97.5% with the alkaline lysis buffer method, 91.5% with the Proteinase K/SDS lysis buffer method, and 84.8% using the N-lauroylsarcosine salt solution method. The mean allele drop out rate was 16.7%, 43.9%, 2.0%, 9.8%, and 18.9%, respectively, for each lysis method using single male lymphocytes as a template. CONCLUSION(S) Based on these results, DNA extraction using an alkaline lysis buffer results in more efficient rates of DNA amplification and less allele drop out than the other methods of DNA extraction tested. This method is suitable for the lysis of single cells in clinical preimplantation genetic diagnosis.

Polycystic ovary syndrome is not associated with polymorphisms of the TCF7L2, CDKAL1, HHEX, KCNJ11, FTO and SLC30A8 genes

Insulin resistance is a core feature of polycystic ovary syndrome (PCOS). Recently, genome‐wide association studies have reported a number of single‐nucleotide polymorphisms (SNPs) with reproducible associations and susceptibilities to type 2 diabetes. We examined the potential association between the diabetogenic genes uncovered in the genome‐wide association studies and PCOS in Korean women.

Vitamin D deficiency in women with polycystic ovary syndrome.

Objective To investigate: the prevalence of vitamin D deficiency in Korean women with polycystic ovary syndrome (PCOS), and the relationship between vitamin D status and clinical or metabolic features in this group. Methods We recruited 38 women with PCOS using the Rotterdam criteria. A total of 109 premenopausal control women were matched with patients based on age and body mass index. Serum 25-hydroxy vitamin D concentrations less than 20 ng/mL were classified as frank vitamin D deficiency. Since vitamin D may play a significant role in metabolic disturbances in women with PCOS, correlations between clinical or metabolic parameters and vitamin D status were analyzed separately in patients and controls. Results Women with PCOS showed no differences in the level of 25-hydroxy vitamin D (19.6±6.6 ng/mL in patients vs. 20.1±7.4 ng/mL in controls, respectively, p=0.696) or prevalence of vitamin D deficiency (57.9% in patients vs. 56.5% in controls, respectively, p=0.880). In addition, we did not find any correlations between serum vitamin D level and clinical or metabolic profiles in either PCOS patients or controls. Conclusion Our study found no differences in the absolute level of serum vitamin D between PCOS patients and matched controls. Prevalence of vitamin D deficiency was equally common among both patients and controls. Additionally, we did not find any correlations between serum vitamin D level and clinical or metabolic profiles, suggesting that the role of vitamin D in the pathogenesis of PCOS is not yet clear.

Complete phenotypic and metabolic profiles of a large consecutive cohort of untreated Korean women with polycystic ovary syndrome.

OBJECTIVE To investigate the complete metabolic and phenotypic profiles of a large cohort of untreated, consecutively recruited Korean women with polycystic ovary syndrome (PCOS), for whom a registry for Korean women with PCOS was constructed. DESIGN Observational study. SETTING Three infertility clinics and 10 university hospitals. PATIENT(S) Eight hundred sixty-five women with PCOS were recruited using the Rotterdam criteria. INTERVENTION(S) Standardized evaluation protocol and web-based case report form. MAIN OUTCOME MEASURE(S) Metabolic and phenotypic profiles. RESULT(S) The subjects with PCOS mainly consisted of young and nonobese women. The most problematic subjective symptom was menstrual disturbance or infertility, and, on average, the patients seemed to menstruate every 2 months. PCO morphology was observed in 96.5% of the patients. Although few women visited hospitals owing to HA symptoms alone, hirsutism was observed in one-third of the patients (33.9%) and half (47.4%) of the patients had biochemical HA. About one-fifth (20.1%) of the patients had generalized obesity, and one-third (33.2%) had central obesity. Prevalence of dyslipidemia, diabetes, hypertension, and metabolic syndrome were 35.7%, 3.5%, 4.0%, and 13.7%, respectively. Prevalence of prediabetes was 20.8%, and a substantial proportion of additional subjects with normal fasting plasma glucose or oral glucose tolerance tests were identified as having prediabetes by hemoglobin A1C testing. CONCLUSION(S) Our well-defined cohort provided comprehensive estimates of the features of metabolic and phenotypic profiles related to PCOS in Korean women. Further longitudinal follow-up studies are needed to investigate the changes in phenotypic and metabolic markers in this PCOS cohort.

Peroxisome Proliferator-Activated Receptor-γ and Its Coactivator-1α Gene Polymorphisms in Korean Women with Polycystic Ovary Syndrome

Background/Aims: To investigate whether the peroxisome proliferator-activated receptor-γ (PPAR-γ) Pro12Ala and the PPAR-γ coactivator-1α (PGC-1α) Gly482Ser polymorphisms were associated with polycystic ovary syndrome (PCOS). Methods: Genetic analyses of the PPAR-γ Pro12Ala and the PGC-1α Gly482Ser polymorphisms were performed in 184 patients with PCOS and 256 controls. Hormone levels, biochemical and clinical features were analyzed according to these polymorphisms. Results: Neither the PPAR-γPro12Ala nor the PGC-1α Gly482Ser polymorphism showed significant differences in genotypic distribution between women with PCOS and controls. In PCOS patients, women with the non-Pro/Pro genotypes of the PPAR-γ Pro12Ala polymorphism showed statistically significantly higher HDL levels than those with the Pro/Pro genotype (p = 0.002). PCOS patients who had the Ser/Ser genotype of the PGC-1α Gly482Ser polymorphism had significantly higher levels of postprandial 2-hour insulin than those with the Gly/Ser genotype (p = 0.045). Conclusions: Neither the PPAR-γPro12Ala nor the PGC-1α Gly482Ser polymorphism were supposed to be susceptible genes in PCOS. However, in PCOS patients, the PPAR-γPro12Ala and the PGC-1α Gly482Ser polymorphism may modulate the concentrations of serum HDL levels and postprandial 2-hour insulin level, respectively.

Effects of insulin-sensitizing agents and insulin resistance in women with polycystic ovary syndrome

Objective The aim of this study was to investigate the effect of insulin sensitizing agents on hormonal and metabolic parameters as well as menstrual patterns in women with polycystic ovary syndrome (PCOS). Methods One hundred and twenty-three patients with PCOS were included. Metformin was administered to patients at 1,500 mg or 1,700 mg daily for 3 months. If the patients had no improvement of the menstrual cycle or metformin-related adverse effects developed, the patients changed medication to a daily dose of either 15 mg pioglitazone or up to 45 mg. Then resumption of a regular menstrual cycle or recovery of ovulation was evaluated. Hormonal and metabolic profiles were compared between the response and non-response group to insulin sensitizing agents. Results One hundred and five patients with PCOS were treated with metformin for 3 months. Forty-eight patients (45.7%) showed improvement of menstrual cycle regularity after 3 months of metformin use, whereas 57 patients (54.3%) had no change. The mean free testosterone measured after 3 months of treatment was significantly lower in metformin responders than in non-responders. The other parameters did not differ between the groups. Of the 23 patients who used pioglitazone for 3 to 6 months, 19 patients (82.6%) showed improvement in their menstrual cycles. Conclusion Metformin treatment seems to be effective for the improvement of menstrual cyclicity irrespective of insulin resistance in women with PCOS. When metformin related adverse effect occurred, pioglitazone would be effective for aiding the resumption of the menstrual cycle.

Prevalence of metabolic syndrome is higher among non-obese PCOS women with hyperandrogenism and menstrual irregularity in Korea.

Background Hyperandrogenism (HA) has been linked with several components of metabolic syndrome (MetS). Few studies in Asian women have evaluated the important risk factors for and prevalence of MetS according to PCOS subtype. In this study, we investigated differences in metabolic parameters and the prevalence of MetS in two major phenotypic subgroups of PCOS in Korea. Furthermore, we investigated the relationship between HA-associated parameters and MetS. Materials and Methods This cross-sectional observational study was conducted from May 2010 to December 2011 in Korea. A total of 837 females with PCOS, aged 15–40, were recruited from Departments of Obstetrics and Gynecology at 13 hospitals. Of those, 700 subjects with either polycystic ovaries (PCO)+HA+oligomenorrhea/amenorrhea (O) or PCO+O were eligible for this study. MetS was diagnosed according to the modified National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines and the International Diabetes Federation (IDF) criteria. Results MetS was more prevalent in the PCO+HA+O group (19.7%) than in the PCO+O (11.9%) group. There were statistically significant trends for an increased risk of MetS in the PCO+HA+O group compared to the PCO+O group. After adjustment for age, the odds ratio of MetS was 2.192 in non-obese subjects with PCO+HA+O compared to those with PCO+O, whereas the risk of MetS was not different in obese patients. Multivariate logistic regression analysis showed that high free androgen index and low sex hormone-binding globulin were significantly associated with MetS in non-obese women with PCOS, with odds ratios of 4.234 (95% CI, 1.893–9.474) and 4.612 (95% CI, 1.978–10.750), respectively. However, no associations were detected between MetS and SHBG and FAI in obese PCOS subjects. Conclusions Our results indicate that HA and its associated parameters (FAI and SHBG) are significantly associated with MetS in non-obese PCOS subjects, whereas this association was not observed in obese subjects.