Jin Ju Kim

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.

Androgen receptor gene CAG repeat polymorphism in women with polycystic ovary syndrome

OBJECTIVE To evaluate the role of the androgen receptor (AR) gene CAG repeat in women with polycystic ovary syndrome (PCOS). DESIGN Case control study. SETTING University department of obstetrics and gynecology. PATIENT(S) Women with (n = 114) or without (n = 205) PCOS. INTERVENTION(S) Peripheral blood sampling was done for DNA analysis and serum hormone measurements. MAIN OUTCOME MEASURE(S) CAG repeat length and serum androgen levels. RESULT(S) No statistically significant CAG repeat length differences were found between patients and controls. We conducted a detailed analysis after dividing PCOS patients according to their free testosterone levels. The high free testosterone group had a statistically significantly longer mean biallelic average (24.0 +/- 2.0 vs. 23.0 +/- 1.5), short (22.5 +/- 1.8 vs. 21.7 +/- 1.9), and long (25.5 +/- 2.9 vs. 24.4 +/- 1.9) allelic lengths than the normal free testosterone group. In PCOS patients, a statistically significant correlation was found between biallelic average length and free testosterone concentration, either unadjusted or after adjustment. CONCLUSION(S) The AR gene CAG repeat polymorphism may contribute to the serum concentration of free testosterone in PCOS patients. A subset of PCOS patients with relatively longer CAG repeats (less AR activity) tended to show a higher serum androgen concentration.

Estrogen receptor α gene polymorphisms in patients with idiopathic premature ovarian failure

BACKGROUND It has been reported that polymorphisms in the estrogen receptor (ER)-alpha gene (ESR1) may be associated with reproductive patterns of women. This study was performed to investigate whether the genetic polymorphisms of the ER-alpha gene are associated with idiopathic premature ovarian failure (POF) in a Korean population. METHODS The subjects were 126 idiopathic POF patients and 221 post-menopausal controls recruited from university hospitals between 1999 and 2004. Genotyping was performed by MGB primer/probe Taqman assay. Haplotypes were deduced by using the Haploview version 4.1. Bonferroni correction was applied for the correction of multiple testing. RESULTS There was no significant difference in the allele distribution of the ER-alpha gene (TA)n repeats between the POF and the control group. For the PvuII polymorphism, the POF group showed a higher frequency of TT genotype compared with the controls (41.3 versus 26.3%, P = 0.004, 98.75% CI 1.8-28.2%). No significant difference was found in the distribution of the XbaI polymorphism between the POF and the control group. Haplotype analysis showed that the frequency of TA haplotype was significantly higher in the POF patients compared with the controls (64.7 versus 52.7%, P = 0.002, 98.75% CI 2.4-21.6%). CONCLUSIONS These findings suggest that the ER-alpha gene polymorphisms may be associated with idiopathic POF.

Dyslipidemia in women with polycystic ovary syndrome

Dyslipidemia is a very common metabolic abnormality in women with polycystic ovary syndrome (PCOS). Insulin resistance is a key pathophysiology of PCOS, thus dyslipidemia in women with PCOS may be consistent with those found in an insulin resistant state. In recent meta-analysis, triglycerides and low-density lipoprotein (LDL) cholesterol levels were 26 mg/dL and 12 mg/dL higher, and high-density lipoprotein cholesterol concentration was 6 mg/dL lower in women with PCOS than those of controls. Alterations in LDL quality also have been reported in women with PCOS: women with PCOS have an increased proportion of atherogenic small dense LDL or decreased mean LDL particle size. However, in a recent Korean study, non-obese Korean women with PCOS had no significant quantitative or qualitative changes in LDL cholesterol profile. Lipoprotein (a) has been identified as an independent risk factor for coronary heart disease, and its elevation in PCOS patients has been consistently reported in diverse studies including non-obese Korean population. Some studies have investigated apolipoprotein (Apo) A-I and ApoC-I levels in women with PCOS and levels of ApoA-I, which has cardio-protective effects, were significantly lower in women with PCOS than those of controls. ApoC-I is known to increase the postprandial serum lipid level that is common in coronary artery disease patients, and one study reported that such an elevation may be the earliest variation of lipid abnormality in women with PCOS. In conclusion, women with PCOS should receive a complete lipid test, and lifestyle modification, including diet and exercise, is the first line therapy for all women with PCOS and is particularly important for those with dyslipidemia.

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.

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.

Type-specific prevalence of high-risk human papillomavirus by cervical cytology and age: Data from the health check-ups of 7,014 Korean women

Objective We investigated the type-specific high-risk human papillomavirus (HPV) prevalence and distribution according to cervical cytology and age in healthy Korean women. Methods A retrospective cross-sectional study was conducted with 7,014 consecutive subjects undergoing both liquid-based cervical cytology and HPV genotyping test by DNA chip for cervical cancer screening. The type-specific prevalence and distribution of individual high-risk HPV types were assessed according to cervical cytology and age groups (<30, 30-39, 40-49, 50-59, and ≥60 years old). Results In total, the most common HPV genotype was HPV58 (23.9% of all high-risk HPV-positive subjects), followed by HPV16 (21.8%), HPV52 (16.6%), and HPV18 (11.7%). Regarding cervical cytology and age groups, the proportion of HPV56 strongly increased with the increasing severity of cervical cytology (P for trend=0.041). An age-specific decline in the overall high-risk HPV prevalence was reaffirmed, and the proportion of HPV52 declined markedly with age (P for trend=0.014). Conclusion The type-specific prevalence of high-risk HPV types significantly varies according to cervical cytology and age. It may imply that these types have different to develop into precancerous lesions in normal cervix.

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.

X chromosome inactivation patterns in patients with idiopathic premature ovarian failure

BACKGROUND X chromosome aberrations have been reported as the cause of extremely skewed X chromosome inactivation (XCI). The purpose of this study was to investigate whether skewed XCI is associated with idiopathic premature ovarian failure (POF). METHODS The XCI status was evaluated in Korean women by the methylation assay of androgen receptor locus in 126 idiopathic POF patients (35.3 +/- 13.9 years old, mean +/- SD) and 126 age-matched controls (35.2 +/- 13.9 years). The incidence of skewed XCI in POF group was compared with that of control. The correlation between age and skewed XCI was also evaluated within both groups. RESULTS The incidence of extremely skewed XCI (>or=90%) was 3.9 versus 2.7% (P = 0.710) in POF and control group, respectively. No significant differences were found in the incidence of skewed XCI on all three levels (>or=90, >or=80 and >or=70%) compared between these two groups. The calculation of correlation coefficients showed that, in both POF and control group, there were no significant correlations between age and XCI ratio. Neither was there increasing tendency of skewed XCI according to the increase of age in both groups. Furthermore, there were no significant differences when the XCI ratios were analysed according to the age of onset of ovarian failure. CONCLUSIONS The incidence of skewed XCI in Korean POF population was not significantly different from control, implying that skewed XCI may not be associated with idiopathic POF. There were also no significant correlations between age and skewed X-inactivation patterns in both groups.