Association between Biomarkers of Low-grade Inflammation and Sex Hormones in Women with Polycystic Ovary Syndrome.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) have higher circulating levels of C-reactive protein, but the relationship between inflammation and endocrine function in PCOS remains poorly understood. Thus, this study aimed to investigate the association between low-grade inflammation and sex hormones in women with PCOS. DESIGN AND PATIENTS: A comprehensive panel of biomarkers of inflammation was measured in serum of 63 women with PCOS using proximity extension assay technology. Associations of 65 biomarkers with sex hormones were assessed without and with adjustment for age and body mass index (BMI). RESULTS: In the unadjusted analysis, 20 biomarkers were positively correlated with 17-OH-progesterone (17-OH-P), 14 with prolactin and 6 with free testosterone, whereas inverse associations were found for 16 biomarkers with sex hormone-binding globulin (SHBG), 6 with luteinizing hormone (LH) and 6 with estrogen (all p<0.05). Among the positive associations, correlations were mainly found for five chemokines (CXCL11, CCL4, MCP-4/CCL13, CXCL5, CXCL6) and for VEGF-A, LAP-TGFß1, TNFSF14 and MMP-1. Inverse associations with sex hormones were mainly present for two chemokines (CXCL1, MCP-2/CCL8), CDCP1, CST5 and CSF-1. Adjustment for age and BMI reduced the number of biomarker associations for SHBG and estrogen, but had hardly any impact on associations with 17-OH-P, prolactin, free testosterone and LH. CONCLUSION: Women with PCOS feature BMI-independent associations between biomarkers of inflammation and certain sex steroid and hypophyseal hormones. Most of these inflammation-related biomarkers were chemokines, which may be relevant as potential mediators of the increased cardiometabolic risk of women with PCOS.

The influence of thyroid disorders on bone density and biochemical markers of bone metabolism.

Background Thyroid dysfunction, predominantly hyperthyroidism, has been previously linked to impaired bone mass density (BMD) and increased risk of fractures. On the other hand, data in the field of hypothyroidism (HT) are missing. The purpose of the present study was to investigate the impact of thyroid disorders on bone density serum and urine calcium (Ca) and phosphate (P) as well as serum osteocalcin and alkaline phosphatase and urine hydroxyproline in a series of post-menopausal women. Materials and methods The study was conducted in the Reproductive Endocrinology Outpatient Clinic of our hospital. A consecutive series of post-menopausal women was included, after excluding patients under hormone treatment (including levothyroxine supplementation) and those who received raloxifene, tamoxifen or tibolone during the study period as well as those who received treatment during the previous 12 months were excluded from the present study. Results Overall, 188 women were included in the present study. Among them, 143 women had normal thyroid function, 32 women had hyperthyroidism and 13 women had HT. Correlation of thyroid function indices with osteoporosis indices revealed statistically significant correlations between thyroxine (T4) and free triiodothyronine (T3) with T-, Z-scores and BMD. Logistic regression analysis concerning the impact of HT and hyperthyroidism on T-score, Z-score and bone mass density revealed that both pathological entities negatively affect bone health (p < 0.05). Conclusion The findings of our study suggest that not only hyperthyroidism, but also HT negatively affects BMD. Future studies should investigate this association and corroborate our findings.

Correlation of platelet to lymphocyte and neutrophil to lymphocyte ratio with hormonal and metabolic parameters in women with PCOS.

Background The purpose of our study is to evaluate the association of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) with hormonal and metabolic parameters in patients with polycystic ovarian syndrome (PCOS) in order to assess whether these ratios may become useful tools during the evaluation of the severity of low grade inflammation. Methods The present study is based in secondary outcomes from a prospectively collected patient database. A total of 266 women with PCOS participated in this study and blood a complete blood count examination (CBC) that was used for the calculation of PLR and NLR was available in 182 patients. Results Association statistics revealed that PLR had a significant correlation to 17-OH progesterone (r = -0.177, p = 0.024) and Matsuda index values (r = 0.234, p = 0.009), whereas NLR was correlated with follicle stimulating hormone (FSH) (r = -0.204, p = 0.007), free testosterone (r = 320, p < 0.001), Δ4-androstendione (r = 0.234, p = 0.003), sex hormone binding globulin (SHBG) (r = -0.350, p < 0.002) and high-density lipoprotein (HDL) (r = -0.171, p = 0.039). Conclusion According to the findings of our study, both PLR and NLR seem to be correlated with some hormonal and metabolic indices. This association is clearer in the case of NLR and serum androgens as it seems to be positively affected by their levels. PLR and NLR were not affected by the presence of obesity.

The impact of mild hypercholesterolemia on glycemic and hormonal profiles, menstrual characteristics and the ovarian morphology of women with polycystic ovarian syndrome.

Background The severity of polycystic ovarian syndrome (PCOS) has been clearly associated with insulin resistance, obesity and metabolic syndrome. The purpose of the present cross-sectional study is to investigate whether mild hypercholesterolemia alters the biochemical and clinical profile of PCOS patients. Methods Our study is based on a prospectively collected population of women of reproductive age who were diagnosed with PCOS according to the definition of the Rotterdam European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ASRM/ESHRE) criteria. For the correlation analysis we used the non-parametric Spearman's rank correlation coefficient. Partial correlation was also performed to control for potential confounders observed in the univariate analysis. Results Overall, 235 patients were included. Their mean age ranged between 14 and 45 years old and the body mass index (BMI) between 17 and 54. Women with mild hypercholesterolemia had a higher BMI and their fasting insulin was increased as well as indices of insulin resistance [Homeostatic model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), Matsuda index] compared to women with PCOS with normal cholesterol levels. Correlation statistics suggested that the effect of serum lipids on the hormonal profile of patients was weak. Both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) exerted a significant mild negative correlation to glucose and insulin. However, after controlling the results for BMI and age (the two variables that were found significantly different in the univariate analysis) we observed that this effect was non-significant. Conclusion Mild hypercholesterolemia does not affect the hormonal profile of patients with PCOS; hence, to date, there is no evidence to suggest its treatment for the correction of menstrual and hormonal abnormalities in PCOS women.

Dehydroepiandrosterone-Sulfate, Insulin Resistance and Ovarian Volume Estimation in Patients With Polycystic Ovarian Syndrome.

Objective: To investigate the potential association of DHEA-S with metabolic and hormonal alterations and with disorders of ovarian morphology. Materials and methods: The present study was based on women with PCOS that attended the Gynaecological Endocrinology - Paediatric and Adolescence Endocrinology Department of our clinic. Overall, 321 patients who met the Rotterdam ESHRE/ ASRM - Sponsored criteria for the definition of PCOS were included. Women's personal medical history was recorded, anthropometric parameters were assessed and blood was drawn for analysis of metabolic and hormonal parameters. A gynaecological ultrasound was also performed to evaluate ovarian morphology. Results: Correlation analysis revealed a significant negative correlation of DHEA-S with the mean volume of the right and left ovary and with the maximum volume of the largest ovary. This finding remained significant after adjusting for age and BMI (ß ± SE = -0.39 ± 0.17, p = 0.023 in the case of mean ovarian volume and ß ± SE = -0.36 ± 0.17, p = 0.032 in the case of the maximum volume of the maximum ovarian volume). Conclusion: The findings of our study reveal a clear negative association of DHEA-S with ovarian volume. To date, however, current evidence in this field are restricted to experimental animal models. Future clinical studies are needed in this field to corroborate our findings.

The impact of the metabolic syndrome on bone mass density: a prospective case control study.

Background Obesity and metabolic syndrome (MetS) during the perimenopausal period and in menopause have been linked to altered bone mass density (BMD) in various experimental studies. However, current clinical studies provide conflicting results in this field. The purpose of the present study was to evaluate this association. Materials and methods We conducted a prospective case control study that was based on a consecutive series of menopausal women who attended the Reproductive Endocrinology Outpatient Clinic of our hospital between January 2013 and December 2016. Results One hundred and forty post-menopausal women were included in the present study. After stratifying the women in two groups according to the presence of MetS we observed that bone turnover markers remained unaffected by the presence of MetS (p > 0.05). On the other hand, both the T- and Z-scores of women with MetS were significantly higher compared to healthly postmenopausal women [T-score: 0.4 (-0.7 to 1.3) vs. -1 (-1.62 to -0.1), p < 0.001] [Z-score: 0.55 (-0.3 to 1.7) vs. -0.4 (-1.1 to 0.4), p = 0.003]. Conclusions According to the findings of our study the presence of MetS during the perimenopausal years seems to have a mild benefit on bone mass density. The pathophysiology that underlies this effect remains unclear as bone turnover markers seem to be unaffected by MetS.

Subclinical hypothyroidism does not influence the metabolic and hormonal profile of women with PCOS.

Background Subclinical hypothyroidism (SCH) is present in 5%-10% of polycystic ovary syndrome (PCOS) patients. To date, its impact on the metabolic and hormonal profile of those women remains controversial. The purpose of our study is to evaluate the impact of SCH on the glycemic, lipid and hormonal profile of PCOS patients. Materials and methods We conducted a prospective case control study of patients that attended the Department of Gynecological Endocrinology of our hospital. Results Overall, 280 women with PCOS were enrolled during a time period of 7 years (2009-2015). Twenty-one patients (7.5%) suffered from SCH. The anthropometric characteristics were comparable among women with PCOS and those with SCH + PCOS. The prevalence of acne, hirsutism and anovulation did not differ. Significant differences were observed in the 2-h oral glucose tolerance test (OGTT) (p = 0.003 for glucose and p = 0.046 for insulin). The QUICKI, Matsuda and homeostatic model assessment-insulin resistance (HOMA-IR) indices where, however, similar. No difference in serum lipids was observed. Slightly elevated levels of follicle stimulating hormone (FSH) and testosterone were noted. The remaining hormonal parameters remained similar among groups. Similarly, the ovarian volume and the endometrial thickness did not differ. Conclusions The impact of SCH on the metabolic and hormonal profile of PCOS patients seems to be negligible. Future studies are needed in the field and their conduct in a multi-institutional basis seems to be required, given the small prevalence of SCH among women with PCOS.

The effect of Vitamin D supplementation on hormonal and glycaemic profile of patients with PCOS: A meta-analysis of randomised trials.

BACKGROUND: Vitamin D deficiency is frequently manifested in women with polycystic ovarian syndrome (PCOS). To date, supplementation of deficient patients has not been correlated with the hormonal and metabolic status of these patients. PURPOSE: We aimed to investigate the impact of vitamin D supplementation on the hormonal and metabolic profile of PCOS women. MATERIALS AND METHODS: We searched Medline, Scopus, ClinicalTrials.gov and Cochrane Central Register databases for published randomised controlled trials. The meta-analysis was performed with the RevMan 5.3.5 software. RESULTS: Nine studies were included in the present meta-analysis which investigated the impact of vitamin D supplementation in 647 patients. According to our meta-analysis neither serum testosterone (MD 0.04 ng/mL, 95% CI -0.09 to 0.17) nor serum LH (MD -0.48 IU/mL, 95% CI -1.97 to 1.00) were significantly affected by vitamin D supplementation in any of the subgroup comparisons. On the contrary, serum DHEAS was significantly affected by vitamin D (MD -32.24 µg/dL, 95% CI -32.24 to -14.01) an effect which was mainly affected by the vitamin D vs placebo comparison. Vitamin D supplementation did not have an impact on fasting glucose (MD 0.42 mg/dL, 95% CI -2.75 to 3.60) or fasting insulin (MD 1.27 µU/mL, 95% CI -1.42 to 3.97) levels. HOMA-IR was, however, increased among patients that received placebo compared to vitamin D (MD 0.52, 95% CI 0.39-0.65). CONCLUSION: There is no evidence to support that vitamin D supplementation significantly benefits PCOS patients. However, given the relatively small number of enrolled patients further studies are needed to elucidate this field.

Hyperandrogenemia in women with polycystic ovary syndrome: prevalence, characteristics and association with body mass index.

BACKGROUND: Hyperandrogenemia is one of the major diagnostic features for the diagnosis of polycystic ovary syndrome (PCOS). The aim of this study was to estimate the prevalence and the characteristics of hyperandrogenemia in women with PCOS and to investigate the association of clinical and biochemical characteristics with body mass index (BMI) according to the presence of hyperandrogenemia. MATERIALS AND METHODS: We studied 266 women diagnosed with PCOS. Hyperandrogenemia was defined by testosterone (T) and/or free testosterone (FT) and/or ∆4 androstenedione (Δ4-A) higher than 75% of the upper limits of each hormone. Patients were stratified in two groups according to a BMI threshold of 25 kg/m2. RESULTS: Hyperandrogenemia was present in 78.2% of the patients. Elevated levels of T were found in 58.4%, while elevated levels of FT and Δ4-A were found in 42.5% and 34.1% of patients. In normal weight women (BMI≤25 kg/m2) with hyperandrogenemia lower values of hip circumference and HOMA-IR and increased levels of T, FT, Δ4-A, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), white blood cells (WBC) and neutrophils were observed compared to women without hyperandrogenemia. Also, in overweight women higher levels of T, FT, Δ4-A, 17-OHP, DHEAS and cortisol were measured, while lower thyroid-stimulating hormone (TSH) levels were comparable to women without hyperandrogenemia. CONCLUSION: This study showed high prevalence of hyperandrogenemia in PCOS women. Women with BMI≤25 kg/m2 have significant differences in androgens, WBC, neutrophils and HOMA-IR and women with BMI≥25 kg/m2 in androgens, TSH and cortisol according to the presence or not of hyperandrogenemia.

Clinical and Biochemical Characteristics in PCOS Women With Menstrual Abnormalities.

Objective: The purpose of the present study was to examine the impact of menstrual cycle abnormalities among patients with polycystic ovary syndrome (PCOS) on biochemical and anthropometric characteristics. Materials and methods: We conducted a prospective observational study of patients 17-35 years of age with PCOS that attended the department of Gynecological Endocrinology of our hospital. Results: A total of 309 women with PCOS participated in the study. In total, 72.2% suffered from menstrual cycle disorders. In our study 15.1% of women were overweight and 24% were obese. Also, 36% of the sample had androgenetic alopecia and 56.4% had acne. According to the stepwise discriminant analysis, we observed that glucose displayed the strongest association to the menstrual status (F to eliminate = 14.13), followed by endometrial thickness (F to eliminate = 10.89), waist circumference (F to eliminate = 10.17), LH levels (F to eliminate = 8.15) and PRL (F to eliminate = 4.45). Significantly higher levels of LH and TSH and lower levels of prolactin were found in women with menstrual disorders compared to those with normal menstrual cycles. Fasting glucose was also considerably higher among these patients although markers of insulin resistance such as the Matsuda, Quicki and HOMA-IR indices did not differ. Conclusion: According to the findings of our study PCOS patients with menstrual disorders exhibit hormonal alterations and elevated fasting glucose. Future studies are needed in this field to corroborate our findings and determine the anthropometric and biochemical profile of patients with menstrual cycle irregularities.

The amount and duration of smoking is associated with aggravation of hormone and biochemical profile in women with PCOS.

We investigated the association between the amount and duration of smoking on biochemical, clinical parameters and the ovarian morphology in women with polycystic ovary syndrome (PCOS). That was a retrospective study. These women were divided into two groups, non-smokers (217) and smokers (92). The amount of cigarettes and duration of smoking was measured in pack-years. Both groups underwent clinical evaluation, biochemical and hormone analysis, transvaginal ultrasound and oral glucose tolerance tests (OGTT). The mean value of the number of cigarettes was 14.8 (±8.8) and the median value of pack-years in the smokers group was 4.0 (1.5-7.5). Smokers group has significantly higher free testosterone (F-T), 17-hydroxyprogesterone (17-OHP), delta 4 androstenedione (Δ4-A), T4, low-density lipoprotein (LDL), and white blood cells (WBC). During correlation of all the above parameters and pack-years, there has been significant positive correlation in F-T and Δ4-A. The participants with more pack-years showed statistically higher values of F-T and Δ4-A. There was also a significant positive correlation between total cholesterol, triglycerides, WBC and pack-years of the participants. Prolactin (PRL) has been inversely associated with pack-years. We concluded that the increase of pack-years aggravated lipid profile, WBC and decreased PRL levels, in PCOS patients.

The contribution of sildenafil (Viagra) to ovarian stimulation with gonadotropins in a woman with poor ovarian response.

We aim to present the first case of a pregnancy achieved by administering sildenafil (Viagra) to a woman not responding to controlled ovarian hyperstimulation (COH) with the sole use of gonadotropins. A 37-year-old woman underwent COH, as part of an intracytoplasmic sperm injection (ICSI) cycle, with the combination of r-FSH and HMG for 13 d, without evidence of follicular growth. The addition of oral sildenafil at a dose of 50 mg per day for a total of five doses improved the ovarian response and resulted in the retrieval of 10 oocytes. Three embryos were transferred to the uterine cavity resulting in a successful pregnancy and, eventually, the delivery of a healthy neonate. Conclusively, the use of sildenafil as an adjunct to COH protocols may enhance ovarian response in a woman with poor ovarian response (POR) and merits further research.

Ovarian SAHA syndrome is associated with a more insulin-resistant profile and represents an independent risk factor for glucose abnormalities in women with polycystic ovary syndrome: a prospective controlled study.

BACKGROUND: SAHA syndrome is characterized by the tetrad: seborrhea, acne, hirsutism, and androgenetic alopecia. No previous study has examined the prevalence of glucose abnormalities in ovarian SAHA and explored whether it may be an independent risk factor for glucose abnormalities. OBJECTIVE: In a prospective controlled study, we investigated the spectrum of glucose abnormalities in ovarian SAHA and explored whether it is associated with a more insulin-resistant profile. METHODS: In all, 316 patients with a diagnosis of polycystic ovary syndrome (PCOS) (56 with SAHA) and 102 age-matched healthy women were examined and underwent a 2-hour oral glucose tolerance test. Serum glucose homeostasis parameters, hormones, and adipokines were determined. RESULTS: SAHA prevalence was 17.7% in patients with PCOS and predominance of the severe PCOS phenotype. Ovarian SAHA was independently associated with a more insulin-resistant profile (higher homeostatic model assessment of insulin resistance score, lower quantitative insulin sensitivity check index [QUICKI] and MATSUDA indices, and relative hypoadiponectinemia), and represented an independent risk factor for glucose abnormalities regardless of anthropometric features, age, and PCOS phenotype. LIMITATION: There was no performance of skin biopsies. CONCLUSION: The prompt recognition of SAHA syndrome in women with PCOS permits an earlier diagnosis and surveillance of metabolic abnormalities, especially in Mediterranean PCOS population exhibiting a lower prevalence of glucose abnormalities.

The prevalence of glucose metabolism abnormalities in Greek women with polycystic ovary syndrome.

The prevalence of glucose metabolism abnormalities in PCOS women worldwide varies between 10 and 40% but there are no data in Greek PCOS women. In this retrospective study the prevalence of glucose abnormalities and the indices of insulin resistance (IR) and whole-body insulin sensitivity were estimated in a Greek population with PCOS. Impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and type 2 diabetes mellitus (t2DM) were calculated. The prevalence of IGT, IFG and t2DM in our PCOS population was 7.6, 5.1 and 1.7%, respectively. The total prevalence of glucose abnormalities was estimated as 14.1%. The prevalence of t2DM was three- to four-fold higher than in the general Greek female population of the same age as this was estimated by 2, recently published studies. PCOS women with increased BMI and waist circumference and age greater than 30 years, present more severe IR and decreased whole-body insulin sensitivity. Our data indicates a relatively high prevalence of glucose intolerance and t2DM in a Greek population with PCOS. Obese women with PCOS are in higher risk to develop glucose abnormalities and probably t2DM later in life and therefore every woman diagnosed with PCOS should undergo a 2-h post load OGTT.

Infertility reversed by glucocorticoids and full-term pregnancy in a couple with previously undiagnosed nonclassic congenital adrenal hyperplasia.

OBJECTIVE: To report the case of a couple with infertility and two unsuccessful previous attempts of ovarian stimulation for in vitro fertilization (IVF), whose nonclassic congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (21-OHD) was diagnosed and verified by molecular studies. DESIGN: Case report. SETTING: Outpatient practice and academic hospital. PATIENT(S): A woman with hyperandrogenism, luteal phase deficiency, and polycystic ovaries, and a man with oligospermia, a high rate of abnormal forms of spermatozoa (>95%), decreased sperm motility, and normal testicular volume. INTERVENTION(S): Ultrasonography, semen analysis, endocrinologic assays, corticosteroids. MAIN OUTCOME MEASURE(S): Increased basal and adrenocorticotropic hormone (ACTH) stimulated 17α-hydroxyprogesterone (17-OHP) values were detected in both partners. CYP21A2 genotyping revealed compound heterozygosity in both wife and husband (wife: p.P30L/p.P453S; husband: p.P453S /p.V281L). RESULT(S): Hydrocortisone, 30 mg/day orally, was administered to both wife and husband. Forty days later, a pregnancy was detected. The prospective mother continued to receive hydrocortisone (25 mg/day) adjusted according to her hormone status. After a full-term uneventful pregnancy, a completely normal female was born. The baby had NC-CAH (genotype p.P30L/p.V281L). CONCLUSION(S): Nonclassic congenital adrenal hyperplasia, a potential cause of infertility in couples, can be successfully treated with corticosteroids.

Immune response parameters during labor and early neonatal life.

AIM: Selected cytokines, associated with Th1 and Th2 immune response and inflammation, were studied in order to evaluate the relation between their release into maternal and neonatal circulation, during labour, and after birth, in comparison with those in adults. MATERIALS AND METHODS: Cytokine concentrations were determined by very sensitive immunoassays, in maternal serum (MS), umbilical cord (UC), neonatal serum, the 1st (1N) and 5th (5N) day postpartum and in adult controls. RESULTS: Both IL-2 and IL-4 cytokine concentrations in UC were markedly elevated, compared to adult and MS ones. IL-2 decreased significantly in 5N, while IL-4 remained unchanged. IFN-gamma UC values were significantly lower than those in adults and MS, increasing significantly in 5N. Neonatal serum sIL-2R and sIL-4R were markedly higher than those in adults and MS. IL-1beta, IL-6, sIL-6R, sTNFRI and sTNFRII concentrations in MS and all with TNF-alpha in neonatal serum were significantly higher than in adults. IFN-gamma, IL-1beta, IL-6, TNF-alpha, IL-2R, IL-4R concentrations in MS, 1N and 5N were dependent on the mode of delivery. CONCLUSION: The results of this comparative study are indicative for a meaningful role for the studied cytokines and their receptors in: i) the development of neonatal immune system, ii) the regulation of immune response during labour and early life, and iii) the initiation of the processes of labour.

An update to 21-hydroxylase deficient congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme 21-hydroxylase (21-OH) is distinguished in classical (C-CAH) and non-classical form (NC-CAH), and it is also one of the most common autosomal recessive inherited disorders in humans. The prevalence of C-CAH is between 1:10,000 and 1:15,000 among the live neonates of North America and Europe while the NC-CAH occurs in approximately 0.2% of the general white population. The highest incidence of CAH (1:282 and 1:2141, respectively) has been evaluated in Yupik Eskimos in Alaska and in the populations of the island La Reunion (France), while the lower was detected in New Zealand newborns (0.3%). Nowadays, it has been established that except for the adrenal cortex in CAH cases, the adrenal medulla was also affected. In human 21-OH deficient adrenal gland it has been discovered that not only the chromaffin cells formed extensive neurites, expanding between adrenocortical cells, but also that the adrenal androgens promote outgrowth, whereas glucocorticoids preserve neuroendocrine cells. It seems that normal cortisol secretion by the adrenal cortex is necessary for adrenomedullary organogenesis. The synthesis of 21-OH is controlled by the active CYP21A2 gene located at a distance of 30 kb from a highly homologous pseudogene designated CYP21A1P.

Predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities.

OBJECTIVE: The study aimed to estimate the incidence of increased nuchal translucency in the first trimester ultrasound scan results (cut-off limit 2.5 mm) and to evaluate the predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities. METHODS: We used the ultrasound scan results of nuchal translucency evaluation and the results of chromosomal analysis of the invasive prenatal control performed as a result of increased nuchal translucency. RESULTS: We collected 2183 nuchal translucency ultrasound scans in which we detected 21 embryos with a pathologic value (0.96%). We collected the data of 168 cases of invasive prenatal control due to increased nuchal translucency from which 122 cases were found. A total of 122 cases of pregnant women undergone an invasive prenatal diagnostic method due to increased nuchal translucency, of which 11 fetuses were found with trisomy 21 (Down syndrome) (9%), 3 fetuses with trisomy 13 (Patau syndrome) (2.45%), 3 fetuses with monosomy 45XO (Turner syndrome) (2.45%) and 1 fetus with translocation (0.8%). CONCLUSIONS: The positive predictive value of the increased fetal nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities based on the results of the chromosomal-genetic analysis of the invasive prenatal diagnostic procedures is 14.8%.

Congenital adrenal hyperplasia because of 21-hydroxylase deficiency. A genetic disorder of interest to obstetricians and gynecologists.

Congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme 21-hydroxylase (21-OH), is distinguished in its classical and nonclassical form and is one of the most common autosomal recessive inherited diseases in humans. The classical form appears between 1:5000 and 1:15000 among the live neonates of North America and Europe, whereas the nonclassical form occurs in approximately 0.2% of the general white populations. Three alleles are associated with the 21-OH locus and can be combined in various ways to individuals who are either unaffected, heterozygote carriers, or affected with the classical or nonclassical disease. Variable signs and symptoms of hyperandrogenism are common to both types of the disorder. In women with CAH, hyperandrogenism may be present, extending from virilization of external genitalia and salt-wasting in classical (C)-CAH cases, to menstrual irregularity, obesity, short stature, infertility or subfertility and skin disorders such as hirsutism, in nonclassical (NC)-CAH cases. These clinical characteristics of NC-CAH cases do not differ unmarkedly from those shown in patients with polycystic ovary syndrome, idiopathic hirsutism, or hyperinsulinemia. The significant advances in molecular biology and gene analysis over the past 2 decades have led to the development of novel sensitive methods of DNA analysis and study, including polymerase chain reaction and Southern blot analysis. Thus it has been revealed that the 21-OH gene (CYP21A2) and its nonfunctional pseudogene (CYP21A1P) are located on chromosome 6 (6p21.3), sharing a high homology of about 98%. Inactivating mutations occur as complete gene deletions, large gene conversions and pseudogene-derived mutations.

The prevalence of non-classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Greek women with hirsutism and polycystic ovary syndrome.

UNLABELLED: The study was aimed to find out the prevalence of non-classical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (21-OHdef) among Greek women with hirsutism and polycystic ovary syndrome (PCOS) and to compare the results of ACTH stimulated 17-hydroxyprogesterone 60 min (17-OHP60) values, with human leukocyte antigens (HLA) phenotypes, in any patient diagnosed as having NC-CAH. One hundred and seven women with hirsutism and PCOS were included in the study. All were presented at the Reproductive Endocrinology Outpatient Clinic with hirsutism and PCOS. After ACTH stimulation test, 10 women were diagnosed as having NC-CAH because of high 17-OHP60 values >or=36 nmol/l, and 97 as having PCOS. Ten (10.3%) of the 97 women presented hormonal findings compatible with adrenal hyper-response due to ACTH testing, because of hyperstimulated 17-OHP60 values >or=21 nmol/l and <32 nmol/l. The HLA typing of 10 patients with NC-CAH revealed the phenotypes B14, DR1, B35, B7 and B44 which present positively genetic linkage disequilibrium with 21-OHdef, as reported in the literature. IN CONCLUSION: In Greek women with hirsutism and PCOS we have found that: a. The prevalence of NC-CAH among these women is relatively high and reaches at 10%. b. The HLA phenotypes B(14), DR(1), B(35), B(7) and B44 were found in high frequency in these NC-CAH patients. c. Adrenal NC-CAH due to 21-OHdef as well as adrenal hyperactivity, revealed after ACTH testing, constitutes an important reason of hirsutism and PCOS in these Greek women and both reach a rate of 20%.