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Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among females. PCOS is associated with various metabolic and cardiovascular complications, including insulin resistance, dyslipidemia, and an increased risk of type 2 diabetes mellitus and cardiovascular disease. The role of serum prolactin (PRL) in the development of these complications in PCOS is not well understood., Aim: This study aims to investigate the correlation between serum PRL levels and metabolic and cardiovascular risk factors in Greek women with PCOS., Methods: The study utilized secondary outcomes from a prospectively collected patient database at the Third Department of Obstetrics and Gynecology, Medical School of the University of Athens. Data were collected from patients who visited the Gynecological Endocrinology - Pediatric and Adolescence Endocrinology Outpatient Clinic between January 2007 and December 2015. Measurements of various parameters, including PRL levels, BMI, waist circumference, hormone levels, lipid profiles, and insulin sensitivity, were obtained. Statistical analyses, including Mann-Whitney tests, chi-square tests, Spearman correlations, and multiple linear regression analyses, were conducted using SPSS software (IBM Corp., Armonk, NY, USA)., Results: The study included 247 women with PCOS, with a mean age of 24.7 years. Participants were divided into two groups based on the median PRL level. Women with higher PRL levels (>14.9) had lower BMI and waist circumference, higher levels of certain hormones and insulin sensitivity, and lower levels of fasting insulin, total cholesterol, and total lipids. Factors associated with lower PRL levels included being overweight/obese and smoking more than 10 cigarettes per day. Higher age, BMI, waist circumference, and certain hormone levels were associated with lower PRL levels., Conclusion: The findings suggest a correlation between serum PRL levels and metabolic and cardiovascular risk factors in Greek women with PCOS. Further research is needed to elucidate the role of PRL in the pathophysiology of PCOS and to explore its potential as a diagnostic and therapeutic target., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kastrinakis et al.)

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-TGFβ1, 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., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

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.

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.

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.

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.

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.

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., (© 2017 John Wiley & Sons Ltd.)

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 (β ± SE = -0.39 ± 0.17, p = 0.023 in the case of mean ovarian volume and β ± 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.

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.

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.

Purpose: The aim of this study was to estimate the prevalence, to evaluate the characteristics of the metabolic syndrome (MetS) in Greek women with polycystic ovary syndrome (PCOS) and to investigate the correlation of MetS with body mass index (BMI)., Methods: In a prospective controlled study, 230 Greek female patients with PCOS and 155 age-matched healthy controls were enrolled. Diagnosis of PCOS was based on the revised criteria of Rotterdam. Both groups were examined for MetS. Diagnosis of MetS was based on the revised criteria of International Diabetes Federation (IDF)., Results: The prevalence of the MetS was 12.6 %, nearly sevenfold higher than the controls. Elevated fasting plasma glucose (7.0 vs. 1.9 %) and elevated triglycerides (10.4 vs. 3.2 %) were more frequent in the PCOS cohort (p < 0.05). Women with PCOS presented statistically higher BMI in comparison with the controls (p < 0.001). Subsequently, the prevalence of MetS was estimated in three groups: normal, overweight and obese subdivided according to BMI. The latter two groups showed significant differences compared with the healthy controls (24.5 vs. 8.8 %, p = 0.050)., Conclusion: In conclusion, this study showed high prevalence of MetS and increased BMI in Greek PCOS women. In addition, it demonstrated the higher prevalence of MetS in obese PCOS women in comparison with the controls. These results are placing them at increased risk for cardiovascular disease and diabetes in the future and underline the necessity of periodic screening, appropriate diet and exercise program.

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.

Unlabelled: The purpose of this study was to investigate the of areas where the soil is contaminated by Toxocara ova and also to assess seroepidemiological positivity in a Greek pregnant women population (ELISA IgG test)., Materials and Methods: The authors carried out an examination of soil samples collected from different areas of Athens and Piraeus (Kazakos method). Blood serum was only collected from pregnant women living and conducting activities in places close to the places where the soil sample's were collected for at least a decade (ELISA IgG assay)., Results: The authors suggest a correlation between the positive response in the ELISA assay IgG antibodies and the activities of people where soil was contaminated by Toxocara eggs. In conclusion, the prevalence of Toxocara canis infection in a population of Greek pregnant women was found to be a rate of 17.16% and the soil contamination rate of 17.08%.

Women with polycystic ovary syndrome (PCOS) are often characterized by adiposity and insulin resistance (IR). Recent studies in patients with obesity and diabetes mellitus type 2 (DMt2) indicate that adiponectin and resistin may play a role in the pathophysiology of IR. The aim of this study was to identify a possible correlation between the plasma levels of adiponectin and resistin and IR in patients with PCOS. Thirty-one women of reproductive age were enrolled in this prospective study after being diagnosed with PCOS and IR according to Rotterdam and American Diabetes Association (ADA) criteria, respectively. Every patient was treated with a daily dose of 1275 mg metformin for 6 months. Adiponectin, resistin, and the primary hormonal and metabolic parameters of the syndrome were evaluated at entry and endpoint of treatment. Adiponectin plasma levels were reduced after metformin treatment, but resistin levels were not significantly affected. Our study suggests that circulating levels of adiponectin should be evaluated with skepticism in patients with PCOS. The adipokine's role in the manifestation of IR in PCOS remains unclear and needs further investigation.

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.

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., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Aim: To determine the prevalence and frequency of non classical congenital adrenal hyperplasia (NC-CAH) due to 21-OHD at the time of clinical presentation and at the peripubertal period in a substantial sample of Greek women with acne and to investigate the correlation of serum T, 17-OHP and DHEA-S with acne appearance at the time of clinical presentation., Methods: One hundred and twenty-three unselected women with hyperandrogenemic symptoms were examined. After the ACTH stimulation test, 6 (4.9%) women were diagnosed with NC-CAH due to 21-OHD., Results: There was not any statistical significant difference in the frequency of peripubertal acne between NC-CAH group of patients (6.4%) and patients with hyperandrogenemia of other aetiology (93%), mainly ovarian (P = 0.41). However, there was a statistical significant difference in the prevalence of acne at the time of clinical examination between the two groups (P = 0.04). Acne was present in 83.3% of women with NC-CAH vs. 41.02% of women in the hyperandrogenic group without NC-CAH. A statistically significant decrease of acne from the peripubertal time to the time of clinical examination in the group of women with hyperandrogenemia of other aetiology (-21.37%) was observed compared to women with NC-CAH (P < 0.001)., Conclusion: We have shown that acne persists from peripubertal period to adult life in NC-CAH women whereas it tends to diminish in women with hyperandrogenemia of other aetiology. Acne is a prominent finding in women with NC-CAH. Serum concentrations of 17-OHP after ACTH stimulation (17-OHP6O ) should be investigated in women with persistent acne in adult life., (© 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.)

Background: Hormone therapy (HT) is the treatment of choice for the alleviation of menopausal symptoms; concerns, however, about its concomitant long-term health risks have limited its use. DT56a is a unique enzymatic isolate of soybeans. The purpose of our study was to evaluate the efficacy and safety of DT56a, compared to HT, in symptomatic post-menopausal women., Subjects and Methods: Eighty-nine post-menopausal women were studied prospectively. Women with climacteric symptoms were randomly assigned to receive eitherDT56a (no.=27) or oral low dose continuous combined HT (no.=26). Symptomatic women not wishing to receive any treatment served as controls (no.=36). Menopausal symptoms as assessed through the Kupperman index, serum lipids and lipoproteins, calcium, as well as bone mineral density (BMD), endometrial thickness, and mammography were assessed at baseline and at 12 months., Results: Patients receiving HT and DT56a showed a significant and independent decrease in menopausal symptoms (mean difference in Kupperman score, DT56a group: -3.98, HT group -5.601, no treatment group +1.76, p-value <0.001). Lumbar spine BMD T-score was significantly lower in women receiving no treatment, as opposed to the two treatment arms which showed no significant change (No treatment, baseline: -0.60, final: -0.85, p=0.001; HT, baseline: -84, final -0.99, p=0.79; DT56a, baseline -0.51, final: -0.76, p=0.75). No differences in femoral bone density, ET or mammography classification were detected in any of the treatment arms. Likewise, serum lipids or lipoproteins did not differ between the three groups., Conclusions: DT56a decreased menopausal symptoms significantly and in the same degree as HT.

Objective: Recently, it has been debated whether the new polycystic ovary syndrome (PCOS) phenotypes, according to the Rotterdam criteria, share the same metabolic risk with the classic ones (National Institutes of Health 1990). Our study sought to compare the prevalence of metabolic syndrome (MS) and glucose homeostasis disorders in Greek women with classic and new PCOS phenotypes., Materials and Methods: Two hundred and sixty-six Greek PCOS women were recruited and divided into groups according to two of the three Rotterdam criteria that they fulfilled. Two subgroups were formed; the first represented the classic phenotypes and the second the new phenotypes. The clinical, biochemical, and ultrasound characteristics of both groups were explored. All subjects were evaluated for MS and underwent a 2-h glucose tolerance test to assess insulin resistance (IR) as measured by the homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and MATSUDA indices., Results: 62.4% of PCOS women were classified as classic NIH phenotypes of which 32 women had MS (prevalence 19.6%). Only 4 patients categorized in the newer phenotypic groups had MS (prevalence 4.1%). Among the subjects with classic phenotypes, 11.7% exhibited impaired glucose tolerance (3-fold higher percentage compared to patients with newer phenotypes). Regarding IR indices, HOMA-IR was significantly higher and QUICKI significantly lower for classic phenotypes., Conclusions: Greek PCOS women with classic phenotypes are at increased risk for MS and impaired glucose homeostasis compared to women with newer phenotypes. A subclassification of PCOS permits the earlier recognition and closer surveillance of women whose metabolic profile indicates potential risks for adverse health outcomes.

Background: Since 2003, when the American Society for Reproductive Medicine (ASRM) and European Society of Human Reproduction and Embryology (ESHRE) sponsored consensus established criteria for polycystic ovarian syndrome (PCOS) diagnosis, the phenotypic spectrum of the syndrome has been significantly broadened., Purpose of the Study: This survey makes an effort to distinguish PCOS according to phenotypic expression and to estimate its prevalence in a Greek population., Materials and Methods: Greek women from 18 to 35 years of age, who visited the outpatient department, claiming either irregular menstruation (oligo- or anovulation, OA) or clinical manifestations of hyperandrogenemia (HA) were recruited. They gave full disease history and underwent clinical examination, including transvaginal ultrasound (TVUS) scan to identify PCO morphology. Blood samples were collected to perform hormonal and metabolic analyses. Acute or chronic disorders were excluded. Finally, 266 PCOS women constituted the study population., Conclusions: The full-blown phenotype (HA+OA+PCO) is the predominant phenotype in this Greek population.

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.

Objective: To present a case of a young woman with ovarian endometrioid adenocarcinoma arising from an endometriotic cyst and review of the literature., Case Report: A 33-year-old woman, gravid 2, para 2 was admitted to our department with a 5 cm adnexal mass. Diagnostic laparoscopy was performed and pathological examination demonstrated an endometriotic cyst with an area of an ovarian endometrioid adenocarcinoma well differentiated, with no capsular invasion. One month after the operation the patient underwent MRI which revealed a 6 cm mass in the Douglas pouch. The multidisciplinary oncology council decided on exploratory laparotomy, which revealed no pathology. After that the multidisciplinary oncology council decided on adjuvant chemotherapy and the patient received four cycles of carboplatin/taxol., Conclusion: It should always be considered that even when there are no risk factors for malignancy occurrence, a high index of suspicion is necessary and will help to prevent delay in the diagnosis of this rare neoplasm.

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., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Women with polycystic ovary syndrome (PCOS) may have increased cortical bone mineral density (BMD) and probably higher bone material quality as well as better resistance in the compression strength of the tibia, measured by peripheral quantitative computed tomography (pQCT), in comparison with that of age-matched healthy subjects., Methods: Thirty women with PCOS, (15 lean and 15 obese) and 15 age-matched healthy controls were enrolled in this study. The clinical, biochemical and ultrasound characteristics of the two groups were evaluated. Using pQCT, the following parameters were measured: volumetric cortical density (CBD) and volumetric trabecular density (TBD) BMD, total bone cross-sectional area (ToA), cortical area (CoA), cortical thickness (CRT-THK-C) and finally the strength-strain index (SSI)., Results: The geometrical parameters (CoA, ToA, CRT-THK-C), the SSI as well as the TBD were increased in the PCOS women; however, these differences did not achieve statistical significance between lean PCOS women, obese PCOS women, and controls. Conversely, CBD was significantly higher in PCOS women compared with controls (P < 0.000) and furthermore in lean PCOS women compared with obese ones (P < 0.01040)., Conclusions: The PCOS women of our study seem to have a higher quality of bone material in the distal tibia and probably a better resistance of bone in the compression strength without alterations in bone mass and geometry (especially the lean PCOS women), indicating that our oligomenorrheic and hyperandrogonemic PCOS women may be protected from the development of osteoporosis and fracture risk later in life.

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.

Background: Radioactive iodine has been used effectively in the diagnosis and treatment of thyroid diseases. Since radiation is delivered to the whole body, including the ovaries, there is reasonable concern as to whether there is a possibility of mutagenic effect on germ cells., Case Report: A 33-year-old woman with a differentiated papillary carcinoma. (T2N0M0), underwent radiotherapy three weeks after surgery and one year afterwards she became pregnant. At the 38th week of gestation she delivered vaginally a healthy female neonate weighing 3100 g. The child at the age of five years is healthy with no signs of malignancy or other disease., Discussion: Washout of 131I of the whole body takes place in a few days. Nevertheless, most guidelines recommend avoiding pregnancy for four to six or even 12 months after RAI treatment or scanning. As reported in our case a normal uncomplicated pregnancy can follow an operative and complementary treatment of thyroid cancer.

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.

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 (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.

Young, normotensive, and non-obese women with polycystic ovary syndrome (PCOS) may present abnormal hemodynamic alterations (HA). The purpose of this study was to investigate heart rate (HR), intima-media thickness (IMT), and diameter (DCCA) in the common carotid arteries (CCA), flow velocities, and resistance index in both extracranial carotid and vertebral arteries (VA), in the abdominal aorta (AO) and in the renal arteries (RA) in PCOS women and matched controls. This was a case-control study conducted at a tertiary University Hospital. We studied 53 PCOS women and 53 healthy matched volunteers as controls. The previously reported parameters were assessed using color Doppler ultrasonography. HR, IMT in the CCA, and peak systolic velocity in all examined arteries were significantly increased in PCOS women compared to controls. On the contrary, DCCA was significantly decreased in PCOS women compared to controls. End diastolic velocity (EDV) in both VA and RA, in the AO and in the left extracranial carotid system was significantly increased in the PCOS group compared to controls. Furthermore, the peripheral resistance (PR) of AO and right external carotid artery was also found to be increased while in both RA and in left VA, PR was decreased. No further statistical significant HA in EDV and PR were noted. The results of this study provide evidence for a mild hyperdynamic circulation in young, normotensive, non-obese women with PCOS compared to controls, indicating a mild sympathetic activation at an early age, which may be an underlying cause of hypertension and cardiovascular risk.

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%.

In young members of a large family from a Greek island with a closed society, clinical and hormonal symptoms of 21-OH deficiency (CAH) were present. To discriminate those affected from those unaffected, we measured the basal and ACTH stimulated 30 values of 17-hydroxyprogesterone (17-0HP) progesterone (P) and cortisol (F) in combination with HLA-phenotypes in 25 out of 40 members of this family. The indices of the Gutai30-min assessment (17-0HP+P response to ACTH testing at 30 min), GF (F response at 30 min) and the ratio GF30/Guai30 named the Marina index were evaluated. The Marina index showed a very statistically significant difference among the three groups (p < 0.001). HLA phenotypes of the members of groups A and B showed a powerful association with B14, DR1, B7, and B35 phenotypes that were related with 21-OH/CAH. In conclusion, in our study population, a high incidence of a clinically asymptomatic form of 21-OHdef was found only after the ACTH stimulation test. The Marina index seems to be of high diagnostic value in classifying disease severity.

Objective: To evaluate the cytokine concentration patterns during the first 5 days of life by measuring serum concentrations of type-1 cytokines, like interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and type-2 cytokines, like IL-4, as well as the receptors of IL-2 (sIL-2R) and IL-4 (sIL-4R) during the early neonatal period., Subjects and Methods: Forty-two healthy term neonates were included in the study. Cytokine concentrations were measured in umbilical cord, in the 1st and 5th day after birth and compared with those in serum of 30 healthy adults., Results: IL-2 concentrations presented a decrease trend from umbilical cord to 5th day, while sIL-2R showed a significant elevation from umbilical cord to 5th day after birth. IL-4 concentrations did not differ significantly among umbilical cord, the 1st and the 5th day, while the sIL-4R showed the highest values in the 1st day after birth. Both IL-4 and sIL-4R concentrations in neonatal samples were elevated compared to adults. IFN-gamma concentrations increased significantly from umbilical cord to 5th day of life., Conclusion: Our findings indicate a dysregulation among IL-2, IL-4 and IFN-gamma concentrations during the 1st day after birth, favoring a more precocious expression of IL-2 and IL-4 against IFN-gamma that seems to be ameliorated in the end of the 1st week of life.

We present two rare cases of successful full-term pregnancies in a young woman suffering from lupus erythematosus for two years, who had subfertility problems and two missed abortions, before and after the diagnosis of lupus, with assisted reproduction. She received 10 mg of prednisolone daily from ovulation induction (with recombinant FSH--50 IU) until delivery, together with acetylsalicylic acid from ovulation induction until the 37th week of gestation and finally progesterone in high doses from the last insemination until the 12th week of gestation.

Autoimmune hemolytic anemia is a rare disorder. A 34-year old woman presented with thrombophlebitis after her first delivery, during puerperium. A high titer of cold agglutinins was found. Lymphomas, systemic lupus erythematosus, and tumors were excluded. She conceived again. Due to the anemia she had frequent blood transfusions and she delivered at 38 weeks of gestation.

Congenital adrenal hyperplasia due to deficiency of the enzyme 21-hydroxylase (21-OH), a cytochrome P450 enzyme located in the endoplasmic reticulum and which catalyzes the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progestene to deoxycorticosterone, is distinguished in its classical and non-classical form and is also one of the most common autosomal recessive inherited diseases in humans. The classical form appears in a rate between 1:5000 and 1:15,000 among the live neonates of North America and Europe, while the non-classical form occurs in approximately 0.2% of the general white population. This rate is especially high between the Ahskenazi Jews and a part (ie Italians, Hispanics) of the Mediterranean populations. Three alleles are associated with the 21-OH locus and can be combined in several ways in individuals who are either unaffected, heterozygote carriers, or affected with classical or non-classical disease. Variable signs and symptoms of hyperandrogenism, such as hirsutism, acne, virilization of the external genitalia and/or the body, short stature, menstrual irregularities, are common to both types of the disorder. Among the genes responsible for the synthesis of the enzyme 21-OH and the antigens of HLA system, exist both a proven genetic linkage and a proven genetic linkage disequilibrium. HLA-Bw47, HLAB5 and HLA-B35 are the most common haplotypes usually met in the classical form, while the haplotype HLA-B14DR1 is the most recurrent in the non-classical form of the disease. The significant advances in molecular biology and gene analysis over the past two decades have led to the development of novel sensitive methods of DNA analysis and study, such as polymerase chain reaction and southern blot analysis. Thus, it has been revealed that the synthesis of enzyme 21-OH is controlled by two genes, the active CYP21B gene and the CYP21A pseudogene. All three forms of the disease have a known sequence of gene changes owing to mutations in isolated proteins or whole series of genes due to translocations or deletions of genetic material.

Objective: The purpose of this study was to evaluate thyroid function and TSH and cortisol (F) secretion in hyperandrogenemic women with nonclassical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (Group A) when compared with women with hyperandrogenemic symptoms (menstrual irregularities, hirsutism, acne, seborrhea and sterility) of other etiologies (Group B)., Methods: Seventy-two women were subjected to stimulation of the adrenal cortex with i.v. ACTH administration in the early proliferative phase of the menstrual cycle. Basal plasma TSH, T3, T4, and FTI as well as basal and ACTH-stimulated plasma F and 17-hydroxyprogesterone levels were determined., Results: According to internationally accepted criteria and HLA haplotyping, we diagnosed 28 NC-CAH patients as well as affected heterozygotes of the disease. No significant difference was found in the plasma T3, T4, or FTI or F concentrations between the women of the two groups. On the contrary, plasma TSH levels were significantly lower in patients with 21-hydroxylase deficiency when compared to the women with hyperandrogenemic symptoms of other etiologies., Conclusion: The results of this study support a dysfunction of the hypothalamic-pituitary-thyroidal axis due to altered ACTH secretion patterns.

The purpose of this prospective study was to determine the incidence of any form of 21 alpha-hydroxylase deficiency among Greek women with hyperandrogenic symptoms, and to test the predictive value of basal serum 17-hydroxyprogesterone (17-OHP) in the early follicular phase as a screening index for patient preselection to adrenocorticotropic hormone (ACTH) testing. Eighty-eight unselected women with hyperandrogenic symptoms were examined in the Gynecological Endocrinology Unit of the Second Department of Obstetrics and Gynecology of Athens University. Using the ACTH-stimulated 17-OHP values at 60 minutes (17-OHP60) the study population was divided into four groups (A, B, C and D). Clinical and basal hormonal parameters as well as serum 17-OHP60 values and human leukocyte antigens were studied. Both clinical and basal hormonal parameters could be used to distinguish only patients with severe 21 alpha-hydroxylase deficiency (group A). In contrast, patients with moderate non-classical congenital adrenal hyperplasia (NC-CAH; group B), heterozygotes for NC-CAH (group C), and unaffected females (group D) can be diagnosed and classified only by serum 17-OHP60 values. In conclusion, the incidence of NC-CAH in Greek females with hyperandrogenic symptoms is 3.4%. The positive predictive value of basal 17-OHP is only 13% for this disease. Only 17-OHP60 helps to diagnose and classify moderate and mild forms of NC-CAH. Thus, it seems that ACTH testing is imperative in every subject suspected of this enzymatic disorder.

Pretreatment values of CEA, CA125, SCC and TPS were measured in 130 women with 1) ovarian carcinoma (n = 25), 2) breast cancer (n = 20), 3) endometrial cancer (n = 14), 4) cervical squamous cell carcinoma (n = 20), 5) cervical adenocarcinoma (n = 9) and 6) benign gynaecological diseases (n = 42) in order to evaluate the usefulness of multiple markers in diagnosing and monitoring patients with gynaecological cancer. Antigen values were significantly higher in the cancer groups than those in the benign one (p < 0.0001). CEA values were significantly elevated in the 2nd and 5th groups, CA125 in the 1st and 5th, SCC in the 4th and 5th, and TPS in the 1st, 2nd and 5th compared to the remaining groups (p < 0.04-p < 0.0001). In advanced stage diseases, significantly higher antigen values, except for SCC, than those in limited tumours were measured (p < 0.05-p < 0.0001). In conclusion, our results suggest that, multiple markers may be more efficient than the use of single markers in accurately identifying malignant from benign gynaecological diseases and in monitoring cancer patients.

Background: Cytokines are considered as part of host defence to infection or injury., Material and Methods: Pretreatment values of TNF and sIL-2R were measured in 132 women with a) ovarian carcinoma (n = 25), b) breast cancer (n = 20), c) endometrial cancer (n = 15), d) cervical squamous cell carcinoma (n = 19), e) cervical adenocarcinoma (n = 11) and f) benign gynecological diseases (n = 42) in order to evaluate whether these cytokines could be useful in the discrimination of malignant from benign gynecological diseases., Results: Both TNF and sIL-2R were significantly higher in all cancer groups together (mean +/- SD: 30 +/- 11 pg/mL and 1293 +/- 465 U/mL respectively), than those in the benign group (16.0 +/- 6 pg/mL and 626 +/- 233 U/mL, respectively; p < 0.0001), while no significant differences were found for TNF and sIL-2R values in the five cancer groups. Significantly higher cytokine values were measured in the advanced stage diseases (33 +/- 11 pg/mL and 1705 +/- 192 U/mL), than those in the limited cancer (26 +/- 12 pg/mL, p < 0.05 and 916(521 U/mL, p < 0.0001)., Conclusions: Our results suggest that, cytokines may be useful in the discrimination of malignant from benign gynecological diseases and in monitoring tumor activity in patients early in the malignancy process.

Carcinoembryonic antigen (CEA), CA125, and squamous cell carcinoma antigen (SCC) were evaluated in paired vaginal fluid and serum samples from 69 women, mean age 40.6 (20-78) years. Fifteen of the subjects were normal females (controls), 12 were pregnant, 20 had benign gynecological diseases, 5 presented severe cervical dysplasias and 17 suffered from cancer of the genital tract. Highly elevated CEA, CA125 and SCC concentrations (median, range) were found in vaginal fluid: 186 ng/ml (12-5420); 890 U/ml (54-65000); 1600 ng/ml (27-13000) respectively, compared with those in the paired serum samples: 1 ng/ml (0.5-8.6); 12 U/ml (3.0-1590); 1 ng/ml (0.3-19). Vaginal fluid CEA, CA125 and SCC values were significantly different among the five studied groups (p < 0.0002; p < 0.02: p < 0.002 respectively), being significantly higher in the patients with benign gynecological diseases, compared with those in the patients with malignancies of the genital tract (p < 0.0001; p < 0.02; p < 0.005), and those in controls (p < 0.02; p < 0.007; p < 0.02 respectively). The results of this study suggest that: 1) CEA, CA125 and SCC seem to be normal constituents of vaginal fluid. 2) The distribution of CEA, CA125 and SCC between vaginal fluid and the circulation is affected by pregnancy, inflammation and cancer of the genital tract.

Late onset congenital adrenal hyperplasia due to 21 alpha-hydroxylase deficiency (LO21OH def), as many other diseases, is the cause of hirsutism, menstrual disorders, infertility (PCO-like symptoms). We evaluated the reliability of a new biochemical marker for screening LO-21OH def in 47 women with PCO-like symptoms and 11 men, members of their families, comparing the results of separation using this new marker with those of HLA-haplotyping in 21 members of the patient population. All subjects were stimulated with 0.25 mg synthetic ACTH iv. Serum progesterone (P), 17-hydroxyprogesterone (17-OHP) and cortisol (F) at 0, 15, 30, 45 and 60 min following ACTH administration were determined and the new marker, namely the difference between 60min and 0min of the ratio F/17-OHP [delta F/17-OHP (60 min -0 min)] was calculated. According to the established biochemical criteria for the detection of LO-21OH def cases, (Gutai 30 min > or = 12 ng/dl/min and 17-OHP 60 min > or = 12 ng/ml for severe 21-OH def and Gutai 30 min < 6.5 ng/dl/min and 17-OHP 60 min < 5 ng/ml for "healthy" individuals regarding 21-OH def) two groups, A and B respectively, were separated from the patient population. In group A (n = 8), with LO-21OH def, the new marker showed negative values in all cases, while in group B (n = 9), without LO-21OH def, this marker was positive. The remaining subjects, depending on the results of the new marker were separated in 2 subgroups, Cneg (n = 28), with negative values, composed, consequently, of members with 21-OH def and Cpos (n = 13), with positive values, composed, consequently, of subjects with absence of LO-21OH def. HLA-typing was in agreement with the results of screening by the new marker, in 20 out of 21 cases, while there was only one false negative result. In conclusion, the proposed biochemical marker delta F/17-OHP (60 min-0 min) seems to be a reliable parameter for the LO-21OH def detection among young women with PCO-like symptoms as well as males suspected for congenital adrenal hyperplasia.

The aim of this study was to classify the degree of 21 alpha-hydroxylase deficiency in patients suspected for non-classic 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). In 66 selected subjects (45 young women with polycystic ovary (PCO)-like symptoms and members of their families, of whom 12 were men), progesterone, 17-hydroxyprogesterone (17-OHP) and cortisol were measured at 0, 15, 30, 45 and 60 min after adrenocorticotropic hormone (ACTH) stimulation. The markers [(17-OHP at 30 min--17-OHP at 0 min) + (progesterone at 30 min--progesterone at 0 min)]/30 proposed by Gutai and the ratio of cortisol to 17-OHP at 30 min (cortisol30/17-OHP30) were calculated and cluster analysis was performed using the above two markers and 17-OHP at 60 min (17-OHP60). Our patients were grouped by cluster analysis into four Groups: I, II, III and IV (n = 3, 11, 35 and 16, respectively) with (1) Gutai (mean +/- SE) 107.0 +/- 21.7, 29.9 +/- 4.4, 10.5 +/- 0.54 and 4.0 +/- 0.37 ng/dl per min, respectively, (2) 17-OHP60 169.7 +/- 28.3, 10.8 +/- 1.3, 4.6 +/- 0.2 and 3.7 +/- 0.4 ng/ml, respectively, and (3) cortisol/17-OHP30 0.97 +/- 0.28, 38.5 +/- 6.9, 82.3 +/- 5.5 and 112.0 +/- 8.9, respectively. All three markers showed highly significant differences between the four groups (p < 0.0001). The patterns of 17-OHP, cortisol and cortisol/17-OHP ratio following ACTH testing revealed the degree of 21-hydroxylase deficiency in every group. HLA typing effected in 20 studied individuals confirmed the classification derived from cluster analysis. Thus, it seems that Groups I, II and III include, respectively, patients with severe, mild and minimal forms of non-classic 21-hydroxylase-deficient CAH, while in patients of Group IV the hyperandrogenemic symptoms are of different etiology. In conclusion, the concurrent evaluation of the three markers together with the variations of 17-OHP, cortisol and the cortisol/17-OHP ratio after ACTH testing enhance the accurate identification of a patient suspected for non-classic 21-hydroxylase-deficient CAH in relation to the severity of the enzymatic defect.

sIL-2R and NSE were measured in 24 patients with small cell carcinoma (NSCC) of the lung, in 25 patients with non small cell carcinoma (NSCC) and in 20 controls matched for age, sex and smoking habits. Significantly elevated values of sIL-2R and NSE were found in the SCC group (mean +/- SEM: 2103 +/- 314.4 U/ml and 44.5 +/- 7.3 ng/ml respectively), compared to those in the NSCC group (1079 +/- 104.5 U/ml and 3.64 +/- 0.8 ng/ml, p < 10(-7) respectively) and to controls (561 +/- 44.6 U/ml and 1.7 +/- 0.3 ng/ml p < 10(-5). In the SCC group, 83.3% of sIL-2R and 87.5% of NSE values were above cut-off (900 U/ml and 10 ng/ml respectively), while in the NSCC group, 48% of sIL-2R and only 8% of NSE values were above cut-off. In the controls, all values of both parameters were below cut-off. The results suggest that sIL-2R and NSE in concurrent measurements may help in decision making as regards treatment and prognosis.