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It has been shown that environmental factors play a role in the development of obesity and insulin resistance in PCOS women. There is a bulk of evidence that endocrine-disrupting chemicals, advanced glycated end products, and vitamin D deficiency contribute to these disorders. The results of in vitro and in vivo studies have demonstrated different mechanisms involved in the development of these conditions. They suggest new ways of treatment. In addition, they point to the importance of avoidance of exposure to deleterious environmental factors.

Bisphenol A (BPA) is classified as an endocrine disruptor (ED) and it can interact with variety of hormone receptors leading to hormonal disruption and increased risk of various adverse health effects. Reducing human exposure to BPA is one of the main challenges of public health, as it is constantly present in daily life. A low-cost and commonly applied method to enable determination of BPA in the patient's body has yet to be developed. Currently available techniques are expensive, time-consuming, and require access to highly equipped analytical chemistry laboratories. Here we describe a fast and cheap engineered lateral flow assay of our design, to detect of BPA in urine samples. The technology not only provides an opportunity to perform rapid medical diagnostics without the need for an access to the central laboratory but also a means for self-diagnosis by the patient. The addition of β-glucuronidase improves the sensitivity of detection as it releases the free BPA from glucuronide complexes in urine. This invention may become a demonstrated analytical means for lowering human exposure to BPA and probably also to other EDs and consequently, may be useful in decrease of the risk for several lifestyle diseases.

The objective of the study was to measure the levels of 25-hydroxyvitamin D [25(OH)D] and vitamin D binding protein (VDBP) and assess their relationships with cardiovascular risk factors in women with the polycystic ovary syndrome (PCOS). A group of 267 women, aged 20–35 years (24.7 ± 4.9): 167 with PCOS and 100 healthy women were divided according to body mass index. Biochemical and hormonal parameters were measured. Free and bioavailable 25(OH)D were calculated using the mathematical equations. The percentage of body fat and visceral fat deposit were assessed by DXA. In the normal weight control group total, free, bioavailable 25(OH)D (p

Background: Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods: The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings: Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p

Background: Polycystic ovary syndrome (PCOS) constitutes one of the most common endocrine diseases that should be considered as a continuum. This life span disease is originating in foetal life and through long reproductive period falling into long-term consequences extending beyond menopause. Hence, it is considered to increase diabetes risk as well cardiovascular risk and outcomes. However, the natural course of the disorder is not completely understood, and recent data suggest differences in the evolution of the disease between normal-weight and obese patients, indicating that the cardiometabolic effects may be an epiphenomenon of the obesity and not of PCOS per se. We aimed to define the evolution of normal-weight Caucasian women with PCOS through the years. Materials and Methods: In this multicenter cross-sectional case control study 763 normal-weight women with PCOS according to Rotterdam criteria and 376 age and BMI-matched controls were included. The study group was further divided into three age groups, representing women post-adolescence, of reproductive age, and of late reproductive age to menopause. All the subjects were assessed clinically, biochemically, hormonally, and with the means of pelvic ultrasound. Results: Waist circumference, WHR, FG score, glucose, lipids, gonadotropin, androgen levels as well as HOMA-IR and ovarian volume were significantly higher in the PCOS group in comparison to controls. No statistical difference was noted among PCOS women diagnosed with the Rotterdam criteria vs. those who met the NIH criteria. Age subgroup analysis showed that androgens remained significantly higher among PCOS and controls, whereas insulin and lipid levels, as well as HOMA-IR, were comparable between PCOS and controls in all age groups. Pearson correlations of studied parameters with age revealed a significant negative association of age with waist circumference, FG score, androgens (testosterone, FAI, DHEAS, D4), insulin, FSH, and HOMA-IR. Finally, multiple regression analysis of factors affecting HOMA-IR disclosed a negative association with age (r:-0.123, p: 0.001) and a positive association with BMI (r: 0.105, p: 0.004) and DHEAS (r: 0.175, p: 0.001). Conclusions: Lipids, androgens, insulin resistance, and menstrual cyclicity are gradually improved in an age-dependent manner in PCOS lean patients and age and BMI matched controls. Normal-weight PCOS women exhibit a higher degree of IR and dyslipidaemia compared to their healthy peers, but these aberrations improve gradually. If PCOS women retain their normal weight over the years, they may develop a metabolic and hormonal profile comparable to that of their peers without PCOS later in life.

Obesity and its complications constitute a major health problem in postmenopausal women. The identification of the obesity phenotype, especially that of metabolically healthy obese (MHO) patients, is a necessary part of obesity treatment protocols. There are several methods to define MHO, but unfortunately, all of them are arbitrary and inconsistent. The aim of this work was to determine whether lipid accumulation product (LAP) could be used as a marker of the MHO phenotype in postmenopausal women. A sample of 345 Polish postmenopausal women aged 50-60years old participated in the study. Participants were classified as obese when their BMI was >27. Receiver operating characteristic curve analysis was performed to estimate the best cutoff for the LAP index value to identify postmenopausal women without metabolic syndrome components. We found that the best cutoff value was LAP ≤29.9, and this value was used to define MHO individuals. With this definition, the identification of MHO individuals could be made when both of the following criteria were met: LAP index ≤29.9 and no arterial hypertension (SBP

Polycystic ovary syndrome (PCOS) diagnosis and therapy still arouse a lot of controversy. Each year brings new information, so, having collected the experience of three scientific societies, we present contemporary recommendations concerning PCOS diagnostics and treat-ment. In adult female diagnosis, we still use the Rotterdam criteria, which is two out of three of the follwing characteristics: a) ovulation abnormality, b) clinical or biochemical hyperandrogenism, and c) polycystic ovaries. In the case of teenagers, diagnostic criteria are as follows: menstruation disturbances two years after menarche and clinical or biochemical hyperandrogenism. The presence of polycysti-cally abnormal ovaries is not necessary. The consensus paper presents the threats resulting from imperfect diagnostic methods applied in PCOS (hyperandrogenism diagnostics, ultrasound examination of ovaries). Suggested therapy includes personalised schemes according to the dominant PCOS phenotype, i.e. metabolic, hyperandrogenic, or reproductive ones.

Polycystic ovary syndrome (PCOS) diagnosis and therapy still arouse a lot of controversy. Each year brings new information, so, having collected the experience of three scientific societies, we present contemporary recommendations concerning PCOS diagnostics and treat-ment. In adult female diagnosis, we still use the Rotterdam criteria, which is two out of three of the follwing characteristics: a) ovulation abnormality, b) clinical or biochemical hyperandrogenism, and c) polycystic ovaries. In the case of teenagers, diagnostic criteria are as follows: menstruation disturbances two years after menarche and clinical or biochemical hyperandrogenism. The presence of polycysti-cally abnormal ovaries is not necessary. The consensus paper presents the threats resulting from imperfect diagnostic methods applied in PCOS (hyperandrogenism diagnostics, ultrasound examination of ovaries). Suggested therapy includes personalised schemes according to the dominant PCOS phenotype, i.e. metabolic, hyperandrogenic, or reproductive ones.

The appearance of menopause is combined with the incidence of many diseases typical of middle age, i.e., thyroid disorders, osteoporosis, and cardiovascular diseases. Thyroid disorders, especially subclinical hypothyroidism and subclinical hyperthyroidism, are frequent medical conditions among postmenopausal women. The prevalence of metabolic syndrome and osteoporosis significantly increases in postmenopausal women [1]. Many symptoms appear due to decreased estrogen level; however, chronic diseases influence quality of life as well. One of them is thyroid diseases, which are associated with risk factors for osteoporosis and cardiovascular diseases. Some symptoms of chronic diseases may mimic or modify the clinical expression of climacteric symptoms. Menopause and thyroid disease may present with similar symptoms, i.e., sweating, heart palpitations, insomnia, irritability, or mood changes, which suggest menopause, hyperthyroidism, or both. In addition, weight gain, constipation, skin atrophy, and hair atrophy are climacteric symptoms as well as symptoms of hypothyroidism [2]. With aging, the level of thyroid-stimulating hormone (TSH) remains within normal range and occasionally has a tendency to increase [3]. Reduction of thyroid iodine uptake, free thyroid hormone synthesis, and catabolism of free thyroxine (FT4) are observed. In addition, reverse triiodothyronine (rT3) level increases [3].

Metformin (MET) is the most widely used oral antidiabetic agent, currently recommended as first-line therapy not only for all newly diagnosed type 2 diabetes mellitus (DM2) patients but also for prediabetic syndromes associated with insulin resistance (IR). MET has been used in the treatment of DM2 for over 50 years and has been found to be safe and efficacious both as monotherapy and in combination with other oral antidiabetic agents and insulin. Its major clinical advantage is not causing hypoglycemia or weight gain. Besides its use in DM2, there is interest in the use of MET for the treatment of polycystic ovary syndrome, diabetic nephropathy, and gestational diabetes [1]. This drug also counteracts the cardiovascular complications associated with DM2 [2]. Another possible benefit for MET use is the prevention of DM2 in obese prediabetic patients, antiproliferative effect associated with decreased cancer risk and improved cancer prognosis, and anabolic impact on bones [3, 4].

Irisin (Ir), a recently identified adipo-myokine, cleaved and secreted from the protein FNDC5 in response to physical activity, has been postulated to induce the differentiation of a subset of white adipocytes into brown fat and to mediate the beneficial effects on metabolic homeostasis. Metabolic syndrome (MS), a cluster of factors leading to impaired energy homeostasis, affects a significant proportion of subjects suffering from polycystic ovary syndrome (PCOS). The aim of our study was to investigate the relationship between Ir plasma concentrations and metabolic disturbances. The study group consisted of 179 PCOS patients and a population of 122 healthy controls (both groups aged 25-35 years). A subset of 90 subjects with MS was isolated. A positive association between Ir plasma level and MS in the whole group and in controls was found. In subjects with high adipose body content (>40%), Ir was higher than in lean persons (

With the reference to the position statements of the Endocrine Society, the Paediatric Endocrine Society, and the European Society of Paediatric Endocrinology, the Polish Society of Endocrinology points out the adverse health effects caused by endocrine disrupting chemicals (EDCs) commonly used in daily life as components of plastics, food containers, pharmaceuticals, and cosmetics. The statement is based on the alarming data about the increase of the prevalence of many endocrine disorders such as: cryptorchidism, precocious puberty in girls and boys, and hormone-dependent cancers (endometrium, breast, prostate). In our opinion, it is of human benefit to conduct epidemiological studies that will enable the estimation of the risk factors of exposure to EDCs and the probability of endocrine disorders. Increasing consumerism and the industrial boom has led to severe pollution of the environment with a corresponding negative impact on human health; thus, there is great necessity for the biomonitoring of EDCs in Poland.

Introduction: The aim was to assess associations among PCOS and NAFLD, the lipoprotein lipase polymorphism gene, and metabolic disorders in PCOS. Material and methods: In 184 women with PCOS and 125 healthy, premenopausal volunteers, sex steroids, lipids, glucose, insulin, aminotransferases, free androgen index (FAI), HOMA-IR and E2/T were calculated. Hepatic steatosis was determined by ultrasound. Whole genomic DNA was isolated from blood leucocytes. Lipoprotein lipase polymorphisms rs268 and rs328 were analysed by polymerase chain reaction (PCR) and minisequencing. Results: 57.6% of PCOS women had NAFLD, while women without PCOS had NAFLD in 49.6%. PCOS-NAFLD women had higher BMI, WHR and waist circumference compared to women with PCOS without NAFLD and women without PCOS. PCOS-NAFLD women had lower SHBG, E2/T ratio, and higher FAI compared to other groups. ALT levels were higher in PCOS women with NAFLD compared to other groups. PCOS women with and without NAFLD had higher fasting glucose and insulin and HOMA compared to women without PCOS. Women with PCOS had higher triglycerides and lower HDL-C compared to women without PCOS. There was no evidence that evaluated polymorphisms influenced hepatic steatosis in women with and without PCOS. Conclusions: PCOS is not an independent factor influencing NAFLD in women. The influences on NAFLD incidence in women are BMI > 25 kg/m², glucose level > 80 mg/dL, E2/T 19 IU/L as independent factors. Hyperandrogenism in PCOS may increase the risk of NAFLD indirectly by obesity, insulin resistance, and directly by the hepatotoxic effect. Polymorphisms rs328 and rs268 of the lipoprotein lipase gene do not affect the occurrence of NAFLD in women with PCOS or without PCOS. (Endokrynol Pol 2014; 65 (6): 416–421)

Wstep: Osoby z zespolem metabolicznej otylości z prawidlową masa ciala (MONW), mimo prawidlowego wskaźnika masy ciala (BMI), są narazone na powiklania typowe dla otylości. Moze to wynikac z subklinicznego stanu zapalnego, wynikającego z nadmiernego gromadzenia tkanki tluszczowej brzusznej. Celem pracy byla ocena związku pomiedzy nagromadzeniem tkanki tluszczowej, szczegolnie okolicy brzusznej, a stezeniem wybranych cytokin prozapalnych — interleukiny 6, 18 i bialka C-reaktywnego (CRP), biorących udzial w aterogenezie. Material i metody: Badaniem objeto 342 osoby (218 kobiet, 124 mezczyzn w wieku 20–40 lat, z BMI > 27 kg/m2), mieszkancow Wroclawia. Grupe podzielono ze wzgledu na wartośc wskaźnika insulinooporności (HOMA): 90 osob — grupa MONW ( HOMA < 1.69), 252 osoby — grupa kontrolna. Oceniono parametry antropometryczne, stezenia IL-6, IL-18, CRP, glukozy, insuliny oraz wskaźniki insulinowrazliwości i insulinooporności. Wyniki: Stezenie CRP bylo istotnie wyzsze w grupie kobiet MONW niz kontrolnej (3,26 vs. 1,97, p = 0,03). Stezenia IL-6 i IL-18 nie roznily sie pomiedzy grupami, zarowno u kobiet, jak i u mezczyzn. Dodatnią korelacje zanotowano miedzy stezeniem IL-6 a wskaźnikiem centralizacji tluszczu u kobiet. Stwierdzono dodatnią korelacje miedzy stezeniem CRP a BMI, wskaźnikiem talia– biodra, obwodem talii u obu plci. U kobiet istniala takze dodatnia korelacja miedzy CRP a wskaźnikami HOMA i FIRI i ujemna ze wskaźnikiem QUICKI. Wnioski: Zwiekszone gromadzenie tluszczu okolicy brzusznej u zdrowych, mlodych osob, wiąze sie z podwyzszonym stezeniem CRP. (Endokrynol Pol 2014; 65 (6): 449–455)

The protective effect of vitamin D against several cancers including colorectal cancer is modulated by the vitamin D receptor (VDR) and its ligand, the active form of vitamin D. VDR response has been found to play a role in various genes encoding proteins involved in crucial cellular pathways. Single nucleotide polymorphisms (SNPs) of the VDR gene that modulate its activity are located in the promoter region, exons 2-9, and their vicinity and also in the 3'UTR region. Some of them have been previously studied in relation to cancer susceptibility and prognosis. The aim of our study was to investigate four polymorphisms, BsmI, ApaI, TaqI, and FokI, of the VDR gene in Polish patients with sporadic colorectal cancer and to evaluate their association with susceptibility to cancer. We found a significant association between the BsmI genotype and cancer (individuals with the bb genotype are more susceptible to cancer compared to those with other genotypes, p = 0.025, Fisher's exact test for 2 × 2 table). Also, the TT genotype at TaqI and the AA genotype at ApaI are correlated with a higher risk of cancer (p = 0.00071 and p = 1.0 × 10(-5), respectively). We found relatively strong linkage disequilibrium between the TaqI and ApaI loci (T with A and t with a, respectively). Both of these loci are associated with cancer. We do not observe any such association for the FokI polymorphism. In conclusion, a small modification in VDR expression may play a role in such a multipathway process as tumorigenesis.

Introduction: Polycystic ovary syndrome (PCOS) is associated with an increasing number of metabolic comorbidities. About 50% of PCOS patients are obese, and insulin resistance affects up to 70% of these women. The endocannabinoid system contributes to human energy homeostasis. CNR1 is a biological candidate for human obesity and related metabolic disorders. The aim of this study was to determine the relationships between CNR1 polymorphisms and anthropometric and metabolic parameters in PCOS women. Material and methods: 130 women diagnosed with PCOS according to the Rotterdam criteria were recruited. The control group consisted of 70 healthy women. Medical history was taken, and physical examination as well as assessment of anthropometric (body mass, height, waist and hip circumference, BMI, waist-to-hip ratio [WHR]) and metabolic parameters (glucose and insulin, the insulin resistance index HOMA, lipid profile) was carried out. Genetic studies to detect six CNR1 gene polymorphisms were performed. Results: The total cholesterol and low-density lipoprotein (LDL) cholesterol levels in PCOS women carrying T/T genotype of rs2023239CNR1 polymorphism were higher than in those with C/T and C/C. There were no statistical differences in other metabolic parameters or in the value of BMI and WHR between the variants of rs2023239 CNR1 polymorphism. The other studied polymorphisms of the CNR1 gene were not associated with anthropometric or metabolic parameters in PCOS women. There were no differences in anthropometric or metabolic parameters between the variants of studied polymorphisms of the CNR1 gene in control women. Conclusions: On the basis of our study, it seems that CNR1 polymorphisms are not associated with obesity and metabolic disorders, including insulin resistance, in PCOS women.

The latest list of reimbursed medicines includes, as a new addition, metformin for the treatment of polycystic ovary syndrome (PCOS), which is extremely important for practicing physicians. While this paper briefly summarises the current state of knowledge on PCOS, its main aim is to remind the reader about the effectiveness of metformin in women with PCOS in controlling glycaemia, increasing tissue sensitivity to insulin and affecting endothelial function, vascular inflammation, lipid profile and other risk factors of atherosclerosis, which suggests its cardioprotective effects. The paper also discusses the clinical effect of metformin relative to hyperandrogenism, menstrual cycle disorders and ovulation induction. The paper concludes with an algorithm for the diagnosis and management of PCOS.

Background. Age-related decrease in bone marrow erythropoietic capacity is often accompanied by the telomere length shortening in peripheral white blood cells. However, limited and conflicting data hamper the conclusive opinion regarding this relationship. Therefore, the aim of this study was to assess an association between telomere length and peripheral blood cell count parameters in the Polish elderly population.Material and Methods. The substudy included 1573 of 4981 subjects aged 65 years or over, participants of the population-based PolSenior study. High-molecular-weight DNA was isolated from blood mononuclear cells. Telomere length (TL) was measured by QRT-PCR as abundance of telomere template versus a single gene copy encoding acidic ribosomal phosphoprotein P0.Results. Only white blood count (WBC) was significantly different in TL tertile subgroups in all subjects (P=0.02) and in men (P=0.01), but not in women. Merely in men significant but weak positive correlations were found between TL and WBC (r=0.11,P<0.05) and RBC (r=0.08,P<0.05). The multiple regression analysis models confirmed a weak, independent contribution of TL to both RBC and WBC.Conclusions. In the elderly, telomere shortening limits hematopoiesis capacity to a very limited extent.

The factor V (FV) plays an important role in the coagulation process and belongs to the group of factors that significantly increases the risk of thrombophilia. Our study presents a novel, rapid method for the detection of FV (R506Q) mutation using minisequencing approach.Samples of peripheral blood were obtained from 300 females of the Lower Silesian population. Minisequencing, as one of the polymerase chain reaction (PCR)-based methods, was used for detection the of FV (R506Q) point mutations. The allele restriction mutation system PCR (ARMS-PCR) verifying method was applied.By using minisequencing reaction we examined the FV genotypes in the female group who experienced at least one unexplained spontaneous miscarriage. The results of the ARMS-PCR, as a verifying test, were fully consistent with the results of the minisequencing technique.One of the many factors which may cause thrombophilia is the FV gene mutation R506Q. A full validation of the minisequencing method was carried out in order to apply this method to clinical tests. The validation shows that the minisequencing technique is highly precise and may be used in routine diagnostics of the FV R506Q mutation.

The aim of this work was to evaluate whether the FokI and BsmI polymorphisms of the VDR gene are associated with anthropometric and biochemical features of cardiovascular disease (CVD) in a Caucasian population aged over 65, participants of the Polish PolSenior study. We performed the study on randomly selected subjects: 427 women and 454 men aged over 65. Measurements of anthropometric parameters were carried out and biochemical parameters were estimated using commercial kits. VDR polymorphisms (rs10735810, rs1544410) were genotyped by PCR and FRLP. The prevalence of BsmI genotypes was 50% Bb, 23% bb, 27% BB in women and 48% Bb, 20% bb, 32% BB in men. The prevalence of FokI was 48% Ff, 22% ff, 30% FF in women and 50% Ff, 18% ff, 32% FF in men. The women bearing the rare allele b differ in homeostatic model assessment (HOMA) (p < 0.049) from women bearing common allele B, and the men differ in insulin level (p < 0.047) and HOMA (p < 0.017). There were no significant differences in anthropometric or biochemical parameters between genotypes in FokI in female and male groups. The common allele B is connected with biochemical risk factors of CVD in older Caucasian men and women.

Metabolism is controlled through homeostatic system consisting of central centers, gut hormones, hormones from adipose tissue and the other hormonal axes. This cooperation is based on cross-talk between central and peripheral signals. Among them the hypothalamus plays a crucial role, with interconnected nuclei forming neuronal circuits. Other regions in the brain, such as the brain stem, the endocannabinoid system, the vagal afferents, are also involved in energy balance. The second component is peripheral source of signals − the gastrointestinal tract hormones. Additionally, adipokines from adipose tissue, thyrotropic, gonadotropic and somatotropic axes play a role in energy homeostasis. Knowledge about all components of this neuroendocrine circuit will be helpful in developing novel therapeutic approaches against the metabolic syndrome and its components.

Abstract: Both descriptive and longitudinal studies of aging are nowadays a subject of growing interest in different countries worldwide. However, in Poland and other Central–Eastern European countries, such comprehensive, nationally representative, multidimensional studies were never performed in the past in elderly population. The present paper describes the PolSenior project including its objectives, sample selection and structure, methods, fieldwork procedures and study flow. The aim of the project was to examine medical, psychological and socioeconomic aspects of aging in Poland. The research sample included 5695 respondents (2899 males and 2796 females) split into six equally sized age groups of elderly individuals (65–69 years, 70–74 years, 75–79 years, 80–84 years, 85–89 years, 90 + years) and one group of subjects just about to enter old age (55-59 years). Subjects were recruited using three stage stratified, proportional draw. The response rate was 42% and ranged from 32% to 61% between provinces. The study consisted of three visits performed by trained nurses including questionnaire survey, comprehensive geriatric assessment and blood and urine sampling. The questionnaire consisted of medical and specific socioeconomic questions. The comprehensive geriatric assessment included blood pressure and anthropometric measurements, as well as selected scales and tests routinely used in the examination of elderly subjects. Blood and urine samples were collected from 4737 and 4526 individuals, respectively. More than 50 biochemical parameters were measured, and DNA was isolated and banked. In a selected group of 1018 subjects, a medical examination by a physician was performed. The self-rated health was lower in females than in males in age groups 70–84, but similar in individuals of both sexes aged 65-69 and  85 years. Besides providing data on health and functioning of elderly population, the PolSenior project aims to analyze interrelationships between different elements of health and social status, and between genetics and health status in advanced age. The results of the PolSenior project will facilitate prioritizing the state's public health and social policies in elderly population. Such a program provides also an excellent starting point for longitudinal studies and a basis for comparative analysis between Poland and other European countries or regions.

Five to ten percent of women of reproductive age suffer from polycystic ovary syndrome (PCOS). Leptin, NPY, galanin, cholecystokinin (CCK) are involved in the regulation of eating behavior. PPARγ are receptors that are probably involved in hyperandrogenism. This study was designed to assess associations between the Pro12Ala PPARγ2 gene polymorphism and satiety factors in PCOS. Fifty-four PCOS women and 51 healthy women were studied. Leptin, NPY, galanin, CCK levels, and genetic studies to detect Pro12Ala PPARγ2 gene polymorphism were assessed. The leptin levels in the PCOS women carrying Pro12Ala genotype were higher than in those with Pro12Pro and Ala12Ala. The PCOS women had higher leptin and NPY levels and lower galanin levels. Obese PCOS patients had lower CCK levels. Conclusions: In the PCOS women, a single Ala allele may have a protective role as far as hyperleptinemia is concerned. The PCOS women may reveal a disrupted central leptin/NPY feedback loop with some shifts in food intake.

The risk of cardiovascular diseases (CVD) in women increases with menopausal stage. Obesity with metabolic disorders is the most important risk factor for CVD. The incidence of this phenotype of obesity increases in postmenopausal women. The endocannabinoid system plays an important role in regulation of several metabolic pathways. The aim of this work was to investigate whether genetic variations in the cannabinoid receptor gene (CNR1) can affect cardiovascular risk factors (e.g. fat distribution, obesity, fasting glucose, lipid profile, blood pressure, and free androgen and estrogen indexes) in postmenopausal women.The rs806381, rs10485170, rs6454674, and rs2023239 polymorphisms of the CNR1 gene were genotyped in 384 randomly selected postmenopausal Polish women (aged 50-60) using the minisequencing technique.The rs806381, rs10485170, rs6454674, and rs2023239 polymorphisms were not significantly associated with anthropometric measures (waist circumference, carbohydrate and lipid metabolism, body mass index [BMI], total fat, glucose, insulin, fasting insulin resistance index [FIRI]). However, the rs2023239 polymorphism was associated with the free androgen index (p = 0.03).It seems that further genotyping of the endocannabinoid receptor gene cannot be used as a significant marker of predisposition to CVD in postmenopausal women, but it would be interesting to study this interrelation on a larger population of postmenopausal women.

Vitamin D co-regulates the synthesis of sex hormones. Therefore, the aim of this study was to determine whether the presence of certain genotypes of the vitamin D receptor gene (VDR) is associated with the serum levels of sex hormones in the elderly Polish population.The rs10735810, rs1544410, rs7975232, and rs731236 polymorphisms of VDR, the serum levels of testosterone and estradiol, as well as free estrogen index (FEI) and free androgen index (FAI) were evaluated in 360 women and 400 men aged 65-90years selected from 5695 respondents of the PolSenior survey.Only the rs1544410 VDR polymorphism was associated with the serum levels of sex hormones. The prevalence of rs1544410 genotypes was 38% BB, 46% Bb, and 16% bb in women and 41% BB, 44% Bb, and 15% bb in men. In women the frequency of the B allele was p=0.61 and b allele q=0.39, while in men it was p=0.63 and q=0.37, respectively. We found significant differences in the serum testosterone level (p0.0004) and FAI (p0.0015) between the rs1544410 genotypes in women but not in men. Higher mean testosterone level and higher mean FAI were observed in women with a rare bb genotype in comparison to a common BB genotype.We hypothesize that in women the increase in VDR expression associated with a rare genotype of the rs1544410 polymorphism of this gene may be associated with an increase in testosterone and FAI levels.

Obesity is epidemic of 21st century, its visceral form is associated with increased risk for type 2 diabetes, cardiovascular disease, hypertension and increased mortality due to consequences of the disease. This type of obesity is a common diagnostic and therapeutic problem in gynecological practice. This especially concerns polycystic ovary disease, in which this type of obesity with its metabolic consequences is one of the important factors in etiology and additionally may lead to remote metabolic and cardiovascular problems. Another group of women in which this type of obesity plays an important role are climacteric women in whom redistribution of adipose tissue with increase in visceral fat deposit occurs. On the basis of current viewpoints and own experiences, the authors propose a diagnostic-therapeutic algorithm in women with visceral obesity and polycystic ovary disease or climacteric period. In case with cardiovascular risk factors (waist circumference over than 80 cm, serum triglycerides over 1.7 mmol/l, HDL cholesterol lower than 1.0 mmol/l, blood pressure over 130/85 mmHg and fast serum glucose levels over 100 mg/dl) the therapeutic model focuses on the recognize risk factors. It must be considered that diet and physical activity play a very important role in the therapy.

Obesity is defined as the excess of body fat and results from interactions between genes and the environment. The factors contributing to obesity are unsuitable nutrition and food overproduction, poor physical activity, mental stress, psychoemotional disorders, and metabolic and hormonal disturbances [1].

Glypican-4 (Gpc4) is an adipokine which interacts with the insulin receptor and affects insulin sensitivity in proteoglycans. Insulin resistance plays a crucial role in the etiology of polycystic ovary syndrome (PCOS). PCOS is associated with metabolic disturbances such as abdominal obesity, dyslipidemia and type 2 diabetes. Thus, higher levels of Gpc4 released from visceral adipose tissue in women with PCOS may suggest an increased risk of cardiovascular disease (CVD).The aim of this pilot study was to determine whether the serum Gpc4 level is associated with cardiovascular risk predictors in women with PCOS.Sixty-two women with PCOS according to the Rotterdam criteria (20-35 years old) and 43 healthy controls were studied. Cardiovascular risk predictors such as obesity indices, fat deposits according to dual-energy X-ray absorptiometry, biochemical lipid profile parameters and Homeostasis Model Assessment were estimated.The serum Gpc4 level in PCOS women was significantly higher (2.61 ± 1.17 ng/ml) than in the control group (1.55 ± 0.47 ng/ml) and correlated with waist circumference, waist-to-hip ratio, total fat and android fat deposit to gynoid fat deposit ratio only in the PCOS group.The Gpc4 level was higher in the PCOS group and correlated with CVD risk predictors, especially fat distribution.

The role of endogenous vitamin D and vitamin D receptor (VDR) gene polymorphism in polycystic ovary syndrome (PCOS) is still controversial.The objective of this study was to investigate for the first time in women with "classic" PCOS phenotype and healthy controls the role of the serum endogenous vitamin D level and VDR gene polymorphisms in PCOS etiology.Ninety-two women with "classic" PCOS phenotype and 85 controls from lower Silesia with comparable body mass index (BMI) were studied. In all women the waist circumference, android/gynoid fat deposit, parameters of lipid and glucose metabolism, testosterone, free androgen index, sex hormone binding globulin (SHBG) and vitamin D were evaluated. Also, VDR gene polymorphisms rs731236, rs7975232, rs1544410 and rs10735810 were assessed.Serum vitamin D levels in both groups were comparable. Also high, comparable frequencies of hypovitaminosis and vitamin D deficiency in both groups were observed. Women with "classic" PCOS phenotype had statistically significantly higher values of all measured parameters, except serum SHBG and high-density lipoprotein (HDL)-cholesterol, which were lower. The frequency of VDR genotype polymorphism was also comparable in both groups.For the first time, we show that endogenous vitamin D deficiency and VDR polymorphisms are not associated with homogeneous "classic" PCOS phenotype.

With the reference to the position statements of the Endocrine Society, the Paediatric Endocrine Society, and the European Society of Paediatric Endocrinology, the Polish Society of Endocrinology points out the adverse health effects caused by endocrine disrupting chemicals (EDCs) commonly used in daily life as components of plastics, food containers, pharmaceuticals, and cosmetics. The statement is based on the alarming data about the increase of the prevalence of many endocrine disorders such as: cryptorchidism, precocious puberty in girls and boys, and hormone-dependent cancers (endometrium, breast, prostate). In our opinion, it is of human benefit to conduct epidemiological studies that will enable the estimation of the risk factors of exposure to EDCs and the probability of endocrine disorders. Increasing consumerism and the industrial boom has led to severe pollution of the environment with a corresponding negative impact on human health; thus, there is great necessity for the biomonitoring of EDCs in Poland.

Aging in women is associated with several hormonal and metabolic disorders. Sex hormone transformation in aging women is associated with fat distribution changes caused by insulin resistance and an atherogenic lipids profile. Cardiovascular diseases (CVD) are the most common reason for mortality in women over 50 years of age. We studied the CVD risk factors and hormonal status in aging women participating in the PolSenior study. We concluded that aging has an important influence on body mass index and serum high-density lipoprotein cholesterol levels in women. Hormonal status, such as serum oestradiol, free oestradiol index and free androgen index, correlated significantly with CVD predictors in women. Also, sex hormone-binding globulin (SHGB) showed a significant influence on CVD predictors in women, but the influence of aging must also be included. The endogenous serum vitamin D concentration decreases with biological age; in patients with levels lower than 20.0 ng/ml we can expect an atherogenic lipids profile. Thyroid diseases (especially hypothyroidism) are common disorders in aging women, but less than 57 % of them are treated.

Persistent and bothersome somatic and mental complaints occurring in the premenstrual phase in women, referred to as the premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD), affect from 3 to 40% of women, depending on their severity. This paper presents a diagnostic and therapeutic algorithm based on current data and own experience. The etiology of PMS is still unclear, but sex steroids produced by the corpus luteum of the ovary are thought to provoke symptoms, as the cyclicity disappears in anovulatory cycles due to several reason, e.g. functional hyperprolactinemia. PMS symptoms are largely affected by the serotonin system as well as the gamma-aminobutyric acid (GABA) in the central nervous system (CNS), in association with the effect of progesterone metabolites, e.g. allopregnenolon. The etiology of PMS is multifactoral, involving behavior, diet, alcohol consumption, smoking, and physical activity. For these reasons, non-medical therapy, including modification and supplementation of the diet, relaxation techniques, and increased physical activity, plays a significant role. Several pharmacological treatments appear to be effective. The therapeutic modality depends on the kind of hormonal disturbances and involves drugs inhibiting the secretion of prolactin, re-uptake of serotonin, or inhibition of ovulation. The beneficial effects of Vitex agnus castus (VAC) therapy in women with PMS encourage further long-term randomized trials comparing standard medical treatment modalities.

Background Although suspected, relationships between sex steroids and bone mineral density (BMD) are not fully defined in male population. According to recent data there may also exist an association between low BMD and atherosclerosis. Objective Our aim was to investigate relationships between serum sex steroids and BMD, and between BMD and atherosclerosis in men with coronary artery disease (CAD). Subjects and methods We recruited for the study 55 men aged 40–60 years with angiographically confirmed CAD and 30 healthy, age-matched controls. In each of the examined subjects serum levels of total testosterone (T), estradiol (E 2 ), estrone and DHEA-S, as well as femoral neck, lumbar spine and total skeleton BMD were measured. Results We found that the prevalence of osteopenia/osteoporosis recognized on spine and/or femoral BMD ( T -score below −1.0) did not differ between men with CAD and healthy controls (respectively 47% versus 47%; p = 0.8 in χ 2 Yates test). The mean BMD value at different regions did not differ between both groups either. Hormonal status of men with CAD and normal BMD was similar to men with CAD and osteopenia/osteoporosis except for the level of testosterone. After adjustment for age and BMI, men with lower BMD had lower testosterone and lower T/E 2 ratio than men with normal BMD (geometric means for testosterone were respectively: 16.1 ± 8.3 versus 16.2 ± 4.2; p 2 ratio it was: 202.1 ± 94.7 versus 222.8 ± 83.9; p = 0.05). However, we did not find any correlation between sex hormones concentrations and bone mineral density. There was a relationship between the advance of atherosclerosis (ranged by number of stenotic arteries) and BMD: men with the most advanced form of the disease (three-vessels) had the lowest femoral neck BMD. The groups did not differ in lumbar spine BMD. Conclusions Our data suggest that in middle-aged men with CAD: (1) lower serum testosterone and lower T/E 2 ratio are associated with lower BMD; (2) advance of coronary atherosclerosis is inversely related to femoral neck BMD, however this relationship is weak and requires further investigation.

The etiology of obesity is multifactorial and still unclear. Genetic factors play a significant role and include several gene candidates: polymorphisms of genes for ss(2)-adrenoreceptor, resistin, estrogen receptor-a and peroxisome proliferator-activated receptor-gamma. Moreover, peptides regulating hunger and satiety, e.g. leptin, galanin, cholecystokinin and neuropeptide Y, and altered nutritional patterns have been implicated. Also, factors associated with aging, e.g. decreased levels of growth hormone and dehydroepiandrosterone, and the activity of the sympathetic nervous system (resting metabolism and thermogenesis) cannot be disregarded. Participation of the sex steroids and inflammatory factors has also been postulated in the etiology of obesity. Three phenotypes of obesity are postulated; however, the visceral (abdominal) phenotype is typical of postmenopausal women and is characterized by several metabolic disorders with high risks of diabetes mellitus type 2 and cardiovascular disease. On the basis of personal experience and data from evidence-based medicine, diagnostic-therapeutic algorithms of climacteric obesity are presented.

The aim of the present study was to investigate the influence of endogenous estradiol and estrogen and estrogen-progestin therapies on concentration in pre- and postmenopausal women.The study groups consisted of 26 women with surgical menopause (mean+/-standard deviation (SD): age 51.8+/-2.6 years, body mass index (BMI) 26.45+/-4.56 kg/m(2)), 54 with natural menopause (mean+/-SD: age 50.5+/-3.0 years, BMI 25.75+/-4.09 kg/m(2)) and 40 premenopausal controls (mean+/-SD: age 48.3+/-2.3 years, BMI 26.23+/-4.12 kg/m(2)). The group with surgical menopause received estradiol transdermally (50 microg/day) and those with natural menopause received additionally medroxyprogesterone acetate (5 mg/day) for the last 12 days of the cycle. Before and after 4 months of therapy, body weight, waist and hip circumferences and blood pressure were measured, and BMI and waist-to-hip ratio (WHR) were calculated. Serum leptin, follicle-stimulating hormone (FSH), estradiol (E(2)), testosterone, prolactin and dehydroepiandrosterone sulfate (DHEAS) were measured prior to and after treatment.Leptin concentrations did not differ statistically among the groups. No correlations between leptin and E(2), FSH, prolactin, testosterone and DHEAS concentrations were found in any of the groups before and after treatment. Leptin level correlated positively with body mass, BMI and hip and waist circumferences in all groups. There were no correlations between leptin and WHR in the pre- and postmenopausal groups. In the premenopausal group and in some postmenopausal groups, serum leptin level correlated with blood pressure.Endogenous E(2) and androgens in premenopausal women and estrogen and estrogen-progestin therapies in postmenopausal subjects do not influence serum leptin concentrations. Leptin level is related to body mass and BMI, but not to sex hormone status. The distribution of adipose tissue and the type of obesity (android or gynoid) have no influence on serum leptin concentration. The correlation between serum leptin level and blood pressure requires further investigation.

Estradiol (E2) has antioxidant properties. The role of progestins in antioxidant defense is still unknown. We have evaluated the influence of E2 and E2 plus medroxyprogesterone acetate (MPA) on serum lipid peroxide (LPO) levels, a marker of free radical reactions, and serum total antioxidant status (TAS) in postmenopausal women. Subjects consisted of 26 women with surgical menopause, before and after 4 months of estrogen replacement therapy (ERT; E2), and 54 women with natural menopause on hormone replacement therapy (HRT; E2 plus MPA). Forty premenopausal women served as a control group. Serum E2 was estimated by radioimmunoassay, follicle-stimulating hormone by IRMA methods, LPO and TAS by colorimetric methods. Before therapy, LPO levels in the postmenopausal women were significantly higher (p0.001) than in the control group. After both ERT and HRT, LPO decreased significantly and did not differ between both groups and the control group. TAS was significantly lower in postmenopausal women (p0.001) than in the control group before therapy. After both ERT and HRT, TAS increased significantly and did not differ between both groups and the control group. We conclude that oxidative stress is increased after menopause. ERT and HRT inhibit the generation of free radicals and raise antioxidant potential to the levels found in premenopausal women. MPA did not influence the antioxidant action of E2.