Browsing by Author "Vujovic, S. (57225380338)"

Objectives: This randomized study aimed to evaluate the correlation between bone mineral densities (BMD) measured at different sites and the frequency of vertebral fractures in a group of Serbian postmenopausal women. Method: BMD was measured in 130 naïve postmenopausal women by dual X-ray absorptiometry (DXA) at the ultra-distal part of the forearms, at the hip and at the lumbar spine. At each of the measurement sites, the patients were categorized as osteoporotic, or osteopenic, or in the reference range. Vertebral fractures were examined using thoracic and lumbar spine radiography. Results: A T-score at different skeletal sites showed discordance in the site-specific region. Vertebral fractures were found in 58.82% of patients with hip osteopenia, in 45% with forearm osteopenia and in 54.54% with lumbar spine osteoporosis. Conclusions: The study confirmed that the reduction of BMD depends on age and choice of measurement site. The best correlation was obtained in the women with osteopenia at all measurement sites. The discovery of vertebral fractures by lateral thoracic and lumbar spine radiography improves prompt treatment. Reference values of BMD do not exclude vertebral fractures. Of vertebral fractures, 72.5% were asymptomatic and thus spine radiographies are obligatory. Currently discussed is the position of DXA for measuring BMD as a method of detection for patients at risk of fracture. © 2016 International Menopause Society.

People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient’s mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies. © 2016, Springer Science+Business Media New York.

People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient’s mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies. © 2016, Springer Science+Business Media New York.

Objectives: Visceral fat is more harmful than subcutaneous fat. Women with high amounts of visceral fat have an increased risk of metabolic syndrome (MetS), insulin resistance and low level of serum vitamin D. Methods: This was a prospective, randomized and controlled study. Postmenopausal women (n = 101) aged 45–70 years were included. The assessed parameters were: body mass index (BMI), waist circumference (WC), 25-hydroxyvitamin D (25-OHD) status, serum insulin and HOMA-IR, bone mineral density, total fat mass, fat mass index (FMI) measured by DXA, and muscle strength. Results: Significantly lower values of 25-OHD (35.26 ± 1.61 nmol/l) were found in women with MetS compared to those without MetS (47.52 ± 3.47nmol/l) (t = 3.699; p < 0.000). A significant negative correlation was observed between 25-OHD levels and: WC (rhoWC = −0.94; p < 0.004), BMI (rhoBMI = −0.80; p < 0.002), FMI (rhoFMI = −0.31; p < 0.002) and impaired fasting glucose (IFG) (rhoIFG = −0.23; p < 0.001). The percentage of body fat was statistically significantly higher in the group with insufficient 25-OHD (39.6%) and in the group with a deficit of 25-OHD (48.2%), compared with the maximum permitted percentage body fat of 35% for a female (t = −22.63; p < 0.002). The average hand grip strength of these moderately obese participants was 27.4 ± 4.7 kg. It was significantly lower than the normative grip strength for referent range groups (t = −21.65; p < 0.001). Conclusion: A low 25-OHD level in postmenopausal women is associated with high body fat, metabolic syndrome, low muscular strength and osteopenia. © 2016 International Menopause Society.

Objective It has previously been reported that estrogen receptor-alpha (ERα) gene (ESR1: estrogen receptor 1) polymorphisms are associated with premature ovarian failure (POF). The aim of this study was to investigate whether these genetic polymorphisms of ESR1 are associated with POF in Serbian women. Methods A series of 197 POF cases matched with 547 fertile controls was recruited by the Institute for Endocrinology, Diabetes and Metabolic Disorders of Serbia between 2007 and 2010. Genomic DNA was extracted from saliva using Oragene® DNA sample collection kits. Two single-nucleotide polymorphisms (SNPs), PvuII and XbaI, in ESR1 were genotyped by dynamic allele-specific hybridization. Haplotype analyses were performed with the restriction fragment length polymorphism method. SNP and haplotype effects were analyzed by logistic regression models. Results No significant difference was found in the distribution of ESR1 PvuII and XbaI polymorphisms or haplotypes between the POF and control groups. Conclusion The two ESR1 SNPs, PvuII and XbaI, are not commonly associated with POF in Serbian women and may not contribute to the genetic basis of the condition. © 2014 International Menopause Society.

Objective: This study aimed to investigate the potential role of microsatellite polymorphisms of the estrogen receptor alpha gene (ESR1) TA repeat, estrogen receptor beta gene (ESR2) CA repeat, and androgen receptor gene (AR) CAG and GGN repeats among Serbian women with primary ovarian insufficiency (POI). These microsatellites have been reported to be associated with POI in different racial/ethnic populations. Methods: A cohort of 196 POI cases matched with 544 fertile controls was recruited by the Institute for Endocrinology, Diabetes and Metabolic Disorders of Serbia between 2007 and 2010. DNA was extracted from saliva. The four microsatellites were genotyped using a PCR-based assay to determine the repeat lengths. Results: POI patients carried shorter repeat lengths of ESR2 (CA) n than controls (P = 0.034), but the difference was small. ESR1 (TA) n was on the borderline of statistical differences between groups (P = 0.059). AR (CAG) n and (GGN) n showed no association with POI. Conclusions: We cautiously conclude that microsatellite polymorphisms of gonadal steroid receptor genes might contribute to the genetic basis of POI in Serbian women, but a larger-scale study and family-based studies are warranted to validate our findings even though the sample size in this study is larger than any previously published in this field. © 2018, © 2018 International Menopause Society.

Purpose: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease characterized by impaired adrenal steroidogenesis and most often caused by CYP21A2 gene mutations. For the first time, we reported complete spectrum and frequency of CYP21A2 gene mutations in 61 unrelated patients with classical and non-classical CAH from Serbia. Methods: Direct DNA sequencing of whole CYP21A2 gene and polymerase chain reaction with sequence-specific primers for detection of CYP21A1P/CYP21A2 chimeras were combined. Results: We identified 18 different pathogenic alleles - two of them novel. Mutation detection rate was highest in patients with salt-wasting form of CAH (94.7 %). The most prevalent mutation was intron 2 splice site mutation, c.290-13A/C>G (18.5 %). Other mutation frequencies were: CYP21A1P/CYP21A2 chimeras (13 %), p.P30L (13 %), p.R356W (11.1 %), p.G110fs (7.4 %), p.Q318X (4.6 %), p.V281L (4.6 %), p.I172N (2.8 %), p.L307fs (2.8 %), p.P453S (1.9 %), etc. Mainly, frequencies were similar to those in Slavic populations and bordering countries. However, we found 6.5 % of alleles with multiple mutations, frequently including p.P453S. Effects of novel mutations, c.386T>C (p.Leu129Pro) and c.493T>C (p.Ser165Pro), were characterized in silico as deleterious. The effect of well-known mutations on Serbian patients' phenotype was as expected. Conclusions: The first comprehensive molecular genetic study of Serbian CAH patients revealed two novel CYP21A2 mutations. This study will enable genetic counseling in our population and contribute to better understanding of molecular landscape of CAH in Europe. © 2015 Italian Society of Endocrinology (SIE).

Purpose: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease characterized by impaired adrenal steroidogenesis and most often caused by CYP21A2 gene mutations. For the first time, we reported complete spectrum and frequency of CYP21A2 gene mutations in 61 unrelated patients with classical and non-classical CAH from Serbia. Methods: Direct DNA sequencing of whole CYP21A2 gene and polymerase chain reaction with sequence-specific primers for detection of CYP21A1P/CYP21A2 chimeras were combined. Results: We identified 18 different pathogenic alleles - two of them novel. Mutation detection rate was highest in patients with salt-wasting form of CAH (94.7 %). The most prevalent mutation was intron 2 splice site mutation, c.290-13A/C>G (18.5 %). Other mutation frequencies were: CYP21A1P/CYP21A2 chimeras (13 %), p.P30L (13 %), p.R356W (11.1 %), p.G110fs (7.4 %), p.Q318X (4.6 %), p.V281L (4.6 %), p.I172N (2.8 %), p.L307fs (2.8 %), p.P453S (1.9 %), etc. Mainly, frequencies were similar to those in Slavic populations and bordering countries. However, we found 6.5 % of alleles with multiple mutations, frequently including p.P453S. Effects of novel mutations, c.386T>C (p.Leu129Pro) and c.493T>C (p.Ser165Pro), were characterized in silico as deleterious. The effect of well-known mutations on Serbian patients' phenotype was as expected. Conclusions: The first comprehensive molecular genetic study of Serbian CAH patients revealed two novel CYP21A2 mutations. This study will enable genetic counseling in our population and contribute to better understanding of molecular landscape of CAH in Europe. © 2015 Italian Society of Endocrinology (SIE).

Background Abdominal obesity and metabolic syndrome are known to increase in prevalence from premenopause to postmenopause. Both are well recognized predictors of cardiovascular disease and diabetes in women. Aims The primary objective of this study was to assess the presence of obesity and metabolic syndrome during the menopause transition in Serbian women who attended health-care centers. The secondary objective was to evaluate the prevalence of ischemic heart disease, stroke and diabetes in this group. Methods Our results present a part of the national epidemiological cross-sectional study assessing prevalence of metabolic syndrome and obesity in Serbia. In all, 1076 women attending 20 health-care centers were assessed. Women were divided into five groups: premenopausal, perimenopausal, early and late postmenopausal and geripausal. Medical history, waist circumference, blood glucose, lipids, and blood pressure were recorded. Results The mean body mass index of all women was 28.5 ± 4.9 kg/m 2. The mean waist circumference of all women was 92 ± 12.5 cm. Both were significantly lower in premenopausal women than in other women. Metabolic syndrome was present in 72% of women, with a significant difference in prevalence between premenopausal women and other groups. High triglyceride levels and hypertension were the most commonly present components of metabolic syndrome. Ischemic heart disease, stroke and diabetes occurred significantly more often in postmenopausal and geripausal women. Conclusion The majority of Serbian women attending health-care centers have abdominal obesity and metabolic syndrome which significantly increase in prevalence in the perimenopausal years. This indicates that preventive measures should be focused on diabetes and cardiovascular disease in the perimenopause. © 2011 International Menopause Society.

The aim of this International Menopause Society White Paper on premature ovarian insufficiency (POI) is to provide the latest information regarding this distressing condition. The impact of POI has far-reaching consequences due to its impact on general, psychological, and sexual quality of life, fertility prospects, and long-term bone, cardiovascular, and cognitive health. Progress in fully understanding the etiology, diagnosis, and optimal management options has been slow thus far due to the complexity of the condition and fragmented research. Recent advances in epidemiological and genetic research have improved our understanding of this condition and randomized prospective trials are being planned to determine the intervention strategies, which will optimize quality of life and long-term well-being. The International Menopause Society has commissioned a number of experts at the forefront of their specialty to define the state of the art in the understanding of this condition, to advise on practical management strategies, and to propose future research strategies. It is hoped that a global task force will subsequently be convened in order to formulate a consensus statement across key societies, to accelerate date collection and analysis of a global POI registry, and to facilitate progress in the key defined areas of research. © 2020 International Menopause Society.