Browsing by Author "Vujovic, Svetlana (57225380338)"

Maintaining body homeostasis is a prerequisite for normal reproductive function, which is vital for the survival of the species and an important process of natural selection. Body weight is an independent regulator of the hypothalamic–pituitary–gonadal axis activity. © 2016, International Society of Gynecological Endocrinology.

Climacterium is the phase in women’s life beginning with the first menopausal symptom and cycle irregularities and ending 1 year after the last menstruation. Endocrinological, biological and clinical changes become apparent at that time. © 2016, International Society of Gynecological Endocrinology.

Osteoporosis and the resulting fractures are major public health issues as the world population is ageing. Various therapies such as bisphosphonates, strontium ranelate and more recently denosumab are available. This clinical guide provides the evidence for the clinical use of selective estrogen modulators (SERMs) in the management of osteoporosis in postmenopausal women. © 2011 Elsevier Ireland Ltd.

Osteoporosis and the resulting fractures are major public health issues as the world population is ageing. Various therapies such as bisphosphonates, strontium ranelate and more recently denosumab are available. This clinical guide provides the evidence for the clinical use of selective estrogen modulators (SERMs) in the management of osteoporosis in postmenopausal women. © 2011 Elsevier Ireland Ltd.

Introduction: Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is a serious cardiovascular event whose incidence rises with increasing age. Aims: To formulate a position statement on the management of the menopause in women with a personal or family history of VTE. Material and methods: Literature review and consensus of expert opinion. Results and conclusions: Randomized controlled trials have shown an increased risk of VTE in oral hormone therapy (HT) users. There are no randomized trial data on the effect of transdermal estrogen on VTE. Recent observational studies and meta-analyses suggest that transdermal estrogen does not increase VTE risk. These clinical observations are supported by experimental data showing that transdermal estrogen has a minimal effect on hepatic metabolism of hemostatic proteins as the portal circulation is bypassed. A personal or family history of VTE, especially in individuals with a prothrombotic mutation, is a strong contraindication to oral HT but transdermal estrogen can be considered after careful individual evaluation of the benefits and risks. Transdermal estrogen should be also the first choice in overweight/obese women requiring HT. Observational studies suggest that micronized progesterone and dydrogesterone might have a better risk profile than other progestins with regard to VTE risk. Although these findings should be confirmed by randomized clinical trials, they strongly suggest that both the route of estrogen administration and the type of progestin may be important determinants of the overall benefit-risk profile of HT. © 2011 Elsevier Ireland Ltd. All rights reserved.

Introduction: Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is a serious cardiovascular event whose incidence rises with increasing age. Aims: To formulate a position statement on the management of the menopause in women with a personal or family history of VTE. Material and methods: Literature review and consensus of expert opinion. Results and conclusions: Randomized controlled trials have shown an increased risk of VTE in oral hormone therapy (HT) users. There are no randomized trial data on the effect of transdermal estrogen on VTE. Recent observational studies and meta-analyses suggest that transdermal estrogen does not increase VTE risk. These clinical observations are supported by experimental data showing that transdermal estrogen has a minimal effect on hepatic metabolism of hemostatic proteins as the portal circulation is bypassed. A personal or family history of VTE, especially in individuals with a prothrombotic mutation, is a strong contraindication to oral HT but transdermal estrogen can be considered after careful individual evaluation of the benefits and risks. Transdermal estrogen should be also the first choice in overweight/obese women requiring HT. Observational studies suggest that micronized progesterone and dydrogesterone might have a better risk profile than other progestins with regard to VTE risk. Although these findings should be confirmed by randomized clinical trials, they strongly suggest that both the route of estrogen administration and the type of progestin may be important determinants of the overall benefit-risk profile of HT. © 2011 Elsevier Ireland Ltd. All rights reserved.

Introduction: Premature ovarian failure (also known as premature menopause) is defined as menopause before the age of 40. It can be "natural" or "iatrogenic" such as after bilateral oophorectomy. It may be either primary or secondary. In the majority of cases of primary POF the cause is unknown. Chromosome abnormalities (especially X chromosome), follicle-stimulating hormone receptor gene polymorphisms, inhibin B mutations, enzyme deficiencies and autoimmune disease may be involved. Secondary POF is becoming more important as survival after treatment of malignancy through surgery, radiotherapy and chemotherapy continues to improve. Aim: To formulate a position statement on the management of premature ovarian failure. Materials and methods: Literature review and consensus of expert opinion. Results and conclusions: Diagnosis should be confirmed with an elevated FSH greater than 40 IU/L and an estradiol level below 50 pmol/L in the absence of bilateral oophorectomy. Further assessment should include thyroid function tests, autoimmune screen for polyendocrinopathy, karyotype (less than 30 years of age) and bone mineral density. Untreated early ovarian failure increases the risk of osteoporosis, cardiovascular disease, dementia, cognitive decline and Parkinsonism. The mainstay of treatment is hormone therapy which needs to be continued until the average age of the natural menopause. With regard to fertility, while spontaneous ovulation may occur the best chance of achieving pregnancy is through donor oocyte in vitro fertilization. It is essential that women are provided with adequate information as they may find it a difficult diagnosis to accept. It is recommended that women with POF are seen in a specialist unit able to deal with their multiple needs. © 2010 Elsevier Ireland Ltd. All rights reserved.

Introduction: Premature ovarian failure (also known as premature menopause) is defined as menopause before the age of 40. It can be "natural" or "iatrogenic" such as after bilateral oophorectomy. It may be either primary or secondary. In the majority of cases of primary POF the cause is unknown. Chromosome abnormalities (especially X chromosome), follicle-stimulating hormone receptor gene polymorphisms, inhibin B mutations, enzyme deficiencies and autoimmune disease may be involved. Secondary POF is becoming more important as survival after treatment of malignancy through surgery, radiotherapy and chemotherapy continues to improve. Aim: To formulate a position statement on the management of premature ovarian failure. Materials and methods: Literature review and consensus of expert opinion. Results and conclusions: Diagnosis should be confirmed with an elevated FSH greater than 40 IU/L and an estradiol level below 50 pmol/L in the absence of bilateral oophorectomy. Further assessment should include thyroid function tests, autoimmune screen for polyendocrinopathy, karyotype (less than 30 years of age) and bone mineral density. Untreated early ovarian failure increases the risk of osteoporosis, cardiovascular disease, dementia, cognitive decline and Parkinsonism. The mainstay of treatment is hormone therapy which needs to be continued until the average age of the natural menopause. With regard to fertility, while spontaneous ovulation may occur the best chance of achieving pregnancy is through donor oocyte in vitro fertilization. It is essential that women are provided with adequate information as they may find it a difficult diagnosis to accept. It is recommended that women with POF are seen in a specialist unit able to deal with their multiple needs. © 2010 Elsevier Ireland Ltd. All rights reserved.

Introduction: There is emerging evidence on the widespread tissue effects of vitamin D. Aims: To formulate a position statement on the role of vitamin D in postmenopausal women. Materials and methods: Literature review and consensus of expert opinion. Results and conclusions: Epidemiological and prospective studies have related vitamin D deficiency with not only osteoporosis but also cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However the evidence is robust for skeletal but not nonskeletal outcomes where data from large prospective studies are lacking. The major natural source of vitamin D is cutaneous synthesis through exposure to sunlight with a small amount from the diet in animal-based foods such as fatty fish, eggs and milk. Vitamin D status is determined by measuring serum 25-hydroxyvitamin D [25(OH)D] levels. Optimal serum 25(OH)D levels are in the region of 30-90 ng/mL (75-225 nmol/L) though there is no international consensus. Levels vary according to time of the year (lower in the winter), latitude, altitude, air pollution, skin pigmentation, use of sunscreens and clothing coverage. Risk factors for low serum 25(OH)D levels include: obesity, malabsorption syndromes, medication use (e.g. anticonvulsants, antiretrovirals), skin aging, low sun exposure and those in residential care. Fortified foods do not necessarily provide sufficient amounts of vitamin D. Regular sunlight exposure (without sunscreens) for 15 min, 3-4 times a week, in the middle of the day in summer generate healthy levels. The recommended daily allowance is 600 IU/day increasing to 800 IU/day in those aged 71 years and older. Supplementation can be undertaken with either vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) with monitoring depending on the dose used and the presence of concomitant medical conditions such as renal disease. © 2011 Elsevier Ireland Ltd. All rights reserved.

Introduction: There is emerging evidence on the widespread tissue effects of vitamin D. Aims: To formulate a position statement on the role of vitamin D in postmenopausal women. Materials and methods: Literature review and consensus of expert opinion. Results and conclusions: Epidemiological and prospective studies have related vitamin D deficiency with not only osteoporosis but also cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However the evidence is robust for skeletal but not nonskeletal outcomes where data from large prospective studies are lacking. The major natural source of vitamin D is cutaneous synthesis through exposure to sunlight with a small amount from the diet in animal-based foods such as fatty fish, eggs and milk. Vitamin D status is determined by measuring serum 25-hydroxyvitamin D [25(OH)D] levels. Optimal serum 25(OH)D levels are in the region of 30-90 ng/mL (75-225 nmol/L) though there is no international consensus. Levels vary according to time of the year (lower in the winter), latitude, altitude, air pollution, skin pigmentation, use of sunscreens and clothing coverage. Risk factors for low serum 25(OH)D levels include: obesity, malabsorption syndromes, medication use (e.g. anticonvulsants, antiretrovirals), skin aging, low sun exposure and those in residential care. Fortified foods do not necessarily provide sufficient amounts of vitamin D. Regular sunlight exposure (without sunscreens) for 15 min, 3-4 times a week, in the middle of the day in summer generate healthy levels. The recommended daily allowance is 600 IU/day increasing to 800 IU/day in those aged 71 years and older. Supplementation can be undertaken with either vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) with monitoring depending on the dose used and the presence of concomitant medical conditions such as renal disease. © 2011 Elsevier Ireland Ltd. All rights reserved.

Objective To identify whether variants found in a large Han Chinese cohort - 8q22.3 SNPs rs3847153 and rs3108910; and one SNP each in HK3 (rs2278493), ESR1 (rs2234693) and BRSK1 (rs12611091) - are associated with premature ovarian failure (POF) in a different ethnic group (Serbian). Design Case-control genetic association study in 197 Serbian POF cases and 552 matched controls. Results None of the SNPs found associated with POF in Chinese cohort were found to be associated in the Serbian sample. Conclusions In contrast to Han Chinese, no association was found between POF in Serbian women and any of the four tested loci: 8q22.3, HK3, ESR1 and BRSK1. This indicates that ethnically distinct populations may show differences in gene-regulating pathways and genes causing POF. © 2013 Elsevier Ireland Ltd.

Objective To identify whether variants found in a large Han Chinese cohort - 8q22.3 SNPs rs3847153 and rs3108910; and one SNP each in HK3 (rs2278493), ESR1 (rs2234693) and BRSK1 (rs12611091) - are associated with premature ovarian failure (POF) in a different ethnic group (Serbian). Design Case-control genetic association study in 197 Serbian POF cases and 552 matched controls. Results None of the SNPs found associated with POF in Chinese cohort were found to be associated in the Serbian sample. Conclusions In contrast to Han Chinese, no association was found between POF in Serbian women and any of the four tested loci: 8q22.3, HK3, ESR1 and BRSK1. This indicates that ethnically distinct populations may show differences in gene-regulating pathways and genes causing POF. © 2013 Elsevier Ireland Ltd.

It is well known that hypertension can be primary or secondary. However, among secondary causes of hypertension, gender-specific hypertension is one lately recognized. © 2016, International Society of Gynecological Endocrinology.

In the ancient Rome, average life duration was 23 years; in Sweden at the end of the eighteenth century, 36.6 years for women and 33.7 for men; and in many European countries at the beginning of the twenty-first century, life expectancy was 72 and 76 years, respectively. The menopause (period in women’s life 1 year after the last menstruation until the end of life) and involutive hypoandrogenism in males (testosterone below 12 nmol/L and typical symptoms) are characterized by decrease of gonadal steroids and initiating of cardiovascular diseases (CVD). Rahman [1] found that women who entered early menopause (40–45 years) had 40% increase of heart disease. Meta-analysis confirmed these data (Table 16.1). © 2018, International Society of Gynecological Endocrinology.

Aim: to test effects of estradiol (E2) 1 mg and drospirenone (DRSP) 2 mg in treatment of normal weight menopausal women with typical menopausal symptoms, hyperinsulinism, and grade I hypertension. Material and methods: The participants were 133 menopausal women, mean age 51.82 ± 3.25 years, body mass index (BMI) 24.9 ± 2.6 kg/m2, waist/hip 0.80 ± 0.05, amenorrhoeic period 2.12 ± 2.10 years. All patients were treated with E2 1 mg and DRSP 2 mg during 12 months period. Blood samples were taken at 8 am before and during 12 months of therapy for: glycemia, lipids, hormonal analysis, follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, testosterone (T), prolactin (PRL), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG). Oral glucose tolerance test (OGTT) was performed with 75 g glucose in order to assess insulin secretion. All had grade I hypertension 24 h blood pressure monitoring was performed before and after 12 months of therapy. Results: E2/DRSP significantly decreased total cholesterol, low-density lipoprotein (LDL), apolipoprotein B (ApoB), and increased high-density lipoprotein cholesterol (HDL) and apolipoprotein A (ApoA). Insulin area under the curve (AUC) significantly decreased (6586.1 ± 4194.2 vs. 5315.3 ± 2895.0, p <.05) and homeostatic model assessment (HOMA) (3.53 ± 2.18 vs. 3.0 ± 1.8, p <.05). FSH, LH decreased, E2 increased significantly. Of 24 h day blood pressure decreased significantly. Conclusions: E2/DRSP represents suitable therapy for hyperinsulinemic, grade I hypertensive menopausal women with typical symptoms and normal weight. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Aim: to test effects of estradiol (E2) 1 mg and drospirenone (DRSP) 2 mg in treatment of normal weight menopausal women with typical menopausal symptoms, hyperinsulinism, and grade I hypertension. Material and methods: The participants were 133 menopausal women, mean age 51.82 ± 3.25 years, body mass index (BMI) 24.9 ± 2.6 kg/m2, waist/hip 0.80 ± 0.05, amenorrhoeic period 2.12 ± 2.10 years. All patients were treated with E2 1 mg and DRSP 2 mg during 12 months period. Blood samples were taken at 8 am before and during 12 months of therapy for: glycemia, lipids, hormonal analysis, follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, testosterone (T), prolactin (PRL), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG). Oral glucose tolerance test (OGTT) was performed with 75 g glucose in order to assess insulin secretion. All had grade I hypertension 24 h blood pressure monitoring was performed before and after 12 months of therapy. Results: E2/DRSP significantly decreased total cholesterol, low-density lipoprotein (LDL), apolipoprotein B (ApoB), and increased high-density lipoprotein cholesterol (HDL) and apolipoprotein A (ApoA). Insulin area under the curve (AUC) significantly decreased (6586.1 ± 4194.2 vs. 5315.3 ± 2895.0, p <.05) and homeostatic model assessment (HOMA) (3.53 ± 2.18 vs. 3.0 ± 1.8, p <.05). FSH, LH decreased, E2 increased significantly. Of 24 h day blood pressure decreased significantly. Conclusions: E2/DRSP represents suitable therapy for hyperinsulinemic, grade I hypertensive menopausal women with typical symptoms and normal weight. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Introduction. Metoidioplasty represents one of the variants of phalloplasty in female transsexuals. Its main characteristic is that it is a one-stage procedure. It involves lengthening and straightening of hypertrophied clitoris to create a neophallus, urethral lengthening to enable voiding while standing, and scrotal reconstruction with insertion of testicle prostheses. Aim. Our aim is to describe our technique and highlight its advantages. Methods. Between September 2002 and April 2007, 82 female transsexuals,aged 18-54 years (mean age 31) underwent one-stage metoidioplasty. Clitoris is lengthened and straightened by division of clitoral ligaments and short urethral plate. Urethroplasty is done with combined buccal mucosa graft and genital skin flaps. Scrotum is created from labia majora in which two testicle prostheses are inserted. Simultaneously, female genitalia are removed. Main Outcome Measures. Patients' personal satisfaction about sensitivity and length of neophallus, possibility to void in standing position, real length of reconstructed urethra as well as complication rate comparing to other published data. Results. The median follow-up was 32 months (range 14-69). The mean neophallic length was 5.7cm (range 4-10). Voiding in standing position was reported in all patients, while dribbling and spraying were noticed in 23 cases and solved spontaneously. There were two urethral strictures and seven fistulas that required secondary minor revision. All patients reported preserved sensation and normal postoperative erection. Testicle prostheses rejection was not observed in any of the patients. Conclusions. Metoidioplasty is a single-stage and time-saving procedure. It could be an alternative to total phalloplasty in female transsexuals who do not wish to have sexual intercourse. Also, it represents a first step in cases where additional augmentation phalloplasty is required. © 2009 International Society for Sexual Medicine.

Introduction. Metoidioplasty represents one of the variants of phalloplasty in female transsexuals. Its main characteristic is that it is a one-stage procedure. It involves lengthening and straightening of hypertrophied clitoris to create a neophallus, urethral lengthening to enable voiding while standing, and scrotal reconstruction with insertion of testicle prostheses. Aim. Our aim is to describe our technique and highlight its advantages. Methods. Between September 2002 and April 2007, 82 female transsexuals,aged 18-54 years (mean age 31) underwent one-stage metoidioplasty. Clitoris is lengthened and straightened by division of clitoral ligaments and short urethral plate. Urethroplasty is done with combined buccal mucosa graft and genital skin flaps. Scrotum is created from labia majora in which two testicle prostheses are inserted. Simultaneously, female genitalia are removed. Main Outcome Measures. Patients' personal satisfaction about sensitivity and length of neophallus, possibility to void in standing position, real length of reconstructed urethra as well as complication rate comparing to other published data. Results. The median follow-up was 32 months (range 14-69). The mean neophallic length was 5.7cm (range 4-10). Voiding in standing position was reported in all patients, while dribbling and spraying were noticed in 23 cases and solved spontaneously. There were two urethral strictures and seven fistulas that required secondary minor revision. All patients reported preserved sensation and normal postoperative erection. Testicle prostheses rejection was not observed in any of the patients. Conclusions. Metoidioplasty is a single-stage and time-saving procedure. It could be an alternative to total phalloplasty in female transsexuals who do not wish to have sexual intercourse. Also, it represents a first step in cases where additional augmentation phalloplasty is required. © 2009 International Society for Sexual Medicine.

Objective To determine whether variants in the SOHLH2 gene contribute to human premature ovarian failure (POF) in different ethnicities. Design Case-control genetic study. Setting University hospitals. Patient(s) Chinese (364 cases) and Serbian (197 cases) women with nonsyndromic POF and ethnically matched controls. Intervention(s) None. Main Outcome Measure(s) Variation analysis of the SOHLH2 gene. Result(s) Eleven novel heterozygous variants were identified in cohorts of POF but were absent in matched controls. These included the nonsynonymous variants p.Glu79Lys (n = 2 cases), p.Glu105Gly, and p.Thr321Pro, which were found among four Chinese POF cases, and p.Leu120Phe (n = 3 cases) and p.Leu204Phe, which were found among four Serbian women. Protein alignments reveal that p.Glu79Lys and p.Glu105Gly involve amino acids highly conserved among mammals, both of which are predicted to be deleterious. The c.-210G>T found in the Chinese POF cohort lies in the core promoter region, which is enriched with transcription factor binding sites and CpG islands. In the Serbian cohort, the variant most likely to have a deleterious effect is c.530+6T>G, which is predicted to affect RNA splicing and result in nonsense mediated decay of transcripts. The other variants are less likely to be deleterious. Disturbing the expression, transactivation or homo-/ heterodimerization of the SOHLH2 protein could result in ovarian failure. Overall, four of the 11 novel variants seem plausible explanations for POF; the other seven variants are less likely but cannot be categorically excluded. Conclusion(s) Our identification of novel variants in the SOHLH2 gene, in women with POF of both Chinese and Serbian origin, strongly suggests an important role for SOHLH2 in human POF etiology. © 2014 American Society for Reproductive Medicine, Published by Elsevier Inc. All rights reserved.

Genetic and environmental factors influence the quality of life and well-being. Breaking of adaptive mechanisms, induced by stressors, triggers diseases. Premature ovarian insufficiency (POI) is characterized by oligo/amenorrhea, high gonadotropin, and low estradiol levels in women younger than 40 years of age. Known etiological factors inducing POI include chromosomal abnormalities, enzyme changes, autoimmune diseases, FSH receptor gene polymorphism, inhibin B mutation, infectious disease, adnexectomy, radiotherapy, uterine artery embolization, etc. Unknown factors include stressors, inflammation, telomerase shortening, biological clock acceleration, etc. Early POI symptoms, significantly decreasing the quality of life, are hot flushes, irritability, anxiety, depression, mood swings, loss of concentration, insomnia, loss of libido, etc. Late complications include cardiovascular diseases, osteoporosis, metabolic syndrome, cognitive changes, Alzheimer’s disease, urogenital dysfunction, decreased fertility rate, etc. Diagnosis is confirmed by FSH >40 IU/L (or 25 IU/L), estradiol <50 pmol/L, and oligo/amenorrhea in women younger than 40 years of age. Also, suggested analyses are AMH, inhibin B, prolactin, dehydroepiandrosterone sulfate (DHEAS), free testosterone, free thyroxin (fT4), thyroid-stimulating hormone (TSH), cortisol, vitamin D, and oral glucose tolerance test (OGTT). Visualization methods include ultrasound examination of uterus, ovaries, and breasts and osteodensitometry. In untreated POI patients, mortality rate is increased. Therapy with estroprogestogens, and all other insufficient hormones (testosterone, fT4, DHEAS, vitamin D, etc.), has to be initiated immediately and continued without age limits, depending on individual needs, in order to achieve the best quality of life. © 2023, International Society of Gynecological Endocrinology.