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Mette H Viuff Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark

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Claus H Gravholt Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark

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In this commentary, we discuss the state of affairs concerning the clinical care of females with Turner syndrome (TS) in Germany. TS is a rare disease and new international guidelines describe an appropriate setup for optimal clinical care. Several countries have implemented a program with centralized adult Turner syndrome clinics, which are now found in France, Denmark, the Netherlands, Sweden, parts of England and possibly other countries, but hitherto not in Germany. Such an approach should ensure the availability of high quality multi-disciplinary care for all women with TS to be treated and to detect all the conditions that have been associated with TS, which typically appear at odd times during the lifetime of a female with TS. Care should be offered at no added cost for the patient, and treatment with relevant drugs should be available at reasonable cost for the individual patient. Currently, it is quite problematic that many female sex hormone preparations are not available at low cost in a number of countries. Additional problems include supply chain issue which lead to patients not being able to buy their usual drug for a certain period of time. We think it is timely that countries improve the care for individuals with rare conditions, such as TS.

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Karim Gariani Service of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, Geneva University Hospitals and Geneva University, Geneva, Switzerland

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François R Jornayvaz Service of Endocrinology, Diabetes, Nutrition and Therapeutic Patient Education, Geneva University Hospitals and Geneva University, Geneva, Switzerland
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. NAFLD encompasses a whole spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The latter can lead to hepatocellular carcinoma. Furthermore, NASH is the most rapidly increasing indication for liver transplantation in western countries and therefore represents a global health issue. The pathophysiology of NASH is complex and includes multiple parallel hits. NASH is notably characterized by steatosis as well as evidence of hepatocyte injury and inflammation, with or without fibrosis. NASH is frequently associated with type 2 diabetes and conditions associated with insulin resistance. Moreover, NASH may also be found in many other endocrine diseases such as polycystic ovary syndrome, hypothyroidism, male hypogonadism, growth hormone deficiency or glucocorticoid excess, for example. In this review, we will discuss the pathophysiology of NASH associated with different endocrinopathies.

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Veronica Kieffer
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Kate Davies University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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Christine Gibson University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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Morag Middleton University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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Jean Munday University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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Shashana Shalet University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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Lisa Shepherd University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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Phillip Yeoh University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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This competency framework was developed by a working group of endocrine specialist nurses with the support of the Society for Endocrinology to enhance the clinical care that adults with an endocrine disorder receive. Nurses should be able to demonstrate that they are functioning at an optimal level in order for patients to receive appropriate care. By formulating a competency framework from which an adult endocrine nurse specialist can work, it is envisaged that their development as professional practitioners can be enhanced. This is the second edition of the Competency Framework for Adult Endocrine Nursing. It introduces four new competencies on benign adrenal tumours, hypo- and hyperparathyroidism, osteoporosis and polycystic ovary syndrome. The authors and the Society for Endocrinology welcome constructive feedback on the document, both nationally and internationally, in anticipation that further developments and ideas can be incorporated into future versions.

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Yao Chen Hangzhou Fuyang Women and Children Hospital, Hangzhou, China

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Shu-ying Fang Hangzhou Fuyang Women and Children Hospital, Hangzhou, China

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Polycystic ovary syndrome (PCOS) is a heterogenous endocrine disorder with typical symptoms of oligomenorrhoea, hyperandrogenism, hirsutism, obesity, insulin resistance and increased risk of type 2 diabetes mellitus. Extensive evidence indicates that PCOS is a genetic disease and numerous biochemical pathways have been linked with its pathogenesis. A number of genes from these pathways have been investigated, which include those involved with steroid hormone biosynthesis and metabolism, action of gonadotropin and gonadal hormones, folliculogenesis, obesity and energy regulation, insulin secretion and action and many others. In this review, we summarize the historical and recent findings in genetic polymorphisms of PCOS from the relevant publications and outline some genetic polymorphisms that are potentially associated with the risk of PCOS. This information could uncover candidate genes associating with PCOS, which will be valuable for the development of novel diagnostic and treatment platforms for PCOS patients.

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Sebastião Freitas de Medeiros Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil
Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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Cinthia Marenza Ormond Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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Matheus Antônio Souto de Medeiros Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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Nayara de Souza Santos Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil
Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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Camila Regis Banhara Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil
Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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Márcia Marly Winck Yamamoto Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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Objective

To examine the anthropometric, and metabolic connections of 17-hydroxypregnenolone in the normo- and hyperandrogenemic polycystic ovary syndrome phenotypes.

Materials and methods

This cohort study was conducted at the Julio Muller University Hospital, Cuiabá, Brazil, between January 2014 and July 2016, and 91 normal cycling healthy women, 46 normoandrogenemic and 147 hyperandrogenemic, patients with polycystic ovary syndrome (PCOS) were enrolled according to the Rotterdam criteria. Several anthropometric, biochemical and hormonal parameters were properly verified and correlated with 17-hydroxypregnenolone (17-OHPE) concentrations.

Results

17-OHPE was higher in hyperandrogenemic PCOS than in normoandrogenemic PCOS and in control groups (P = 0.032 and P < 0.001, respectively). In healthy controls, 17-OHPE was positively associated with glucose, free estrogen index, DHEAS and negatively associated with compounds S. In normoandrogenemic PCOS patients, 17-OHPE presented positive correlations with VAI, LAP, cortisol, insulin and HOMA-IR. In the hyperandrogenemic group, 17-OHPE presented significant negative correlations with most anthropometric parameters, HOMA-IR, HOMA %B, estradiol, free estrogen index (FEI), C-peptide, and TG levels and positive correlations with HOMA-S and high-density lipoprotein cholesterol (HDL-C), sex-hormone binding globulin (SHBG), androstenedione (A4) and dehydroepiandrosterone (DHEA). Regarding hyperandrogenemic PCOS, and using a stepwise multiple regression, only HOMA-S and WHR were retained in the model (R 2 = 0.294, P < 0.001).

Conclusion

17-OHPE exhibited different relationships with anthropometric, and biochemical parameters in PCOS patients, depending on the androgen levels. In PCOS subjects with high androgen concentrations, 17-OHPE was negatively associated with most anthropometric parameters, particularly with those used as markers of adipose tissue dysfunction and frequently employed as predictors of cardiovascular disease risk; otherwise, 17-OHPE was positively associated with HDL-C and HOMA-S in this patients. Future studies are required to evaluate the clinical implications of these novel findings.

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Caroline Culen University Clinic of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Diana-Alexandra Ertl University Clinic of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Katharina Schubert University Clinic of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Lisa Bartha-Doering University Clinic of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Gabriele Haeusler University Clinic of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Turner syndrome (TS), although considered a rare disease, is the most common sex chromosome abnormality in women, with an incident of 1 in 2500 female births. TS is characterized by distinctive physical features such as short stature, ovarian dysgenesis, an increased risk for heart and renal defects as well as a specific cognitive and psychosocial phenotype. Given the complexity of the condition, patients face manifold difficulties which increase over the lifespan. Furthermore, failures during the transitional phase to adult care result in moderate health outcomes and decreased quality of life. Guidelines on the optimal screening procedures and medical treatment are easy to find. However, recommendations for the treatment of the incriminating psychosocial aspects in TS are scarce. In this work, we first reviewed the literature on the cognitive and psychosocial development of girls with TS compared with normal development, from disclosure to young adulthood, and then introduce a psychosocial approach to counseling and treating patients with TS, including recommendations for age-appropriate psychological diagnostics. With this work, we aim to facilitate the integration of emphasized psychosocial care in state-of-the-art treatment for girls and women with TS.

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María Dolores Rodríguez Arnao Pediatric Endocrinology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Amparo Rodríguez Sánchez Pediatric Endocrinology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Ignacio Díez López Hospital Universitario Araba, Araba/Alava, Spain

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Joaquín Ramírez Fernández Hospital Universitario Príncipe de Asturias, Oviedo, Spain

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Jose Antonio Bermúdez de la Vega Centro Nuevas Tecnologias, Sevilla, Spain

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Diego Yeste Fernández Hospital Vall d’Hebrón, Barcelona, Spain

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María Chueca Guindulain Complejo Hospitalario de Navarra, Pamplona, Spain

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Raquel Corripio Collado Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain

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Jacobo Pérez Sánchez Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain

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Ana Fernández González Merck S.L.U., Madrid, Spain

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ECOS Spain Study Collaborative Investigator Group
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Background

Non-adherence to r-hGH treatments occurs in a variable percentage of subjects. One problem found when evaluating adherence is the great variability in methods of detection and definitions utilized in studies. This study assessed the level of adherence in subjects receiving r-hGH with the easypod™ electronic device.

Methods

National, multicenter, prospective and observational study involving 238 subjects (144 with GH deficiency (GHD), and 86 with small for gestational age (SGA), 8 with Turner Syndrome), who received r-hGH with easypod™ for at least 3 months before inclusion. The follow-up period was 4 years.

Results

Overall adherence was 94.5%; 97.5% after 6 months, 95.3% after 1 year, 93.7% after 2, 94.4% after 3 and 95.5% after 4 years of treatment. No differences in adherence were observed between prepubertal and pubertal groups and GHD and SGA groups. Change in height after 1 and 2 years, change in height SDS after 1 and 2 years, HV after 1 year, HV SDS after at 1 and 4 years, change in BMI after 1 year and change in BMI SDS at 1 and 2 years showed significant correlation with adherence. No significant differences in adherence according to IGF-I levels were found in follow-up visits or between groups.

Conclusions

The easypod™ electronic device, apart from being a precise and objective measure of adherence to r-hGH treatment, allows high compliance rates to be achieved over long periods of time. Adherence significantly impacts growth outcomes associated with r-hGH treatment.

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Diana-Alexandra Ertl Department of Pulmonology, Allergology and Endocrinology, University Clinic for Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Andreas Gleiss Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria

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Katharina Schubert Department of Pulmonology, Allergology and Endocrinology, University Clinic for Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Caroline Culen Department of Pulmonology, Allergology and Endocrinology, University Clinic for Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Peer Hauck Pediatric Heart Center Vienna, University Clinic for Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Johannes Ott Clinic Division for Gynecologic Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria

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Alois Gessl Division of Endocrinology, University Clinic of Internal Medicine III, Medical University of Vienna, Vienna, Austria

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Gabriele Haeusler Department of Pulmonology, Allergology and Endocrinology, University Clinic for Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria

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Background

Previous studies have shown that only a minority of patients with Turner syndrome (TS) have adequate medical care after transfer to adult care.

Aim of this study

To assess the status of medical follow-up and quality of life (QoL) in adult women diagnosed with TS and followed up until transfer. To compare the subjective and objective view of the medical care quality and initiate improvements based on patients’ experiences and current recommendations.

Methods

39 adult women with TS out of 64 patients contacted were seen for a clinical and laboratory check, cardiac ultrasound, standardized and structured questionnaires (SF-36v2 and Beck depression inventory).

Results

7/39 of the patients were not being followed medically at all. Only 2/39 consulted all the specialists recommended. Comorbidities were newly diagnosed in 27/39 patients; of these, 11 related to the cardiovascular system. Patients in our cohort scored as high as the mean reference population for SF-36v2 in both mental and physical compartments. Obese participants had lower scores in the physical function section, whereas higher education was related to higher physical QoL scores. Adult height slightly correlated positively with physical health.

Conclusion

Medical follow-up was inadequate in our study cohort of adults with TS. Even though their medical follow-up was insufficient, these women felt adequately treated, leaving them vulnerable for premature illness. Initiatives in health autonomy and a structured transfer process as well as closer collaborations within specialities are urgently needed.

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Bo Zhu Department of Obstetrics and Gynecology, Assisted Reproduction Unit, Sir Run Run ShawHospital, Zhejiang University School of Medicine Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, Zhejiang, China
Department of Gynecology and Obstetrics, Wenzhou People’s Hospital, Wenzhou Women and Children Health, Wenzhou, Zhejiang, China

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Yumei Chen Department of Gynecology and Obstetrics, Wenzhou People’s Hospital, Wenzhou Women and Children Health, Wenzhou, Zhejiang, China

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Fang Xu Department of Gynecology and Obstetrics, Wenzhou People’s Hospital, Wenzhou Women and Children Health, Wenzhou, Zhejiang, China

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Xiaolu Shen Department of Gynecology and Obstetrics, Wenzhou People’s Hospital, Wenzhou Women and Children Health, Wenzhou, Zhejiang, China

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Xuanyu Chen Department of Gynecology and Obstetrics, Wenzhou People’s Hospital, Wenzhou Women and Children Health, Wenzhou, Zhejiang, China

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Jieqiang Lv Department of Gynecology and Obstetrics, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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Songying Zhang Department of Obstetrics and Gynecology, Assisted Reproduction Unit, Sir Run Run ShawHospital, Zhejiang University School of Medicine Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, Zhejiang, China

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Background

Androgens excess results in endoplasmic reticulum (ER) stress, which is an important cause of β cells dysfunction. Here, we investigated the molecular regulation of androgens excess, ER stress, and β-cell function in polycystic ovary syndrome (PCOS).

Methods

PCOS mouse model was established by injection of DHEA. Primary cultured mouse islets were used to detect testosterone (TE)-induced ER stress. The response of ER stress, apoptosis, and hyperinsulinemia were analyzed in INS-1 cells with or without TE exposure. Androgen receptor (AR) antagonist and ER stress inhibitor treatment was performed to evaluate the role of TE in ER stress and proinsulin secretion of PCOS mice.

Results

PCOS mice had higher ER stress in islets. TE exposure induced ER stress and apoptosis significantly through sustaining insulin overexpression in β cells, which in turn impaired proinsulin maturation and secretion. Blocking this process could significantly relieve ER stress and apoptosis and improve insulin homeostasis.

Conclusion

ER stress activated by androgens excess in PCOS contributes to β cell dysfunction and hyperinsulinemia.

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Shilpa Lingaiah Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Centre, University of Oulu and Oulu University Hospital, Oulu, Finland

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Laure Morin-Papunen Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Centre, University of Oulu and Oulu University Hospital, Oulu, Finland

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Terhi Piltonen Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Centre, University of Oulu and Oulu University Hospital, Oulu, Finland

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Inger Sundström-Poromaa Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden

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Elisabet Stener-Victorin Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

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Juha S Tapanainen Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Centre, University of Oulu and Oulu University Hospital, Oulu, Finland
Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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Objective

Serum levels of retinol-binding protein 4 (RBP4), an adipokine thought to affect systemic insulin sensitivity, were compared between women with polycystic ovary syndrome (PCOS) and non-PCOS controls to evaluate the association of RBP4 with clinical, hormonal and metabolic parameters of PCOS.

Subjects and methods

Serum RBP4 levels were analysed in 278 women with PCOS (age range 18–57 years) and 191 non-PCOS controls (age 20–53 years) by enzyme-linked immunosorbent assay.

Results

Serum levels of RBP4 were increased in women with PCOS compared with control women in the whole population (45.1 ± 24.0 (s.d.) vs 33.5 ± 18.3 mg/L, P < 0.001). Age-stratified analysis showed that serum RBP4 levels were increased in women with PCOS aged ≤30 years compared with controls (47.7 ± 23.5 vs 27.1 ± 10.4 mg/L, P < 0.001), whereas no significant differences were seen in the other age groups. No significant correlations of RBP4 were seen with either steroids or indices of insulin resistance.

Conclusions

Although serum RBP4 levels were increased in younger women with PCOS compared with age-matched non-PCOS controls, RBP4 does not seem to be a good marker of insulin resistance or other metabolic derangements in women with PCOS.

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