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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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Anastasia K Armeni Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, University of Patras Medical School, Patras, Greece

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Konstantinos Assimakopoulos Department of Psychiatry, University of Patras Medical School, Patras, Greece

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Dimitra Marioli Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, University of Patras Medical School, Patras, Greece

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Vassiliki Koika Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, University of Patras Medical School, Patras, Greece

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Euthychia Michaelidou Department of Biology, University of Patras, Patras, Greece

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Niki Mourtzi Department of Biology, University of Patras, Patras, Greece

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Gregoris Iconomou Department of Psychiatry, University of Patras Medical School, Patras, Greece

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Neoklis A Georgopoulos Division of Reproductive Endocrinology, Department of Obstetrics and Gynaecology, University of Patras Medical School, Patras, Greece

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Over the past decades, research attention has increasingly been paid to the neurobiological component of sexual behavior. The aim of the present study was to investigate the correlation of estrogen receptor α (ERA) gene polymorphism (rs2234693-PvuII) (T→C substitution) and oxytocin receptor gene polymorphism (rs53576) (G→A substitution) with sexuality parameters of young, healthy women. One hundred thirty-three Greek heterosexual women, students in higher education institutions, 20–25 years of age, sexually active, with normal menstrual cycles (28–35 days), were recruited in the study. Exclusion criteria were chronic and/or major psychiatric diseases, use of oral contraceptive pills (OCs), polycystic ovary syndrome (PCOS), thyroid diseases as well as drugs that are implicated in hypothalamus–pituitary–gonadal axis. T allele (wildtype) of rs2234693 (PvuII) polymorphism of ERA gene was correlated with increased levels of arousal and lubrication, whereas A allele (polymorphic) of rs53576 (OXTR) polymorphism was correlated with increased arousal levels. The simultaneous presence of both T allele of rs2234693 (PvuII) and A allele of rs53576 (OXTR) polymorphisms (T + A group) was correlated with increased arousal, orgasm levels as well as female sexual function index full score. To our knowledge, this is the first study to investigate the interaction between ERA and OXTR with regard to sexual function in women. Female sexuality is a complex behavioral trait that encompasses both biological and psychological components. It seems that variability in female sexual response stems from genetic variability that characterizes endocrine, neurotransmitter and central nervous system influences.

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Michelle Hadjiconstantinou University of Leicester, Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK

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Hamidreza Mani University of Leicester, Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK
Department of Diabetes and Endocrinology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK

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Naina Patel University of Leicester, Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK

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Miles Levy Department of Diabetes and Endocrinology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK

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Melanie Davies University of Leicester, Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK
Department of Diabetes and Endocrinology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK

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Kamlesh Khunti University of Leicester, Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK

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Margaret Stone University of Leicester, Diabetes Research Centre, Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK

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Objective

Polycystic ovary syndrome (PCOS) is a lifelong condition. Its symptoms have been linked with psychological consequences, but less attention has been given to the daily implications of living with PCOS. We aimed to explore women’s experiences living with PCOS, and the potential acceptability of group education sessions for this target group.

Methods

Women with PCOS were recruited from an ethnically diverse UK community. Twelve semi-structured interviews were conducted. Analysis was underpinned by the constant comparative approach and involved the identification and exploration of key themes.

Results

Participants reported a range of symptoms linked with PCOS, including problems relating to menstruation and weight difficulties. Hirsutism was reported as the most distressing symptom. Emergent themes included perceptions about symptoms and delays in receiving a diagnosis; psychological distress; practical implications of living with the condition; coping with PCOS and perceived support needs. Some findings were specific to cultural backgrounds. Participants were supportive of the idea of group education for women with PCOS and suggested a need to provide education within the community and health care providers.

Discussion

Women with PCOS experience high psychological distress and difficulties with coping with their condition. Suggested strategies to reduce the negative psychological impact include education at various levels.

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Nafiye Helvaci Department of Internal Medicine, Division of Endocrinology and Metabolism, Hacettepe University School of Medicine, Ankara, Turkey

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Erdem Karabulut Department of Biostatistics, Hacettepe University School of Medicine, Ankara, Turkey

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Ahmet Ugur Demir Department of Chest Diseases, Hacettepe University School of Medicine, Ankara, Turkey

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Bulent Okan Yildiz Department of Internal Medicine, Division of Endocrinology and Metabolism, Hacettepe University School of Medicine, Ankara, Turkey

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Background and Objective

Polycystic ovary syndrome (PCOS) has been reported to be associated with the development of obstructive sleep apnea (OSA). The objective of this meta-analysis is to assess the relationship between PCOS and OSA.

Methods

A literature search was conducted to identify studies linking PCOS with the risk of OSA. Studies in which the presence of OSA was confirmed with overnight polysomnography were included. Random effects models were used to calculate pooled relative risks.

Results

Eight studies conducted in adults and five studies conducted in adolescents were identified. The pooled OSA prevalence was 0.22 (95% confidence interval (CI): 0.08–0.40) in PCOS patients. The pooled prevalence of OSA was higher in adults (0.32, 95% CI: 0.13–0.55) than adolescents (0.08, 95% CI: 0.00–0.30). Risk of OSA was significantly increased in adult patients with PCOS (odds ratio (OR) 9.74, 95% CI: 2.76–34.41). Risk of OSA was not significantly increased in adolescents (OR: 4.54, 95% CI:0.56–36.43).

Conclusions

These findings demonstrate a significant association between PCOS and OSA in adult patients. Considering the increased risk for long-term cardiometabolic disorders associated with both PCOS and OSA, it is important to diagnose and treat OSA in patients with PCOS.

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Xingyan Liu Department of Obstetrics & Gynecology, General Hospital of PLA Eastern Theater (Nanjing General Hospital of Nanjing Military Command), Command, Nanjing, China

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Mei Xu Department of Obstetrics & Gynecology, General Hospital of PLA Eastern Theater (Nanjing General Hospital of Nanjing Military Command), Command, Nanjing, China

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Min Qian Department of Obstetrics & Gynecology, General Hospital of PLA Eastern Theater (Nanjing General Hospital of Nanjing Military Command), Command, Nanjing, China

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Lindong Yang Department of Obstetrics & Gynecology, General Hospital of PLA Eastern Theater (Nanjing General Hospital of Nanjing Military Command), Command, Nanjing, China

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The cytochrome P450 family 17 (CYP17) is associated with hyperandrogenism in women, and the association between CYP17 gene polymorphism and the risk of polycystic ovary syndrome (PCOS) is not definitive. In order to determine whether the CYP17 T/C (rs74357) gene polymorphism is an exposure risk for PCOS, a comprehensive meta-analysis summarizing 19 studies was performed. The pooled odds ratio (OR) and the corresponding 95% CI were measured under five genetic models, and the stratified analyses by ethnicity, Hardy–Weinberg equilibrium, testosterone levels and BMI in controls were carried out to identify the causes of substantial heterogeneity. The overall results validated that the CYP17 T/C (rs74357) gene polymorphism was significantly associated with PCOS risk in four genetic models. Moreover, the outcomes of subgroup analysis by ethnicity indicated that the frequencies of the C allele of CYP17 T/C (rs74357) polymorphism were markedly higher in women from Asia than in Caucasians (T vs C: OR 0.85, 95% CI = 0.74–0.99, P < 0.05). Therefore, these findings suggested that the CYP17 T/C (rs74357) gene polymorphism played an indispensable part in increasing the susceptibility of PCOS when carrying the C allele, which proposed that the polymorphism of the CYP17 gene may be a predictive factor for the risk of PCOS or an important pathway in PCOS-associated metabolic and hormonal dysregulation.

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Silan Zheng School of Medicine, Xiamen University, Xiamen, China

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Meifeng Tong Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China

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Lianqin Dong The School of Clinical Medicine, Fujian Medical University, Fuzhou, China

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Chunmin Du School of Medicine, Xiamen University, Xiamen, China

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Xin Zheng Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China

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Liying Wang Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China

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Peiying Huang Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China

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Wei Liu Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China

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Mingzhu Lin Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China

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Changqin Liu Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China
The School of Clinical Medicine, Fujian Medical University, Fuzhou, China

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Objective

To explore the independent associations of the new adiposity indices lipid accumulation product (LAP) index, visceral adiposity index (VAI), and product of triglycerides and glucose (TyG) with the risks of hepatic steatosis (HS) in women with polycystic ovary syndrome (PCOS).

Design

This is a cross-sectional study with 101 women with PCOS undergoing controlled attenuation parameter (CAP) measurement who were recruited from November 2018 to August 2019. Multivariable logistic regression analysis was performed to determine the associations of adiposity indices with HS.

Result(s)

Among the 101 PCOS patients, the prevalence rate of HS was 70.3%. The PCOS patients with HS have higher percentage of overweight/obesity status, higher level of aminotransferase (AST and ALT), homeostasis model assessment of insulin resistance (HOMA-IR), LAP, VAI, TyG, waist circumference (WC), and BMI (P < 0.05). Partial correlation analysis showed LAP, WC and BMI were significantly positively associated with CAP (P < 0.05) after controlling for confounding factors. Besides, BMI, WC, and CAP were gradually elevated with the increase of LAP level. Further, multivariable logistic regression analysis showed adjusted odd ratio (OR) with associated 95% CI (OR (95% CI)) were respectively 1.09 (1.03–1.16) for LAP, 1.14 (1.05–1.23) for WC, 1.28 (1.08–1.51) for BMI, respectively.

Conclusions

The present study demonstrates that in women with PCOS, except for the traditional adiposity indices (WC and BMI), LAP is independently correlated with the risk of HS.

Open access
Angelica Lindén Hirschberg Division of Obstetrics and Gynaecology, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden.

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Emerging evidence indicates that testosterone, which can increase muscle mass and strength, stimulates erythropoiesis, promotes competitive behaviour, and enhances the physical performance of women. Indeed, the levels of testosterone within the normal female range are related to muscle mass and athletic performance in female athletes. Furthermore, among these athletes, the prevalence of hyperandrogenic conditions, including both polycystic ovary syndrome and rare differences/disorders of sex development (DSD), which may greatly increase testosterone production, are elevated. Thus, if the androgen receptors of an individual with XY DSD are functional, her muscle mass will develop like that of a man. These findings have led to the proposal that essential hyperandrogenism is beneficial for athletic performance and plays a role in the choice by women to compete in athletic activities. Moreover, a recent randomized controlled trial demonstrated a significant increase in the lean mass and aerobic performance by young exercising women when their testosterone levels were enhanced moderately. Circulating testosterone is considered the strongest factor to explain the male advantage in sport performance, ranging between 10 and 20%. It appears to be unfair to allow female athletes with endogenous testosterone levels in the male range (i.e. 10–20 times higher than normal) to compete against those with normal female androgen levels. In 2012, this consideration led international organizations to establish eligibility regulations for the female classification in order to ensure fair and meaningful competition, but the regulations are controversial and have been challenged in court.

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N K Stepto Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia
Australian Institute for Musculoskeletal Science, Victoria University, Melbourne, Victoria, Australia
Medicine-Western Health, Faculty of Medicine, Dentistry and Health Science, Melbourne University, Melbourne, Victoria, Australia

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D Hiam Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia

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M Gibson-Helm Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia

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S Cassar Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia

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C L Harrison Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia

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S K Hutchison Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia

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A E Joham Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia

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B J Canny School of Medicine, University of Tasmania, Hobart, Tasmania, Australia

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A Moreno-Asso Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia
Australian Institute for Musculoskeletal Science, Victoria University, Melbourne, Victoria, Australia

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B J Strauss Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
Division of Diabetes, Endocrinology & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK

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N Hatzirodos The Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, Australia

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R J Rodgers The Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, Australia

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H J Teede Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia
Diabetes and Endocrine Units, Monash Health, Clayton, Victoria, Australia

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Objective

Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor β (TGFβ)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways.

Methods

A secondary analysis from a cross-sectional study was undertaken in women with (n = 30) or without (n = 29) PCOS across lean and overweight BMIs. A subset of participants with (n = 8) or without (n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was sampled before and 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training.

Results

We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFβ signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3.

Conclusions

We provide new insights into defects in early insulin signalling, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFβ ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance.

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Carla Scaroni Dipartimento di Medicina, U.O.C. Endocrinologia, Università di Padova, Padova, Italy

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Nora M Albiger Dipartimento di Medicina, U.O.C. Endocrinologia, Università di Padova, Padova, Italy

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Serena Palmieri Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy

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Davide Iacuaniello Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Napoli, Italy

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Chiara Graziadio Department of Experimental Medicine, University La Sapienza, Rome, Italy

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Luca Damiani Department of Medical Sciences, Endocrinology and Internal Medicine Section, University of Ferrara, Ferrara, Italy

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Marialuisa Zilio Dipartimento di Medicina, U.O.C. Endocrinologia, Università di Padova, Padova, Italy

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Antonio Stigliano Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, University La Sapienza, Rome, Italy

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Annamaria Colao Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Napoli, Italy

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Rosario Pivonello Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Napoli, Italy

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the Altogether to Beat Cushing’s Syndrome (ABC) study group
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The distinction between pseudo-Cushing’s states (PCS) and Cushing’s syndrome (CS) poses a significant clinical challenge even for expert endocrinologists. A patient’s clinical history can sometimes help to distinguish between them (as in the case of alcoholic individuals), but the overlap in clinical and laboratory findings makes it difficult to arrive at a definitive diagnosis. We aim to describe the most common situations that can give rise to a condition resembling overt endogenous hypercortisolism and try to answer questions that physicians often face in clinical practice. It is important to know the relative prevalence of these different situations, bearing in mind that most of the conditions generating PCS are relatively common (such as metabolic syndrome and polycystic ovary syndrome), while CS is rare in the general population. Physicians should consider CS in the presence of additional features. Appropriate treatment of underlying conditions is essential as it can reverse the hormonal abnormalities associated with PCS. Close surveillance and a thorough assessment of a patient’s hormone status will ultimately orient the diagnosis and treatment options over time.

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Ewa Stogowska Department of Internal Medicine and Metabolic Diseases, Medical University of Bialystok, Bialystok, Poland

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Karol Adam Kamiński Department of Population Medicine and Civilization Diseases Prevention, Medical University of Bialystok, Bialystok, Poland

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Bartosz Ziółko Techmo, Kraków, Poland

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Irina Kowalska Department of Internal Medicine and Metabolic Diseases, Medical University of Bialystok, Bialystok, Poland

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The subject of vocal changes accompanying pathological conditions, although still not well explored, seems to be promising. The discovery of laryngeal receptors for sex hormones and thyroid hormones can strongly support the hypothesis of changes in voice due to various endocrinopathies. On the other hand, the impairment of the proper function of the vocal apparatus can also be caused in the process of the microvasculature complications of diabetes mellitus. This review was a comprehensive summary of the accessible literature concerning the influence of selected endocrinopathies on subjective and objective voice parameters. We analysed a total number of 16 English-language research papers from the PubMed database, released between 2008 and 2021, describing vocal changes in reproductive disorders such as polycystic ovary syndrome and congenital adrenal hyperplasia, thyroid disorders in shape of hypo- or hyperthyroidism and type 2 diabetes mellitus. The vast majority of the analysed articles proved some changes in voice in all mentioned conditions, although the detailed affected vocal parameters frequently differed between research. We assume that the main cause of the observed conflicting results might stem from non-homogeneous methodology designs of the analysed studies.

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