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Dorte Glintborg Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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Hanne Mumm Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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Jens Juul Holst Department of Biomedical Sciences and NNF Centre for Basic Metabolic Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

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Marianne Andersen Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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Context

Insulin resistance in polycystic ovary syndrome (PCOS) may increase the risk of reactive hypoglycaemia (RH) and decrease glucagon-like peptide-1 (GLP-1) secretion. The possible effects of treatment with oral contraceptives (OCP) and/or metformin on GLP-1 secretion and risk of RH in PCOS is undetermined.

Setting

Outpatient clinic.

Patients and interventions

Randomized, controlled clinical trial. Ninety women with PCOS were randomized to 12-month treatment with OCP (150 mg desogestrel + 30 mg ethinylestradiol), metformin (2 g/day) or metformin + OCP. Five-hour oral glucose tolerance tests (5-h OGTT) measuring fasting and area under the curve (AUC) for GLP-1, glucose, insulin and C-peptide were performed before and after the intervention period. Sixty-five women completed the study and 34 weight-matched healthy women were included as controls.

Main outcome measures

Changes in GLP-1, glucose, insulin and C-peptide during 5-h OGTT.

Results

Fasting GLP-1 levels increased during metformin + OCP vs OCP treatment, whereas AUC GLP-1 levels were unchanged during medical treatment. The prevalence of reactive hypoglycemia increased from 9/65 to 14/65 after intervention (P < 0.01) and was more common after treatment with metformin + OCP (increase from 3/23 to 6/23, P = 0.01). Reactive hypoglycaemia was associated with higher insulin and C-peptide levels during 5-h OGTT, but was unassociated with BMI and AUC GLP-1. GLP-1 levels were comparable in PCOS vs controls. AUC GLP-1 levels were significantly lower in obese vs lean patients and were inversely associated with BMI.

Conclusions

AUC GLP-1 levels were unchanged during treatment. Increased risk of hypoglycemia during metformin + OCP could be associated with increased insulin secretion.

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Sarantis Livadas Endocrine Unit, Athens Medical Centre, Athens, Greece

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Christina Bothou Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Zurich, Zurich, Switzerland

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Justyna Kuliczkowska-Płaksej Department of Endocrinology, Diabetology and Isotope Therapy, University of Medicine, Wrocław, Poland

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Ralitsa Robeva Ushate ‘acad. IV. Penchev’, Department of Endocrinology, Faculty of Medicine, Medical University-Sofia, Sofia, Bulgaria

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Andromahi Vryonidou Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital, Athens, Greece

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Jelica Bjekic Macut Department of Endocrinology, UMC Bežanijska Kosa, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Ioannis Androulakis Endocrine Unit, Athens Medical Centre, Athens, Greece

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Milica Opalic Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Zadalla Mouslech 1st Medical Propedeutic, Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Andrej Milewicz Department of Endocrinology, Diabetology and Isotope Therapy, University of Medicine, Wrocław, Poland

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Alessandra Gambineri Department of Medical and Surgical Science-DIMEC Endocrinology Unit, University of Bologna – S. Orsola-Mapighi Hospital, Italy

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Dimitrios Panidis Gynaecological Endocrinology Infirmary of the Second Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Djuro Macut Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Background

Polycystic ovary syndrome (PCOS) is considered a risk factor for the development of type 2 diabetes mellitus (T2DM). However, which is the most appropriate way to evaluate dysglycemia in women with PCOS and who are at increased risk are as yet unclear.

Aim of the study

To determine the prevalence of T2DM, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in PCOS women and potential factors to identify those at risk.

Subjects and methods

The oral glucose tolerance test (OGTT), biochemical/hormonal profile, and ovarian ultrasound data from 1614 Caucasian women with PCOS and 362 controls were analyzed in this cross-sectional multicenter study. The data were categorized according to age and BMI.

Results

Dysglycemia (T2DM, IGT, and IFG according to World Health Organization criteria) was more frequent in the PCOS group compared to controls: 2.2% vs 0.8%, P = 0.04; 9.5% vs 7.4%, P = 0.038; 14.2% vs 9.1%, P = 0.002, respectively. OGTT was essential for T2DM diagnosis, since in 88% of them basal glucose values were inconclusive for diagnosis. The presence of either T2DM or IFG was irrespective of age (P = 0.54) and BMI (P = 0.32), although the latter was associated with IGT (P = 0.021). There was no impact of age and BMI status on the prevalence of T2DM or IFG. Regression analysis revealed a role for age, BMI, fat deposition, androgens, and insulin resistance for dysglycemia. However, none of the factors prevailed as a useful marker employed in clinical practice.

Conclusions

One-third of our cohort of PCOS women with either T2DM or IGT displayed normal fasting glucose values but without confirming any specific predictor for dysglycemic condition. Hence, the evaluation of glycemic status using OGTT in all women with PCOS is strongly supported.

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Renata C Scalco Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil
Disciplina de Endocrinologia, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, São Paulo, Brazil
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Ericka B Trarbach Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Edoarda V A Albuquerque Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Thais K Homma Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Thais H Inoue-Lima Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Mirian Y Nishi Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Berenice B Mendonca Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Alexander A L Jorge Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Most patients with Turner syndrome (TS) need hormone replacement therapy because of hypergonadotropic hypogonadism; individual outcomes, however, are highly variable. Our objective was to assess the influence of five estrogen receptor 1 gene (ESR1) polymorphisms (rs543650, rs1038304, rs2046210, rs2234693 and rs9340799) on adult height, breast development, uterine volume and bone mineral density (BMD). We studied 91 TS patients from a tertiary hospital using adult estrogen dose. In our group, ESR1 rs2234693 was associated with femoral neck and total hip BMD, and it accounted for around 10% of BMD variability in both sites (P < 0.01). Patients homozygous for C allele in this polymorphism had significantly lower femoral neck BMD (0.699 ± 0.065 g/cm2 vs 0.822 ± 0.113 g/cm2, P = 0.008) and total hip BMD (0.777 ± 0.118 g/cm2 vs 0.903 ± 0.098 g/cm2, P = 0.009) than patients homozygous for T allele. The other four ESR1 polymorphisms were not able to predict any of the above estrogen therapy outcomes in an isolated manner. Patients homozygous for the haplotype GCG formed by polymorphisms rs543650, rs2234693 and rs9340799 had an even more significantly lower femoral neck BMD (0.666 ± 0.049 vs 0.820 ± 0.105 g/cm2, P = 0.0047) and total hip BMD (0.752 ± 0.093 vs 0.908 ± 0.097 g/cm2, P = 0.0029) than patients homozygous for haplotypes with a T allele in rs2234693. In conclusion, homozygosity for C allele in ESR1 rs2234693 and/or for GCG haplotype appears to be associated with lower femoral neck and total hip BMD. We believe that the identification of polymorphisms related to estrogen outcomes may contribute to individualization of treatment in TS.

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Valentina Guarnotta Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza ‘G. D’Alessandro’ (PROMISE), Sezione di Malattie Endocrine, del Ricambio e della Nutrizione, Università di Palermo, Palermo, Italy

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Silvia Lucchese Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza ‘G. D’Alessandro’ (PROMISE), Sezione di Malattie Endocrine, del Ricambio e della Nutrizione, Università di Palermo, Palermo, Italy

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Mariagrazia Irene Mineo Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza ‘G. D’Alessandro’ (PROMISE), Sezione di Malattie Endocrine, del Ricambio e della Nutrizione, Università di Palermo, Palermo, Italy

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Donatella Mangione Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza ‘G. D’Alessandro’ (PROMISE), Sezione di Ostetricia e Ginecologia, Università di Palermo, Palermo, Italy

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Renato Venezia Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza ‘G. D’Alessandro’ (PROMISE), Sezione di Ostetricia e Ginecologia, Università di Palermo, Palermo, Italy

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Piero Luigi Almasio Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza ‘G. D’Alessandro’ (PROMISE), Sezione di Gastroenterologia ed Epatologia, Università di Palermo, Palermo, Italy

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Carla Giordano Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza ‘G. D’Alessandro’ (PROMISE), Sezione di Malattie Endocrine, del Ricambio e della Nutrizione, Università di Palermo, Palermo, Italy

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Objective

The aim of this study is to clarify, in girls with premature pubarche (PP), the influence of premature androgenization on the prevalence of polycystic ovary syndrome (PCOS).

Design and patients

Ninety-nine PP girls, 63 who developed PCOS and 36 who did not develop PCOS, were retrospectively included. Clinical, anthropometric, and metabolic parameters were evaluated at the time of diagnosis of PP and after 10 years from menarche to find predictive factors of PCOS.

Results

Young females with PP showed a PCOS prevalence of 64% and showed a higher prevalence of familial history of diabetes (P = 0.004) and a lower prevalence of underweight (P = 0.025) than PP-NO-PCOS. In addition, girls with PP-PCOS showed higher BMI (P < 0.001), waist circumference (P < 0.001), total testosterone (P = 0.026), visceral adiposity index (VAI) (P = 0.013), total cholesterol (P < 0.001), LDL-cholesterol (P < 0.001), non-HDL cholesterol (P < 0.001) and lower age of menarche (P = 0.015), ISI-Matsuda (P < 0.001), DIo (P = 0.002), HDL cholesterol (P = 0.026) than PP-NO-PCOS. Multivariate analysis showed that WC (P = 0.049), ISI-Matsuda (P < 0.001), oral disposition index (DIo) (P < 0.001), VAI (P < 0.001), total testosterone (P < 0.001) and LDL-cholesterol (P < 0.001) are independent predictive factors for PCOS in girls with PP.

Conclusions

Our study established a strong association between multiple risk factors and development of PCOS in PP girls. These risk factors are predominantly related to the regulation of glucose, lipid, and androgen metabolism. Among these factors, WC, ISI-Matsuda, DIo, VAI, total testosterone, and LDL-cholesterol predict PCOS.

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M von Wolff Division of Gynaecological Endocrinology and Reproductive Medicine, University Women’s Hospital, Bern University Hospital, University of Bern, Bern, Switzerland

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C T Nakas University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Laboratory of Biometry, University of Thessaly, Volos, Greece

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M Tobler Division of Gynaecological Endocrinology and Reproductive Medicine, University Women’s Hospital, Bern University Hospital, University of Bern, Bern, Switzerland
Division of Pneumology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

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T M Merz Division of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

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M P Hilty Intensive Care Unit, University Hospital, Zurich, Switzerland

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J D Veldhuis Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, Centre for Translational Science Activities, Mayo Clinic, Rochester, New York, USA

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A R Huber Centre for Laboratory Medicine, Cantonal Hospital, Aarau, Switzerland

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J Pichler Hefti Division of Pneumology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

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Humans cannot live at very high altitude for reasons, which are not completely understood. Since these reasons are not restricted to cardiorespiratory changes alone, changes in the endocrine system might also be involved. Therefore, hormonal changes during prolonged hypobaric hypoxia were comprehensively assessed to determine effects of altitude and hypoxia on stress, thyroid and gonadal hypothalamus–pituitary hormone axes. Twenty-one male and 19 female participants were examined repetitively during a high-altitude expedition. Cortisol, prolactin, thyroid-stimulating hormone (TSH), fT4 and fT3 and in males follicle-stimulating hormone (FSH), luteinizing hormone (LH) and total testosterone were analysed as well as parameters of hypoxemia, such as SaO2 and paO2 at 550 m (baseline) (n = 40), during ascent at 4844 m (n = 38), 6022 m (n = 31) and 7050 m (n = 13), at 4844 m (n = 29) after acclimatization and after the expedition (n = 38). Correlation analysis of hormone concentrations with oxygen parameters and with altitude revealed statistical association in most cases only with altitude. Adrenal, thyroid and gonadal axes were affected by increasing altitude. Adrenal axis and prolactin were first supressed at 4844 m and then activated with increasing altitude; thyroid and gonadal axes were directly activated or suppressed respectively with increasing altitude. Acclimatisation at 4844 m led to normalization of adrenal and gonadal but not of thyroid axes. In conclusion, acclimatization partly leads to a normalization of the adrenal, thyroid and gonadal axes at around 5000 m. However, at higher altitude, endocrine dysregulation is pronounced and might contribute to the physical degradation found at high altitude.

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M Boering Isala, Diabetes Centre, Zwolle, The Netherlands

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P R van Dijk Isala, Diabetes Centre, Zwolle, The Netherlands
Isala, Department of Internal Medicine, Zwolle, The Netherlands

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S J J Logtenberg Diakonessenhuis, Department of Internal Medicine, Utrecht, The Netherlands
Langerhans Medical Research group, Zwolle, The Netherlands

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K H Groenier Isala, Diabetes Centre, Zwolle, The Netherlands
Department of General Practice, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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B H R Wolffenbuttel Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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R O B Gans Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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N Kleefstra Isala, Diabetes Centre, Zwolle, The Netherlands
Langerhans Medical Research group, Zwolle, The Netherlands
Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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H J G Bilo Isala, Diabetes Centre, Zwolle, The Netherlands
Isala, Department of Internal Medicine, Zwolle, The Netherlands
Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

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Aims

Elevated sex hormone-binding globulin (SHBG) concentrations have been described in patients with type 1 diabetes mellitus (T1DM), probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII), or subcutaneous (SC), influences SHBG concentrations among T1DM patients.

Methods

Post hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (±13) years, diabetes duration 23 (±11) years, and hemoglobin A1c (HbA1c) 8.7 (±1.1) (72 (±12) mmol/mol). As secondary outcomes, testosterone, 17-β-estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were analyzed.

Results

Estimated mean change in SHBG was −10.3nmol/L (95% CI: −17.4, −3.2) during CIPII and 3.7nmol/L (95% CI: −12.0, 4.6) during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was −6.6nmol/L (95% CI: −17.5, 4.3); −12.7nmol/L (95% CI: −25.1, −0.4) for males and −1.7nmol/L (95% CI: −24.6, 21.1) for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; −15.8nmol/L (95% CI: −24.2, −7.5) and −8.3nmol/L (95% CI: −14.4, −2.2), respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2U/L (95% CI: 0.1, 2.2) among males.

Conclusions

SHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids.

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Liza Haqq School of Science and Technology, University of New England, Armidale, New South Wales 2351, Australia

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James McFarlane School of Science and Technology, University of New England, Armidale, New South Wales 2351, Australia

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Gudrun Dieberg School of Science and Technology, University of New England, Armidale, New South Wales 2351, Australia

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Neil Smart School of Science and Technology, University of New England, Armidale, New South Wales 2351, Australia

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Polycystic ovarian syndrome (PCOS) affects 18–22% of women at reproductive age. We conducted a systematic review and meta-analysis evaluating the expected benefits of lifestyle (exercise plus diet) interventions on the reproductive endocrine profile in women with PCOS. Potential studies were identified by systematically searching PubMed, CINAHL and the Cochrane Controlled Trials Registry (1966–April 30, 2013) systematically using key concepts of PCOS. Significant improvements were seen in women receiving lifestyle intervention vs usual care in follicle-stimulating hormone (FSH) levels, mean difference (MD) 0.39 IU/l (95% CI 0.09 to 0.70, P=0.01), sex hormone-binding globulin (SHBG) levels, MD 2.37 nmol/l (95% CI 1.27 to 3.47, P<0.0001), total testosterone levels, MD −0.13 nmol/l (95% CI −0.22 to −0.03, P=0.008), androstenedione levels, MD −0.09 ng/dl (95% CI −0.15 to −0.03, P=0.005), free androgen index (FAI) levels, MD −1.64 (95% CI −2.94 to −0.35, P=0.01) and Ferriman–Gallwey (FG) score, MD −1.01 (95% CI −1.54 to −0.48, P=0.0002). Significant improvements were also observed in women who received exercise-alone intervention vs usual care in FSH levels, MD 0.42 IU/l (95% CI 0.11 to 0.73, P=0.009), SHBG levels, MD 3.42 nmol/l (95% CI 0.11 to 6.73, P=0.04), total testosterone levels, MD −0.16 nmol/l (95% CI −0.29 to −0.04, P=0.01), androstenedione levels, MD −0.09 ng/dl (95% CI −0.16 to −0.03, P=0.004) and FG score, MD −1.13 (95% CI −1.88 to −0.38, P=0.003). Our analyses suggest that lifestyle (diet and exercise) intervention improves levels of FSH, SHBG, total testosterone, androstenedione and FAI, and FG score in women with PCOS.

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Tao Mei Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China
Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China

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Jianhe Zhang Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China

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Liangfeng Wei Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China

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Xingfeng Qi Department of Pathology, Fuzhou General Hospital, Fuzhou, China

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Yiming Ma Department of Neurosurgery, Liuzhou General Hospital, Liuzhou, China

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Xianhua Liu Department of Pathology, Fuzhou General Hospital, Fuzhou, China

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Shaohua Chen Department of Pathology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China

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Songyuan Li Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China

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Jianwu Wu Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China

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Shousen Wang Department of Neurosurgery, Fuzhou General Hospital, Fuzhou, China

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Tumor cells require large amounts of energy to sustain growth. Through the mediated transport of glucose transporters, the uptake and utilization of glucose by tumor cells are significantly enhanced in the hypoxic microenvironment. Pituitary adenomas are benign tumors with high-energy metabolisms. We aimed to investigate the role of expression of glucose transporter 3 (GLUT3) and glucose transporter 1 (GLUT1) in pituitary adenomas, including effects on size, cystic change and hormone type. Pituitary adenomas from 203 patients were collected from January 2013 to April 2017, and immunohistochemical analysis was used to detect the expression of GLUT3 and GLUT1 in tumor specimens. GLUT3-positive expression in the cystic change group was higher than that in the non-cystic change group (P = 0.018). Proportions of GLUT3-positive staining of microadenomas, macroadenomas, and giant adenomas were 22.7 (5/22), 50.4 (66/131) and 54.0% (27/50), respectively (P = 0.022). In cases of prolactin adenoma, GLUT3-positive staining was predominant in cell membranes (P = 0.000006), while in cases of follicle-stimulating hormone or luteotropic hormone adenoma, we found mainly paranuclear dot-like GLUT3 staining (P = 0.025). In other hormonal adenomas, GLUT3 was only partially expressed, and the intensity of cell membrane or paranuclear punctate staining was weak. In contrast to GLUT3, GLUT1 expression was not associated with pituitary adenomas. Thus, our results indicate that the expression of GLUT3 in pituitary adenomas is closely related to cystic change and hormonal type. This study is the first to report a unique paranuclear dot-like GLUT3 staining pattern in pituitary adenomas.

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Mikkel Andreassen Department of Endocrinology, Faculty of Health Science, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Faculty of Health Science, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Ulla Feldt-Rasmussen Department of Endocrinology, Faculty of Health Science, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Niels Jørgensen Department of Growth and Reproduction, Faculty of Health Science, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Objective

Gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) are released from the pituitary gland and stimulate Leydig cells to produce testosterone and initiates spermatogenesis. Little is known about how and when the deterioration of semen quality occurs in patients with adult-onset gonadotropin insufficiency.

Design and methods

A retrospective study comprising 20 testosterone-deficient men (median age, 29 years) with acquired pituitary disease who delivered semen for cryopreservation before initiation of testosterone therapy. Semen variables and hormone concentrations were compared to those of young healthy men (n = 340).

Results

Thirteen of 20 patients (65%) and 82% of controls had total sperm counts above 39 million and progressive motile spermatozoa above 32% (P = 0.05). For the individual semen variables, there were no significant differences in semen volume (median (intraquartile range) 3.0 (1.3–6.8) vs 3.2 (2.3–4.3) mL, P = 0.47), sperm concentration 41 (11–71) vs 43 (22–73) mill/mL (P = 0.56) or total sperm counts (P = 0.66). One patient had azoospermia. Patients vs controls had lower serum testosterone 5.4 (2.2–7.6) vs 19.7 (15.5–24.5) nmol/L (P = 0.001), calculated free testosterone (cfT) 145 (56–183) vs 464 (359–574) pmol/L (P < 0.001), LH 1.5 (1.1–2.1) vs 3.1 (2.3–4.0) U/L (P = 0.002) and inhibin b (P < 0.001). Levels of FSH were similar (P = 0.63). Testosterone/LH ratio and cfT/LH ratio were reduced in patients (both P < 0.001).

Conclusions

Despite Leydig cell insufficiency in patients with acquired pituitary insufficiency, the majority presented with normal semen quality based on the determination of the number of progressively motile spermatozoa. In addition, the data suggest reduced LH bioactivity in patients with pituitary insufficiency.

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Yunting Lin Department of Surgical Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China

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Endi Song Department of Internal Medicine, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang, China

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Han Jin Department of Medicine, Ningbo University, Ningbo, Zhejiang, China

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Yong Jin Department of Internal Medicine, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang, China

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Background

Reproductive hormones may be a risk factor for cardiovascular disease (CVD), but their influence is often underestimated. Obesity can exacerbate the progression of CVD. Arterial stiffness (AS) is correlated with the risk of CVD. Brachial-ankle pulse wave velocity (baPWV) has served as a practical tool for assessing AS with broad clinical applications. This study aimed to investigate the association between reproductive hormones and baPWV in obese male and female subjects.

Methods

A retrospective case–control design was designed. AS was assessed using baPWV, with a baPWV ≥ 1400 cm/s indicating increased AS. Between September 2018 and October 2022, 241 obese subjects with increased AS were recruited from Ningbo Yinzhou No. 2 Hospital. The control group consisted of 241 obese subjects without increased AS. A 1:1 propensity score matching was performed to correct potential confounders by age and sex. We additionally performed a sex-based sub-analysis.

Results

Correlation analysis demonstrated that luteinizing hormone (LH) (r = 0.214, P = 0.001) and follicle-stimulating hormone (FSH) (r = 0.328, P < 0.001) were positively correlated with baPWV in obese male subjects. In the multivariate conditional logistic regression analysis, FSH (OR = 1.407, 95% CI = 1.040–1.902, P = 0.027) rather than LH (OR = 1.210, 95% CI = 0.908–1.612, P = 0.194) was independently and positively associated with increased AS in obese male subjects. However, there was no significant correlation between reproductive hormones and baPWV in women.

Conclusions

Our study identified FSH as a potential risk factor for arteriosclerosis in obese male subjects. This provides a novel and intriguing perspective on the pathogenesis of CVD in obese subjects.

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