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  • Abstract: Kallmann x
  • Abstract: Klinefelter x
  • Abstract: menopause x
  • Abstract: puberty x
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Rohit Barnabas Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Swati Jadhav Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, India

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Anurag Ranjan Lila Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Sirisha Kusuma Boddu Consultant Pediatric Endocrinology & Diabetes, Rainbow Children’s Hospital, Hyderabad, India

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Saba Samad Memon Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Sneha Arya Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Samiksha Chandrashekhar Hegishte Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Manjiri Karlekar Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Virendra A Patil Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Vijaya Sarathi Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, India

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Nalini S Shah Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Tushar Bandgar Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India

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Background

The data on Leydig cell hypoplasia (LCH) resulting from biallelic Luteinizing hormone/chorionic gonadotropin receptor (LHCGR) inactivating variants is limited to case series.

Methods

We aim to describe our patients and perform systematic review of the patients with LHCGR inactivating variants in the literature. Detailed phenotype and genotype data of three patients from our centre and 85 (46,XY: 67; 46,XX: 18) patients from 59 families with LHCGR-inactivating variants from literature were described.

Results

Three 46,XY patients (age 6–18 years) from our center, with two reared as females, had two novel variants in LHCGR. Systematic review (including our patients) revealed 72 variants in 88 patients. 46,XY patients (n = 70, 56 raised as females) presented with pubertal delay (n = 41) or atypical genitalia (n = 17). Sinnecker score ≥3 (suggesting antenatal human chorionic gonadotropin (hCG) inaction) was seen in 80% (56/70), and hCG-stimulated testosterone was low (<1.1 ng/mL) in 77.4% (24/31), whereas puberty/postpubertal age, high luteinizing hormone (LH) (97.6%, 41/42) and low (<1.0 ng/mL) basal testosterone (94.9%, 37/39) was observed in most. Follicle stimulating hormone was elevated in 21/51 of these patients. Variants with <10% receptor function were exclusively seen in cohorts with Sinnecker 4/5 (10/15 vs 0/5, P = 0.033). 46,XX patients (n = 18) presented with oligo/amenorrhea and/or anovulatory infertility and had polycystic ovaries (7/9) with median LH of 10 IU/L (1.2–38).

Conclusion

In summary, this study comprehensively characterizes LHCGR variants, revealing genotype-phenotype correlations and informing clinical management of LCH. In 46,XY LCH patients, pubertal LH inaction is uniform with variable severity of antenatal hCG inaction. Few mutant LHCGR have differential actions for LH and hCG.

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Hans Valdemar López Krabbe Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Jørgen Holm Petersen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark

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Louise Laub Asserhøj Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Fertility, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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Trine Holm Johannsen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Peter Christiansen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Rikke Beck Jensen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Line Hartvig Cleemann Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Casper P Hagen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Lærke Priskorn Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Niels Jørgensen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Katharina M Main Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Lise Aksglaede Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Adult patients with Klinefelter syndrome (KS) are characterized by a highly variable phenotype, including tall stature, obesity, and hypergonadotropic hypogonadism, as well as an increased risk of developing insulin resistance, metabolic syndrome, and osteoporosis. Most adults need testosterone replacement therapy (TRT), whereas the use of TRT during puberty has been debated. In this retrospective, observational study, reproductive hormones and whole-body dual-energy x-ray absorptiometry-derived body composition and bone mineral content were standardized to age-related standard deviation scores in 62 patients with KS aged 5.9–20.6 years. Serum concentrations of total testosterone and inhibin B were low, whereas luteinizing hormone and follicle-stimulating hormone were high in patients before TRT. Despite normal body mass index, body fat percentage and the ratio between android fat percentage and gynoid fat percentage were significantly higher in the entire group irrespective of treatment status. In patients evaluated before and during TRT, a tendency toward a more beneficial body composition with a significant reduction in the ratio between android fat percentage and gynoid fat percentage during TRT was found. Bone mineral content (BMC) did not differ from the reference, but BMC corrected for bone area was significantly lower when compared to the reference. This study confirms that patients with KS have an unfavorable body composition and an impaired bone mineral status already during childhood and adolescence. Systematic studies are needed to evaluate whether TRT during puberty will improve these parameters.

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Zheng Chen Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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Haixia Zeng Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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Qiulan Huang Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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Cuiping Lin Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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Xuan Li Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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Shaohua Sun Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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Jian-ping Liu Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

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The aim of the study was to investigate the changes in serum glypican 4 (GPC4) and clusterin (CLU) levels in patients with polycystic ovary syndrome (PCOS) as well as their correlation with sex hormones and metabolic parameters. A total of 40 PCOS patients and 40 age-matched healthy women were selected. Serum GPC4 and CLU levels were compared between the PCOS and control groups, and binary logistic regression was used to analyze the relative risk of PCOS at different tertiles of serum GPC4 and CLU concentrations. Stepwise linear regression was used to identify the factors influencing serum GPC4 and CLU levels in PCOS patients. Serum GPC4 (1.82 ± 0.49 vs 1.30 ± 0.61 ng/mL, P < 0.001) and CLU (468.79 ± 92.85 vs 228.59 ± 82.42 µg/mL, P < 0.001) were significantly higher in PCOS patients than in healthy women after adjustment for body mass index (BMI). In the PCOS group, serum GPC4 was positively correlated with follicle-stimulating hormone, fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride, and CLU (P < 0.05), whereas serum CLU was positively correlated with BMI, FPG, FINS, and HOMA-IR (P < 0.05). Multiple stepwise linear regression analysis showed that HOMA-IR was independently associated with serum GPC4, and BMI and HOMA-IR were independently associated with CLU (P < 0.05). Serum GPC4 and CLU levels were significantly higher in PCOS patients than in healthy women, suggesting that GPC4 and CLU may be markers associated with insulin resistance in women with PCOS.

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Xinyuan Zhang Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China

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Suiyan Li School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China

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Hongwei Liu Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Huai Bai Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Qingqing Liu Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Chunyi Yang Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Ping Fan Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Oxidative stress and metabolic disorders are involved in the pathogenesis of polycystic ovary syndrome (PCOS). Heme oxygenase 2 (HMOX2) plays a critical role in preserving heme metabolism as well as in modulating glycolipid metabolism, oxidative stress, and inflammation. This study examined the correlation between HMOX2 G554A (rs1051308) and A-42G (rs2270363) genetic variants with the risk of PCOS and assessed the effects of these genotypes on clinical, hormonal, metabolic, and oxidative stress indices using a case–control design that included 1014 patients with PCOS and 806 control participants. We found that the allelic and genotypic frequencies of the HMOX2 G554A and A-42G polymorphisms were comparable between the PCOS and control groups in Chinese women (P > 0.05). Nevertheless, it was discovered that patients with the AA or AG genotype of A-42G polymorphism had notably elevated levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo)B, and/or apoB/apoA1 ratio than those with the GG genotypes (P < 0.05). Patients with the GG or AG genotype of G554A polymorphism had elevated serum levels of LH, FSH, E2, LH/FSH ratio, TC, HDL-C, LDL-C, apoB, and/or apoB/apoA1 ratio and lower 2-h glucose concentration compared with those with the AA genotype (P < 0.05). Our findings indicate a potential association between the genetic variants and endocrine abnormalities in the reproductive system and metabolic irregularities in glycolipid levels in patients, thus suggesting their potential role in the pathogenesis of PCOS.

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Andre Madsen Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Lise Aksglaede Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Objective

Klinefelter syndrome (KS) is the most common sex chromosome disorder and genetic cause of infertility in males. A highly variable phenotype contributes to the fact that a large proportion of cases are never diagnosed. Typical hallmarks in adults include small testes and azoospermia which may prompt biochemical evaluation that typically shows extremely high follicle-stimulating hormone and low/undetectable inhibin B serum concentrations. However, in prepubertal KS individuals, biochemical parameters are largely overlapping those of prepubertal controls. We aimed to characterize clinical profiles of prepubertal boys with KS in relation to controls and to develop a novel biochemical classification model to identify KS before puberty.

Methods

Retrospective, longitudinal data from 15 prepubertal boys with KS and data from 1475 controls were used to calculate age- and sex-adjusted standard deviation scores (SDS) for height and serum concentrations of reproductive hormones and used to infer a decision tree classification model for KS.

Results

Individual reproductive hormones were low but within reference ranges and did not discriminate KS from controls. Clinical and biochemical profiles including age- and sex-adjusted SDS from multiple reference curves provided input data to train a ‘random forest’ machine learning (ML) model for the detection of KS. Applied to unseen data, the ML model achieved a classification accuracy of 78% (95% CI, 61–94%).

Conclusions

Supervised ML applied to clinically relevant variables enabled computational classification of control and KS profiles. The application of age- and sex-adjusted SDS provided robust predictions irrespective of age. Specialized ML models applied to combined reproductive hormone concentrations may be useful diagnostic tools to improve the identification of prepubertal boys with KS.

Open access
Elinor Chelsom Vogt Department of Clinical Science, University of Bergen, Bergen, Norway
K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway

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Francisco Gómez Real Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway

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Eystein Sverre Husebye Department of Clinical Science, University of Bergen, Bergen, Norway
K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway

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Sigridur Björnsdottir Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden

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Bryndis Benediktsdottir Medical Faculty, University of Iceland, Reykjavik, Iceland
Department of Sleep, Landspitali University Hospital Reykjavík, Reykjavik, Iceland

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Randi Jacobsen Bertelsen Department of Clinical Science, University of Bergen, Bergen, Norway

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Pascal Demoly University Hospital of Montpellier, IDESP, Univ Montpellier-Inserm, Montpellier, France

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Karl Anders Franklin Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden

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Leire Sainz de Aja Gallastegui Unit of Epidemiology and Public Health, Department of Health, Basque Government, Vitoria-Gasteiz, Spain

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Francisco Javier Callejas González Department of Respiratory Medicine, Albacete University Hospital, Albacete, Spain

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Joachim Heinrich Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Munich, Germany
Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia

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Mathias Holm Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Nils Oscar Jogi Department of Clinical Science, University of Bergen, Bergen, Norway

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Benedicte Leynaert Université Paris-Saclay, Inserm U1018, Center for Epidemiology and Population Health, Integrative Respiratory Epidemiology Team, Villejuif, France

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Eva Lindberg Department of Medical Sciences, Respiratory, Allergy and Sleep Medicine, Uppsala University, Uppsala, Sweden

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Andrei Malinovschi Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden

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Jesús Martínez-Moratalla Pneumology Service of the General University Hospital of Albacete, Albacete, Spain
Albacete Faculty of Medicine, Castilla-La Mancha University, Albacete, Spain

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Raúl Godoy Mayoral Department of Respiratory Medicine, Albacete University Hospital, Albacete, Spain

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Anna Oudin Section of Sustainable Health, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

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Antonio Pereira-Vega Juan Ramón Jiménez University Hospital in Huelva, Huelva, Spain

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Chantal Raherison Semjen INSERM, EpiCene Team U1219, University of Bordeaux, Talence, France

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Vivi Schlünssen Department of Public Health, Environment, Work and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark
The National Research Center for the Working Environment, Copenhagen, Denmark

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Kai Triebner Department of Clinical Science, University of Bergen, Bergen, Norway

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Marianne Øksnes Department of Clinical Science, University of Bergen, Bergen, Norway
K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway

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Objective

To investigate markers of premature menopause (<40 years) and specifically the prevalence of autoimmune primary ovarian insufficiency (POI) in European women.

Design

Postmenopausal women were categorized according to age at menopause and self-reported reason for menopause in a cross-sectional analysis of 6870 women.

Methods

Variables associated with the timing of menopause and hormone measurements of 17β-estradiol and follicle-stimulating hormone were explored using multivariable logistic regression analysis. Specific immunoprecipitating assays of steroidogenic autoantibodies against 21-hydroxylase (21-OH), side-chain cleavage enzyme (anti-SCC) and 17alpha-hydroxylase (17 OH), as well as NACHT leucine-rich-repeat protein 5 were used to identify women with likely autoimmune POI.

Results

Premature menopause was identified in 2.8% of women, and these women had higher frequencies of nulliparity (37.4% vs 19.7%), obesity (28.7% vs 21.4%), osteoporosis (17.1% vs 11.6%), hormone replacement therapy (59.1% vs 36.9%) and never smokers (60.1% vs 50.9%) (P < 0.05), compared to women with menopause ≥40 years. Iatrogenic causes were found in 91 (47%) and non-ovarian causes in 27 (14%) women, while 77 (39%) women were classified as POI of unknown cause, resulting in a 1.1% prevalence of idiopathic POI. After adjustments nulliparity was the only variable significantly associated with POI (odds ratio 2.46; 95% CI 1.63–3.42). Based on the presence of autoantibodies against 21 OH and SCC, 4.5% of POI cases were of likely autoimmune origin.

Conclusion

Idiopathic POI affects 1.1% of all women and almost half of the women with premature menopause. Autoimmunity explains 4.5% of these cases judged by positive steroidogenic autoantibodies.

Open access
Giuseppe Grande Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy

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Andrea Graziani Department of Medicine, University of Padova, Padova, Italy

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Antonella Di Mambro Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy

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Riccardo Selice Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy

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Alberto Ferlin Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy
Department of Medicine, University of Padova, Padova, Italy

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Low bone mass is common in men with Klinefelter syndrome (KS), with a prevalence of 6–15% of osteoporosis and of 25–48% of osteopenia. Reduced bone mass has been described since adolescence and it might be related to both reduced bone formation and higher bone resorption. Although reduced testosterone levels are clearly involved in the pathogenesis, this relation is not always evident. Importantly, fracture risk is increased independently from bone mineral density (BMD) and testosterone levels. Here we discuss the pathogenesis of osteoporosis in patients with KS, with a particular focus on the role of testosterone and testis function. In fact, other hormonal mechanisms, such as global Leydig cell dysfunction, causing reduced insulin-like factor 3 and 25-OH vitamin D levels, and high follicle-stimulating hormone and estradiol levels, might be involved. Furthermore, genetic aspects related to the supernumerary X chromosome might be involved, as well as androgen receptor expression and function. Notably, body composition, skeletal mass and strength, and age at diagnosis are other important aspects. Although dual-energy x-ray absorptiometry is recommended in the clinical workflow for patients with KS to measure BMD, recent evidence suggests that alterations in the microarchitecture of the bones and vertebral fractures might be present even in subjects with normal BMD. Therefore, analysis of trabecular bone score, high-resolution peripheral quantitative computed tomography and vertebral morphometry seem promising tools to better estimate the fracture risk of patients with KS. This review also summarizes the evidence on the best available treatments for osteoporosis in men with KS, with or without hypogonadism.

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Nathalie Ly Department of Endocrinology and Reproductive Medicine, Reference Center for Rare Endocrine Diseases of Growth and Development, Reference Center for Gynecological Rare Diseases, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France
EndoERN, APHP Consortium Pitie Salpetriere Hospital, Necker Hospital, Paris, France

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Sophie Dubreuil Department of Endocrinology and Reproductive Medicine, Reference Center for Rare Endocrine Diseases of Growth and Development, Reference Center for Gynecological Rare Diseases, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France
EndoERN, APHP Consortium Pitie Salpetriere Hospital, Necker Hospital, Paris, France

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Philippe Touraine Department of Endocrinology and Reproductive Medicine, Reference Center for Rare Endocrine Diseases of Growth and Development, Reference Center for Gynecological Rare Diseases, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France
EndoERN, APHP Consortium Pitie Salpetriere Hospital, Necker Hospital, Paris, France
Sorbonne University, Paris, France

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Objective

Growth hormone (GH) and insulin-like growth factors (IGFs) are not mandatory for reproductive life, but data suggest their synergistic action with follicle-stimulating hormone throughout ovarian folliculogenesis. We aimed to evaluate the association of IGF-1 level on clinical pregnancy rate after ovarian stimulation, with or without intrauterine insemination, in women with GH deficiency (GHD) treated with GH replacement therapy (GHRT) at conception.

Design and methods

Data from 19 women with both GHD and hypogonadotropic hypogonadism referred to our reproductive medicine department were retrospectively collected. IGF-1 levels were assessed in a single laboratory, and values were expressed in s.d. from the mean.

Results

Amongst the seven patients receiving GHRT during ovarian stimulation, higher IGF-1 levels were significantly associated with clinical pregnancy (+0.4 s.d. vs–1.6 s.d., P = 0.03). Amongst the 24 pregnancies obtained by the 19 infertile patients, pregnancy loss was less frequent with the addition of GHRT than without (1 miscarriage out of 8 total pregnancies vs 4 miscarriages out of 16 total pregnancies).

Conclusions

This is the first study evaluating the association of IGF-1 level on clinical pregnancy rate in GH-treated women at conception. When taking care of female infertility due to hypogonadotropic hypogonadism, practitioners should enquire about the associated GHD and IGF-1 levels. To ensure higher clinical pregnancy chances, practitioners should aim for IGF-1 values at conception, ranging from 0 s.d. to +2 s.d., and, if necessary, could discuss initiation or increase GH treatment. Prospective studies should help strengthen our results.

Open access
Jennifer K Y Ko Department of Obstetrics and Gynecology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China

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Jinghua Shi Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China

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Raymond H W Li Department of Obstetrics and Gynecology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China

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William S B Yeung Department of Obstetrics and Gynecology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China

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Ernest H Y Ng Department of Obstetrics and Gynecology, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China

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Objective

Vitamin D receptors are present in the female reproductive tract. Studies on the association between serum vitamin D level and pregnancy rate of in vitro fertilization (IVF) showed inconsistent results and focused on a single fresh or frozen embryo transfer cycle. The objective of our study was to evaluate if serum vitamin D level before ovarian stimulation was associated with the cumulative live birth rate (CLBR) of the first IVF cycle.

Design

Retrospective cohort study.

Methods

Women who underwent the first IVF cycle from 2012 to 2016 at a university-affiliated reproductive medicine center were included. Archived serum samples taken before ovarian stimulation were analyzed for 25(OH)D levels using liquid chromatography-mass spectrometry.

Results

In total, 1113 had pregnancy outcome from the completed IVF cycle. The median age (25th–75th percentile) of the women was 36 (34–38) years and serum 25(OH)D level was 53.4 (41.9–66.6) nmol/L. The prevalence of vitamin D deficiency (less than 50 nmol/L) was 42.2%. The CLBR in the vitamin D-deficient group was significantly lower compared to the non-deficient group (43.9%, 208/474 vs 50.9%, 325/639, P  = 0.021, unadjusted), and after controlling for women’s age, BMI, antral follicle count, type and duration of infertility. There were no differences in the clinical/ongoing pregnancy rate, live birth rate and miscarriage rate in the fresh cycle between the vitamin D deficient and non-deficient groups.

Conclusions

Vitamin D deficiency was prevalent in infertile women in subtropical Hong Kong. The CLBR of the first IVF cycle in the vitamin D-deficient group was significantly lower compared to the non-deficient group.

Open access
Signe Kirkegaard Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Nanna Maria Uldall Torp Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Stig Andersen Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Geriatrics, Aalborg University Hospital, Aalborg, Denmark

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Stine Linding Andersen Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

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Endometriosis and polycystic ovary syndrome (PCOS) are common gynecological disorders that constitute a significant burden of disease in women of fertile age. The disorders share a link to female reproduction and infertility; however, divergent effects on menstrual cycle, related hormones, and body composition have been proposed. Disorders of the thyroid gland including abnormal thyroid dysfunction (hyperthyroidism or hypothyroidism) and/or markers of thyroid autoimmunity similarly show a female predominance and onset in younger age groups. We reviewed the literature on the association between endometriosis, PCOS, and thyroid disease up until July 1, 2023, and identified 8 original studies on endometriosis and thyroid disease and 30 original studies on PCOS and thyroid disease. The studies were observational and heterogeneous regarding the design, sample size, and definitions of exposure and outcome; however, a tendency was seen toward an association between hyperthyroidism and endometriosis. Especially an association between endometriosis and slightly elevated levels of thyroid-stimulating hormone receptor antibodies has been found and corroborated in studies from different populations. On the other hand, the literature review turned a focus toward an association between hypothyroidism and PCOS, however, with uncertainties as to whether the association is caused by hypothyroidism per se and/or the thyroid autoantibodies (thyroid peroxidase and thyroglobulin antibodies). More evidence is needed to substantiate an association between endometriosis, PCOS, and thyroid disease, and to differentiate between the role of thyroid function and thyroid autoimmunity. Furthermore, studies are warranted to extend knowledge on the different disease characteristics and underlying mechanisms.

Open access