Search Results

You are looking at 11 - 20 of 477 items for

  • Abstract: adrenarche x
  • Abstract: amenorrhoea x
  • Abstract: fertility x
  • Abstract: Gender x
  • Abstract: Hypogonadism x
  • Abstract: infertility x
  • Abstract: Kallmann x
  • Abstract: Klinefelter x
  • Abstract: menarche x
  • Abstract: menopause x
  • Abstract: puberty x
  • Abstract: testes x
  • Abstract: Turner x
  • Abstract: ovary x
  • Abstract: follicles x
Clear All Modify Search
Angela Köninger
Search for other papers by Angela Köninger in
Google Scholar
PubMed
Close
,
Philippos Edimiris
Search for other papers by Philippos Edimiris in
Google Scholar
PubMed
Close
,
Laura Koch
Search for other papers by Laura Koch in
Google Scholar
PubMed
Close
,
Antje Enekwe
Search for other papers by Antje Enekwe in
Google Scholar
PubMed
Close
,
Claudia Lamina Department of Gynecology and Obstetrics, Division of Genetic Epidemiology, Vitateq Biotechnology GmbH, University of Duisburg-Essen, D-45122 Essen, Germany

Search for other papers by Claudia Lamina in
Google Scholar
PubMed
Close
,
Sabine Kasimir-Bauer
Search for other papers by Sabine Kasimir-Bauer in
Google Scholar
PubMed
Close
,
Rainer Kimmig
Search for other papers by Rainer Kimmig in
Google Scholar
PubMed
Close
, and
Hans Dieplinger Department of Gynecology and Obstetrics, Division of Genetic Epidemiology, Vitateq Biotechnology GmbH, University of Duisburg-Essen, D-45122 Essen, Germany
Department of Gynecology and Obstetrics, Division of Genetic Epidemiology, Vitateq Biotechnology GmbH, University of Duisburg-Essen, D-45122 Essen, Germany

Search for other papers by Hans Dieplinger in
Google Scholar
PubMed
Close

Oxidative stress seems to be present in patients with polycystic ovary syndrome (PCOS). The aim of this study was to evaluate the correlation between characteristics of PCOS and serum concentrations of afamin, a novel binding protein for the antioxidant vitamin E. A total of 85 patients with PCOS and 76 control subjects were investigated in a pilot cross-sectional study design between 2009 and 2013 in the University Hospital of Essen, Germany. Patients with PCOS were diagnosed according to the Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Afamin and diagnostic parameters of PCOS were determined at early follicular phase. Afamin concentrations were significantly higher in patients with PCOS than in controls (odds ratio (OR) for a 10 mg/ml increase in afamin=1.3, 95% CI=1.08–1.58). This difference vanished in a model adjusting for age, BMI, free testosterone index (FTI), and sex hormone-binding globulin (SHBG) (OR=1.05, 95% CI=0.80–1.38). In patients with PCOS, afamin correlated significantly with homeostatic model assessment-insulin resistance (HOMA-IR), fasting glucose, BMI, FTI, and SHBG (P<0.001), but in a multivariate linear model, only HOMA-IR remained significantly associated with afamin (P=0.001). No correlation was observed between afamin and androgens, LH, FSH, LH/FSH ratio, antral follicle count, ovarian volume, or anti-Müllerian hormone. In conclusion, elevated afamin values may indicate a state of oxidative stress and inflammation, strongly associated with IR and offering an indicator of impaired glucose tolerance in patients with PCOS irrespective of obesity.

Open access
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

Search for other papers by Hans Valdemar López Krabbe in
Google Scholar
PubMed
Close
,
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

Search for other papers by Jørgen Holm Petersen in
Google Scholar
PubMed
Close
,
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

Search for other papers by Louise Laub Asserhøj in
Google Scholar
PubMed
Close
,
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

Search for other papers by Trine Holm Johannsen in
Google Scholar
PubMed
Close
,
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

Search for other papers by Peter Christiansen in
Google Scholar
PubMed
Close
,
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

Search for other papers by Rikke Beck Jensen in
Google Scholar
PubMed
Close
,
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

Search for other papers by Line Hartvig Cleemann in
Google Scholar
PubMed
Close
,
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

Search for other papers by Casper P Hagen in
Google Scholar
PubMed
Close
,
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

Search for other papers by Lærke Priskorn in
Google Scholar
PubMed
Close
,
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

Search for other papers by Niels Jørgensen in
Google Scholar
PubMed
Close
,
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

Search for other papers by Katharina M Main in
Google Scholar
PubMed
Close
,
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

Search for other papers by Anders Juul in
Google Scholar
PubMed
Close
, and
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

Search for other papers by Lise Aksglaede in
Google Scholar
PubMed
Close

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.

Open access
Alan D Rogol Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA

Search for other papers by Alan D Rogol in
Google Scholar
PubMed
Close

The overall incidence of sex chromosome aneuploidies is approximately 1 per 500 live-born infants, but far more common at conception. I shall review the fertility aspects of the sex chromosome trisomies, XXY, XYY, and XXX, with special reference to the karyotype 45,X/47,XXX. Each has a ‘specific’ (but variable) phenotype but may be modified by mosaicism. Although the alterations in the hypothalamic–pituitary–gonadal axis are important (and discussed), the emphasis here is on potential fertility and if one might predict that at various epochs within an individual’s life span: fetal, ‘mini’-puberty, childhood, puberty, and adulthood. The reproductive axis is often affected in females with the 47,XXX karyotype with diminished ovarian reserve and accelerated loss of ovarian function. Fewer than 5% of females with Turner syndrome have the 45,X/47,XXX karyotype. They have taller stature and less severe fertility issues compared to females with the 45,X or other forms of Turner syndrome mosaicism. For the 47,XXY karyotype, non-obstructive azoospermia is almost universal with sperm retrieval by micro-testicular sperm extraction possible in slightly fewer than half of the men. Men with the 47,XYY karyotype have normal to large testes and much less testicular dysfunction than those with the 47,XXY karyotype. They do have a slight increase in infertility compared to the reference population but not nearly as severe as those with the 47,XXY karyotype. Assisted reproductive technology, especially micro-testicular sperm extraction, has an important role, especially for those with 47,XXY; however, more recent data show promising techniques for the in vitro maturation of spermatogonial stem cells and 3D organoids in culture. Assisted reproductive technology is more complex for the female, but vitrification of oocytes has shown promising advances.

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

Search for other papers by Zheng Chen in
Google Scholar
PubMed
Close
,
Haixia Zeng Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

Search for other papers by Haixia Zeng in
Google Scholar
PubMed
Close
,
Qiulan Huang Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

Search for other papers by Qiulan Huang in
Google Scholar
PubMed
Close
,
Cuiping Lin Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

Search for other papers by Cuiping Lin in
Google Scholar
PubMed
Close
,
Xuan Li Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

Search for other papers by Xuan Li in
Google Scholar
PubMed
Close
,
Shaohua Sun Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

Search for other papers by Shaohua Sun in
Google Scholar
PubMed
Close
, and
Jian-ping Liu Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China

Search for other papers by Jian-ping Liu in
Google Scholar
PubMed
Close

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.

Open access
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

Search for other papers by Xinyuan Zhang in
Google Scholar
PubMed
Close
,
Suiyan Li School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China

Search for other papers by Suiyan Li in
Google Scholar
PubMed
Close
,
Hongwei Liu Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

Search for other papers by Hongwei Liu in
Google Scholar
PubMed
Close
,
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

Search for other papers by Huai Bai in
Google Scholar
PubMed
Close
,
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

Search for other papers by Qingqing Liu in
Google Scholar
PubMed
Close
,
Chunyi Yang Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

Search for other papers by Chunyi Yang in
Google Scholar
PubMed
Close
, and
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

Search for other papers by Ping Fan in
Google Scholar
PubMed
Close

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.

Open access
E Kohva Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Faculty of Medicine, Department of Physiology, University of Helsinki, Helsinki, Finland

Search for other papers by E Kohva in
Google Scholar
PubMed
Close
,
P J Miettinen Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

Search for other papers by P J Miettinen in
Google Scholar
PubMed
Close
,
S Taskinen Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Department of Pediatric Surgery, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

Search for other papers by S Taskinen in
Google Scholar
PubMed
Close
,
M Hero Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

Search for other papers by M Hero in
Google Scholar
PubMed
Close
,
A Tarkkanen Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Faculty of Medicine, Department of Physiology, University of Helsinki, Helsinki, Finland

Search for other papers by A Tarkkanen in
Google Scholar
PubMed
Close
, and
T Raivio Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Faculty of Medicine, Department of Physiology, University of Helsinki, Helsinki, Finland

Search for other papers by T Raivio in
Google Scholar
PubMed
Close

Background

We describe the phenotypic spectrum and timing of diagnosis and management in a large series of patients with disorders of sexual development (DSD) treated in a single pediatric tertiary center.

Methods

DSD patients who had visited our tertiary center during the survey period (between 2004 and 2014) were identified based on an ICD-10 inquiry, and their phenotypic and molecular genetic findings were recorded from patient charts.

Results

Among the 550 DSD patients, 53.3% had 46,XY DSD; 37.1% had sex chromosome DSD and 9.6% had 46,XX DSD. The most common diagnoses were Turner syndrome (19.8%, diagnosed at the mean age of 4.7 ± 5.5 years), Klinefelter syndrome (14.5%, 6.8 ± 6.2 years) and bilateral cryptorchidism (23.1%). Very few patients with 46,XY DSD (7%) or 46,XX DSD (21%) had molecular genetic diagnosis. The yearly rate of DSD diagnoses remained stable over the survey period. After the release of the Nordic consensus on the management of undescended testes, the age at surgery for bilateral cryptorchidism declined significantly (P < 0.001).

Conclusions

Our results show that (i) Turner syndrome and Klinefelter syndrome, the most frequent single DSD diagnoses, are still diagnosed relatively late; (ii) a temporal shift was observed in the management of bilateral cryptorchidism, which may favorably influence patients’ adulthood semen quality and (iii) next-generation sequencing methods are not fully employed in the diagnostics of DSD patients.

Open access
Nathalia G B P Ferreira Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

Search for other papers by Nathalia G B P Ferreira in
Google Scholar
PubMed
Close
,
Joao L O Madeira Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

Search for other papers by Joao L O Madeira in
Google Scholar
PubMed
Close
,
Peter Gergics Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil

Search for other papers by Peter Gergics in
Google Scholar
PubMed
Close
,
Renata Kertsz Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

Search for other papers by Renata Kertsz in
Google Scholar
PubMed
Close
,
Juliana M Marques Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

Search for other papers by Juliana M Marques in
Google Scholar
PubMed
Close
,
Nicholas S S Trigueiro Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

Search for other papers by Nicholas S S Trigueiro in
Google Scholar
PubMed
Close
,
Anna Flavia Figueredo Benedetti University of Michigan Medical School, Department of Human Genetics, Ann Arbor, Michigan, United States

Search for other papers by Anna Flavia Figueredo Benedetti in
Google Scholar
PubMed
Close
,
Bruna V Azevedo Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

Search for other papers by Bruna V Azevedo in
Google Scholar
PubMed
Close
,
Bianca H V Fernandes Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil
Universidade de São Paulo, Zebrafish Facility, São Paulo, São Paulo, Brazil

Search for other papers by Bianca H V Fernandes in
Google Scholar
PubMed
Close
,
Debora D Bissegatto Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

Search for other papers by Debora D Bissegatto in
Google Scholar
PubMed
Close
,
Isabela P Biscotto Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

Search for other papers by Isabela P Biscotto in
Google Scholar
PubMed
Close
,
Qing Fang Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil

Search for other papers by Qing Fang in
Google Scholar
PubMed
Close
,
Qianyi Ma Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil

Search for other papers by Qianyi Ma in
Google Scholar
PubMed
Close
,
Asye B Ozel Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil

Search for other papers by Asye B Ozel in
Google Scholar
PubMed
Close
,
Jun Li Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil

Search for other papers by Jun Li in
Google Scholar
PubMed
Close
,
Sally A Camper Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil

Search for other papers by Sally A Camper in
Google Scholar
PubMed
Close
,
Alexander A L Jorge Unidade de Endocrinologia Genética, Laboratório de Endocrinologia Celular e Molecular LIM25, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

Search for other papers by Alexander A L Jorge in
Google Scholar
PubMed
Close
,
Berenice B Mendonça Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

Search for other papers by Berenice B Mendonça in
Google Scholar
PubMed
Close
,
Ivo J P Arnhold Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

Search for other papers by Ivo J P Arnhold in
Google Scholar
PubMed
Close
, and
Luciani R Carvalho Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

Search for other papers by Luciani R Carvalho in
Google Scholar
PubMed
Close

Context

Congenital hypopituitarism is a genetically heterogeneous condition. Whole exome sequencing (WES) is a promising approach for molecular diagnosis of patients with this condition.

Objectives

The aim of this study is to conduct WES in a patient with congenital hypopituitarism born to consanguineous parents, CDH2 screening in a cohort of patients with congenital hypopituitarism, and functional testing of a novel CDH2 variant.

Design

Genomic DNA from a proband and her consanguineous parents was analyzed by WES. Copy number variants were evaluated. The genetic variants were filtered for population frequency (ExAC, 1000 genomes, gnomAD, and ABraOM), in silico prediction of pathogenicity, and gene expression in the pituitary and/or hypothalamus. Genomic DNA from 145 patients was screened for CDH2 by Sanger sequencing.

Results

One female patient with deficiencies in growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone and ectopic posterior pituitary gland contained a rare homozygous c.865G>A (p.Val289Ile) variant in CDH2. To determine whether the p.Val289Ile variant in CDH2 affects cell adhesion properties, we stably transfected L1 fibroblast lines, labeled the cells with lipophilic dyes, and quantified aggregation. Large aggregates formed in cells expressing wildtype CDH2, but aggregation was impaired in cells transfected with variant CDH2 or non-transfected.

Conclusion

A homozygous CDH2 allelic variant was found in one hypopituitarism patient, and the variant impaired cell aggregation function in vitro. No disease-causing variants were found in 145 other patients screened for CDH2 variants. Thus, CDH2 is a candidate gene for hypopituitarism that needs to be tested in different populations.

Significance statement

A female patient with hypopituitarism was born from consanguineous parents and had a homozygous, likely pathogenic, CDH2 variant that impairs cell aggregation in vitro. No other likely pathogenic variants in CDH2 were identified in 145 hypopituitarism patients.

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

Search for other papers by Elinor Chelsom Vogt in
Google Scholar
PubMed
Close
,
Francisco Gómez Real Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway

Search for other papers by Francisco Gómez Real in
Google Scholar
PubMed
Close
,
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

Search for other papers by Eystein Sverre Husebye in
Google Scholar
PubMed
Close
,
Sigridur Björnsdottir Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden

Search for other papers by Sigridur Björnsdottir in
Google Scholar
PubMed
Close
,
Bryndis Benediktsdottir Medical Faculty, University of Iceland, Reykjavik, Iceland
Department of Sleep, Landspitali University Hospital Reykjavík, Reykjavik, Iceland

Search for other papers by Bryndis Benediktsdottir in
Google Scholar
PubMed
Close
,
Randi Jacobsen Bertelsen Department of Clinical Science, University of Bergen, Bergen, Norway

Search for other papers by Randi Jacobsen Bertelsen in
Google Scholar
PubMed
Close
,
Pascal Demoly University Hospital of Montpellier, IDESP, Univ Montpellier-Inserm, Montpellier, France

Search for other papers by Pascal Demoly in
Google Scholar
PubMed
Close
,
Karl Anders Franklin Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden

Search for other papers by Karl Anders Franklin in
Google Scholar
PubMed
Close
,
Leire Sainz de Aja Gallastegui Unit of Epidemiology and Public Health, Department of Health, Basque Government, Vitoria-Gasteiz, Spain

Search for other papers by Leire Sainz de Aja Gallastegui in
Google Scholar
PubMed
Close
,
Francisco Javier Callejas González Department of Respiratory Medicine, Albacete University Hospital, Albacete, Spain

Search for other papers by Francisco Javier Callejas González in
Google Scholar
PubMed
Close
,
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

Search for other papers by Joachim Heinrich in
Google Scholar
PubMed
Close
,
Mathias Holm Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Mathias Holm in
Google Scholar
PubMed
Close
,
Nils Oscar Jogi Department of Clinical Science, University of Bergen, Bergen, Norway

Search for other papers by Nils Oscar Jogi in
Google Scholar
PubMed
Close
,
Benedicte Leynaert Université Paris-Saclay, Inserm U1018, Center for Epidemiology and Population Health, Integrative Respiratory Epidemiology Team, Villejuif, France

Search for other papers by Benedicte Leynaert in
Google Scholar
PubMed
Close
,
Eva Lindberg Department of Medical Sciences, Respiratory, Allergy and Sleep Medicine, Uppsala University, Uppsala, Sweden

Search for other papers by Eva Lindberg in
Google Scholar
PubMed
Close
,
Andrei Malinovschi Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden

Search for other papers by Andrei Malinovschi in
Google Scholar
PubMed
Close
,
Jesús Martínez-Moratalla Pneumology Service of the General University Hospital of Albacete, Albacete, Spain
Albacete Faculty of Medicine, Castilla-La Mancha University, Albacete, Spain

Search for other papers by Jesús Martínez-Moratalla in
Google Scholar
PubMed
Close
,
Raúl Godoy Mayoral Department of Respiratory Medicine, Albacete University Hospital, Albacete, Spain

Search for other papers by Raúl Godoy Mayoral in
Google Scholar
PubMed
Close
,
Anna Oudin Section of Sustainable Health, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

Search for other papers by Anna Oudin in
Google Scholar
PubMed
Close
,
Antonio Pereira-Vega Juan Ramón Jiménez University Hospital in Huelva, Huelva, Spain

Search for other papers by Antonio Pereira-Vega in
Google Scholar
PubMed
Close
,
Chantal Raherison Semjen INSERM, EpiCene Team U1219, University of Bordeaux, Talence, France

Search for other papers by Chantal Raherison Semjen in
Google Scholar
PubMed
Close
,
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

Search for other papers by Vivi Schlünssen in
Google Scholar
PubMed
Close
,
Kai Triebner Department of Clinical Science, University of Bergen, Bergen, Norway

Search for other papers by Kai Triebner in
Google Scholar
PubMed
Close
, and
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

Search for other papers by Marianne Øksnes in
Google Scholar
PubMed
Close

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
David Mark Robertson Department of Molecular and Translational Sciences, Hudson Institute of Medical Research, Monash University, Clayton, Victoria, Australia
School of Women’s & Children’s Health, Discipline of Obstetrics and Gynaecology, University of New South Wales, Sydney, Australia

Search for other papers by David Mark Robertson in
Google Scholar
PubMed
Close
,
Chel Hee Lee Clinical Research Support Unit, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Search for other papers by Chel Hee Lee in
Google Scholar
PubMed
Close
, and
Angela Baerwald Department of Obstetrics, Gynecology & Reproductive Sciences, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Search for other papers by Angela Baerwald in
Google Scholar
PubMed
Close

It is recognised that ovarian factors, including steroid and protein hormones, are critical in the feedback regulation of pituitary gonadotropins; however, their individual contributions are less defined. The aim of this study was to explore the reciprocal relationships between ovarian and pituitary hormones across the normal ovulatory menstrual cycle as women age. FSH, LH, oestradiol, progesterone, inhibin A, inhibin B and anti-mullerian hormone (AMH) were measured in serum collected every 1–3 days across one interovulatory interval (IOI) from 26 healthy women aged 18–50 years. The antral follicle count (AFC) for follicles 2–5 mm, >6 mm and 2–10 mm were tabulated across the IOI. Independent associations between ovarian hormones/AFC vs pituitary follicle-stimulating hormone (FSH) and luteinising hormone (LH) were investigated using multivariate regression analysis. The data were sub-grouped based on the presence or absence luteal phase-dominant follicles (LPDF). Serum oestradiol and AMH were inversely correlated with FSH in both follicular and luteal phases. Inhibin B correlated inversely with FSH and LH in the late follicular phase and directly in the luteal phase. AFC, inhibin A and progesterone were not key predictors of either FSH or LH. The strong association between AMH and FSH with age implies that AMH, as well as oestradiol and inhibin B are important regulators of FSH. The change in feedback response of inhibin B with both FSH and LH across the cycle suggests two phases of the negative feedback.

Open access
Henrik Falhammar Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

Search for other papers by Henrik Falhammar in
Google Scholar
PubMed
Close
,
Hedi Claahsen-van der Grinten Department of Pediatric Endocrine Disease, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Search for other papers by Hedi Claahsen-van der Grinten in
Google Scholar
PubMed
Close
,
Nicole Reisch Medizinische Klinik and Poliklinik IV, Department of Endocrinology, University Hospital Munich, Munich, Germany

Search for other papers by Nicole Reisch in
Google Scholar
PubMed
Close
,
Jolanta Slowikowska-Hilczer Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Lodz, Poland

Search for other papers by Jolanta Slowikowska-Hilczer in
Google Scholar
PubMed
Close
,
Anna Nordenström Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
Department of Paediatric Endocrinology, Astrid Lindgren Children Hospital, Karolinska University Hospital, Stockholm, Sweden

Search for other papers by Anna Nordenström in
Google Scholar
PubMed
Close
,
Robert Roehle Coordinating Center for Clinical Studies, Charité Universitätsmedizin, Berlin, Germany

Search for other papers by Robert Roehle in
Google Scholar
PubMed
Close
,
Claire Bouvattier Paris-Sud University, Orsay, France
Department of Pediatric Endocrinology, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France

Search for other papers by Claire Bouvattier in
Google Scholar
PubMed
Close
,
Baudewijntje P C Kreukels Department of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands

Search for other papers by Baudewijntje P C Kreukels in
Google Scholar
PubMed
Close
,
Birgit Köhler Department of Paediatric Endocrinology and Diabetology, Charité Universitätsmedizin, Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany

Search for other papers by Birgit Köhler in
Google Scholar
PubMed
Close
, and
on behalf of the dsd-LIFE group
Search for other papers by on behalf of the dsd-LIFE group in
Google Scholar
PubMed
Close

Objective

The knowledge about health status in adults with disorder of sex development (DSD) is scarce.

Design and methods

A cross-sectional observational study in 14 European tertiary centers recruited 1040 participants (717 females, 311 males, 12 others) with DSD. Mean age was 32.4 ± 13.6 year (range 16–75). The cohort was divided into: Turner (n = 301), Klinefelter (n = 224), XY-DSD (n = 222), XX-DSD (excluding congenital adrenal hyperplasia (CAH) and 46,XX males) (n = 21), 46,XX-CAH (n = 226) and 45,X/46,XY (n = 45). Perceived and objective health statuses were measured and compared to European control data.

Results

In DSD, fair to very good general health was reported by 91.4% and only 8.6% reported (very) bad general health (controls 94.0% and 6.0%, P < 0.0001). Longstanding health issues other than DSD and feeling limited in daily life were reported in 51.0% and 38.6%, respectively (controls 24.5% and 13.8%, P < 0.0001 both). Any disorder except DSD was present in 84.3% (controls 24.6%, P < 0.0001). Males reported worse health than females. In the subgroup analysis, Klinefelter and 46,XX-DSD patients reported bad general health in 15.7% and 16.7%, respectively (Turner 3.2% and CAH 7.4%). Comorbidities were prevalent in all DSD subgroups but Klinefelter and Turner were most affected. Early diagnosis of DSD and a healthy lifestyle were associated with less comorbidities.

Conclusions

Overall, general health appeared to be good but a number of medical problems were reported, especially in Klinefelter and Turner. Early diagnosis of DSD and a healthy lifestyle seemed to be important. Lifelong follow-up at specialized centers is necessary.

Open access