Search Results

You are looking at 101 - 110 of 233 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: transsexual x
  • Abstract: sperm* x
  • Abstract: ovary x
  • Abstract: follicles x
Clear All Modify Search
Claus H Gravholt Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

Search for other papers by Claus H Gravholt in
Google Scholar
PubMed
Close
,
Alberto Ferlin Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy

Search for other papers by Alberto Ferlin in
Google Scholar
PubMed
Close
,
Joerg Gromoll Centre of Reproductive Medicine and Andrology, Münster, Germany

Search for other papers by Joerg Gromoll in
Google Scholar
PubMed
Close
,
Anders Juul Department of Growth and Reproduction Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Anders Juul in
Google Scholar
PubMed
Close
,
Armin Raznahan Section on Developmental Neurogenomics, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland, USA

Search for other papers by Armin Raznahan in
Google Scholar
PubMed
Close
,
Sophie van Rijn Clinical Neurodevelopmental Sciences, Leiden University, Leiden, The Netherlands and TRIXY Center of Expertise, Leiden University Treatment and Expertise Centre (LUBEC), Leiden, The Netherlands

Search for other papers by Sophie van Rijn in
Google Scholar
PubMed
Close
,
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
,
Anne Skakkebæk Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark

Search for other papers by Anne Skakkebæk in
Google Scholar
PubMed
Close
,
Nicole Tartaglia Department of Pediatrics, Developmental Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA

Search for other papers by Nicole Tartaglia in
Google Scholar
PubMed
Close
, and
Hanna Swaab Clinical Neurodevelopmental Sciences, Leiden University, Leiden, The Netherlands and TRIXY Center of Expertise, Leiden University Treatment and Expertise Centre (LUBEC), Leiden, The Netherlands

Search for other papers by Hanna Swaab in
Google Scholar
PubMed
Close

The 3rd International Workshop on Klinefelter Syndrome, Trisomy X, and 47,XYY syndrome was held in Leiden, the Netherlands, on September 12–14, 2022.

Here, we review new data presented at the workshop and discuss scientific and clinical trajectories. We focus on shortcomings in knowledge and therefore point out future areas for research.

We focus on the genetics and genomics of supernumerary sex chromosome syndromes with new data being presented. Most knowledge centre specifically on Klinefelter syndrome, where aspects on testosterone deficiency and the relation to bone, muscle and fat were discussed, as was infertility and the treatment thereof. Both trisomy X and 47,XYY syndrome are frequently affected by infertility.

Transitioning of males with Klinefelter syndrome was addressed, as this seemingly simple process in practise is often difficult.

It is now realized that neurocognitive changes are pervasive in all supernumerary sex chromosome syndromes, which were extensively discussed. New intervention projects were also described, and exciting new data concerning these were presented.

Advocacy organizations were present, describing the enormous burden carried by parents when having to explain their child’s specific syndrome to most professionals whenever in contact with health care and education systems. It was also pointed out that most countries do not have health care systems that diagnose patients with supernumerary sex chromosome syndromes, thus pinpointing a clear deficiency in the current genetic testing and care models.

At the end of the workshop, a roadmap towards the development of new international clinical care guidelines for Klinefelter syndrome was decided.

Open access
Jan-Bernd Stukenborg NORDFERTIL Research Lab Stockholm, Pediatric Endocrinology Unit, Department of Women’s and Children’s Health, Karolinska Institutet and University Hospital, Stockholm, Sweden

Search for other papers by Jan-Bernd Stukenborg in
Google Scholar
PubMed
Close
,
Kirsi Jahnukainen NORDFERTIL Research Lab Stockholm, Pediatric Endocrinology Unit, Department of Women’s and Children’s Health, Karolinska Institutet and University Hospital, Stockholm, Sweden
Division of Haematology-Oncology and Stem Cell Transplantation, Children’s Hospital, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland

Search for other papers by Kirsi Jahnukainen in
Google Scholar
PubMed
Close
,
Marsida Hutka MRC Centre for Reproductive Health, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK

Search for other papers by Marsida Hutka in
Google Scholar
PubMed
Close
, and
Rod T Mitchell MRC Centre for Reproductive Health, The Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh, UK
Edinburgh Royal Hospital for Sick Children, Edinburgh, UK

Search for other papers by Rod T Mitchell in
Google Scholar
PubMed
Close

Testicular function and future fertility may be affected by cancer treatment during childhood. Whilst survival of the germ (stem) cells is critical for ensuring the potential for fertility in these patients, the somatic cell populations also play a crucial role in providing a suitable environment to support germ cell maintenance and subsequent development. Regulation of the spermatogonial germ-stem cell niche involves many signalling pathways with hormonal influence from the hypothalamo-pituitary-gonadal axis. In this review, we describe the somatic cell populations that comprise the testicular germ-stem cell niche in humans and how they may be affected by cancer treatment during childhood. We also discuss the experimental models that may be utilized to manipulate the somatic environment and report the results of studies that investigate the potential role of somatic cells in the protection of the germ cells in the testis from cancer treatment.

Open access
Bruno Donadille Service d’Endocrinologie et Médecine de la Reproduction, Centre de Référence des Maladies Endocrines Rares de la Croissance, Hôpital Saint Antoine, Groupe Hospitalier Universitaire Est, AP-HP, Paris, France

Search for other papers by Bruno Donadille in
Google Scholar
PubMed
Close
,
Muriel Houang Service d’Explorations Fonctionnelles Endocriniennes, Centre de Référence des Maladies Endocrines Rares de la Croissance, Hôpital Trousseau, Groupe Hospitalier Universitaire Est, AP-HP, Paris, France

Search for other papers by Muriel Houang in
Google Scholar
PubMed
Close
,
Irène Netchine Service d’Explorations Fonctionnelles Endocriniennes, Centre de Référence des Maladies Endocrines Rares de la Croissance, Hôpital Trousseau, Groupe Hospitalier Universitaire Est, AP-HP, Paris, France
Université Pierre et Marie Curie, Sorbonne Université, Paris, France

Search for other papers by Irène Netchine in
Google Scholar
PubMed
Close
,
Jean-Pierre Siffroi Université Pierre et Marie Curie, Sorbonne Université, Paris, France
INSERM UMR_S933, Paris, France

Search for other papers by Jean-Pierre Siffroi in
Google Scholar
PubMed
Close
, and
Sophie Christin-Maitre Service d’Endocrinologie et Médecine de la Reproduction, Centre de Référence des Maladies Endocrines Rares de la Croissance, Hôpital Saint Antoine, Groupe Hospitalier Universitaire Est, AP-HP, Paris, France
Université Pierre et Marie Curie, Sorbonne Université, Paris, France
INSERM UMR_S933, Paris, France

Search for other papers by Sophie Christin-Maitre in
Google Scholar
PubMed
Close

Human 3 beta-hydroxysteroid dehydrogenase deficiency (3b-HSD) is a very rare form of congenital adrenal hyperplasia resulting from HSD3B2 gene mutations. The estimated prevalence is less than 1/1,000,000 at birth. It leads to steroidogenesis impairment in both adrenals and gonads. Few data are available concerning adult testicular function in such patients. We had the opportunity to study gonadal axis and testicular function in a 46,XY adult patient, carrying a HSD3B2 mutation. He presented at birth a neonatal salt-wasting syndrome. He had a micropenis, a perineal hypospadias and two intrascrotal testes. HSD3B2 gene sequencing revealed a 687del27 homozygous mutation. The patient achieved normal puberty at the age of 15 years. Transition from the paediatric department occurred at the age of 19 years. His hormonal profile under hydrocortisone and fludrocortisone treatments revealed normal serum levels of 17OH-pregnenolone, as well as SDHEA, ACTH, total testosterone, inhibin B and AMH. Pelvic ultrasound identified two scrotal testes of 21 mL each, without any testicular adrenal rest tumours. His adult spermatic characteristics were normal, according to WHO 2010 criteria, with a sperm concentration of 57.6 million/mL (N > 15), 21% of typical forms (N > 4%). Sperm vitality was subnormal (41%; N > 58%). This patient, in contrast to previous reports, presents subnormal sperm parameters and therefore potential male fertility in a 24-years-old patient with severe 3b-HSD deficiency. This case should improve counselling about fertility of male patients carrying HSD3B2 mutation.

Open access
Rossella Cannarella Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

Search for other papers by Rossella Cannarella in
Google Scholar
PubMed
Close
,
Andrea Crafa Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

Search for other papers by Andrea Crafa in
Google Scholar
PubMed
Close
,
Sandro La Vignera Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

Search for other papers by Sandro La Vignera in
Google Scholar
PubMed
Close
,
Rosita A Condorelli Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

Search for other papers by Rosita A Condorelli in
Google Scholar
PubMed
Close
, and
Aldo E Calogero Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

Search for other papers by Aldo E Calogero in
Google Scholar
PubMed
Close

Background

Animal studies suggest that insulin-like growth factor 1 (IGF1) may influence the function of the hypothalamus–pituitary–testicular axis, especially in childhood, but the evidence in humans is scanty. Laron syndrome, a human model of IGF1 deficiency, may help to solve this issue.

Purpose

This systematic review aims to analyze puberty onset and progression, testicular volume, gonadotropin, and total testosterone serum levels, sperm parameters and fertility, and penile length in patients with Laron syndrome.

Methods

Specific keywords were used. All data on male patients with Laron syndrome were included.

Results

Seventeen articles matched the inclusion criteria and were entered in the analysis, for a total of 125 male patients. Puberty was absent in 8.9% and delayed in 35.6% of untreated patients of pubertal age. After onset, the duration of the pubertal process was prolonged in 76.9% of untreated patients. The growth spurt was absent in 52.6% and delayed in 31.6% of untreated patients. The testicular volume was small in the two patients who did not receive any treatment. Treatment with IGF1 increased gonadotropin and testosterone serum levels in five out of five patients of pubertal age. No effect was found in four out of four patients younger than 5 years. No study reported data on sperm parameters and fertility. Micropenis occurred in 67.2% of patients.

Conclusion and future perspectives

Delayed puberty is common in patients with Laron syndrome. The growth hormone–IGF1 axis may influence the time of puberty onset. Serum levels of IGF1 should be investigated in children with delayed puberty, scarce progression of testicular growth, and/or micropenis. IGF1 levels might be measured in children with delayed puberty, poor testicular growth, and/or micropenis.

Open access
Jens F Rehfeld Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Search for other papers by Jens F Rehfeld in
Google Scholar
PubMed
Close

The birth certificate for endocrinology was Bayliss’ and Starling’s demonstration in 1902 that regulation of bodily functions is not only neuronal but also due to blood-borne messengers. Starling named these messengers hormones. Since then transport via blood has defined hormones. This definition, however, may be too narrow. Thus, today we know that several peptide hormones are not only produced and released to blood from endocrine cells but also released from neurons, myocytes, immune cells, endothelial cells, spermatogenic cells, fat cells, etc. And they are often secreted in cell-specific molecular forms with more or less different spectra of activity. The present review depicts this development with the story about cholecystokinin which was discovered in 1928 as a hormone and still in 1976 was conceived as a single blood-borne peptide. Today’s multifaceted picture of cholecystokinin suggests that time may be ripe for expansion of the hormone concept to all messenger molecules, which activate their target cells – irrespective of their road to the target (endocrine, neurocrine, neuronal, paracrine, autocrine, etc.) and irrespective of their kind of activity as classical hormone, growth factor, neurotransmitter, adipokine, cytokine, myokine, or fertility factor.

Open access
A Rehfeld Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Denmark
Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen, Rigshospitalet, Denmark

Search for other papers by A Rehfeld in
Google Scholar
PubMed
Close
,
D L Egeberg Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen, Rigshospitalet, Denmark

Search for other papers by D L Egeberg in
Google Scholar
PubMed
Close
,
K Almstrup Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen, Rigshospitalet, Denmark

Search for other papers by K Almstrup in
Google Scholar
PubMed
Close
,
J H Petersen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen, Rigshospitalet, Denmark
Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark

Search for other papers by J H Petersen in
Google Scholar
PubMed
Close
,
S Dissing Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

Search for other papers by S Dissing in
Google Scholar
PubMed
Close
, and
N E Skakkebæk Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen, Rigshospitalet, Denmark

Search for other papers by N E Skakkebæk in
Google Scholar
PubMed
Close

Human sperm cell function must be precisely regulated to achieve natural fertilization. Progesterone released by the cumulus cells surrounding the egg induces a Ca2+ influx into human sperm cells via the CatSper Ca2+-channel and thereby controls sperm function. Multiple chemical UV filters have been shown to induce a Ca2+ influx through CatSper, thus mimicking the effect of progesterone on Ca2+ signaling. We hypothesized that these UV filters could also mimic the effect of progesterone on sperm function. We examined 29 UV filters allowed in sunscreens in the US and/or EU for their ability to affect acrosome reaction, penetration, hyperactivation and viability in human sperm cells. We found that, similar to progesterone, the UV filters 4-MBC, 3-BC, Meradimate, Octisalate, BCSA, HMS and OD-PABA induced acrosome reaction and 3-BC increased sperm penetration into a viscous medium. The capacity of the UV filters to induce acrosome reaction and increase sperm penetration was positively associated with the ability of the UV filters to induce a Ca2+ influx. None of the UV filters induced significant changes in the proportion of hyperactivated cells. In conclusion, chemical UV filters that mimic the effect of progesterone on Ca2+ signaling in human sperm cells can similarly mimic the effect of progesterone on acrosome reaction and sperm penetration. Human exposure to these chemical UV filters may impair fertility by interfering with sperm function, e.g. through induction of premature acrosome reaction. Further studies are needed to confirm the results in vivo.

Open access
Pamela Stratton Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

Search for other papers by Pamela Stratton in
Google Scholar
PubMed
Close
,
Neelam Giri Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

Search for other papers by Neelam Giri in
Google Scholar
PubMed
Close
,
Sonia Bhala Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

Search for other papers by Sonia Bhala in
Google Scholar
PubMed
Close
,
Martha M Sklavos Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

Search for other papers by Martha M Sklavos in
Google Scholar
PubMed
Close
,
Blanche P Alter Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

Search for other papers by Blanche P Alter in
Google Scholar
PubMed
Close
,
Sharon A Savage Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

Search for other papers by Sharon A Savage in
Google Scholar
PubMed
Close
, and
Ligia A Pinto Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

Search for other papers by Ligia A Pinto in
Google Scholar
PubMed
Close

Fanconi anemia (FA), dyskeratosis congenita-related telomere biology disorders (DC/TBD), and Diamond–Blackfan anemia (DBA) are inherited bone marrow failure syndromes (IBMFS) with high risks of bone marrow failure, leukemia, and solid tumors. Individuals with FA have reduced fertility. Previously, we showed low levels of anti-Müllerian hormone (AMH), a circulating marker of ovarian reserve, in females with IBMFS. In males, AMH may be a direct marker of Sertoli cell function and an indirect marker of spermatogenesis. In this study, we assessed serum AMH levels in pubertal and postpubertal males with FA, DC/TBD, or DBA and compared this with their unaffected male relatives and unrelated healthy male volunteers. Males with FA had significantly lower levels of AMH (median: 5 ng/mL, range: 1.18–6.75) compared with unaffected male relatives (median: 7.31 ng/mL, range: 3.46–18.82, P = 0.03) or healthy male volunteers (median: 7.66 ng/mL, range: 3.3–14.67, P = 0.008). Males with DC/TBD had lower levels of AMH (median: 3.76 ng/mL, range: 0–8.9) compared with unaffected relatives (median: 5.31 ng/mL, range: 1.2–17.77, P = 0.01) or healthy volunteers (median: 5.995 ng/mL, range: 1.57–14.67, P < 0.001). Males with DBA had similar levels of AMH (median: 3.46 ng/mL, range: 2.32–11.85) as unaffected relatives (median: 4.66 ng/mL, range: 0.09–13.51, P = 0.56) and healthy volunteers (median: 5.81 ng/mL, range: 1.57–14.67, P = 0.10). Our findings suggest a defect in the production of AMH in postpubertal males with FA and DC/TBD, similar to that observed in females. These findings warrant confirmation in larger prospective studies.

Open access
Sakina Kherra CHU Parnet Hopital, Algiers, Algeria

Search for other papers by Sakina Kherra in
Google Scholar
PubMed
Close
,
Wendy Forsyth Paterson Royal Hospital for Sick Children, Yorkhill, Glasgow, UK

Search for other papers by Wendy Forsyth Paterson in
Google Scholar
PubMed
Close
,
Filiz Mine Cizmecioglu Paediatric Endocrinology and Diabetes Department, Kocaeli University, Kocaeli, Turkey

Search for other papers by Filiz Mine Cizmecioglu in
Google Scholar
PubMed
Close
,
Jeremy Huw Jones Department of Pediatric Endocrinology, Royal Hospital for Children Glasgow, NHS Greater Glasgow and Clyde, Glasgow, UK

Search for other papers by Jeremy Huw Jones in
Google Scholar
PubMed
Close
,
Mariam Kourime Abderrahim Harouchi Hôpital, Casablanca, Morocco

Search for other papers by Mariam Kourime in
Google Scholar
PubMed
Close
,
Heba Hassan Elsedfy Pediatrics Department, Ain Shams University, Cairo, Egypt

Search for other papers by Heba Hassan Elsedfy in
Google Scholar
PubMed
Close
,
Sameh Tawfik Department of Pediatrics, Maadi Hospital, Cairo, Egypt

Search for other papers by Sameh Tawfik in
Google Scholar
PubMed
Close
,
Andreas Kyriakou Department of Pediatric Endocrinology, Royal Hospital for Children Glasgow, NHS Greater Glasgow and Clyde, Glasgow, UK

Search for other papers by Andreas Kyriakou in
Google Scholar
PubMed
Close
,
Mohamad Guftar Shaikh Department of Pediatric Endocrinology, Royal Hospital for Children Glasgow, NHS Greater Glasgow and Clyde, Glasgow, UK

Search for other papers by Mohamad Guftar Shaikh in
Google Scholar
PubMed
Close
, and
Malcolm David Cairns Donaldson Section of Child Health, Glasgow University School of Medicine, Glasgow, UK

Search for other papers by Malcolm David Cairns Donaldson in
Google Scholar
PubMed
Close

Background

Hypogonadism is a key feature of Prader–Willi syndrome (PWS) but clear strategies for hormone replacement are lacking.

Objective

To evaluate the gonadal status and outcome in patients attending a Scottish PWS clinic from 1991 to 2019.

Methods

In 93 (35F:56M) patients, median follow-up 11.2 years, gonadal and pubertal status were assessed clinically. Pelvic ultrasound findings and basal/stimulated gonadotrophins were compared with age-matched controls.

Results

Females:of 22 patients aged > 11, 9 had reached B4–5, while 5 were still at B2–3, and 6 remained prepubertal. Eight patients experienced menarche aged 9.8–21.4 years, none with a normal cycle. Uterine length and ovarian volumes were normal but uterine configuration remained immature, with low follicular counts. Gonadotrophins were unremarkable, serum oestradiol 129 (70–520) pmol/L. Only 5 patients received oestrogen replacement. Males:fifty-four (96%) patients were cryptorchid (9 unilateral). Weekly hCG injections resulted in unilateral/bilateral descent in 2/1 of 25 patients. Of 37 boys aged > 11, 14 (9 with failed/untreated bilateral cryptorchidism) failed to progress beyond G1, 15 arrested at G2–3 (testes 3–10 mL), and 8 reached G4–5. Gonadotrophins were unremarkable except in boys at G2–5 in whom FSH was elevated: 12.3/27.3 vs 3.25/6.26 U/L in controls (P < 0.001). In males aged > 13, testosterone was 3.1 (0.5–8.4) nmol/L. Androgen therapy, given from 13.5 to 29.2 years, was stopped in 4/24 patients owing to behavioural problems.

Conclusion

Despite invariable hypogonadism, few females and only half the males with PWS in this study received hormone replacement. Double-blind placebo-controlled crossover trials of sex steroids are required to address unproven behavioural concerns.

Open access
Shuang Ye Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

Search for other papers by Shuang Ye in
Google Scholar
PubMed
Close
,
Yuanyuan Xu Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

Search for other papers by Yuanyuan Xu in
Google Scholar
PubMed
Close
,
Jiehao Li Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

Search for other papers by Jiehao Li in
Google Scholar
PubMed
Close
,
Shuhui Zheng Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

Search for other papers by Shuhui Zheng in
Google Scholar
PubMed
Close
,
Peng Sun Department of Pathology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

Search for other papers by Peng Sun in
Google Scholar
PubMed
Close
, and
Tinghuai Wang Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

Search for other papers by Tinghuai Wang in
Google Scholar
PubMed
Close

The role of G protein-coupled estrogen receptor 1 (GPER) signaling, including promotion of Ezrin phosphorylation (which could be activated by estrogen), has not yet been clearly identified in triple-negative breast cancer (TNBC). This study aimed to evaluate the prognostic value of GPER and Ezrin in TNBC patients. Clinicopathologic features including age, menopausal status, tumor size, nuclear grade, lymph node metastasis, AJCC TNM stage, and ER, PR and HER-2 expression were evaluated from 249 TNBC cases. Immunohistochemical staining of GPER and Ezrin was performed on TNBC pathological sections. Kaplan–Meier analyses, as well as logistic regressive and Cox regression model tests were applied to evaluate the prognostic significance between different subgroups. Compared to the GPER-low group, the GPER-high group exhibited higher TNM staging (P = 0.021), more death (P < 0.001), relapse (P < 0.001) and distant events (P < 0.001). Kaplan–Meier analysis showed that GPER-high patients had a decreased OS (P < 0.001), PFS (P < 0.001), LRFS (P < 0.001) and DDFS (P < 0.001) than GPER-low patients. However, these differences in prognosis were not statistically significant in post-menopausal patients (OS, P = 0.8617; PFS, P = 0.1905; LRFS, P = 0.4378; DDFS, P = 0.2538). There was a significant positive correlation between GPER and Ezrin expression level (R = 0.508, P < 0.001) and the effect of Ezrin on survival prognosis corresponded with GPER. Moreover, a multivariable analysis confirmed that GPER and Ezrin level were both significantly associated with poor DDFS (HR: 0.346, 95% CI 0.182–0.658, P = 0.001; HR: 0.320, 95% CI 0.162–0.631, P = 0.001). Thus, overexpression of GPER and Ezrin may contribute to aggressive behavior and indicate unfavorable prognosis in TNBC; this may correspond to an individual’s estrogen levels.

Open access
Kristin Ottarsdottir Primary Health Care, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Kristin Ottarsdottir in
Google Scholar
PubMed
Close
,
Margareta Hellgren Primary Health Care, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Margareta Hellgren in
Google Scholar
PubMed
Close
,
David Bock Biostatistics, School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

Search for other papers by David Bock in
Google Scholar
PubMed
Close
,
Anna G Nilsson Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden

Search for other papers by Anna G Nilsson in
Google Scholar
PubMed
Close
, and
Bledar Daka Primary Health Care, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Search for other papers by Bledar Daka in
Google Scholar
PubMed
Close

Purpose

We aimed to investigate the association between SHBG and the homeostatic model assessment of insulin resistance (HOMA-Ir) in men and women in a prospective observational study.

Methods

The Vara-Skövde cohort is a random population of 2816 participants living in southwestern Sweden, aged 30–74. It was recruited between 2002 and 2005, and followed up in 2012–2014. After excluding participants on insulin therapy or hormone replacement therapy, 1193 individuals (649 men, 544 women) were included in the present study. Fasting blood samples were collected at both visits and stored in biobank. All participants were physically examined by a trained nurse. SHBG was measured with immunoassay technique. Linear regressions were computed to investigate the association between SHBG and HOMA-Ir both in cross-sectional and longitudinal analyses, adjusting for confounding factors.

Results

The mean follow-up time was 9.7 ± 1.4 years. Concentrations of SHBG were significantly inversely associated with log transformed HOMA-Ir in all groups with estimated standardized slopes (95% CI): men: −0.20 (−0.3;−0.1), premenopausal women: −0.26 (−0.4;−0.2), postmenopausal women: −0.13 (−0.3;−0.0) at visit 1. At visit 2 the results were similar. When comparing the groups, a statistically significant difference was found between men and post-menopausal women (0.12 (0.0;0.2) P value = 0.04). In the fully adjusted model, SHBG at visit 1 was also associated with HOMA-Ir at visit 2, and the estimated slopes were −0.16 (−0.2;−0.1), −0.16 (−0.3;−0.1) and −0.07 (−0.2;0.0) for men, premenopausal and postmenopausal women, respectively.

Main conclusion

Levels of SHBG predicted the development of insulin resistance in both men and women, regardless of menopausal state.

Open access