Search Results
You are looking at 11 - 20 of 464 items for
- Abstract: adrenarche x
- Abstract: amenorrhoea x
- Abstract: fertility x
- Abstract: Gender x
- Abstract: Hypogonadism x
- Abstract: infertility x
- Abstract: Klinefelter x
- Abstract: menarche x
- Abstract: menopause x
- Abstract: testes x
- Abstract: transsexual x
- Abstract: Turner x
- Abstract: sperm* x
- Abstract: ovary x
- Abstract: follicles x
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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.
School of Life Science and Engineering, Southwest Jiaotong 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.
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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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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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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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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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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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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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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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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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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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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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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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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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.
School of Women’s & Children’s Health, Discipline of Obstetrics and Gynaecology, University of New South Wales, Sydney, Australia
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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.
Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
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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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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.
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Objective
Gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) are released from the pituitary gland and stimulate Leydig cells to produce testosterone and initiates spermatogenesis. Little is known about how and when the deterioration of semen quality occurs in patients with adult-onset gonadotropin insufficiency.
Design and methods
A retrospective study comprising 20 testosterone-deficient men (median age, 29 years) with acquired pituitary disease who delivered semen for cryopreservation before initiation of testosterone therapy. Semen variables and hormone concentrations were compared to those of young healthy men (n = 340).
Results
Thirteen of 20 patients (65%) and 82% of controls had total sperm counts above 39 million and progressive motile spermatozoa above 32% (P = 0.05). For the individual semen variables, there were no significant differences in semen volume (median (intraquartile range) 3.0 (1.3–6.8) vs 3.2 (2.3–4.3) mL, P = 0.47), sperm concentration 41 (11–71) vs 43 (22–73) mill/mL (P = 0.56) or total sperm counts (P = 0.66). One patient had azoospermia. Patients vs controls had lower serum testosterone 5.4 (2.2–7.6) vs 19.7 (15.5–24.5) nmol/L (P = 0.001), calculated free testosterone (cfT) 145 (56–183) vs 464 (359–574) pmol/L (P < 0.001), LH 1.5 (1.1–2.1) vs 3.1 (2.3–4.0) U/L (P = 0.002) and inhibin b (P < 0.001). Levels of FSH were similar (P = 0.63). Testosterone/LH ratio and cfT/LH ratio were reduced in patients (both P < 0.001).
Conclusions
Despite Leydig cell insufficiency in patients with acquired pituitary insufficiency, the majority presented with normal semen quality based on the determination of the number of progressively motile spermatozoa. In addition, the data suggest reduced LH bioactivity in patients with pituitary insufficiency.
K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway
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Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway
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K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway
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Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden
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Department of Sleep, Landspitali University Hospital Reykjavík, Reykjavik, Iceland
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Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
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Albacete Faculty of Medicine, Castilla-La Mancha University, Albacete, Spain
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The National Research Center for the Working Environment, Copenhagen, Denmark
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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.
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Universidade de São Paulo, Zebrafish Facility, São Paulo, São Paulo, Brazil
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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.
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Imperial College London, Institute of Reproductive and Developmental Biology, London, UK
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Malmö University Hospital, Reproductive Medicine Center, Malmö, Sweden
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Objective
During androgen ablation in prostate cancer by the standard gonadotropin-releasing hormone (GnRH) agonist treatment, only luteinizing hormone (LH) is permanently suppressed while circulating follicle-stimulating hormone (FSH) rebounds. We explored direct prostatic effects of add-back FSH, after androgen ablation with GnRH antagonist, permanently suppressing both gonadotropins.
Methods
The effects of recombinant human (rFSH) were examined in mice treated with vehicle (controls), GnRH antagonist degarelix (dgx), dgx + rFSH, dgx + flutamide, or dgx + rFSH + flutamide for 4 weeks. Prostates and testes size and expression of prostate-specific and/or androgen-responsive genes were measured. Additionally, 33 young men underwent dgx-treatment. Seventeen were supplemented with rFSH (weeks 1–5), and all with testosterone (weeks 4–5). Testosterone, gondotropins, prostate-specific antigen (PSA), and inhibin B were measured.
Results
In dgx and dgx + flutamide treated mice, prostate weight/body weight was 91% lower than in controls, but 41 and 11%, respectively, was regained by rFSH treatment (P = 0.02). The levels of seminal vesicle secretion 6, Pbsn, Nkx3.1, beta-microseminoprotein, and inhibin b were elevated in dgx + rFSH-treated animals compared with only dgx treated (all P < 0.05). In men, serum inhibin B rose after dgx treatment but was subsequently suppressed by testosterone. rFSH add-back had no effect on PSA levels.
Conclusions
These data provide novel evidence for the direct effects of FSH on prostate size and gene expression in chemically castrated mice. However, in chemically castrated men, FSH had no effect on PSA production. Whether FSH effects on the prostate in humans also require suppression of the residual adrenal-derived androgens and/or a longer period of rFSH stimulation, remains to be explored.
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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.
