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You are looking at 101 - 110 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 overproduction of adrenocorticotropic hormone (ACTH), in conditions such as Cushing’s disease and congenital adrenal hyperplasia (CAH), leads to significant morbidity. Current treatment with glucocorticoids does not adequately suppress plasma ACTH, resulting in excess adrenal androgen production. At present, there is no effective medical treatment in clinical use that would directly block the action of ACTH. Such a therapy would be of great clinical value. ACTH acts via a highly selective receptor, the melanocortin-2 receptor (MC2R) associated with its accessory protein MRAP. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and the high degree of ligand specificity suggest that antagonism of this receptor could provide a useful therapeutic strategy in the treatment of conditions of ACTH excess. To this end, we screened an extensive library of low-molecular-weight drug-like compounds for MC2R antagonist activity using a high-throughput homogeneous time-resolved fluorescence cAMP assay in Chinese hamster ovary cells stably co-expressing human MC2R and MRAP. Hits that demonstrated MC2R antagonist properties were counter-screened against the β2 adrenergic receptor and dose–response analysis undertaken. This led to the identification of a highly specific MC2R antagonist capable of antagonising ACTH-induced progesterone release in murine Y-1 adrenal cells and having selectivity for MC2R amongst the human melanocortin receptors. This work provides a foundation for the clinical investigation of small-molecule ACTH antagonists as therapeutic agents and proof of concept for the screening and discovery of such compounds.
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Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
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With increasing evidence of emotional well-being disorders associated with polycystic ovary syndrome (PCOS), effective screening processes are of utmost importance. We studied the impact of using questionnaires to screen for emotional and psychosexual well-being across different models of care for PCOS. We analysed the data from the surveys to assess the difference in the prevalence of emotional and psychosexual ill-being across ethnicity and region. In this prospective cohort study, we invited all women attending consultations for PCOS in Birmingham, UK, and Bengaluru and Navi Mumbai, India. Those who consented to participate in the study were invited to complete a pre-clinic survey about socio-demographic data, Hospital Anxiety and Depression Scale (HADS), Body Image Concern Inventory (BICI), Beliefs about Obese Person scale (BAOP), and Female Sexual Function Index score (FSFI) and a post-clinic survey on clinic experience, lifestyle advice, and specialist referral. A total of 115 women were included in this study. The rate of questionnaire completion was 98.3% (113/115), 97.4% (112/115), 93.04% (107/115), and 84.3% (97/115) for HADS, BICI, BAOP, and FSFI, respectively. In the post-clinic survey, 28.8% reported they were screened for anxiety, 27.1% for depression, and 45.8% for body image concerns. The prevalence of anxiety, depression, and body dysmorphic disorder through pre-clinic survey was 56.5% (50.0% UK vs 59.5% India, P = 0.483), 16.5% (13.9% UK vs 17.7% India, P = 0.529), and 29.6% (36.1% UK vs 26.6% India, P = 0.208), respectively. Surveys with validated questionnaires can improve screening for emotional and psychosexual well-being associated with PCOS which may be missed by ad hoc screening during consultations.
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Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China
Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China
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Objective
Anti-Müllerian hormone (AMH) is recognized as the most important biomarker for ovarian reserve. In this cross-sectional study, we aimed to explore the potential association of AMH with central obesity or general obesity in women with polycystic ovary syndrome (PCOS).
Methods
In this cross-sectional study, 179 patients with PCOS were enrolled and underwent anthropometric measurements (BMI and waist circumference (WC)) and serum AMH level detection. Pearson’s correlation and multivariable logistic regression analyses were performed to determine the associations of AMH with central obesity and general obesity.
Results
Subjects with increasing BMI showed significantly lower values of AMH (median (interquartile range (IQR)) 8.95 (6.03–13.60) ng/mL in normal weight group, 6.57 (4.18–8.77) ng/mL in overweight group, and 6.03 (4.34–9.44) ng/mL in obesity group, P = 0.001), but higher levels of systolic blood pressure, fasting insulin, total cholesterol, triglycerides, LDL-c, obesity indices (WC, hip circumferences, waist-to-hip ratio, waist-to-height ratio (WHtR), and Chinese visceral adiposity index (CVAI)). Compared with the group of PCOS women without central obesity, the group with central obesity had significantly lower value of AMH (median (IQR) 8.56 (5.29–12.96) ng/mL vs 6.22 (4.33–8.82) ng/mL; P = 0.003). Pearson’s correlation analysis showed that AMH was significantly and negatively correlated with BMI (r = −0.280; P < 0.001), WC (r = −0.263; P < 0.001), WHtR (r = −0.273; P < 0.001), and CVAI (r = −0.211; P = 0.006). Multivariate logistic regression analysis with adjustment for potential confounding factors showed that AMH was independently and negatively associated with central obesity but was not significantly associated with general obesity.
Conclusions
AMH was independently and negatively associated with central obesity. Closely monitoring the WC and AMH should be addressed in terms of assessing ovarian reserve in women with PCOS.
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Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark
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In this commentary, we discuss the state of affairs concerning the clinical care of females with Turner syndrome (TS) in Germany. TS is a rare disease and new international guidelines describe an appropriate setup for optimal clinical care. Several countries have implemented a program with centralized adult Turner syndrome clinics, which are now found in France, Denmark, the Netherlands, Sweden, parts of England and possibly other countries, but hitherto not in Germany. Such an approach should ensure the availability of high quality multi-disciplinary care for all women with TS to be treated and to detect all the conditions that have been associated with TS, which typically appear at odd times during the lifetime of a female with TS. Care should be offered at no added cost for the patient, and treatment with relevant drugs should be available at reasonable cost for the individual patient. Currently, it is quite problematic that many female sex hormone preparations are not available at low cost in a number of countries. Additional problems include supply chain issue which lead to patients not being able to buy their usual drug for a certain period of time. We think it is timely that countries improve the care for individuals with rare conditions, such as TS.
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
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Unit of Gynecology and Obstetrics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
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Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
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Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
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Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
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Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
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Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
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Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
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Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, Rome, Italy
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Medical Department Pronokal Group, Barcelona, Spain
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Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
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Unit of Gynecology and Obstetrics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
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Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
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Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
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Objective
The aim of this study isto assess the efficacy of a very low-calorie ketogenic diet (VLCKD) method vs a Mediterranean low-calorie diet (LCD) in obese polycystic ovary syndrome (PCOS) women of a reproductive age.
Design
Randomized controlled open-label trial was performed in this study. The treatment period was 16 weeks; VLCKD for 8 weeks then LCD for 8 weeks, according to the Pronokal® method (experimental group; n = 15) vs Mediterranean LCD for 16 weeks (control group; n = 15). Ovulation monitoring was carried out at baseline and after 16 weeks, while a clinical exam, bioelectrical impedance analysis (BIA), anthropometry, and biochemical analyses were performed at baseline, at week 8, and at week 16.
Results
BMI decreased significantly in both groups and to a major extent in the experimental group (−13.7% vs −5.1%, P = 0.0003). Significant differences between the experimental and the control groups were also observed in the reduction of waist circumference (−11.4% vs −2.9%), BIA-measured body fat (−24.0% vs −8.1%), and free testosterone (−30.4% vs −12.6%) after 16 weeks (P = 0.0008, P = 0.0176, and P = 0.0009, respectively). Homeostatic model assessment for insulin resistance significantly decreased only in the experimental group (P = 0.0238) but without significant differences with respect to the control group (−23% vs −13.2%, P > 0.05). At baseline, 38.5% of participants in the experimental group and 14.3% of participants in the control group had ovulation, which increased to 84.6% (P = 0.031) and 35.7% (P > 0.05) at the end of the study, respectively.
Conclusion
In obese PCOS patients, 16 weeks of VLCKD protocol with the Pronokal® method was more effective than Mediterranean LCD in reducing total and visceral fat, and in ameliorating hyperandrogenism and ovulatory dysfunction.
Significance statements
To the best of our knowledge, this is the first randomized controlled trial on the use of the VLCKD method in obese PCOS. It demonstrates the superiority of VLCKD with respect to Mediterranean LCD in reducing BMI with an almost selective reduction of fat mass and a unique effect of VLCKD in reducing visceral adiposity, insulin resistance, and in increasing SHBG with a consequent reduction of free testosterone. Interestingly, this study also demonstrates the superiority of the VLCKD protocol in improving ovulation, whose occurrence increased by 46.1% in the group treated by the VLCKD method against a rise of 21.4% in the group treated by Mediterranean LCD. This study extends the therapeutic approach possibilities in obese PCOS women.
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Université Pierre et Marie Curie, Sorbonne Université, Paris, France
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INSERM UMR_S933, Paris, France
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Université Pierre et Marie Curie, Sorbonne Université, Paris, France
INSERM UMR_S933, Paris, France
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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.
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Turner syndrome (TS), although considered a rare disease, is the most common sex chromosome abnormality in women, with an incident of 1 in 2500 female births. TS is characterized by distinctive physical features such as short stature, ovarian dysgenesis, an increased risk for heart and renal defects as well as a specific cognitive and psychosocial phenotype. Given the complexity of the condition, patients face manifold difficulties which increase over the lifespan. Furthermore, failures during the transitional phase to adult care result in moderate health outcomes and decreased quality of life. Guidelines on the optimal screening procedures and medical treatment are easy to find. However, recommendations for the treatment of the incriminating psychosocial aspects in TS are scarce. In this work, we first reviewed the literature on the cognitive and psychosocial development of girls with TS compared with normal development, from disclosure to young adulthood, and then introduce a psychosocial approach to counseling and treating patients with TS, including recommendations for age-appropriate psychological diagnostics. With this work, we aim to facilitate the integration of emphasized psychosocial care in state-of-the-art treatment for girls and women with TS.
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Background
Non-adherence to r-hGH treatments occurs in a variable percentage of subjects. One problem found when evaluating adherence is the great variability in methods of detection and definitions utilized in studies. This study assessed the level of adherence in subjects receiving r-hGH with the easypod™ electronic device.
Methods
National, multicenter, prospective and observational study involving 238 subjects (144 with GH deficiency (GHD), and 86 with small for gestational age (SGA), 8 with Turner Syndrome), who received r-hGH with easypod™ for at least 3 months before inclusion. The follow-up period was 4 years.
Results
Overall adherence was 94.5%; 97.5% after 6 months, 95.3% after 1 year, 93.7% after 2, 94.4% after 3 and 95.5% after 4 years of treatment. No differences in adherence were observed between prepubertal and pubertal groups and GHD and SGA groups. Change in height after 1 and 2 years, change in height SDS after 1 and 2 years, HV after 1 year, HV SDS after at 1 and 4 years, change in BMI after 1 year and change in BMI SDS at 1 and 2 years showed significant correlation with adherence. No significant differences in adherence according to IGF-I levels were found in follow-up visits or between groups.
Conclusions
The easypod™ electronic device, apart from being a precise and objective measure of adherence to r-hGH treatment, allows high compliance rates to be achieved over long periods of time. Adherence significantly impacts growth outcomes associated with r-hGH treatment.
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Background
Previous studies have shown that only a minority of patients with Turner syndrome (TS) have adequate medical care after transfer to adult care.
Aim of this study
To assess the status of medical follow-up and quality of life (QoL) in adult women diagnosed with TS and followed up until transfer. To compare the subjective and objective view of the medical care quality and initiate improvements based on patients’ experiences and current recommendations.
Methods
39 adult women with TS out of 64 patients contacted were seen for a clinical and laboratory check, cardiac ultrasound, standardized and structured questionnaires (SF-36v2 and Beck depression inventory).
Results
7/39 of the patients were not being followed medically at all. Only 2/39 consulted all the specialists recommended. Comorbidities were newly diagnosed in 27/39 patients; of these, 11 related to the cardiovascular system. Patients in our cohort scored as high as the mean reference population for SF-36v2 in both mental and physical compartments. Obese participants had lower scores in the physical function section, whereas higher education was related to higher physical QoL scores. Adult height slightly correlated positively with physical health.
Conclusion
Medical follow-up was inadequate in our study cohort of adults with TS. Even though their medical follow-up was insufficient, these women felt adequately treated, leaving them vulnerable for premature illness. Initiatives in health autonomy and a structured transfer process as well as closer collaborations within specialities are urgently needed.
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Objective
This study sought to determine the effect of the recombinant human growth hormone (rhGH) treatment of Turner syndrome (TS) on height outcome.
Methods
We searched in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews. A literature search identified 640 records. After screening and full-text assessment, 11 records were included in the systematic review. Methodological quality was assessed using the Cochrane Risk of Bias tool. RevMan 5.3 software was used for meta-analysis. We also assessed the quality of evidence with the GRADE system.
Results
Compared with controls, rhGH therapy led to increased final height (MD = 7.22 cm, 95% CI 5.27–9.18, P < 0.001, I2 = 4%; P = 0.18), height standard deviation (HtSDS) (SMD = 1.22, 95% CI 0.88–1.56, P < 0.001, I2 = 49%; P = 0.14) and height velocity (HV) (MD 2.68 cm/year; 95% CI 2.34, 3.02; P < 0.001, I2 = 0%; P = 0.72). There was a small increase in bone age (SMD 0.32 years; 95% CI 0.1, 0.54; P = 0.004, I2 = 73%; P = 0.02) after rhGH therapy for 12 months. What is more, the rhGH/oxandrolone combination therapy suggested greater final height (MD 2.46 cm; 95% CI 0.73, 4.18; P = 0.005, I2 = 32%; P = 0.22), increase and faster HV (SMD 1.67 cm/year; 95% CI 1.03, 2.31; P < 0.03, I2 = 80%; P < 0.001), with no significant increase in HtSDS and bone maturation compared with rhGH therapy alone.
Conclusions
For TS patients, rhGH alone or with concomitant use of oxandrolone treatment had advantages on final height.
