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- Abstract: adrenarche x
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- Abstract: Gender x
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Polish Mother’s Memorial Hospital–Research Institute, Lodz, Poland
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Polish Mother’s Memorial Hospital–Research Institute, Lodz, Poland
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Background
Though insulin resistance (IR) is common in polycystic ovary syndrome (PCOS), there is no agreement as to what surrogate method of assessment of IR is most reliable.
Subjects and methods
In 478 women with PCOS, we compared methods based on fasting insulin and either fasting glucose (HOMA-IR and QUICKI) or triglycerides (McAuley Index) with IR indices derived from glucose and insulin during OGTT (Belfiore, Matsuda and Stumvoll indices).
Results
There was a strong correlation between IR indices derived from fasting values HOMA-IR/QUICKI, r = −0.999, HOMA-IR/McAuley index, r = −0.849 and between all OGTT-derived IR indices (e.g. r = −0.876, for IRI/Matsuda, r = −0.808, for IRI/Stumvoll, and r = 0.947, for Matsuda/Stumvoll index, P < 0.001 for all), contrasting with a significant (P < 0.001), but highly variable correlation between IR indices derived from fasting vs OGTT-derived variables, ranging from r = −0.881 (HOMA-IR/Matsuda), through r = 0.58, or r = −0.58 (IRI/HOMA-IR, IRI/QUICKI, respectively) to r = 0.41 (QUICKI/Stumvoll), and r = 0.386 for QUICKI/Matsuda indices. Detailed comparison between HOMA-IR and IRI revealed that concordance between HOMA and IRI was poor for HOMA-IR/IRI values above 75th and 90th percentile. For instance, only 53% (70/132) women with HOMA-IR >75th percentile had IRI value also above 75th percentile. There was a significant, but weak correlation of all IR indices with testosterone concentrations.
Conclusions
Significant number of women with PCOS can be classified as being either insulin sensitive or insulin resistant depending on the method applied, as correlation between various IR indices is highly variable. Clinical application of surrogate indices for assessment of IR in PCOS must be therefore viewed with an extreme caution.
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Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
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Steroid hormones play clinically important and specific regulatory roles in the development, growth, metabolism, reproduction and brain function in human. The type 1 and 2 11-beta hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 2) have key roles in the pre-receptor modification of glucocorticoids allowing aldosterone regulation of blood pressure, control of systemic fluid and electrolyte homeostasis and modulation of integrated metabolism and brain function. Although the activity and function of 11β-HSDs is thought to be understood, there exists an open reading frame for a distinct 11βHSD-like gene; HSD11B1L, which is present in human, non-human primate, sheep, pig and many other higher organisms, whereas an orthologue is absent in the genomes of mouse, rat and rabbit. We have now characterised this novel HSD11B1L gene as encoded by 9 exons and analysis of EST library transcripts indicated the use of two alternate ATG start sites in exons 2 and 3, and alternate splicing in exon 9. Relatively strong HSD11B1L gene expression was detected in human, non-human primate and sheep tissue samples from the brain, ovary and testis. Analysis in non-human primates and sheep by immunohistochemistry localised HSD11B1L protein to the cytoplasm of ovarian granulosa cells, testis Leydig cells, and gonadatroph cells in the anterior pituitary. Intracellular localisation analysis in transfected human HEK293 cells showed HSD1L protein within the endoplasmic reticulum and sequence analysis suggests that similar to 11βHSD1 it is membrane bound. The endogenous substrate of this third HSD enzyme remains elusive with localisation and expression data suggesting a reproductive hormone as a likely substrate.
INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France
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INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France
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INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France
INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France
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INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France
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INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Mont‐Saint‐Aignan, France
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Hirsutism induced by hyperandrogenism can be associated with polycystic ovary syndrome, 21-hydroxylase (OH) deficiency or androgen-secreting tumors, including ovarian and adrenal tumors. Adrenal androgen-secreting tumors are frequently malignant. Adrenal oncocytomas represent rare causes of hyperandrogenism. The aim of the study was to investigate steroidogenic enzyme expression and steroid secretion in an androgen-secreting adrenal oncocytoma in a young woman presenting with hirsutism. Hyperandrogenism was diagnosed on the basis of elevated plasma Δ4-androstenedione and testosterone levels. Pelvic ultrasound was normal, CT scanning revealed a right adrenal mass. Androgens were assessed in adrenal and ovarian vein samples and proved a right adrenal origin. Adrenalectomy normalized androgen levels and the adrenal tumor was diagnosed as an oncocytoma. Real time-PCR, immunohistochemistry and cell culture studies were performed on tumor explants to investigate the steroid secretion profile. Among enzymes required for cortisol synthesis, 17α-OH and 3β-hydroxysteroid dehydrogenase 2 (3β-HSD2) were highly expressed whereas 21-OH and 11β-OH were weakly produced at the mRNA and/or protein levels. Enzymes involved in testosterone production, 17β-HSD5 and 17β-HSD3, were also detected. ACTH receptor was present in the tissue. Cortisol, Δ4-androstenedione and testosterone secretions by cultured cells were increased by ACTH. These results provide the first demonstration, to our knowledge, of abnormal expression profile of steroidogenic enzymes in an adrenocortical oncocytoma. Our results also indicate that Δ4-androstenedione hypersecretion resulted from high 17α-OH and 3β-HSD2 expression in combination with low expression of 21-OH and 11β-OH. Testosterone production was ascribed to occurrence of 17β-HSD5 and 17β-HSD3. Finally, our results indicate that androgen secretion was stimulated by ACTH.
The Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester, UK
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Department of Diabetes and Endocrinology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK
Diabetes and Endocrinology Department, Kettering General Hospital NHS Foundation Trust, Kettering, UK
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Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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The Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester, UK
Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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The Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester, UK
Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
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Aims
Physical activity has been proposed to be an effective non-pharmacological method of reducing systemic inflammation and therefore may prove particularly efficacious for women with polycystic ovary syndrome (PCOS) who have been shown to have high levels of inflammation and an increased risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD). Therefore, the aim of the present study was to assess whether modest changes in daily step count could significantly reduce levels of inflammatory markers in women with PCOS.
Subjects and Methods
Sixty-five women with PCOS were assessed at baseline and again at 6 months. All had been provided with an accelerometer and encouraged to increase activity levels. Multivariate linear regression analyses (adjusted for age, ethnicity, baseline step count, change in BMI and change in accelerometer wear-time) were used to assess changes in daily step count against clinical and research biomarkers of inflammation, CVD and T2DM.
Results
Mean step count/day at baseline was 6337 (±270). An increase in step count (by 1000 steps) was associated with a 13% reduction in IL6 (β: −0.81 ng/L; 95% CI, −1.37, −0.25, P = 0.005) and a 13% reduction in CRP (β: −0.68 mg/L; 95% CI, −1.30, −0.06, P = 0.033). Additionally, there was a modest decrease in BMI (β: 0.20 kg/m2; 95% CI, −0.38, −0.01, P = 0.038). Clinical markers of T2DM and CVD were not affected by increased step count.
Conclusions
Modest increases in step count/day can reduce levels of inflammatory markers in women with PCOS, which may reduce the future risk of T2DM and CVD.
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Polycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular disease in women. Hyperhomocysteinemia (H-Hcy) is closely related to arterial stiffness (AS) in patients with cardiovascular disease. This study aimed to investigate the relationship between serum homocysteine(Hcy) level and brachial-ankle pulse wave velocity (baPWV) in Chinese women with PCOS. A total of 124 PCOS women were enrolled and divided into two groups according to their baPWV values: normal, baPWV < 1400 cm/s and high AS, baPWV ≥ 1400 cm/s. Univariate analysis was performed to investigate the relative factors for baPWV, and multiple regression analysis was used to evaluate the association of Hcy with baPWV. The group with high AS (n = 35) had higher Hcy levels than the other group (n = 89; P < 0.05). Moreover, univariate analysis revealed that serum Hcy was positively correlated with baPWV (r = 0.133, P < 0.01). In multiple regression analysis, the age-adjusted serum Hcy level was positively correlated with baPWV (β = 0.201, P < 0.01). It remained positively associated with baPWV (β = 0.145, P < 0.01) after further adjustments for age, BMI, PCOS duration, systolic blood pressure, and homeostasis model assessment-insulin resistance as well as several other factors correlated with baPWV. Our results demonstrated that H-Hcy was significantly and independently related to elevated baPWV, suggesting that Hcy might play a role in the pathologic process of AS in women with PCOS. Further researches with more subjects are needed to explore whether Hcy would be a promising biomarker for the stratification management of PCOS women.
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Background
Polycystic ovary syndrome (PCOS) is a multi-symptom disorder linked with a range of metabolic and hormonal disturbances. Psychological and sexual aspects of PCOS also need to be considered.
Objective of the study
This study aimed to assess sexual satisfaction (SS) in PCOS patients and eumenorrheic controls (CON). The relationships between SS, depressive symptoms, health-related quality of life (HRQoL), and hormonal and metabolic profiles were evaluated.
Methods
In this study, 190 patients with PCOS (mean age 26.34 ± 5.47 years) and 197 age-matched CON (mean age 27.12 ± 4.97 years) were enrolled. All subjects completed Polish version of the Sexual Satisfaction Questionnaire (SSQ), WHO Quality of Life-BREF (WHOQOL-BREF), and the Center for Epidemiologic Studies Depression Scale-Revised (CESD-R) questionnaire. Fasting blood samples were collected to assess hormonal, lipid, and glucose profiles. Anthropometric measures were collected. Metabolic syndrome (MS) was evaluated according to the IDF-AHA/NHLBI criteria.
Results
Patients with PCOS and MS had lower SS vs non-MS-PCOS. There were no significant differences in the level of SS, presence of depressive symptoms, or HRQoL between PCOS and CON (P > 0.05). Negative correlations were found between the SS level and BMI, waist circumference, and waist-to-height ratio in PCOS women. However, overweight or obese PCOS women did not differ in SS levels vs normal-weight PCOS patients. The social dimension of WHOQOL-BREF was the only significant predictor of SS in PCOS patients.
Conclusions
SS in PCOS women appears to be undisturbed. However, MS in PCOS patients could negatively influence SS. The level of SS should be assessed in PCOS women, especially if MS is present.
Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil
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Objective
To verify whether aging can modify the clinical and biochemical characteristics of women with polycystic ovary syndrome (PCOS).
Material and methods
This observational cross-sectional study was conducted at the reproductive endocrinology clinics of Julio Muller University Hospital and Tropical Institute of Reproductive Medicine in Cuiabá, MT, Brazil, between 2003 and 2017. Both, 796 PCOS and 444 non-PCOS normal cycling women underwent the same examination. PCOS was diagnosed using the Rotterdam criteria as recommended for adolescent and adult subjects. Anthropometric, metabolic, and endocrinological modifications with aging were initially examined in the two groups: control and PCOS. Further analyses were performed after a 5-year age stratification of data throughout the reproductive period. All participants signed a consent form approved by the local ethical committee.
Results
Biomarkers of adiposity were more remarkable in African descendant PCOS women. Body weight, waist/hip ratio, fat mass, and BMI were higher in PCOS women and tended to increase at all 5 age-strata, between ≤19 and 35 years of age. Serum androgen levels decreased with aging, markedly in PCOS subjects (P < 0.01 for all age-strata comparisons), but remained elevated when compared with the levels found in controls. Carbohydrate markers, triglycerides, and total cholesterol tended to increase over time in PCOS (P < 0.01 for all age-strata comparisons). Total cholesterol also tended to increase with age in non-PCOS women (P = 0.041).
Conclusion
The present study has shown that the advancing age influences many features of PCOS women. Biochemical hyperandrogenism, the core criterion recommended in the current systems to define the syndrome, showed statistically significant tendencies to decrease with aging progression but did not normalize. The use of age-adjusted features for the diagnosis of PCOS are recommended.
Department of Endocrinology and Diabetes, Pakistan Kidney and Liver Institute and Research Centre, Knowledge City, Lahore, Pakistan
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Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
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Context
Endothelial microparticles (EMPs) are novel, surrogate biomarkers of endothelial function and have been shown to be elevated in women with polycystic ovary syndrome (PCOS). It remains poorly understood how pharmacological options for managing PCOS affect EMP levels.
Objective
To characterise and compare the effects of empagliflozin vs metformin on the circulating levels of EMPs in overweight/obese women with PCOS.
Methods
This was a randomised, comparative, 12-week single-centre trial conducted at the Academic Diabetes, Endocrinology and Metabolism Research Centre, Hull, UK. This analysis includes data from 39 overweight/obese women with PCOS who completed the study and were randomised to empagliflozin (15 mg/day) (n = 19) or metformin (1500 mg/day) (n = 20). Blood samples were collected at baseline and 12 weeks after treatment and analysed for specific surface proteins (ICAM-1, VCAM-1, PECAM-1, E-selectin and endoglin) expressed by circulating EMPs using flow cytometry.
Results
In the empagliflozin group, ICAM-1 (P = 0.006), E-selectin (P = 0.016) and VCAM-1 (P = 0.001) EMPs increased significantly following 12 weeks of treatment, but no changes were seen in PECAM-1 (P = 0.93) or endoglin (P = 0.13) EMPs. In the metformin group, VCAM-1 EMPs (P < 0.001) increased significantly after 12 weeks of treatment, whereas all other EMPs remained unchanged. When data were expressed as percentage change from baseline in each group, no significant differences were seen between groups for any biomarker (P-values from 0.22 to 0.80).
Conclusions
Short-term administration of empagliflozin and metformin in overweight/obese women with PCOS appear to increase EMPs expressed by endothelial cells during their activation.
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Polycystic ovary syndrome (PCOS) is a chronic endocrine and metabolic disease. Gut microbiota is closely related to many chronic diseases. In this study, we conducted a cross-sectional study and recruited 30 obese (OG) and 30 non-obese (NG) women with PCOS, 30 healthy women (NC) and 11 healthy but obese women (OC) as controls to investigate the characteristic gut microbiota and its metabolic functions in obese and non-obese patients with PCOS. The blood and non-menstrual faecal samples of all the participants were collected and analysed. As a result, the Hirsutism score, LH/FSH and serum T level in NG and OG both increased significantly compared with their controls (P < 0.05). High-throughput 16S rRNA gene sequencing revealed that the abundance and diversity of the gut microbiota changed in patients with PCOS. The linear discriminant analysis (LDA) indicated that Lactococcus was the characteristic gut microbiota in NG, while Coprococcus_2 in OG. Correlation heatmap analysis revealed that the sex hormones and insulin levels in human serum were closely related to the changes in the gut microbiota of NG and OG. Functional prediction analysis demonstrated that the citrate cycle pathway enriched both in NG and OG, and other 12 gut bacterial metabolic pathways enriched in NG. This study highlighted significant differences in the gut microbiota and predictive functions of obese and non-obese women with PCOS, thereby providing insights into the role and function of the gut microbiota that may contribute to the occurrence and development of PCOS in obese and non-obese women.
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Objective
To estimate the effect of oral contraceptives (OC) containing different progestins on parameters of lipid and carbohydrate metabolism through a systematic review and meta-analysis.
Patients and methods
Premenopausal women aged 18 or older, who received oral contraceptives containing chlormadinone, cyproterone, drospirenone, levonorgestrel, desogestrel, dienogest, gestodene or norgestimate, for at least 3 months. Outcome variables were changes in plasma lipids, BMI, insulin resistance and plasma glucose. We searched MEDLINE and EMBASE for randomized trials and estimated the pooled within-group change in each outcome variable using a random-effects model. We performed subgroup analyses by study duration (<12 months vs ≥12 months) and polycystic ovary syndrome (PCOS) status.
Results
Eighty-two clinical trials fulfilled the inclusion criteria. All progestins (except dienogest) increased plasma TG, ranging from 12.1 mg/dL for levonorgestrel (P < 0.001) to 35.1 mg/dL for chlormadinone (P < 0.001). Most progestins also increased HDLc, with the largest effect observed for chlormadinone (+9.6 mg/dL, P < 0.001) and drospirenone (+7.4 mg/dL, P < 0.001). Meanwhile, levonorgestrel decreased HDLc by 4.4 mg/dL (P < 0.001). Levonorgestrel (+6.8 mg/dL, P < 0.001) and norgestimate (+11.5 mg/dL, P = 0.003) increased LDLc, while dienogest decreased it (–7.7 mg/dL, P = 0.04). Cyproterone slightly reduced plasma glucose. None of the progestins affected BMI or HOMA-IR. Similar results were observed in subgroups defined by PCOS or study duration.
Conclusion
Most progestins increase both TG and HDLc, their effect on LDLc varies widely. OC have minor or no effects on BMI, HOMA-IR and glycemia. The antiandrogen progestins dienogest and cyproterone displayed the most favorable metabolic profile, while levonorgestrel displayed the least favorable.
