Association between serum estradiol level, sex hormone binding globulin level, and bone mineral density in middle-aged postmenopausal women

Background Changes in sex hormones are thought to play an important role in bone health in postmenopausal women. Our aim in this study was to evaluate the association between levels of estradiol (E2), which is the most potent endogenous estrogen, and sex hormone binding globulin (SHBG) and bone mineral density (BMD) among postmenopausal women, 40–59 years of age. Methods Using data from the National Health and Nutrition Examination Survey 2013–2016, we performed weighted multivariable linear regression models to evaluate the associations between serum levels of E2 and SHBG and lumbar BMD. A weighted generalized additive model and smooth curve fitting were used to address potential nonlinearity. Results A total of 608 postmenopausal women were included in the analysis. The serum E2 level was positively associated with lumbar BMD, after adjusting for other covariates (β 0.65; 95% confidence interval (CI) 0.38–0.93). An inverted U-shaped association between the serum E2 level and lumbar BMD was further identified, with the point of inflection at an E2 level of 70 pg/mL. There was no significant association between the SHBG level and lumbar BMD (β 0.01; 95% CI − 0.30 to 0.31). However, the association between these two variables was U-shaped, with the point of inflection at an SHBG level of 65 nmol/L. Conclusions Based on our findings, it may be beneficial to appropriately increase serum E2 levels to promote bone health in postmenopausal women with low estrogen levels. Considering the inverted U-shaped association, an excessive E2 level may be harmful to BMD. In addition, increasing the SHBG level to within the normal range (65–144 nmol/L) may be considered.

Homozygous SHBG Variant (rs6258) Linked to Gonadotropin-Independent Precocious Puberty in a Young Girl

Sex hormone-binding globulin (SHBG) in the blood is a major determinant of bioactivity for key sex steroids such as testosterone and estradiol. Low serum levels of SHBG have been associated with obesity, polycystic ovaries and metabolic syndrome, and other states associated with hyperandrogenemia. A 9-year, 6-month-old girl presented with a history of peripheral precocious puberty and aggressive behavior. The patient’s SHBG level was remarkably low for her age, at less than 5 nmol/L [reference range for a girl with a bone age of 10 years, 73 nmol/L (SEM= 10)](1). Upon genetic and protein analysis, the patient was found to have a homozygous missense potentially pathogenic variant in the SHBG gene (c.554 C>T, p.P185L); her parents were asymptomatic heterozygote carriers. Laboratory investigations supported the possible involvement of this genetic alteration in the patient’s phenotype. Various analyses of this variant support its pathogenicity, although the exact mechanism remains unclear. In conclusion, we present a genetic SHBG variant in the homozygote state that may have been associated with gonadotropin-independent precocious puberty in a young girl.

Association of Serum Sex-Hormone-Binding Globulin in Pregnant Women with Gestational Diabetes Mellitus

Background & objective: Gestational diabetes mellitus (GDM) is a common pregnancy complication and is associated with increase maternal and neonatal morbidity. Circulating Sex hormone-binding globulin (SHBG) levels are inversely associated with insulin resistance, and insulin resistance is the hallmark of GDM. This study was carried out to investigate SHBG level in pregnancy and to analyze the association of SHBG with GDM. Materials & Methods: This case-control study was carried out in the antenatal clinic of the department of obstetrics & gynecology, BSMMU, Shahbag, Dhaka, over a period of 12 months between August 2017 to July 2018. Participants were 80 in number, aged between 18 to 35 years, having singleton pregnancy with 24 to 28 weeks of gestation. 40 GDM cases were enrolled as the case, and 40 non-GDM cases were enrolled as the control. Pregnant women with overt diabetes/diabetes in pregnancy, previous history of GDM, pre-eclampsia, gestational/chronic hypertension, known case of liver disease, thyroid disorder, acute or chronic renal disease, congenital fetal anomaly, multiple pregnancies, smoking, H/O polycystic ovary syndrome (PCOS) was excluded from the study. Comparison of means made by using Student t-test and categorical data were analyzed by Chi-square Test, and Pearson's correlation was utilized between serum sex-hormone binding globulin level nmol/L with fasting plasma glucose (mmol/L) and 2-hour after 75g glucose (mmol/L). Statistical significance was set at p < 0.05. Results: The median value of serum SHBG was 245.0nmol/L (195.8-278.1) in the case group and 390.1nmol/L (310.2-465.3) in the control group. Women with GDM were found to have significantly lower levels of SHBG compared to the controls (p<0.05). There was a moderate negative significant correlation (r=-0.621; p=0.001) between fasting plasma glucose (mmol) with serum SHBG (nmol/l) in GDM patients. On the other hand, there was a weak negative but not significant correlation (r=-0.229; p=0.155) was found between 2 hours after plasma glucose with serum SHBG in the GDM group. Conclusion: A significantly lower SHBG level is associated with GDM. TAJ 2021; 34: No-1: 80-85

Sex-specific Associations of Sex Hormone Binding Globulin with CKD and Kidney Function: A Univariable and Multivariable Mendelian Randomization Study in the UK Biobank

BackgroundKidney function declines faster in men. Testosterone levels may mediate the sex disparity. Correspondingly, levels of sex hormone binding globulin (SHBG), which modulates sex hormones, might also be relevant to the lower kidney function in men. The sex-specific role of SHBG is unclear.MethodsA sex-specific, Mendelian randomization (MR) study provided unconfounded estimates of SHBG levels among the United Kingdom Biobank population. Univariable MR applied 357 single nucleotide polymorphisms (SNPs) in men and 359 SNPs in women. These published SNPs strongly (P<5×10−8) predict SHBG level. They were profiled in 179,916 white British men (6016 patients with CKD) and 212,079 white British women (5958 patients with CKD), to obtain the effect of SHBG on CKD, albuminuria, and eGFR. Multivariable MR controlling for testosterone was used to assess the effect of SHBG on CKD and kidney function independent of testosterone in men.ResultsGenetically predicted higher SHBG was associated with a lower risk of CKD in men (odds ratio [OR], 0.78 per SD; 95% confidence interval [95% CI], 0.65 to 0.93) but had no benefit in women. The effect in men remained in multivariable MR, allowing for testosterone (OR, 0.61; 95% CI, 0.45 to 0.82).ConclusionsGenetically predicted higher SHBG was associated with a lower risk of CKD and better kidney function in men, but not in women, suggesting that SHBG may play a role in CKD specifically in men. Identifying drivers of SHBG and the underlying pathways could provide new insights into CKD prevention and treatment.

POLY CYSTIC OVARIAN SYNDROME: AN UPDATED REVIEW

Polycystic ovarian syndrome(PCOS) is the most common endocrine and inflammatory disorder in women associated with oligo-anovulatory infertility and cardiometabolic disorder. Insulin plays a vital role in PCOS; it is also responsible for regulating the action of ovarian and liver metabolic enzymes and also involved in the production of Androgens. The hyperandrogenism prevalence nearly (70-80%). In PCOS, the target tissue is controlled by sex hormone-binding globulin(SHBG) because this is a type of protein produced by hepatic and tightly bind with testosterone and as well as dihydrotestosterone (DHT) and estradiol.[3] Currently study reported, associated with rs6259 polymorphism with link SHBG level and PCOS in most Indian women, nearly 3-5%. The PCOS cases associated with isolated functional adrenal hyperandrogenism and the remaining case of PCOS maybe lack clinical evidence of steroids secretory dysfunction. Most of the females are obese in PCOS; the treatment approaches of PCOS are towards improving insulin tolerance reduce the level of androgen and maintain the normal menstrual cycle and regulate proper fertility. Nonpharmacological approaches are also helpful, like proper exercise, weight management, and maintain healthy diets. The etiology is still unclear, not clear, and has no cure. Some studies reported dysregulation of the gut microbiome and played the crucial role played in Pathogenesis in PCOS.

The relationship between components of metabolic syndrome and plasma level of sex hormone-binding globulin

Plasma concentration of sex hormone-binding globulin (SHBG), as an androgen binding protein, is impressed by many physiological and environmental factors. Recent studies have shown that plasma level of SHBG is related to some components of metabolic syndrome (MetS); however, in contrast, few articles failed to show any associations between SHBG and MetS. So, this study was conducted to investigate the relationship between Components of Metabolic Syndrome and Plasma Level of Sex Hormone-Binding Globulin. In this study, after measuring the plasma level of SHBG in 84 individuals, the relation between MetS and the plasma level of SHBG was investigated. After evaluating the plasma level of SHBG and metabolic abnormalities in men and women, we investigated the factors which mentioned above in two groups including patients with and without MetS. Also, the metabolic abnormalities which evaluated in this study including plasma level of 25-hydroxyvitamin D, serum uric acid (SUA), Albumin, lipid profiles and etc. according to five components of MetS. Our result shows that SHBG could contributed to some laboratory parameters such as LDL-C (P<0.05), total cholesterol (P<0.05), triglycerides (P<0.05) and etc. in men, but not in women. On the other hand, we observed that concentration of SHBG is higher in patients with MetS (P<0.05); however, results from our experiment showed that there is no relation between lower level of SHBG and five components of MetS such as central obesity, raised fasting plasma glucose (FPG) (P>0.05), reduced HDL-C (P>0.05), raised triglycerides (P>0.05) and raised blood pressure (P>0.05) in both men and women. There is a significant association between SHBG and Log-Hip Circumference (P<0.05), Non-HDL-C (P<0.05) and Log-25(OH)D (P<0.05) was seen in this cross-section study in both men and women. Results obtained from our study suggest that SHBG is not a powerful enough factor to use as a predictor of MetS alone and there is no association between plasma level of SHBG and development of five components of MetS, however, lower SHBG level may contributed to lipid profiles.

Triglycerides, independent of Ferriman Gallwey Score, is a main determinant of free testosterone index in PCOS

Background: Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, affecting 5-20% of women worldwide. Hyperandrogenism, as the primary characteristic of PCOS, is not always present in every patient. The hyperandrogenic phenotype of PCOS patients is influenced by both hormonal and metabolic dysfunctions. Therefore, this study aims to determine the correlation between hormone profile, lipid profile, and clinical profile with free testosterone index in subjects with PCOS. Methods: This prospective cross-sectional study was conducted in the Dr. Cipto Mangunkusumo General Hospital between July 2014 and December 2016. The study involved 76 women with PCOS, who were classified into 2 subgroups: 39 subjects in the hyperandrogenism group and 37 subjects in the non-hyperandrogenism group. Each subject underwent physical examination, blood sample collection, and USG examination. Bivariate analysis was done using independent t-tests and Mann Whitney U-tests, while multivariate analysis was done using logistic regression. Results: Triglyceride and testosterone level showed weak (r = 0.232, p = 0.044) and moderate (r = 0.460, p ¡ 0.001) positive correlation with FTI, while SHBG level showed moderate negative correlation (r = -0.483, p ¡ 0.001). Triglyceride was also found to be determinant of hyperandrogenism condition in PCOS patient (OR 0.02, 95% CI 0.00–0.04, p = 0.013). However, there was no significant difference observed between FGS and hyperandrogenism (p = 0.43). Conclusions: Triglycerides, testosterone, and SHBG were associated with hyperandrogenism in PCOS patients, while FGS showed no such association.

PO-289 Lipidomic analysis of blood serum from prepubertal boys with different BMI

Objective Childhood obesity is a worldwide health problem which may causes metabolic diseases such as hyperglycemia, hyperlipidemia, hypertension and hyperuricemia. It is well know that lipid metabolites regulate fatty acid and glucose homeostasis. Lipidomics is the comprehensive analysis of lipid metabolites which include their quantitation and metabolic pathways. The intention of this study is to identify the circulating lipid species which are altered in obese prepubertal boys. Methods A total number of 72 boys aged 10.28 ±0.69 years old were included into this study, and divided into normal(NC), overweight(OW) and obese group(OB). The degree of maturation of all boys were measured by bone age and sex hormones. Then we measured the form indexes, blood lipids, blood glucose level to identify the current state of all boys. Serum indexes were detected by CLIA and ELISA methods. A lipidomic method was established by using a Waters Acquity UPLCI-Class liquid system combined with Waters Xevo G2-SQ-TOF mass spectrometry system. The identification and analysis of lipid metabolites were complished by using MassLynx 4.1, Progenesis QI software and LipidMaps database. Statistical analyzes were performed using SPSS22.0 software. Results (1)The waist-to-hip ratio, bone age and HDL-c levels ware significant lower in OW and OB groups. The TG level was significant higner in OB group. The DHEA and SHBG levels was significant higner in OW and OB groups and the other sex hormones are not . (2) In this study, 153 most significant different lipid metabolites were founded, incluing 3 diacylglycerol, 32 triglyceride, 1 Phosphatidyl cholines, 1 Phosphatidylinositol, 3 Sphingomyelin, 1 Ceramide which significant higher in OW&OB group; 4 diacylglycerol, 17 Phosphatidic acid, 32 Phosphatidyl cholines, 4 Phosphatidylinositol, 13 Phosphatidylserine, 18 Phosphatidyl ethanolamine, 3 Phosphoglycerides, 13 Sphingomyelin and 6 Ceramide which significant lower in OW&OB group. Among all this metabolites, 8 lipids (fold change ≥5) were founded as the significant biomarkers related prepubertal obesity , including 1 Phosphatidyl cholines, 1 phosphatidylserine, 2 sphingomyelin and 4 Triglyceride. What’s more, the level of SM(d16:1/24:0) and TG(15:0/17:1/20:3) which measured by UPLC-QTOF/MS are highly positive correlated with the level of serum SHBG; PC(18:0/0:0) and TG(16:1/18:0/20:3) are highly negtive correlated with serum SHBG. Conclusions Overweight and obese prepubertal boys showed disorder in lipid metabolism and bone growth. The lipidomic results showed lower SHBG level is related with the disorder of lipid metabolism. We suggest that further studies on these metabolites could help us gain a better understanding of the relationship between obesity and growth disorder.

Are thyroid nodules associated with sex-related hormones? A cross-sectional SPECT-China study

ObjectiveLittle is known about the association between thyroid nodules (TNs) and endogenous sex hormones. We aimed to investigate the relationship between TNs and sex-related hormones among men in China.SettingThe data were obtained from a cross-sectional study Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China study, 2014–2015) based on the population.ParticipantsIn total, 4024 men over 18 years of age who were not using hormone replacement therapy and who underwent complete assays of the serum total testosterone (T), oestradiol (E2), follicle-stimulating hormone (FSH), luteinising hormone (LH) and sex hormone-binding globulin (SHBG) levels as well as thyroid ultrasonography (US) enrolled in this study.ResultsOf the 4024 participants (54.15±13.08 years old), 1667 participants (41.4%) had TNs. Men with TN(s) (TN(+) group) had significantly lower levels of total T and SHBG and higher E2/T levels compared with the men without TN(s) (TN(−) group) (p<0.05). The TN prevalence decreased with the quartiles of the SHBG level (p<0.05). Binary logistic analysis showed that lower quartiles of SHBG had a greater risk of TN(s) (all p for trend <0.05). This association persisted in the fully adjusted model (p for trend=0.017), in which, for the lowest compared with the highest quartile of SHBG, the OR of TN(s) was 1.42 (95% CI 1.07 to 1.89). No statistically significant association was found between sex-related hormones and US characteristics associated with malignancy (nodule >10 mm, microcalcification and a ‘taller’ than ‘wider’ shape).ConclusionsTNs are highly prevalent in men in China. A lower SHBG level was significantly associated with TN among men. The potential role of SHBG in the pathogenesis of the TN remains to be elucidated.