SHBG Levels Research Articles

Comprehensive Analysis of the Association Between Sex Hormones and Body Mass Components Among Men Adults: Results From a Large Population-Based Study.

As the human body ages, adverse body composition status such as sarcopenia and obesity become obvious phenotypes which can cause numerous health problems. We aimed to comprehensively investigate the association of sex hormones and body mass components in adult men of various age groups. We analysed national representative population data from the US National Health and Nutrition Examination Survey. Generalized linear model regression analyses were used to evaluate the association between sex hormones (total testosterone [TT], bio-available testosterone [BT], sex hormone-binding globulin [SHBG], estradiol [E2] and testosterone to estradiol ratio [T/E ratio]) and body mass components (weight, body mass index (BMI), total lean mass, appendicular lean mass, bone mineral content, total fat and trunk fat). The collection and testing time of blood samples were not fixed and there was no strict fasting, but in subsequent analysis we used statistical methods to minimize the impact of random testing. After screening for inclusion and exclusion, 3759 male participants aged 20-85 years old were included in this study. Higher levels of TT, SHBG, BT and T/E ratios were significantly associated with higher total lean mass, appendicular lean mass and bone mineral content, while lower weight, BMI, total fat and trunk fat. For E2 levels in men, we found an opposite trend, with higher E2 levels significantly associated with lower total lean mass and appendicular lean mass, and higher weight, BMI, total fat and trunk fat. Notably, in subgroup analysis, the results showed that there were significant interaction effects of age and smoking history in the association between sex hormones and body mass components. Higher TT levels, BT levels, SHBG levels and T/E ratios are associated with lower body weight and improved body composition in young adult men (characterized by higher lean body mass, higher bone density and lower fat mass). The relationship is especially pronounced among relatively young, nonsmoking men.

Anti-inflammatory effects of resveratrol in treating interstitial cystitis/bladder pain syndrome: a multi-faceted approach integrating network pharmacology, molecular docking, and experimental validation.

This study aims to investigate the anti-inflammatory effects of Resveratrol (RES) in the treatment of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) by integrating network pharmacology, molecular docking, and experimental validation. Potential targets of RES were identified using DrugBank and SwissTargetPrediction, while IC/BPS-related targets were obtained from DisGeNET and Genecards. Molecular docking was performed using UCSF Chimera and SwissDock to validate the binding affinity of RES to key targets. Experimental validation involved treating TNF-α induced urothelial cells with RES, followed by assessments using RT-qPCR, ELISA, and Western blotting. A total of 86 drug targets and 211 disease targets were analyzed, leading to the identification of 8 key therapeutic targets for RES in IC/BPS treatment. Molecular docking revealed a strong affinity of RES for ESR2, with notable interactions also observed with SHBG, PTGS2, PPARG, KIT, PI3KCA, and AKT1. In vitro experiments confirmed that RES significantly alleviated the inflammatory response in TNF-α-induced urothelial cells, normalizing the expression levels of ESR2, SHBG, PPARG, and AKT1. RES can modulate critical pathways involving ESR2, SHBG, PPARG, and AKT1, highlighting its potential as a therapeutic agent for IC/BPS. This study provides a theoretical foundation for the clinical application of RES in treating IC/BPS.

Serum calcium improves the relationship between fluoride exposure and hypothalamic-pituitary-testicular axis hormones levels in males—a cross-sectional study on farmers in the lower reaches of the Yellow River

Numerous studies have reported the toxicity of fluoride to the male reproductive system, but epidemiological evidence is limited. We conducted a cross-sectional study in Kaifeng City, Henan Province in 2011 to explore the association between fluoride exposure and hypothalamic-pituitary-testicular (HPT) axis hormones in men. Morning urinary fluoride (UF), serum HPT axis hormones and serum calcium (SC) concentrations were detected. Percent changes and 95% confidence intervals in HPT axis hormones associated with UF were estimated using adjusted linear regression models, and performed subgroup analysis based on SC levels. The restricted cubic spline model was used to fit nonlinear relationships. For every 10% increase in UF, the concentrations of serum GnRH, T, SHBG and TSI decreased by 2.13%, 2.39%, 2.19% and 1.96%, while E2 and FEI increased by 1.11% and 3.33%. Subgroup analysis showed that for every 10% increase in UF, the levels of GnRH, T, TSI and FTI decreased by approximately 3.15%, 5.49%, 4.47% and 5.14%, while the E2 level increased by 2.92% in low-serum-calcium group (LCG). The levels of GnRH and T decreased by approximately 2.97% and 1.82% in medium-serum-calcium group (MCG). In high-serum-calcium group (HCG), serum SHBG levels decreased by 4.70%, while FTI and FEI levels increased by 4.93% and 4.20% as UF concentration increased (P < 0.05, respectively). The non-linear relationship between serum GnRH and UF concentrations presented an approximately inverted U-shaped curve, with a turning point UF concentration of 1.164 mg/L (P < 0.001), and their nonlinear relationship in LCG and MCG were similar to that in the overall subjects. In conclusion, excessive exposure to fluoride can interfere with male serum HPT axis hormones, and a moderate increase in SC alleviates the effect of fluoride. Prospective cohort studies are essential to confirm the causality.

Associations between Glyphosate Exposure and Glycemic Disorders: A Focus on the Modifying Effect of Sex Hormones.

Widespread glyphosate contamination in the environment and its endocrine-disrupting potential are concerning. However, evidence of glyphosate's effects on glycemic health is limited. To examine the association between glyphosate and glucose homeostasis in the general US population, a total of 3038 individuals were enrolled from the 2013-2016 cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted linear regression and restricted cubic spline curves were used to detect the associations between glyphosate and glycemic disorders. The effects of interactions between sex hormones and glyphosate on glycemic outcomes were evaluated. The results showed that glyphosate was significantly linked to increased glycated hemoglobin A1c (HbA1c) levels (β = 0.01; 95%CI, 0.01 to 0.02; p = 0.001) and the compromised homeostatic model assessment of beta-cell function (HOMA-beta) scores (β = -0.09; 95%CI, -0.17 to -0.01; p = 0.024). More importantly, these "glyphosate-glycemic disorder" associations were significantly modified by sex hormone-binding globulin (SHBG; P for interaction < 0.05), with more pronounced relationships being identified in individuals with low SHBG levels. Our findings indicate that glyphosate is correlated with glucose dyshomeostasis. Individuals with low SHBG levels exhibited susceptibility to glyphosate-related glycemic toxicity; therefore, it might be prudent to determine glycemic health in those subjects with glyphosate exposure.

Association of serum uric acid with male sexual hormones and erectile dysfunction: a bidirectional 2-sample Mendelian randomization analysis.

Observational studies indicated that serum uric acid (SUA) was associated with male sexual hormones and erectile dysfunction (ED). However, their relationship was still heterogeneous. This study conducted 2-sample univariate mendelian randomization (UVMR) and multivariate mendelian randomization (MVMR) to explore the causal relationship between SUA and sexual hormones as well as ED. Genetic variants associated with SUA were derived from the UK Biobank database (N = 437 354). Outcomes from the IEU Open GWAS and summary data sets were sexual hormones (sex hormone-binding globulin [SHBG], testosterone, estradiol [E2], follicle-stimulating hormone, luteinizing hormone) and ED, with 3301 to 625 650 participants. UVMR analysis primarily utilized the inverse variance weighted method, complemented by MVMR analysis. Thorough sensitivity analyses were carried out to ensure the reliability of results. Moreover, mediation analysis was conducted to estimate the mediated effect between SUA and outcomes. The primary outcomes included results of UVMR and MVMR analysis and mediation analysis, along with sensitivity analyses involving the Cochran Q test, the MR Egger intercept test, leave-1-out analysis, and the MR-PRESSO method (mendelian randomization pleiotropy residual sum and outlier). UVMR analysis revealed that an elevated SUA level could decrease levels of SHBG (β = -0.10, P = 1.70 × 10-7) and testosterone (β = -0.10, P = 5.94 × 10-3) and had a positive causal effect on ED (odds ratio,1.10; P = .018). According to reverse mendelian randomization results, increased levels of SHBG (β = -0.06, P = 4.82 × 10-4) and E2 (β = -0.04, P = .037) could also reduce SUA levels. As shown by MVMR analysis, SUA had a negative effect on SHBG and testosterone levels (P <.05), while the significant causal relationship between SUA and ED disappeared. Furthermore, SHBG mediated 98.1% of the effect of SUA on testosterone levels. Results of other mendelian randomization analyses were not statistically significant. No pleiotropy was found by sensitivity analysis in this study. Given the causal relationship between SUA and sexual hormones, we must focus on SUA and E2 levels in men, especially patients with hypogonadism and ED. This study evaluated the causal effect of SUA on male sexual hormones and ED genetically for the first time, clarifying the common biases in observational studies and confirming the negative relationship between SUA and testosterone level. Limitations include a population based on European ancestry, some crossover of the samples, and unobserved confounding factors. Genetic studies provide evidence for the causal relationship between SUA and male sexual hormones (SHBG, testosterone, E2), while the relationship between SUA and ED should be further evaluated.

Causal relationship analysis between 35 blood/urine metabolites and gastroesophageal reflux disease: A Mendelian randomization combined meta-analysis study.

Gastroesophageal reflux disease (GERD) is a common condition worldwide. Despite numerous studies on GERD, the causal relationships between blood/urine metabolites and GERD remain unclear. This study aims to explore the causal relationships between GERD and 35 blood/urine metabolites. In this study, we conducted Mendelian randomization (MR) analyses for 35 blood/urine metabolites with GERD phenotypes from the FinnGen R10 and UKB databases separately. We then performed a meta-analysis of the inverse variance weighted results from the 2 MR analyses and applied multiple corrections to the significant P values from the meta-analysis. Finally, we conducted reverse causality validation for the corrected positive blood/urine metabolite phenotypes with GERD. After conducting MR analysis combined with meta-analysis and performing multiple corrections, we found significant positive causal associations between only 3 blood/urine metabolites and GERD, with no significant reverse associations. Among them, 2 are risk factors for the occurrence of GERD: alanine aminotransferase levels (odds ratio (OR) = 1.120, 95% confidence interval (CI) = 1.064-1.180, P = .0005) and urate levels (OR = 1.095, 95% CI = 1.044-1.147, P = .005). Additionally, sex hormone-binding globulin levels are protective against GERD (OR = 0.928, 95% CI = 0.896-0.961, P = .0009). Elevated levels of the metabolites alanine aminotransferase and urate are associated with an increased risk of GERD, identifying them as risk factors for the condition. In contrast, higher levels of SHBG are linked to a decreased risk of GERD, indicating that SHBG is a protective factor against the disease.

Evaluation of the Potential Clinical Utility of Maternal Serum Biomarkers for Risk Assessment in Gestational Diabetes.

The exact relationships of circulating fibronectin, SHBG, and ILGF-1 with T2DM and GDM remain inconsistent. Therefore, in this study we evaluate their associations in T2DM and GDM. Additionally, we evaluate their correlations with different biochemical parameters. A total of 505 pregnant women (180 with T2DM, 160 GDM patients, and 165 controls) were enrolled in the current study. SHBG, ILGF-1, and fibronectin were estimated by using the ELISA technique. The GDM and T2DM groups had higher ILGF-1 and fibronectin levels than the control group, while having a lower SHGB level. The correlations of clinical characteristics with ILGF-1, SHBG, and fibronectin showed that ILGF-1 in GDM patients was positively associated with HbA1c% and insulin. T2DM was positively related to insulin and insulin resistance, as well. There was a positive association between SHBG and insulin among the T2DM groups. Furthermore, in T2DM individuals, fibronectin was positively related with HbA1c% and glucose. The study suggests that the circulating levels of fibronectin, SHBG, and ILGF-1 are linked to GDM and T2DM risk. Hence, the circulating concentrations of these biomarkers are potentially useful for predicting the risk of GDM as well as developing T2DM.

The relationship between follicle-stimulating hormone and metabolic dysfunction-associated fatty liver disease in men

ObjectivesThe present study aimed to investigate the relationship between male hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) in males.MethodsData from the Fangchenggang Area Male Health and Examination Survey (FAMHES) were used to analyze the male hormone levels between MAFLD patients and controls. Univariate and multivariate logistic regression analyses were performed to identify risk factors for MAFLD. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of male hormones for MAFLD.ResultA total of 1578 individuals were included, with 482 individuals (30.54%) of MAFLD, including 293 (18.57%) with mild disease and 189 (11.98%) with moderate-to-severe disease. The MAFLD patients were significantly older than those without MAFLD. The LH, FSH, and SHBG levels in the MAFLD patients were significantly greater than those in the control group. Age, FSH, LH, SHBG, and estradiol were all risk factors for MAFLD. Age, FSH, and LH were risk factors for moderate-to-severe MAFLD. FSH was an independent risk factor for MAFLD and moderate-to-severe MAFLD. FSH showed an excellent diagnostic value, with an AUC of 0.992 alone and 0.996 after adjusting age.ConclusionsOur findings indicate that FSH may be a potential diagnostic and predictive biomarker for MAFLD.

Impact of Psoriasis on Male Fertility: A Case-Control Study

Abstract Background Psoriasis is a common, chronic, relapsing skin disease, currently considered to be an immune mediated inflammatory disease. Several epidemiological studies have shown that patients with immune-mediated inflammatory diseases, including psoriasis, have a higher risk of developing comorbidities, such as cardiovascular disease, metabolic syndrome, diabetes and nonalcoholic fatty liver disease compared to the general population. Aim of the Work to assess gonadal function in psoriatic male patients to know the effect of psoriasis on fertility in these subjects. This evaluation was conducted on a hormonal and seminal background. Patients and Methods This case control study included 40 patients (20 with psoriasis &amp; 20 healthy age and body mass index (BMI) matched controls). They were recruited from the dermatology out-patient clinic of Ain–Shams University Hospitals, during the period from November 2021 till April 2022. The study was approved by Research Ethical Committee of Ain Shams University (FMASU M S 667/2021) and fulfilled all the ethical aspects required for a human research. Results Twenty patients, with a mean age of 30.15 ± 8.04 years, fulfilled the inclusion criteria and were enrolled in our study. The mean BMI was 25.11 ± 3.02. The mean disease duration was 4 (2.5 – 8) years, and the mean PASI score at the time of enrollment 11.25 (5.1 – 15.8)., and. twenty healthy subjects, matched for age and BMI, were also enrolled as a control group Conclusion The evaluation of seminal fluid analysis and hormone profiles among psoriasis patients showed minor variability. However, it was evident that the levels of sex hormones were different in patients with psoriasis compared to healthy controls. Serum estradiol &amp; SHBG levels were significantly increased among psoriasis patients relative to control group while, serum testosterone levels were significantly lower among psoriasis patients relative to control patients.

Association between body mass index and sex hormones among men: Evidence from cross-sectional and Mendelian randomization studies

PurposeThis study aims to investigate the association between Body Mass Index (BMI) and sex hormone levels utilizing a cross-sectional study design alongside Mendelian randomization (MR) analysis. Materials and methodsA cross-sectional study was performed based on National Health and Nutrition Examination Survey (NHANES) 2013–2016. Additionally, a two-sample MR analysis was performed, utilizing Single Nucleotide Polymorphisms (SNPs) associated with BMI identified in a genome-wide association study (GWAS) comprising 339224 individuals. Data on outcomes, including total testosterone (TT, 199569 samples), estradiol (E2, 17134 samples), and sex hormone binding globulin (SHBG, 185211 samples), were sourced from the United Kingdom Biobank (UKB). ResultsIn cross-sectional analysis involving 4092 males, multivariable linear regression demonstrated that each unit increase in BMI was positively correlated with an elevated risk of testosterone deficiency (TD), increased E2 levels, and a reduced TT, SHBG, free androgen index and TT/E2. Subsequent quartile division of BMI revealed, through multivariable logistic regression, that higher BMI quartiles were associated with a greater TD risk, elevated E2 levels, and reduced TT, SHBG, and TT/E2 levels compared to quartile 1 (P for trend <0.001). In the MR analysis, a causal effect was established, with each unit increase in BMI being associated with decreased TT (β = −0.17; 95 % CI −0.24 to −0.09) and SHBG (β = −0.13; 95 % CI −0.21 to −0.05) levels. ConclusionsOur findings unveil a causal link between BMI and reduced TT and SHBG levels in males.

Effectiveness of dual combination therapy of acarbose plus metformin and acarbose plus myo-inositol in ameliorating the metabolic and endocrinologic complications of polycystic ovary syndrome – A randomized controlled trial

IntroductionPCOS, beyond being characterized by reproductive disturbances, is a complicated rapid expanding metabolic and endocrinologic disorder of the recent times. Nearly 70% PCOS women show resistance to insulin. AIM: The aim of the study is to determine and compare the effectiveness of acarbose plus metformin and acarbose plus myo-inositol combination therapy in alleviating the metabolic and endocrinologic complications of PCOS. Materials and methodsAn open labelled RCT was conducted on 168 PCOS women attending the gynaecology clinic at SRM MCH & RC, Chengalpattu and the trial was registered in CTRI (No. CTRI/2022/04/041877). Group A (n = 56) received metformin 500 mg/TID alone; group B (n = 54) received (acarbose 25 mg/TID for 4 weeks then 50 mg/TID for other 20 weeks) along with metformin 500 mg/TID and group C (n = 54) received (acarbose 25 mg/TID for 4 weeks then 50 mg/TID for other 20 weeks) along with myoinositol 1000 mg/BD. All parameters were measured at baseline and at the end of 6 months. ResultsSignificant reduction of LH, LH: FSH, TT, HOMA-IR was observed in all the groups. FSH increased only in metformin group. Increase in serum progesterone and reduction in FI, TGL, LDL were significant only in acarbose plus myo-inositol group. SHBG and HDL increased significantly only in acarbose plus metformin group. No changes in BMI, TC and VLDL were observed in any group. ConclusionTherefore, decrease in FI, HOMA-IR, TGL, LDL seen in acarbose plus myo-inositol group indirectly contributes to cardio-metabolic safety in PCOS. Similarly, a significant increase in SHBG levels with acarbose plus metformin group shows correction of the excess androgen and restoration of ovulation.

SHBG, Free Testosterone, and Type 2 Diabetes Risk in Middle-aged African Men: A Longitudinal Study.

To investigate longitudinal changes in SHBG and free testosterone (free T) levels among Black middle-aged African men, with and without coexistent HIV, and explore associations with incident dysglycaemia and measures of glucose metabolism. This longitudinal study enrolled 407 Black South African middle-aged men, comprising primarily 322 men living without HIV (MLWOH) and 85 men living with HIV (MLWH), with normal fasting glucose at enrollment. Follow-up assessments were conducted after 3.1 ± 1.5 years. At baseline and follow-up, SHBG, albumin, and total testosterone were measured and free T was calculated. An oral glucose tolerance test at follow-up determined dysglycaemia (impaired fasting glucose, impaired glucose tolerance, type 2 diabetes) and glucose metabolism parameters including insulin sensitivity (Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and beta(β)-cell function (disposition index). The primary analysis focussed on MLWOH, with a subanalysis on MLWH to explore whether associations in MLWOH differed from MLWH. The prevalence of dysglycaemia at follow-up was 17% (n = 55) in MLWOH. Higher baseline SHBG was associated with a lower risk of incident dysglycaemia (odds ratio 0.966; 95% confidence interval 0.945-0.987) and positively associated with insulin sensitivity (β = 0.124, P < .001) and β-cell function (β = 0.194, P = .001) at follow-up. Free T did not predict dysglycaemia. In MLWH, dysglycaemia prevalence at follow-up was 12% (n = 10). Neither baseline SHBG nor free T were associated with incident dysglycaemia and glucose metabolism parameters in MLWH. SHBG levels predict the development of dysglycaemia in middle-aged African men but do not exhibit the same predictive value in MLWH.

Физиологическая роль и клиническое значение глобулина, связывающего половые гормоны, у мужчин.

The main physiological functions of globulin that binds sex hormones (SHBG) in the male body are the transport of sex steroids in hydrophilic blood and the creation of a buffer system that smooths out fluctuations in the concentration of free testosterone. In addition, sex hormone binding globulin can limit the biological activity of sex steroids by reducing the concentration of the free fraction of the hormone, but only when the hypothalamicpituitary-testicular axis is non-functioning or inadequately functioning. If the negative feedback mechanism works correctly, the concentration of SHBG will determine the level of total testosterone, but will not affect the free fraction and, accordingly, the biological activity of sex steroids. It is likely that SHBG has other functions, as indicated by the presence of SHBG receptors in some tissues and the mechanism of SHBG transport into the cell through endocytosis, but the physiological role of these processes is currently unclear and requires further study. From a practical point of view, determining the level of SHBG is necessary primarily to calculate the level of free testosterone, since accurate methods for directly measuring free testosterone are not available in clinical practice. Diagnosing hypogonadism based solely on total testosterone levels is associated with the risk of overdiagnosis, since the concentration of SHBG in the blood can have a significant effect on total testosterone levels without changing free testosterone levels. The use of SHBG as a biomarker for a number of diseases and pathological conditions seems promising. Lower SHBG concentrations are associated with an increased risk of diabetes mellitus, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD), and higher SHBG concentrations are associated with an increased risk of osteoporosis and fractures in older men. At the same time, the question remains open whether SHBG is just a biomarker or is involved in the pathogenesis of the development of these diseases?

Folate and Vitamin B12 Levels in Chilean Women with PCOS and Their Association with Metabolic Outcomes.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Many women with PCOS have been found to have an unbalanced diet and deficiencies in essential nutrients. This study aimed to assess the levels of folate and vitamin B12 (B12) and their relationship with metabolic factors in women with PCOS. Anthropometric, clinical, and genetic analyses were conducted to evaluate markers related to one-carbon metabolism in women with PCOS and in a control group. The PCOS group had a higher BMI and HOMA-IR (1.7 vs. 3.1; p < 0.0001). HDL cholesterol levels were 23% lower and triglyceride levels were 74% higher in women with PCOS. Although there were no significant differences in folate and B12 levels between the PCOS and control groups, over 60% of women with PCOS had low B12 levels (<300 pg/mL) and high homocysteine levels. In addition, the MTHFR A1298C and C677T polymorphisms were not associated with PCOS. Moreover, erythrocyte folate levels were positively correlated with fasting glucose, triglycerides, and free androgen index, and negatively correlated with SHBG and LH levels. These results suggest that B vitamins may be associated with the metabolic phenotype in PCOS. This study emphasizes the potential link between folate, vitamin B12, and metabolic and hormonal outcomes in women with PCOS.

Oral exposure to phenanthrene during gestation disorders endocrine and spermatogenesis in F1 adult male mice

Phenanthrene (Phe), a typical low-molecular-weight polycyclic aromatic hydrocarbon (PAH) of three benzene rings, is one of the most abundant PAHs detected in daily diets. Pregnant women and infants are at great risk of Phe exposure. In the present study, Phe was administered to pregnant mice at a dose of 0, 60, or 600 μg/kg body weight six times, and the F1 male mice showed significant reproductive disorders: the testicular weight and testis somatic index were significantly reduced; the levels of serum testosterone, GnRH and SHBG were increased, while the FSH levels were reduced; histological analysis showed that the amount of Sertoli cells and primary spermatocytes in seminiferous tubules was increased, while the amount of secondary spermatocytes and spermatids were decreased in Phe groups. The protein levels of PCNA and androgen receptor were reduced. Differently expressed genes in the testis screened by RNA sequence were enriched in antioxidant capacity, reproduction et al.. Further biochemical tests confirmed that the antioxidant capacity in the F1 testis was significantly inhibited by treatment with Phe during pregnancy. Those results suggested that gestational Phe exposure disordered hypothalamic-pituitary-gonadal (HPG) hormones on the one hand, and on the other hand reduced testicular antioxidant capacity and further arrested cell cycle in F1 adult male mice, which co-caused the inhibition of spermatogenesis.

Plasma SHBG levels as an early predictor of response to bariatric surgery

Plasma SHBG levels as an early predictor of response to bariatric surgery

Polymorphic locus rs8023580 NR2F2-AS1 is associated with breast cancer risk in residents of Central Russia

Breast cancer (BC) is the most common hormone-dependent genetically determined cancer among women. The level of “active” sex hormones in the body, the connection of which with breast cancer is beyond doubt, is determined by the content of the protein transporting sex hormones (SHBG).Aim: To study associations of polymorphic loci linked with the level of SHBG at the full-genomic level of significance with the risk of developing breast cancer.Material and Methods. The work was carried out on a sample of 1,498 women, 358 of whom were BC patients, the control was 1140 individuals. Genotyping of four single nucleotide polymorphic loci (SNP) associated with the level of SHBG was performed according to previously performed genome-wide studies (GWAS): rs7910927 JMJD1C, rs4149056 SLCO1B1, rs8023580 NR2F2-AS1, rs12150660 SHBG. The method of logistic regression was used to search for associations.Results and Discussion. SNP rs8023580 of the NR2F2-AS1 gene is associated with the risk of BC developing. The presence of the CC genotype rs8023580 NR2F2-AS1in a woman has a protective value in the formation of the disease (CCvsTC+TT [recessive model]; OR = 0.58; 95%CI = 0.35–0.96; p = 0.033; pperm = 0.042). SNP rs8023580 NR2F2-AS1 is functionally significant in the liver: it is localized in the enhancer region, affects the level of methylation of the cg01739960 (hg38) genome region, affects the expression of the RP11-327J17.2 gene, determines the interaction of DNA with six transcription factors (Fo xd1,Foxl1,Foxq1,Mef2,PLZF,STAT), which are located in the cis-regulatory region of RNA polymerase II, specific for the DNA binding sequence, and determine the activity of DNA-binding transcription factors specific for RNA polymerase II, are involved in the processes of cellular differentiation and tissue development.Conclusion. The SHBG-enhancing CC genotype rs8023580 of the NR2F2-AS1 gene is a protective factor in the development of BC.

Effects of depot medroxyprogesterone acetate, the copper IUD and the levonorgestrel implant on testosterone, sex hormone binding globulin and free testosterone levels: ancillary study of the ECHO randomized clinical trial

BackgroundRobust information on relative effects of hormonal contraceptives on endogenous androgens is important for understanding beneficial and adverse effects, method choice and development of new methods.MethodsIn this ancillary study at the East London, South Africa site of the ECHO multicentre randomized trial, we compared effects of three contraceptive methods on serum androgen levels among contraceptive users aged 18 to 35 years. Participants were allocated by centrally-managed randomization to open label depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or levonorgestrel implant.The primary outcome was free testosterone at 6 months.ResultsWe analysed stored baseline and 6-month serum samples in 398/615 participants (DMPA-IM 131/205, IUD 135/205 and implant 132/205). Median testosterone levels at baseline were DMPA-IM 0.82, IUD 0.9 and implant 0.87 nmol/L; at 6 months, DMPA 0.68 (lower than IUD, mean percentage difference 28.35, (p < 0.001), IUD 0.86 (unchanged) and implant 0.66, lower than IUD, mean percentage difference − 22.98, p < 0.001).Median SHBG levels at baseline were DMPA 52.4, IUD 50.5 and implant 55.75 nmol/L; at 6 months, DMPA 40.65, lower than IUD (mean percentage difference 21.19, p = 0.005), IUD 49.1 (unchanged), and implant 23.35 nmol/L, lower than IUD (mean percentage difference − 50.04, p < 0.001 and than DMPA (mean percentage difference − 39.45, p < 0.001).Free testosterone levels at baseline were DMPA 10, IUD 12 and implant 11 pmol/L; at 6 months, DMPA 11, less than IUD (mean percentage difference 13.53, p = 0.047), IUD 12 and implant 14, higher than IUD (mean percentage difference 14.15, p = 0.038) and than DMPA, (mean percentage difference 29.60, p < 0.001).ConclusionsThis is the first randomized trial to show lower SHBG and higher free testosterone with the levonorgestrel implant than with DMPA, and contrasts with reports of increased SHBG with combined oral ethinyl estradiol/levonorgestrel use, and reduced androgens (and impaired sexual function) reported with the etonorgestrel implant. The higher free testosterone with the LNG implant might improve sexual function, mood and bone health as well as increasing side-effects such as acne and hirsutism, and is consistent with the greater sexual activity (with respect to multiple sex partners, new sex partner and unprotected sex) with the implant compared with DMPA documented in the ECHO study.ECHO trial registrationClinicalTrials.gov, number NCT02550067 15/09/2015.Plain English summaryContraception, or family planning, is central to the role of women in societies. It is most important to have accurate information on the relative side-effects of various contraceptive options in order to empower women to make informed choices regarding their preferred method.Hormonal contraceptives contain various forms of the female sex hormones, estrogens and/or progestogens. These hormones have direct effects on the users, as well as modifying the levels of the users’ own circulating sex hormones, both the ‘female’ and the ‘male’ sex hormones (androgens).In this study, consenting participants requesting contraception, were allocated randomly to receive either depot medroxyprogesterone acetate (DMPA-IM) a 3-monthly progestogen injection, the copper intrauterine device (IUD), a non-hormonal contraceptive inserted within the womb, or the levonorgestrel implant, a device placed under the skin which releases a progestogen for 5 years.We measured the participants’ androgen levels after 6 months, and found for the first time that the active form of testosterone (free testosterone) was 29% higher with the implant than with DMPA-IM. The level with the IUD was intermediate, and significantly different from the other two methods.This finding is relevant to the effects experienced by users of these methods, because free testosterone has effects on sexual function, bone health and mood, as well as on conditions such as acne and hair distribution patterns.

(273) Influences of Oral Dehydroepiandrosterone (DHEA) Administration on Hormonal Profile, Menopausal Clinical Symptoms and Sexual Function in Early Postmenopausal Symptomatic Women

Abstract Introduction Dehydroepiandrosterone (DHEA) and its sulfate (DHEAs) are steroid hormones secreted by the adrenal glands. The aging process is associated with decreased levels of DHEA and DHEAs, which are the initial causes of many age-related changes. Objective We aimed to evaluate the effects of oral administration of DHEA (50mg/day) on hormonal profile, menopausal clinical symptoms and sexual function in early postmenopausal symptomatic Caucasian women at baseline and after 2, 4 and 6 months of treatment. Methods For our prospective clinical trial, 42 symptomatic early postmenopausal women (50–55±3.5 years) were selected. Participants were divided into two groups. The study group (n-22) received oral DHEA 50mg/day for 6 months and the control group (n-20) received placebo. Serum levels of DHEA, DHEAs, androstenedione (A4), allopregnanolone (3α,5α- THP), progesterone (P4), 17OH progesterone (17OHP), cortisol, testosterone (T), dihydrotestosterone (DHT), estrone (E1), estradiol (E2), SHBG, LH, FSH and β-Endorphin were determined at baseline and after 2, 4 and 6 months of treatment. The results of the Menopause Rating Scale (MRS) and the McCoy Female Sexuality Questionnaire (MFSQ) were evaluated before and after the treatment. Results During the treatment period in the study group, a progressive increase in serum levels of DHEA, DHEAs, A4, T, DHT, E2, E1, 3α,5α-THP and β-Endorphin were observed. P4 and 17OHP levels showed only a slight increase. By the 4th month of treatment and final data, a decrease in cortisol levels was observed. LH and FSH levels gradually decreased. SHBG levels remained constant. After 6 months of treatment, assessing the results of the MRS in the DHEA group showed a progressive improvement of menopausal symptoms. The results of the McCoy questionnaire were also improved in the study group. Conclusions DHEA administration had a significant effect on certain endocrine parameters in early postmenopausal symptomatic Caucasian women, was associated with improvements of menopausal physical symptoms, sexual function and psycho-emotional parameters. Our findings support the hypothesis that administration of DHEA in symptomatic postmenopausal women restores both androgenic and estrogenic milieu and reduces most of the clinical symptoms caused by the changes of these environments during postmenopausal period. On this basis we can assume, that DHEA may be considered as a potentially effective medication for MHT. However, conducting further, more specific clinical trials are needed. Disclosure No.

The Correlation between Sex Hormone-Binding Globulin and Clinical Characteristics According to Anti-Müllerian Hormone in Women with Regular Menstrual Cycles: A Prospective Study.

Polycystic ovarian syndrome (PCOS) can be diagnosed when the anti-Müllerian hormone (AMH) levels are high, but in clinic, women who do not meet the diagnosis of PCOS but have elevated AMH levels are often seen. This study aimed to compare the differences in menstrual cycle patterns and hormone levels in women with regular menstrual cycles, but not PCOS, by dividing them into high and low AMH groups. This multicenter prospective study included 68 healthy women. Participants with regular menstrual cycles were divided into two groups according to their AMH levels. The main outcome measures were menstrual cycle pattern, body mass index, and hormone levels (thyroid stimulating hormone, prolactin, testosterone, sex hormone-binding globulin, and free androgen index), which were compared between the groups according to AMH levels. The ovulation was assessed by performing pelvic ultrasound, and by assessing the hormone levels of the luteinizing hormone and progesterone. The criteria for determining normal and high AMH levels were based on previous literatures. The participants were divided into normal (39 people) and high (29 people) AMH group. No differences were found in age or BMI between the two groups, and no other differences were observed in TSH, prolactin, testosterone, or free androgen index. However, the high AMH group had significantly higher SHBG levels than the normal group (normal group: 65.46 ± 25.78 nmol/L; high group: 87.08 ± 45.05 nmol/L) (p = 0.025). This study is the first to analyze the association between SHBG and AMH levels in women with regular menstrual cycles. Elevated AMH levels are associated with increased levels of SHBG levels.