Sex Hormone-binding Globulin Research Articles

Mendelian randomization study of the relationship between blood and urine biomarkers and lung cancer

IntroductionIdentifying suitable biomarkers is crucial for exploring the pathogenesis, early screening, and therapeutic monitoring of lung cancer. This study aims to analyze comprehensively the associations between lung cancer and biomarkers in blood and urine.MethodsBidirectional two-sample Mendelian randomization (MR) was used to evaluate the potential causal relationships between blood and urine biomarkers and lung cancer. We obtained Single nucleotide polymorphisms (SNPs) related to lung cancer from the 2021 Finnish database of genome-wide association studies, including small cell lung cancer (SCLC), total non-small cell lung cancer (NSCLC), lung adenocarcinoma (LAC), and lung squamous cell carcinoma (LSCC).Data on blood and urine biomarkers were derived from the UK Biobank cohort, comprising 376,807 participants.ResultsWe found a potential inverse causal relationship between total bilirubin and SCLC (β=-0.285, P=0.015, FDR=0.12). Urate was inversely associated with NSCLC (β=-0.158, P=0.004, FDR=0.036*). Serum calcium showed a possible inverse relationship with lung squamous cell carcinoma (β=-0.256, P=0.046, FDR=0.138), while urinary creatinine was positively associated (β=1.233, P=0.024, FDR=0.216). Non-albumin proteins (β=-0.272, P=0.020, FDR=0.180) and total protein (β=-0.402, P=0.009, FDR=0.072) were inversely related to lung squamous cell carcinoma. The AST/ALT ratio was positively associated with lung adenocarcinoma (β=0.293, P=0.009, FDR=0.072). Our reverse Mendelian randomization study found a positive causal association between small cell lung cancer and serum creatinine (β=0.022, P=0.002, FDR=0.018*), while it was inversely associated with the estimated glomerular filtration rate(eGFR)(β=-0.022, P=0.003, FDR=0.027*). A positive causal relationship was also observed with cystatin C (β=0.026, P=0.005, FDR=0.045*) and glycated hemoglobin HbA1c (β=0.013, P=0.014, FDR=0.028*). A negative causal relationship was observed with Gamma_glutamyltransferase (β=-0.013, P=0.019, FDR=0.152). For non-small cell lung cancer, a negative causal relationship was found with albumin (β=-0.024, P=0.002, FDR=0.016*), while a potentially positive causal relationship was observed with cystatin C (β=0.022, P=0.006, FDR=0.054). Possible negative causal relationships were also observed with phosphate (β=-0.013, P=0.008, FDR=0.072) and urinary potassium (β=-0.011, P=0.012, FDR=0.108), while a potential positive causal relationship was observed with C-reactive protein (β=0.013, P=0.040, FDR=0.280).Regarding lung squamous cell carcinoma, an inverse causal relationship was found with eGFR (β=-0.022, P=9.58e-06, FDR=8.62×10-5*), while a positive causal relationship was observed with serum creatinine (β=0.021, P=1.16e−4, FDR=1.05×10-3*). Potential positive causal relationships were observed with Urate (β=0.012, P=0.020, FDR=0.180), urea (β=0.010, P=0.046, FDR=0.141), and glycated hemoglobin HbA1c (β=0.020, P=0.049, FDR P=0.098), whereas a potential negative causal relationship was observed with sex hormone-binding globulin(SHBG) (β=-0.020, P=0.036, FDR=0.108).Lastly, adenocarcinoma was found to have a positive causal association with alkaline phosphatase (β=0.015, P=0.006, FDR=0.033*).ConclusionOur study provides a robust theoretical basis for the early screening and therapeutic monitoring of lung cancer and contributes to understanding the pathogenesis of the disease.

Behenic acid protects the testosterone cycle and prevents the sperm apoptosis and protein loss in phthalate exposure by inhibiting oxidative stress and stimulating ATPase activity

BackgroundPlastic products use phthalate to enhance their flexibility, transparency, and stability, while behenic acid is a carboxylic acid with antioxidant activity. ObjectivesThis study evaluates whether behenic acid can protect the testosterone cycle and prevent the sperm apoptosis and protein loss in phthalate-treated male rats. MethodsThere were 36 male albino rats in all, divided into six equal sets of six rats each: control, behenic acid (13g/kg), behenic acid (26g/kg), diethyl phthalate (10mg/kg), behenic acid (13g/kg) + diethyl phthalate (10mg/kg), and behenic acid (26g/kg) + diethyl phthalate (10mg/kg)-treated groups. Measurements were made of serum male hormones, sex hormone-binding globulin, sodium/potassium ATPase, superoxide dismutase, glutathione, glucose-6-phosphate dehydrogenase, 3β-hydroxysteroid dehydrogenase, protein, and cholesterol in the testis, as well as malondialdehyde in the sperm, testis, and hypothalamus. Sperm monoclonal proliferating antibody Ki-67, sperm counts, motility, and abnormalities were measured. ResultsOral administration of diethyl phthalate increased malondialdehyde, serum follicle stimulating hormone, sex hormone binding globulin, luteinizing hormone, glucose-6-phosphate dehydrogenase, 3β-hydroxysteroid dehydrogenase, cholesterol, total protein, sperm abnormality, and the percentage of spermatogonia, first spermatocyte, second spermatocyte, and spermatid in the testis. Superoxide dismutase, glutathione, serum testosterone and dehydroepiandrosterone sulphate, sperm count and motility, and sodium/potassium-ATPase activity were all reduced. Additionally, all of the previously described parameters reverted to near control values after receiving two doses of behenic acid in phthalate-treated rats; a higher dose of behenic acid had a more effective effect than a lower dose. Conclusionbehenic acid can protect the testosterone cycle and prevent the sperm apoptosis and protein loss in phthalate-treated male rats by inhibiting oxidative stress and stimulating ATPase activity.

Correlations between SHBG, Sex Hormones, Inflammation, and Neurocognitive Decline in Alzheimer's Disease:A Retrospective Study.

Alzheimer's Disease (AD) is characterized by a progressive neurodegenerative process leading to cognitive decline and functional impairment. Endocrine factors, particularly sex hormones and their binding proteins, play a critical role in AD pathophysiology. Understanding the relationship between these factors and AD is essential for developing targeted interventions. To investigate the potential links between sex hormone binding globulin (SHBG) levels, sex hormone profiles, inflammatory markers, and neurocognitive decline in patients with AD. A retrospective case-control investigation was conducted with 110 AD patients who were admitted to our hospital from January 2021 to December 2023, and the patients were classified into either a mild neurocognitive impairment group (n=59) or a moderate to severe neurocognitive impairment group (n=51) according to their cognitive function. Correlation and regression analyses were conducted to examine relationships between variable factors. The study revealed a significant neurocognitive decline in AD patients with lower Mini-- Mental State Examination (MMSE) and higher AD Assessment Scale-Cognitive Subscale (ADAS- Cog) scores in the moderate to severe neurocognitive impairment group compared to the mild neurocognitive impairment group. Additionally, the moderate to severe neurocognitive impairment group significantly increased for SHBG, estradiol, progesterone inflammatory markers [C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β)). It decreased for follicle-stimulating hormone (FSH) and luteinizing hormone (LH)]. Moreover, significant positive correlations were found between SHBG levels and ADAS-Cog scores, and significant negative correlations were found between SHBG levels and MMSE scores. FSH showed significant negative correlations with the MMSE score, while certain inflammatory markers demonstrated significant correlations with neurocognitive abilities. The correlation between sex hormones and inflammatory factors is weak. FSH, LH, SHBG, CRP, IL-6, TNF-α, and IL-1β are risk factors for neurocognitive impairment, while E2 and P are protective factors. The study provides evidence of significant correlations between SHBG levels, sex hormone profiles, inflammatory markers, and neurocognitive decline in AD patients.

Obesity is associated with SHBG levels rather than blood lipid profiles in PCOS patients with insulin resistance

ObjectivePolycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by hormonal imbalances and insulin resistance (IR). Among the metabolic abnormalities associated with PCOS, obesity is often present concurrently. Nevertheless, the correlation between obesity, sex hormone levels, and blood lipid profiles in PCOS patients with IR remains uncertain.MethodsThis is a cross-sectional study including a total of 206 Chinese women diagnosed with PCOS, enrolled between March 2016 and December 2021. The participants’ anthropometric measurements, such as weight, height, waist circumference, and hip circumference, were recorded. Additionally, fasting blood samples were collected to measure various parameters, including fasting glucose, insulin levels, lipid profiles, and sex hormone levels.ResultsOur findings highlight that obesity exhibited a significant correlation with lower levels of sex hormone binding globulin (SHBG) and elevated levels of free androgen index (FAI), fasting insulin, and HOMA-IR in PCOS patients diagnosed with IR. However, no significant association between obesity and blood lipid profiles was observed within this particular group of women.ConclusionThis study suggests that among PCOS patients with IR, lower levels of SHBG and higher levels of FAI are associated with obesity. These findings indicate that SHBG and FAI may have the potential to serve as a biomarker for the initial identification and prognosis of IR in PCOS patients.Trial registrationRetrospectively registered on 25/04/2020 at ClinicalTrials.gov Identifer: NCT04264832.

Metabolic syndrome associated with hyperandrogenism in the reproductive age. Hormonal profile in different ethnicities women

Background. Metabolic syndrome (MS) with hyperandrogenism comorbidity in women is considered a common concept; however, the contribution of the neuroendocrine regulation system indicators to this in reproductive age remains unclear.The aim. To analyze the activity of neuroendocrine regulation system in women of reproductive age of different ethnic groups with metabolic syndrome associated with hyperandrogenism.Materials and methods. The groups of women with MS of Russian (n = 209) and Buryat (n = 84) ethnic groups and a group of women with MS and polycystic ovary syndrome (PCOS) of Russian (n = 23) and Buryat (n = 10) ethnic groups were formed.Results. In women of reproductive age of the Russian ethnic group with MS and PCOS the study noted higher levels of anti-Müllerian hormone (AMH) (p = 0.030), testosterone (Ts) (p = 0.026), free androgen index (FAI) (p < 0.0001), dehydroepiandrosterone sulfate (DHEA-S) (p < 0.0001), and reduced levels of sex hormone-binding globulin (SHBG) (p < 0.0001) in relation to the control; in relation to the group with MS, we discovered increased values of AMH (p < 0.001), Ts (p = 0.030), FAI (p < 0.001), DHEA-S (p < 0.0001), and decreased values of SHBG (p = 0.001). In women of the Buryat ethnic group with MS and PCOS the study recorded increased values of AMH (p = 0.045), Ts (p = 0.002), FAI (p < 0.0001), DHEA-S (p = 0.033), decreased SHBG (p = 0.016) and 17-OH-progesterone (p = 0.027) levels in comparison with the control; in comparison with the group with MS we noted a higher level of DHEA-S (p = 0.006) and a decreased level of SHBG (p = 0.028).Conclusion. Women with metabolic syndrome associated with hyperandrogenism showed more intense changes in the neuroendocrine regulation system relative to control values regardless of ethnicity. In Russian women, the combined syndrome (MS with PCOS) was accompanied by a greater number of hormonal changes compared to the monosyndrome (MS) than in Buryat women. The data obtained indicate the need to assess and control the content of these metabolites in women with MS and PCOS, taking into account ethnicity.

Combined effects and potential mechanisms of phthalate metabolites on serum sex hormones among reproductive-aged women: An integrated epidemiology and computational toxicology study

The reproductive age is a crucial stage for women to bear offspring. However, reproductive-aged women are simultaneously exposed to various phthalates, which may pose a threat to their reproductive health. This study employed generalized linear regression and weighted quantile sum (WQS) regression to explore the associations between monoesters of phthalates (MPAEs) and sex hormones in 913 reproductive-aged women in the National Health and Nutrition Examination Survey. Key risk factors driving hormone disruption were identified based on the weights of the WQS models. Interaction models were used to unravel the synergistic or antagonistic effects between MPAEs. The potential toxicological targets of MPAEs interfering with sex hormone-binding globulin (SHBG) levels were revealed based on prior knowledge and molecular docking of hepatocyte nuclear factor 4α (HNF4α). Compared with the first quartile, mono-benzyl phthalate (MBZP) in the second quartile exhibited a decrease in total testosterone (TT) and TT/E2 (estradiol) ratio. Mono-2-ethyl-5-carboxypentyl phthalate (MECPP) in the fourth quartile showed a decrease in SHBG and TT/E2. Additionally, mono-(carboxyoctyl) phthalate and mono-(carboxynonyl) phthalate (MCNP) were negatively associated with SHBG. Each unit increase in the WQS index of MPAE mixtures was associated with 6.73 % lower SHBG levels (95 %CI: −12.80 %, −0.24 %) with mono-(3-carboxypropyl) phthalate, MCNP, MBZP, and MECPP identified as major risk factors. Interaction analyses revealed that the effects of high-risk MPAEs on SHBG were predominantly antagonistic. Molecular docking suggested that MPAEs might compete to bind tryptophan residues of HNF4α. This study provides key information to help develop the most effective phthalate interventions and improve the reproductive health of reproductive-aged women.

Impact of Black Seed Oil on Male Sex Hormones and Binding Proteins in Alloxan-Induced Diabetic Wistar Rats

Background: Diabetes is a metabolic disease that has a detrimental effect on human health and patients' quality of life. The number of male patients with diabetes is increasing, and so are the infertility problems in the male population. This study aims to investigate the impact of black seed oil (BSO) on male sex hormones and binding proteins in alloxan-induced diabetic Wistar rats. Methods: Forty (40) male Wistar rats weighing 200-250g were randomly allocated into eight (8) groups of five (5) animals per group. Group 1 followed the induction of hyperglycemia, group 2 received normal saline, group 3 received 200mg/kg of metformin, group 4 received 2mg/kg of glimepiride, group 5 received 2.5ml/kg of BSO, group 6 received glimepiride and BSO, group 7 received metformin and BSO, and group 8 received BSO, glimepiride, and metformin. Results: The result shows that diabetes significantly reduced serum and testicular testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels compared to the normoglycemic-controlled group (p<0.05). BSO co-administered with glimepiride significantly increased serum and testicular testosterone levels compared to diabetic control and monotherapy of either glimepiride or black seed oil (p<0.05). There is a positive correlation between glycosylated hemoglobin (HbA1c) and sex hormone binding globulin (SHBG) with r2 = 0.561 while a negative correlation between glycosylated hemoglobin and Androgen binding protein (ABP) with r 2= 0.345. Conclusion Diabetes mellitus exerts an adverse impact on male sex hormones and sex hormone-binding proteins, consequently leading to a detrimental effect on male fertility. However, black seed oil enhances male sex hormones, albeit without normalizing them to normoglycemic levels. Furthermore, glycosylated hemoglobin levels affect both sex hormone-binding globulin (SHBG) and androgen-binding protein (ABP).

The dietary phytochemical index and its relation to polycystic ovary syndrome: a case–control study

BackgroundPolycystic ovary syndrome (PCOS), a hormonal disorder affecting women of reproductive age, can be significantly impacted by diet. This study explores the relationship between a diet rich in phytochemicals, measured by the Dietary Phytochemical Index (DPI), and PCOS, along with associated health markers.MethodsA case–control study design was implemented with 480 individuals diagnosed with PCOS based on the Rotterdam criteria, paired with 480 controls matched in terms of age and BMI. The evaluation encompassed dietary intake, anthropometric measurements, and hormonal/metabolic markers. Additionally, the DPI score was determined based on the consumption of phytochemical-rich foods. The study also examined PCOS-related complications like acne and irregular menstrual cycles, as well as mental health using the Beck Depression Inventory (BDI-II) scores.ResultsWomen with PCOS had significantly lower DPI scores (32.42 vs 43.87, p < 0.001) compared to the control group, indicating a less phytochemical-rich diet. The DPI scores coincided with higher levels of hormones typically associated with PCOS, including Luteinizing Hormone (LH), Dehydroepiandrosterone Sulfate (DHEA-S), and testosterone. Additionally, these scores were associated with markers of metabolic dysfunction such as C-reactive Protein (CRP), Fasting Blood Sugar (FBS), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), while positively correlating with Sex Hormone-Binding Globulin (SHBG) (all p < 0.050).). Higher DPI scores were associated with a significantly reduced risk of PCOS (OR: 0.13, 95% CI: 0.08, 0.23, P for trend: 0.001) and its complications, including acne and irregular menstrual cycles. Interestingly, a positive association emerged, suggesting better mental health (lower BDI-II scores) with higher DPI scores.ConclusionsIn conclusion, this study indicates that lower DPI scores are associated with a higher incidence and severity of PCOS, suggesting that a phytochemical-rich diet could potentially benefit the management of PCOS by enhancing hormonal profiles, metabolic health, and mental well-being in women.

Association of Di(2-ethylhexyl) Phthalate Exposure with Reproductive Hormones in the General Population and the Susceptible Population: A Systematic Review and Meta-Analysis.

Di(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, has hormone-like activity and endocrine-disrupting effects. However, the types of reproductive hormones associated with DEHP vary across the studies. Thus, we conducted a systematic review and meta-analysis to pool existing epidemiological evidence. We searched three databases up to January 31, 2024, for eligible original studies to ultimately include 37 studies from eight countries with a total of 28 911 participants. DEHP exposure was evaluated with urinary metabolites. Since the main types, production sites, blood concentrations, and functions of reproductive hormones differ between men and women, we reported the combined effect values by gender. Subgroup analyses were conducted by age, subfertility status, and the national sociodemographic index (SDI) level. Furthermore, the effect of maternal exposure during pregnancy on children's reproductive hormone levels was analyzed separately. Overall, in general, in men, DEHP was positively correlated with sex hormone binding-globulin (SHBG) and adversely correlated with total testosterone (TT), free androgen index (FAI), and follicle-stimulating hormone (FSH). Results indicated that among men of reproductive age, DEHP exposure was associated with more significant hormonal suppression in infertile men compared with fertile men. Notably, age subgroup analysis among women revealed that postmenopausal women were more vulnerable to DEHP, which was related to lower TT and estradiol (E2). However, this study did not observe a significant association between prenatal DEHP metabolites and reproductive hormone levels in children. Our research identifies the most susceptible hormones (androgen suppression) after DEHP exposure and suggests that infertile men and postmenopausal women are in great need of more attention as sensitive populations.

Exploring the Relationship Between Refractive Errors and Common Chronic Diseases Via Blood Biochemistry Tests: A Large Prospective Cohort Study.

The purpose of this study was to examine the association between refractive errors and common chronic diseases using blood biochemistry tests, and to investigate the associated modifiable risk factors, with the goal of informing and developing effective preventive strategies. A total of 116,245 participants with refractometry at baseline enrolled in the UK Biobank were included in this prospective cohort study. Restricted cubic spline and Cox proportional hazards models were used to detect associations between refractive error, blood biochemistry tests, and common chronic diseases. Interaction effects on the additive scale and effect modification analysis were used to explore excess modifiable risk factors for disease prevention. Spherical equivalent significantly associated with vitamin D, sex hormone binding globulin, apolipoprotein A, blood glucose, and aspartate aminotransferase levels. Subjects with myopia demonstrated a 13% higher risk of type 2 diabetes mellitus (T2DM) incidence compared to those without myopia (hazard ratio [HR] = 1.13, 95% confidence interval [CI] = 1.08-1.19) throughout a median follow-up of 9.12years. Interaction analysis revealed 15% (95% CI = 9%-21%) of this risk was due to myopia-obesity interaction. However, active engagement in physical activity could potentially mitigate this risk (HR = 1.06, 95% CI = 0.93-1.20). Refractive errors were associated with specific blood indicators, particularly noting the association between myopia and higher T2DM incidence in middle-aged and elderly populations. This effect interacts with obesity, and promoting physical activity among myopia individuals provides greater benefits in the prevention of T2DM compared to non-myopic individuals.

Hyperandrogenism after menopause: diagnostic evaluation

Excessive androgen levels in women after menopause often result from an imbalance in ovarian steroid secretion: a rapid decline in estrogen secretion associated with a slow decrease in androgen secretion, compounded by a physiological decrease in sex hormone-binding globulin. Hyperandrogenism is associated with a higher risk of cardiovascular events and gynecological neoplasms, also impacting the emotional well-being of affected women. Therefore, the aim of these guidelines is to guide the clinical physician in the appropriate clinical and biochemical evaluation of hyperandrogenism after menopause, thus optimizing therapeutic outcomes. The most frequent consultation in this stage of life is facial hirsutism associated with hair loss. If the onset of signs is abrupt, severe, associated with virilization and accompanied by serum testosterone levels in the male range, it is necessary to rule out a tumoral origin. A thorough medical history guides the diagnosis. Determination of total testosterone using reliable methods and imaging studies are valid tools to assist when doubts arise in the differential diagnosis.

Gestational diabetes mellitus (GDM): diagnosis using biochemical parameters and anthropometric measurements during the first trimester in the Indian population.

The objective of the study was to use anthropometric measurements (age, BMI, and subcutaneous fat) inconjunction with biochemical parameters (sex hormone-binding globulin (SHBG), homeostasis model assessment-insulin resistance (HOMA-IR), fasting glucose, serum insulin, and total cholesterol) to predict the probability of gestational diabetes mellitus (GDM) in the first trimester. The study enrolled 48 pregnant women with GDM and 64 high-risk pregnant women without GDM. During the first-trimester examination, maternal blood samples were collected to measure SHBG, fasting blood glucose, serum insulin, and total cholesterol levels. Regression model analysis was used to examine the variables that showed statistically significant differences between the groups and were independent predictors of GDM. Receiver operating characteristic (ROC) curve analysis was employed to determine the risk of developing GDM based on cut-off values. The levels of SHBG, HOMA-IR, serum insulin, fasting glucose, and total cholesterol were identified as significant independent markers for predicting GDM. Meanwhile, age, body mass index, and subcutaneous fat values were found to be non-independent predictors of GDM. The areas under the ROC curve were calculated to determine the predictive accuracy of total cholesterol, HOMA-IR, SHBG, and subcutaneous fat for developing into GDM, and were 0.869, 0.977, 0.868, and 0.822 respectively. The sensitivities for a false positive rate of 5 % for predicting GDM were 68.7 , 91.67, 91.7, and 97.9 % for total cholesterol, HOMA-IR, SHBG, and subcutaneous fat, respectively. The independent predictors for the subsequent development of GDM in high-risk pregnancies are HOMA-IR, SHBG, Total cholesterol, and subcutaneous fat (SC) levels. These parameters can be used to create a regression model to predict the occurrence of GDM.

Exploring the relationship between polycystic ovarian syndrome, testosterone, and multiple sclerosis in women: A nationwide cohort study and genome-wide cross-trait analysis.

Women have a higher risk of developing multiple sclerosis (MS), potentially due to hormonal factors. Elevated testosterone levels, common in polycystic ovary syndrome (PCOS), might influence MS risk. To investigate the relationship between PCOS, as a proxy for elevated testosterone levels, and MS risk through phenotypic and genomic analysis. Cox regression models analysed the association between PCOS and MS risk. The genome-wide cross-trait analysis examined the genetic architecture. In a Swedish cohort of 1,374,529 women, 77 (0.3%) with PCOS and 3,654 (0.3%) without PCOS were diagnosed with MS. After adjusting for birth year and obesity, no association was found between PCOS and MS (HR = 0.91, 95% CI = 0.72-1.15), which was confirmed by Mendelian randomization analysis, where genetically predicted PCOS propensity, sex hormone-binding globulin (SHBG), or testosterone levels did not causally affect MS risk (all p-values > 0.05). By exploring horizontal pleiotropy, we identified shared genetic regions and 19 independent pleiotropic SNPs for SHBG with MS and 11 for testosterone with MS. We did not find evidence for a causal role of PCOS, as a proxy of elevated testosterone, in reducing the risk of MS in women. The shared genetic loci between testosterone, SHBG, and MS provide biological insights.

Total testosterone, sex hormone-binding globulin, and free testosterone concentrations and risk of primary liver cancer: A prospective analysis of 200,000 men and 180,000 postmenopausal women.

In most countries, males have ~2-3 times higher incidence of primary liver cancer than females. Sex hormones have been hypothesized to contribute to these differences, but the evidence remains unclear. Using data from the UK Biobank, which included ~200,000 males and ~180,000 postmenopausal females who provided blood samples at recruitment, we estimated hazard ratios (HR2) and 95% confidence intervals (CI) for a doubling in hormone concentration from multivariable adjusted Cox regression for circulating total testosterone, sex-hormone binding globulin (SHBG), and free testosterone concentrations and risk of primary liver cancer. After a median of 11.8 years of follow-up, 531 cases of primary liver cancer were observed, of which 366 occurred in males and 165 occurred in females. Total testosterone and SHBG were shown to be positively associated with liver cancer risk in both males and females (Total testosterone HR2: 3.42, 95% CI:2.42-4.84 and 1.29, 0.97-1.72, respectively; SHBG HR2: 5.44, 4.42-6.68 and 1.52, 1.09-2.12, respectively). However, free testosterone was inversely associated with primary liver cancer in males (HR2: 0.42, 0.32-0.55) and no association was observed in females. When analyses compared two main liver cancer subtypes, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), there was evidence of heterogeneity; associations for total testosterone and SHBG concentrations were only positively associated with HCC in both males (HR2: 3.56, 2.65-4.79 and 7.72, 6.12-9.73, respectively) and females (HR2: 1.65, 1.20-2.27 and 6.74, 3.93-11.5, respectively) but not with ICC. Further research understanding the mechanisms of how sex-steroids may influence liver cancer risk is needed.

Identifying causal relationships between 35 blood and urine biomarkers and urologic cancers: MR-meta combined with Bayesian colocalization Mendelian randomization analysis

BackgroundBlood and urine biomarkers have been associated with urologic tumors, but their causal relationship with urologic tumors is unclear.MethodsWe performed a bidirectional Mendelian randomization (MR) analysis of the association between 35 blood and urine biomarkers and urological tumors in our discovery cohort. A Bayesian weighting approach was used to validate the positive results identified in the discovery cohort, and steiger filtering analysis was used to distinguish causality from reverse causality. Bayesian colocalization analysis was used to analyze which single nucleotide polymorphisms (SNPs) specifically co-located between the positive blood and urine biomarkers and the disease phenotypes were driven, and MR-positive results from the discovery cohort and the validation cohort were combined using the MR-meta method.ResultsSeveral blood and urine biomarkers were found to be significantly and causally associated with urologic cancers. Notably, calcium (OR: 1.34, 95%CI 1.10–1.63, P = 0.0040) and sex hormone-binding globulin (SHBG) (OR: 0.81, 95%CI 0.70–0.95, P = 0.0092) were associated with bladder cancer; gamma glutamyl transferase (GGT) (OR: 0.91, 95%CI 0.83–0.99, P = 0.0209), lipoprotein A (Lp(a)) (OR: 1.12, 95%CI 1.01–1.24, P = 0.0399), and insulinlike growth factor 1 (IGF 1) (OR: 1.10, 95%CI 1.01–1.20, P = 0.0220) were linked to prostate cancer (PCa); non albumin protein (OR: 0.78, 95%CI 0.65–0.93, P = 0.0065) and total protein (OR: 0.80, 95%CI 0.64–0.99, P = 0.0380) were linked to renal cancer; and apolipoprotein A (Apo-A) (OR: 0.56, 95%CI 0.32–0.98, P = 0.0426) and urate (OR:1.89, 95%CI 1.03–3.47, P = 0.0399) were associated with renal pelvis cancer. These associations were validated in an independent cohort, with GGT, IGF 1, and Lp(a) being consistently linked to PCa.ConclusionThis study identified significant biomarkers associated with urological cancers in blood and urine. These include GGT, IGF 1, and Lp(a), which are strong biomarkers for PCa. In addition, the findings of this study provide evidence for a handful of risk and protective factors for the development of urologic cancers.

The associations between exposure to mixed environmental endocrine disruptors and sex steroid hormones in men: a comparison of different statistical models

In recent years, worldwide fertility rates have continued to decrease. Humans are frequently exposed to a combination of environmental endocrine disruptors, which can cause male reproductive disorders. The study employed three distinct analytical models to examine the correlation between exposure to a combination of 25 chemicals and sex steroid hormone levels in adult males. This involved evaluating 12 chemicals and their metabolites from personal care and consumer products, as well as 13 metabolites linked to phthalates and plasticisers. The study analysed 25 chemicals and 3 measured sex steroid hormone outcomes, as well as two calculated hormonal outcomes (free androgen index, TT/E2 ratio) in 1262 adult men who participated in the National Health and Nutrition Examination Survey (NHANES) 2013–2016 in the United States. The study employed several statistical methods to estimate the relationships between single chemicals or chemical blends and sex hormones. These methods included linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine (BKMR) regression. The results of the linear regression analysis indicate that chemical exposure has a negative correlation with E2, TT, and FAI, and a positive correlation with SHBG and TT/E2. The mixture effect analyses using the WQS and BKMR models further confirmed that BP3, MECPP, and MECOP were the most highly weighted chemical mixtures. The analyses also suggested that there were differences in the effects of different concentrations of EDCs on sex steroid hormones. Exposure to environmental endocrine-disrupting chemicals (EDCs) has been found to have a negative correlation with estradiol and total testosterone, as well as FAI. Conversely, this exposure has been found to have a positive correlation with sex hormone binding globulin and the TT/E2 ratio. The study also revealed differences in the effects of different concentrations of EDCs.

Pyrethroids and reproductive function: some endocrine disrupting perspectives from molecular simulations.

Pyrethroids are widely used insecticides with huge applications for household as well as agricultural purposes and contribute to improved product quality and higher yields. In recent decades, the demand for pyrethroids has increased significantly due to advantages such as broad-spectrum efficacy, high insecticidal potential, and lower pest resistance. However, several studies have suggested that human exposure to pyrethroids leads to reproductive problems. Sex hormone-binding globulin (SHBG) is an important hormone transport protein regulating the availability of steroids at their target site. The aim of our study was to investigate the structural interactions of commonly used pyrethroids, cypermethrin and deltamethrin, with ligand binding pocket of SHBG. Cypermethrin and deltamethrin were docked into the steroid binding pocket of SHBG using Schrodinger's induced fit docking (IFD) followed by molecular dynamics (MD) simulation studies. The resultant SHBG-pyrethroid complexes from IFD experiments were subjected to structural analysis including the molecular interactions followed by binding energy estimation. The analysis revealed that both the ligands were tightly bound in the SHBG pocket with high percentage of commonality among the SHBG residues between the indicated pyrethroid ligands and the SHBG native ligand, dihydrotestosterone (DHT). The estimated binding energy values for cypermethrin were less but close to the values calculated for the SHBG native ligand, DHT. However, the estimated binding energy values for deltamethrin were higher compared to the values calculated for SHBG native ligand, DHT. Furthermore, the MD simulation results also revealed the higher stability of SHBG-deltamethrin than SHBG-cypermethrin complex. To sum up, the results suggested that deltamethrin has a greater capability than cypermethrin to prevent sex steroid hormone from binding to SHBG, even though both pyrethroids have this ability. Consequently, this might hamper the circulatory transport of sex steroid hormones and their availability at the target site, subsequently interfering with reproductive function.

Sex Differences in Physiological Responses to a National Collegiate Athletic Association Division I Soccer Season.

McFadden, BA, Walker, AJ, Cintineo, HP, Bozzini, BN, Sanders, DJ, Chandler, AJ, and Arent, SM. Sex differences in physiological responses to a National Collegiate Athletic Association Division I soccer season. J Strength Cond Res 38(11): 1891-1899, 2024-Identifying physiological changes that occur in response to workload demands can help to elucidate athlete management and recovery strategies. The purpose of this study was to compare the physical and physiological demands between men and women throughout the course of a collegiate soccer season. Men ( N = 23) and women ( N = 26) soccer players participated in blood draws before preseason (T1) and every 4 weeks thereafter (T2-T4). Workload was determined at all practices and games via heart rate and global positioning satellite monitoring systems. Repeated measures multivariate analysis of variance and linear mixed models were used to assess workload and biomarker responses throughout the season ( p < 0.05). Both teams experienced the highest workloads during the first 4 weeks of the season ( p < 0.05), which was followed by several biomarker perturbations. Sex-by-Time interactions were observed for total cortisol, growth hormone, insulin-like growth factor-1, thyroxine, thyroid-stimulating hormone, vitamin D, and omega 3 fatty acid index ( p < 0.05). Additional Sex effects were observed for free and total testosterone, estrogen, prolactin, sex-hormone binding globulin, creatine kinase, and iron levels ( p < 0.05). Women soccer players experienced further Time effects for free cortisol, iron, ferritin, and percent transferrin saturation ( p < 0.05). Male soccer players experienced additional Time effects for total testosterone, estrogen, creatine kinase, interleukin-6, triiodothyronine, and ferritin ( p < 0.05). Despite similar patterns of change in workloads, differential fluctuations in physiological markers were observed between the sexes. Understanding sex differences in response to comparable workloads may enhance exercise prescriptions for better athlete management plans. Additional strategies to increase iron may be warranted in female athletes.

Associations of Life’s Essential 8 with Low Muscle Mass Mediated by Testosterone, Inflammation and Nutritional Status in US Adults: A Cross-Sectional Study

BackgroundLow muscle mass, defined as appendicular lean mass adjusted for body mass index (BMI), may indicate early skeletal muscle deterioration. ObjectiveThis study aimed to investigate the relationship between Life's Essential 8 (LE8), the updated cardiovascular health (CVH) metrics by the American Heart Association (AHA), and low muscle mass, including the impact of related biomarkers on muscle quality. MethodsThis cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) cycles 2011-2014, selected due to their inclusion of the most recent appendicular lean mass measurements available in the NHANES dataset. Participants aged 20-60 years were included. We employed weighted logistic regression models, restrictive cubic splines (RCS), and weighted quantile sum (WQS) regression to assess the relationship between LE8 scores and low muscle mass. Four mediation models were constructed to explore whether serum testosterone in males, serum sex hormone-binding globulin (SHBG) in females, serum albumin, and systemic immune-inflammation index (SII) mediated the association between LE8 scores and low muscle mass. ResultsHigher LE8 scores are associated with lower odds of low muscle mass. Compared to participants with low cardiovascular health (CVH), those with intermediate and high CVH had 49% (Odds ratio (OR) 0.51, 95% confidence interval (CI) 0.30, 0.87) and 86% (OR 0.14, 95%CI 0.06, 0.29) lower odds of low muscle mass, respectively. Mediation analysis revealed that testosterone, SHBG, SII, and albumin partially mediated the association between LE8 scores and low muscle mass. The WQS regression model indicated that BMI and physical activity might be important factors influencing low muscle mass within the components of LE8. ConclusionsLE8 scores negatively associated with low muscle mass in US adults. Serum testosterone in males and SHBG in females were negative predictors of low muscle mass, while SII was inversely associated. Serum albumin had a beneficial effect on muscle mass.

Sociodemographic, lifestyle, and medical factors associated with calculated free testosterone concentrations in men: individual participant data meta-analyses.

Sociodemographic, lifestyle, and medical variables influence total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations. The relationship between these factors and "free" T remains unclear. We examined 21 sociodemographic, lifestyle, and medical predictors influencing calculated free T (cFT) in community-dwelling men across ages. This is a cross-sectional analysis in 20 631 participants in the Androgens in Men Study. Individual participant data (IPD) were provided by 9 cohorts. Total T was determined using mass spectrometry, SHBG using immunoassays, and cFT using the Vermeulen formula. Associations were analyzed using 2-stage random effects IPD meta-analyses. Cohort median ages ranged from 40 to 76 years and median cFT concentrations from 174.3 to 422.8 pmol/L. In men aged 17-99 years, there was a linear inverse association of cFT with age (-57.2 pmol/L [95% confidence interval, -69.4, -44.9] per 1 SD increase in age). Calculated free T increased with increasing baseline body mass index (BMI) among men with BMI < 23.6 kg/m2, but decreased among men with BMI > 23.6 kg/m2 (-24.7 pmol/L [-29.1, -20.3] per 1 SD increase in the 25.4-29.6 kg/m2 BMI range). Calculated free T was lower in younger men, who were married or in a de facto relationship (-18.4 pmol/L [-27.6, -9.3]) and in men who formerly smoked (-5.7 pmol/L [-8.9, -2.6]), were in poor general health (-14.0 pmol/L [-20.1, -7.8]), and had diabetes (-19.6 pmol/L [-23.0, -16.3]), cardiovascular disease (-5.8 pmol/L [-8.3, -3.2]), or cancer (-19.2 pmol/L [-24.4, -14.1]). Calculated free T was most prominently associated with age and BMI. The linear, inverse association with age, nonlinear association with BMI, and presence of diabetes, cancer, and sociodemographic factors should be considered when interpreting cFT values.