Endogenous Sex Hormone Levels Research Articles

Association of endogenous sex hormone levels with tooth loss due to periodontitis in men and post-menopausal women: Themulti-ethnic study of atherosclerosis.

To investigate the association between endogenous sex hormone levels and history of tooth loss related to periodontitis in healthy middle-aged to older men and post-menopausal women. This cross-sectional study included 5649 participants aged 45-84 (mean age, 63 ± 10 years) from the Multi-Ethnic Study of Atherosclerosis cohort who had sex hormone levels measured and answered a questionnaire regarding perceived periodontal status at exam 1. Multivariable logistic regression was used to examine the association of sex hormones (exposure) with history of tooth loss (outcome), stratified by sex. Among post-menopausal women, higher free testosterone (per 1SD) was associated with a greater prevalence of tooth loss [OR 1.49 (95% CI, 1.08-2.05)], whereas higher sex hormone binding globulin (SHBG) was associated with a lower prevalence of tooth loss [OR 0.74 (0.58-0.94)], after adjustment for cardiometabolic risk factors and reproductive factors. In men, higher free testosterone and lower SHBG were associated with a lower prevalent probability of tooth loss in unadjusted analysis, but these associations lost significance after covariate adjustment. A higher androgenic sex hormone profile in post-menopausal women (i.e., increased free testosterone, lower SHBG) was associated with an increased prevalence of tooth loss, after adjusting cardiometabolic risk factors. No such association was found in men. These findings suggest that sex hormones may influence or serve as a marker for periodontal health.

Positive Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Hypertension May Be Attenuated by Endogenous Sex Hormones: A Nationally Representative Cross-Sectional Study.

Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored. This study included 10 794 adults aged ≥18 years from the China National Human Biomonitoring program. Weighted multiple logistic regression and linear regression were used to examine the associations of serum PFAS with hypertension, diastolic blood pressure, and systolic blood pressure. Joint effects of PFAS mixtures on hypertension, diastolic blood pressure, and systolic blood pressure were evaluated using quantile-based g-computation. Additive and multiplicative interactions were used to assess the role of PFAS with testosterone and estradiol on hypertension. The prevalence of hypertension in Chinese adults was 35.50%. Comparing the fourth quartile with the first quartile, odds ratio (95% CI) of hypertension were 1.53 (1.13-2.09) for perfluorononanoic acid, 1.40 (1.03-1.91) for perfluorodecanoic acid, 1.34 (1.02-1.78) for perfluoroheptane sulfonic acid, and 1.46 (1.07-1.99) for perfluorooctane sulfonic acid. Moreover, PFAS mixtures, with perfluorononanoic acid contributing the most, were positively associated with hypertension, diastolic blood pressure, and systolic blood pressure. PFAS and endogenous hormones had an antagonistic interaction in hypertension. For example, the relative excess risk ratio, attributable proportion, and synergy index for perfluorononanoic acid and estradiol were -3.61 (-4.68 to -2.53), -1.65 (-2.59 to -0.71), and 0.25 (0.13-0.47), respectively. Perfluorononanoic acid, perfluorodecanoic acid, perfluoroheptane sulfonic acid, perfluorooctane sulfonic acid, and PFAS mixtures showed positive associations with hypertension, systolic blood pressure, and diastolic blood pressure. Positive associations of PFAS with hypertension might be attenuated by increased levels of endogenous sex hormones.

The oral contraceptive cycle and its influences on maximal and submaximal endurance parameters in elite handball players.

The usage of the oral contraceptive pill is widespread among athletes of various levels. However, there is limited knowledge on how the intake of the pill alters the submaximal and maximal endurance parameters between the oral contraceptive phases. Therefore, the aim of this study was to examine potential differences between the pill intake and withdrawal phase on endurance-related parameters in first-division handball players. In total, 15 female team handball players performed two graded exercise tests until volitional exhaustion on a motorized treadmill. Tests were performed during the pill intake (days 16-17) and withdrawal phase (day 2-3). Throughout the test, respiratory gases were measured breath-by-breath, and the heart rate was measured continuously. Before and after the graded exercise test, blood samples were obtained in order to assess the blood lactate concentration. Before each test, venous blood samples were taken to determine endogenous sex hormone levels. Ventilatory parameters (O2, CO2, and E, and respiratory equivalents for O2 and CO2) were measured, and the oxidation of fat and carbohydrates was calculated. A paired-sample t-test was used to assess differences between the two time points, and the significance was accepted as p < 0.050. Significant differences with lower values during the consumption phase were found for absolute (mean difference ± SD: 88 ± 131mL∙min-1; p = 0.021) and relative O2peak (mean difference ± SD: 1 ± 2mL∙min-1∙kg-1; p = 0.012). Higher values during the consumption phase were found for submaximal respiratory equivalents for O2 (mean difference ± SD: -1.1 ± 1.7; p = 0.028) and CO2 (mean difference ± SD: -0.9 ± 1.5; p = 0.032). No differences were found for all other parameters, including differences for endogenous sex hormones (p > 0.050). The results of the current study suggest only marginal and physiologically insignificant differences in endurance-related parameters between oral contraceptive phases.

Causal inference of sex hormone-binding globulin on venous thromboembolism: evidence from Mendelian randomisation

BackgroundPrevious cohort studies have shown that exogenous sex hormone use, such as testosterone replacement therapy and oestrogen-containing contraceptives, can increase the risk of venous thromboembolism (VTE). However, the relationship between endogenous sex hormone levels and VTE remains unclear. The goal of the present study was to explore the causal roles of endogenous sex hormones, including hormone-binding globulin (SHBG), bioactive testosterone (BT), and total testosterone (TT), in VTE and its two subgroups, deep vein thrombosis (DVT) and pulmonary embolism (PE).MethodsWe used a genome-wide association study of sex hormones as exposure data and Finnish VTE data as the outcome. Inverse variance weighting, MR-Egger, and weighted median were used for two-sample Mendelian randomisation (MR). Sensitivity analyses included MR-Egger, MR-PRESSO, Cochrane Q test, MR Steiger, leave-one-out analysis, and funnel plot, combined with multivariate MR and replicated MR analyses using larger VTE data from the global biobank meta-analysis initiative. Linkage disequilibrium score regression (LDSC) was used to determine genetic associations and estimate sample overlap.ResultsOur findings genetically predicted that an increase in serum SHBG levels by one standard deviation (SD) caused 25% higher odds for VTE (OR: 1.25, 95% CI: 1.01−1.55) and 58% higher odds for PE (OR: 1.58, 95% CI: 1.20−2.08). LDSC supported the genetic correlation between these two traits and replicated analyses confirm SHBG’s genetic effect on VTE in both sexes (OR: 1.46, 95% CI: 1.20−1.78) and in females (OR: 1.49, 95% CI: 1.17−1.91). In addition, an increase in serum TT levels by one SD caused 32% higher odds for VTE (OR: 1.32, 95% CI: 1.08−1.62) and 31% higher odds for DVT (OR: 1.31, 95% CI: 1.01−1.69); however, LDSC and replicated analyses did not find a genetic correlation between TT and VTE or its subtypes. No significant correlation was observed between BT and all three outcome traits.ConclusionOur study provides evidence that elevated serum SHBG levels, as predicted by genetics, increase VTE risk. However, the causal effect of testosterone levels on VTE requires further investigation.

Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids.

Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure. Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study. The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12-18 months. The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.

Role of sex hormones in neuroinflammation in Alzheimer's disease

AbstractNeuroinflammation, which is mediated by microglia, astrocytes, and infiltrated immune cells and leads to the subsequent production of proinflammatory molecules, is associated with the pathomechanism of Alzheimer's disease (AD). As the incidence of AD is higher in females than males, multiple studies have focused on the relationship between sex hormones and AD pathology. Androgen and estrogen receptors are expressed throughout the brain, including the hippocampus; thus, both sex hormones may regulate brain function, including cognitive function. Endogenous sex hormone levels are depleted by aging and cancer therapies, including prostate cancer and breast cancer therapies. Previous cohort studies have revealed that these conditions may also increase the risk of developing AD. Here we review previous findings from epidemiologic and preclinical studies on AD and provide an overview of the roles of sex hormones as risk factors of AD and regulators of AD pathology, including neuroinflammation. Furthermore, we discuss the therapeutic potential of sex hormone supplementation as a preventive or therapeutic treatment for AD based on the results of randomized control trials.

Associations between endogenous sex hormone levels and adipokine levels in the Multi-Ethnic Study of Atherosclerosis.

Differences in sex hormone levels contribute to differences in cardiovascular disease (CVD) risk. Adipokines play a role in cardiometabolic pathways and have differing associations with CVD. Adipokine levels differ by sex; however, the association between sex hormone profiles and adipokines is not well established. We hypothesized that a more androgenic sex hormone profile would be associated with higher leptin and resistin and lower adiponectin levels among postmenopausal women, with the opposite associations in men. We performed an analysis of 1,811 adults in the Multi-Ethnic Study of Atherosclerosis who had both sex hormones and adipokines measured an average of 2.6 years apart. Sex hormones [Testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG), and dehydroepiandrosterone (DHEA)] were measured at exam 1; free T was estimated. Serum adipokines (leptin, resistin, adiponectin) were measured at exams 2 or 3. We used multivariable linear regression to examine the cross-sectional associations between sex hormones and adipokines. The mean (SD) age was 63 (10) years, 48% were women; 59% non-White participants. For leptin, after adjusting for demographics only, higher free T and lower SHBG, were associated with higher leptin in women; this association was attenuated after further covariate adjustment. However in men, higher free T and lower SHBG were associated with greater leptin levels in fully adjusted models. For adiponectin, lower free T and higher SHBG were associated with greater adiponectin in both women and men after adjustment for CVD risk factors. For resistin, no significant association was found women, but an inverse association with total T and bioT was seen in men. Overall, these results further suggest a more androgenic sex profile (higher free T and lower SHBG) is associated with a less favorable adipokine pattern. These findings may provide mechanistic insight into the interplay between sex hormones, adipokines, and CVD risk.

PS-C28-6: HIGH TESTOSTERONE AND LOW ESTRADIOL SERA LEVELS ARE ASSOCIATED WITH UNSTABLE PLAQUE COMPOSITION IN MEN WITH SEVERE CAROTID ATHEROSCLEROSIS

Background and Objectives: Ischemic strokes caused by the rupture of unstable atherosclerotic plaques in the carotid arteries, are leading causes of mortality and disability worldwide. Sex differences exist in plaque composition, where men are more likely to develop unstable plaques than women. Sex hormones affect vascular reactivity and inflammation, but it remains unclear if they are involved in plaque instability and how their role differs in men and women. Herein, we investigated the association between circulating endogenous sex hormone levels and plaque composition/instability in men and women with severe carotid atherosclerosis. Design and method: Pre-operative fasting blood samples and plaque specimens were collected from post-menopausal women and men greater than 55 years old with severe carotid atherosclerosis who underwent a carotid endarterectomy at McGill-affiliated hospitals in Montreal, Canada. Plaque composition and stability were examined by experienced vascular pathologists according to gold-standard histological classifications. Liquid chromatography-tandem mass spectrometry-based methods were developed to quantify endogenous sex hormones, 17ß-estradiol (E2), testosterone, androstenedione, and dehydroepiandrosterone, in sera samples. Results: Subjects (n = 460) had a mean age of 71.0 ± 9.0, were 68.9% male, and had various comorbidities (hypercholesterolemia [82.6%], hypertension [84.6%], type 2 diabetes [34.5%]). Clinical characteristics were similar among post-menopausal women (n = 143) and men (n = 317) with stable versus unstable plaques. Men had a significantly greater proportion of unstable versus stable plaques compared to women (men unstable: 61.5%, women unstable: 41.3%; P &lt; 0.001), characterized predominantly by a large lipid-rich core, hemorrhage, and high presence of inflammatory cell infiltration. Men with unstable plaques had significantly higher levels of testosterone than men with stable plaques (P = 0.004). In men, testosterone levels were inversely associated with fibrosis (P &lt; 0.05), while directly associated with unstable plaque features, including greater lipid core size (P &lt; 0.05), and a greater presence of foam cells (P &lt; 0.05), neovascularization (P &lt; 0.01), and plaque (P &lt; 0.01) and cap inflammation (P &lt; 0.05). No associations were observed between testosterone levels and plaque features in women. Endogenous E2 levels were inversely associated with neovascularization (P &lt; 0.05) and plaque and cap inflammation (P &lt; 0.001) in men, while inversely associated with fibrosis levels in women (P &lt; 0.05). Conclusion: Our findings suggest that higher testosterone and lower E2 levels are associated with unstable plaque composition in men with carotid atherosclerotic disease and may partly explain the higher proportion of unstable plaques observed among men than women of similar age and comorbidity status. Instead, in women, estradiol appears to play a detrimental role in plaque instability by inversely affecting fibrous tissue levels (a key stabilizing feature of plaques).

Endogenous Steroid Hormone Concentrations and Risk of Endometriosis in Nurses' Health Study II.

Few studies have assessed the association between endogenous steroid hormone levels and a subsequent diagnosis of endometriosis. We prospectively evaluated premenopausal plasma sex hormone levels and the risk of laparoscopically confirmed endometriosis in a nested case-control study within Nurses' Health Study II. Between blood collection (1996-1999) and 2009, we ascertained 446 women with incident endometriosis and matched them to 878 controls through risk-set sampling. We conducted multivariable conditional logistic regression accounting for matching and confounders to estimate relative risks (RRs) and 95% confidence intervals (CIs). Women with greater early follicular-phase total or free estradiol levels had a nonlinear increased risk of endometriosis (early follicular total estradiol: second quartile vs. first, RR=2.23 (95% CI: 1.44, 3.47); third quartile, RR=1.83 (95% CI: 1.16, 2.88); fourth quartile, RR=1.68 (95% CI: 1.05, 2.68); early follicular free estradiol: second quartile vs. first, RR=1.63 (95% CI: 1.05, 2.54); third quartile, RR=2.02 (95% CI: 1.31, 3.12); fourth quartile, RR=1.04 (95% CI: 0.66, 1.65)). Free testosterone assessed in quartile categories was not associated with endometriosis, although a threshold effect was observed, with a positive association among women in the top 2% of free testosterone levels. Levels of mid-luteal-phase total and free estradiol, follicular and luteal estrone, total testosterone, progesterone, and sex hormone binding globulin were not associated with endometriosis risk. These results support the role of sex steroids in endometriosis etiology, although the relationships suggest complex threshold effects.

Abstract 9737: Association of Endogenous Sex Hormone Levels and Myocardial Fibrosis in Men and Post-menopausal Women: The Multi-Ethnic Study of Atherosclerosis

Introduction: Endogenous sex hormone(ESH) imbalances have been linked to a higher risk of heart failure in men and post-menopausal women(PMW). However, experimental studies have found conflicting results regarding ESH' response to myocardial fibrosis(MF). Hypothesis: We hypothesize that at baseline, men and PMW with abnormal ESH profiles will have higher rates of MF measured by CMR T1 mapping and higher rates of myocardial scar detected by CMR during a ten-year follow up. Methods: A total of 1,276 men and 1,048 PMW were included in the MESA with ESH measured at baseline and had undergone CMR 10 years later. All analyses were stratified by sex and age groups (Table1A-B). Multivariable linear regression models were constructed to assess the associations of baseline ESH, ECV, and nativeT1 time. Multivariable logistic regression models were built to determine the associations of baseline ESH and myocardial scar among men. Results: Each 1-SD increment higher free and bioavailable testosterone in older men (≥65) was associated with 2.5% (p=0.008) and 1.0%(p=0.08) lower ECV, respectively, and 21.5%(p=0.03) and13.4%lower native T1(p=0.02). A 1-SD increment greater SHBG level was associated with 2%(p=0.01) higher ECV and 12% higher native T1 (p=0.08)(Table1A). Among post-menopausal women of 44-54 years, a 1-SD increment higher free testosterone was associated with 14% greater native T1 only; however, those between 55-64 years, a 1-SD increment higher total testosterone was associated with 9% lower native T1 (Table1B). Higher levels of estradiol in older men (≥65 years) were independently associated with a significantly higher odds of having a myocardial scar (OR:4.10,95%CI:1.35-12.40;p=0.01). Conclusions: Among older men, lower free testosterone and higher levels of estradiol were independently associated with CMR-defined interstitial MF and replacement fibrosis, respectively. There was no consistent association between ESH and interstitial MF among PMW.

Comparison of three different blood matrices for the quantification of endogenous steroids using UHPLC-MS/MS.

Urine is currently the matrix of choice for the detection of exogenous substances but also for the application of the steroidal module of the Athlete Biological Passport (ABP) consisting in a longitudinal monitoring of steroid biomarkers. To fill the limitations related to urine, the longitudinal monitoring of serum steroids concentration in the so-called 'blood steroid profile' has recently been proposed. Although serum samples are collected much less than urine samples, plasma derived from ABP whole blood samples used for the full blood count could be exploited for the quantification of endogenous steroids. Alternatively, dried blood spots (DBS) that are much easier to collect could also serve as matrix for the steroid profile. In this study, we compared the concentration levels of several endogenous steroids measured in three different blood matrices (serum, plasma and DBS) collected from 100 elite athletes participating in the 2019 Doha World Athletics Championships using UHPLC-MS/MS. Plasma and serum samples were collected by venipuncture, whereas DBS were generated from whole blood samples. Although steroids demonstrated a good agreement between the three matrices, a slight but acceptable underestimation (10%-20%) was observed in plasma compared with serum. The difference between DBS and the two other matrices was dependent of the bias between serum and plasma. We also showed that a generic HCT correction for DBS could be a valuable approach for quantitative measurements. This study demonstrates the possibility to use three different matrices for the quantification of endogenous steroids although the slight discrepancies should be considered for longitudinal evaluation.

Hormone-based models for comparing menstrual cycle and hormonal contraceptive effects on human resting-state functional connectivity

Oral contraceptives (OCs) are widely used yet understudied given their potential for public health consequences. Emerging investigations scaling from single-subject, dense-sampling neuroimaging studies to population-level metrics have linked OCs to altered brain structure and function. Modeling the hypogonadal, hypergonadal, or mixed state effects of OCs in terms of their impact on hormone action in the brain is a valuable approach to synthesizing results across neuroimaging studies and comparing OC effects to companion findings from research on menstrual cycle phase effects on brain anatomy and function. Resting-state functional connectivity studies provide a powerful tool to evaluate the role of OCs on the intrinsic network connectivity that underlies multiple behavioral domains. The preponderance (but not consensus) of the current literature indicates that (1) as the menstrual cycle proceeds from a low to high progesterone state, prefrontal connectivity increases and parietal connectivity decreases; (2) OCs tend to mimic this connectivity pattern; therefore (3) OCs may produce a hyperprogestogenic state in the brain, in spite of overall reductions in endogenous steroid hormone levels. Alternative models are also considered.

Parity History and Later Life Sex Hormone Levels in the Multi-Ethnic Study of Atherosclerosis (MESA)

BackgroundMultiparity is a risk factor for cardiovascular disease (CVD). A more androgenic sex hormone profile, with a higher testosterone (T)/estradiol (E2) ratio, is associated with worse CVD outcomes in women and might be one mechanism linking multiparity to increased CVD risk. We investigated the relationship between parity and sex hormones at mid-to-older age. MethodsWe performed a cross-sectional analysis of 2979 women with data on parity and endogenous sex hormone levels from the Multi-Ethnic Study of Atherosclerosis (MESA), a community-based cohort. Parity and gravidity (our exposures) were categorized as 0 (reference), 1-2, 3-4, or ≥ 5. Our outcome measures were T, E2, sex hormone binding globulin, dehydroepiandrosterone, and T/E2 ratio. Progressively adjusted linear regression was used to evaluate the association of parity/gravidity with sex hormones. ResultsIn multivariable adjusted models, there were no significant associations of parity with E2, dehydroepiandrosterone, and sex hormone binding globulin. Compared with nulliparity, after adjustment for CVD risk factors, women with 1-2 and 3-4 live births had higher T, but this was not significant for grand multiparity (≥ 5 live births). However, grand multigravidity (≥ 5 pregnancies) was associated with 10% (95% confidence interval [CI], 1%-20%) higher T and 14% (95% CI, 1%-29%) higher T/E2, compared with null gravidity. Grand multiparity was associated with an 18% (95% CI, 4%-34%) higher T/E2 ratio compared with nulliparity, after adjustment for CVD risk factors. ConclusionsIn this multiethnic cohort, women with grand multigravidity and grand multiparity had higher T/E2 levels, reflecting a more androgenic sex hormone profile. Longitudinal studies on sex hormones’ influence on the relationship between multiparity and CVD are warranted.

Endogenous Levels of Circulating Androgens Are Not Associated with Risk of Microscopic Colitis.

Microscopic colitis is a chronic inflammatory disease that most commonly affects post-menopausal women. Exogenous hormone use has recently been linked with increased risk of microscopic colitis. Yet, it is unclear whether levels of endogenous sex hormones are also associated with risk of microscopic colitis. To evaluate the association between prediagnostic plasma androgens and subsequent risk of microscopic colitis. We conducted a case-control study nested within prospective cohort studies of the Nurses' Health Study (NHS) and NHSII. Cases of microscopic colitis were each matched to two controls according to age, cohort, menopause status, fasting status, and season of plasma collection. Prediagnosis plasma levels of androgens including dehydroepiandrosterone sulfate, testosterone, and sex hormone-binding globulin were measured. We examined the association of each analyte with risk of microscopic colitis using conditional logistic regression models. Our study included 96 cases of microscopic colitis matched to 190 controls. Plasma levels of testosterone were not associated with risk of microscopic colitis (Ptrend = 0.70). Compared to participants in the lowest quartile of plasma testosterone levels, the aOR of microscopic colitis for women in the highest quartile was 0.88, 95% CI 0.45-1.71. Similarly, we did not observe an association between dehydroepiandrosterone sulfate and sex hormone-binding globulin and risk of microscopic colitis (all Ptrend > 0.52). Among women, prediagnostic circulating levels of testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin are not associated with risk of microscopic colitis.

Association of endogenous sex hormone levels with plaque composition and instability in men and women with severe carotid atherosclerosis

Background and Aims : Sex differences exist in plaque composition, where men are more likely to develop unstable plaques than women. Sex hormones affect vascular reactivity and inflammation, but it remains unclear if they are involved in plaque instability. Herein, we investigated the association between endogenous sex hormones and plaque composition/instability in men and women with severe carotid atherosclerosis.

ENDOGENOUS SEX HORMONES LEVELS ARE ASSOCIATED WITH THE REVISED FRAMINGHAM STROKE RISK PROFILE IN POSTMENOPAUSAL WOMEN – A CROSS-SECTIONAL STUDY IN A SWEDISH COHORT

Objective: Levels of endogenous sex hormones in postmenopausal women have been associated with the risk of cardiovascular diseases. The aim of this study was to investigate the association between eight different endogenous sex hormones and the revised Framingham stroke risk profile (rFSRP) in Swedish postmenopausal women. Design and method: This is an observational cross-sectional study within the Vara Skövde cohort, a Swedish population-based study with the main focus on detecting hypertension and diabetes at an early stage. The participants in the present study were physically examined in 2002–2004, and endogenous sex hormones (-17-hydroxy progesterone, estrone, dihydrotestosterone (DHT), estradiol, dehydroepiandrosterone (DHEA), androstenedione, testosterone, and progesterone) were analyzed with a validated liquid chromatography-tandem mass spectrometry assay. Women 55 years old or older, with estradiol levels lower than 20 pg/mL, and non-users of hormonal therapy were included in the study (N = 146). Outcome variable was rFSRP, which estimates the individual´s 10-year risk of stroke based on blood pressure, smoking, atrial fibrillation, age, previous cardiovascular disease and diabetes status. Regression analyses of log-transformed rFSRP were fitted against sex hormones, adjusting for body mass index (BMI) or waist-to-hip ratio (WHR) (depending on which variable was more associated with hormone levels), C-reactive protein (CRP) and total cholesterol level. Results: Progesterone levels showed a positive association with rFSRP when adjusting for BMI. (18% increase in rFSRP per SD increase in progesterone, p = 0.020). Estrone was positively associated with rFSRP in the model adjusting for BMI (17 % increase in rFSRP per SD increase in estrone level, p = 0.020). Testosterone showed a positive association in the model adjusting for WHR (13 % increase in rFSRP per SD increase in testosterone, p = 0.019). Additional adjustments for CRP and cholesterol did not change the results for any of the hormones. No significant associations between other hormones and rFSRP were observed in this study. Conclusions: Increase in levels of estrone, testosterone and progesterone in postmenopausal women was associated with increase of rFSRP. Prospective studies are warranted for a better understanding of the importance of sex hormone levels for cardiovascular health in postmenopausal women.

Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome.

Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome.Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied.Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding globulin (SHBG), and total testosterone. Shotgun metagenomic sequencing was performed on DNA extracted from faecal samples. Species and metabolic pathway abundances were determined using MetaPhlAn2 and HUMAnN2. Multivariate association with linear models was used to identify microbial species and metabolic pathways associated with OC use and endogenous levels of sex hormones.Results. The percentage variance of the microbial community explained by individual factors ranged from 9.9 % for age to 2.7 % for time since initiation of OC use. We observed no changes in the diversity or composition of the gut microbiome following OC initiation. However, the relative abundance of the biosynthesis pathways of peptidoglycan, amino acids (lysine, threonine, methionine, and tryptophan), and the NAD salvage pathway increased after OC initiation. In addition, serum levels of estradiol and SHBG were positively associated with Eubacterium ramulus, a flavonoid-degrading bacterium. Similarly, microbes involving biosynthesis of l-lysine, l-threonine, and l-methionine were significantly associated with lower estradiol, SHBG, and higher levels of total testosterone.Conclusion. Our study provides the first piece of evidence supporting the association between exogenous and endogenous sex hormones and gut microbiome composition and function.

Reproductive hormone levels, androgen receptor CAG repeat length and their longitudinal relationships with decline in cognitive subdomains in men: The European Male Ageing Study.

ObjectiveIt has been proposed that endogenous sex hormone levels may present a modifiable risk factor for cognitive decline. However, the evidence for effects of sex steroids on cognitive ageing is conflicting. We therefore investigated associations between endogenous hormone levels, androgen receptor CAG repeat length, and cognitive domains including visuoconstructional abilities, visual memory, and processing speed in a large-scale longitudinal study of middle-aged and older men. MethodsMen aged 40-79 years from the European Male Ageing Study (EMAS) underwent cognitive assessments and measurements of hormone levels at baseline and follow-up (mean = 4.4 years, SD ± 0.3 years). Hormone levels measured included total and calculated free testosterone and estradiol, dihydrotestosterone, luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone sulphate and sex hormone-binding globulin. Cognitive function was assessed using the Rey-Osterrieth Complex Figure Copy and Recall, the Camden Topographical Recognition Memory and the Digit Symbol Substitution Test. Multivariate linear regressions were used to examine associations between baseline and change hormone levels, androgen receptor CAG repeat length, and cognitive decline. ResultsStatistical analyses included 1,827 and 1,423 participants for models investigating relationships of cognition with hormone levels and CAG repeat length, respectively. In age-adjusted models, we found a significant association of higher baseline free testosterone (β=-0.001, p=0.005) and dihydrotestosterone levels (β=-0.065, p=0.003) with greater decline on Rey-Osterrieth Complex Figure Recall over time. However, these effects were no longer significant following adjustment for centre, health, and lifestyle factors. No relationships were observed between any other baseline hormone levels, change in hormone levels, or androgen receptor CAG repeat length with cognitive decline in the measured domains. ConclusionsIn this large-scale prospective study there was no evidence for an association between endogenous sex hormone levels or CAG repeat length and cognitive ageing in men. These data suggest that sex steroid levels do not affect visuospatial function, visual memory, or processing speed in middle-aged and older men.

Circulating Sex Hormone Levels and Colon Cancer Risk in Men: A Nested Case-Control Study and Meta-Analysis.

Endogenous sex hormones may contribute to higher colorectal cancer incidence rates in men compared with women, but despite an increased number of studies, clear evidence is lacking. We conducted a comprehensive nested case-control study of circulating concentrations of sex hormones, sex hormone precursors, and sex hormone binding globulin (SHBG) in relation to subsequent colon cancer risk in European men. Concentrations were measured using liquid LC/MS-MS in prospectively collected plasma samples from 690 cases and 690 matched controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). In addition, we conducted a meta-analysis of previous studies on men. Circulating levels of testosterone (OR, 0.68; 95% CI, 0.51-0.89) and SHBG (OR, 0.77; 95% CI, 0.62-0.96) were inversely associated with colon cancer risk. For free testosterone, there was a nonsignificant inverse association (OR, 0.83; 95% CI, 0.58-1.18). In a dose-response meta-analysis of endogenous sex hormone levels, inverse associations with colorectal/colon cancer risk were found for testosterone [relative risks (RR) per 100 ng/dL = 0.98; 95% CI, 0.96-1.00; I2 = 22%] and free testosterone (RR per 1 ng/dL = 0.98; 95% CI, 0.95-1.00; I2 = 0%). Our results provide suggestive evidence for the association between testosterone, SHBG, and male colon cancer development. Additional support for the involvement of sex hormones in male colon cancer.

Backbone extension via peptidomimetics at N-terminal; self-assembled nanofibrous cluster and application to selective progesterone detection in an aqueous medium

Despite the adequacy of the endogenous steroid (progesterone) levels in biological functioning, elevated levels of progesterone hormone have several physiological effects that are amplified due to its direct and indirect uptake from the environment, food products, and medical therapy. So, it is much needed to evaluate the progesterone levels in environmental samples as well as for biological fluids. In this work, we focused on the development of the nano sensing probe for the selective detection of progesterone among the library of steroid hormones belonging to the class of female sex hormones. Herein, functionalization of dipeptide is carried out at N-terminal to produce N-functionalized dipeptide (SS3), and simultaneously, its self-assembly properties are explored. Furthermore, HR-TEM imaging was also performed to examine the morphology of the self-assembled architectures before and after the addition of the steroid hormone. To investigate the binding mechanism of the sensing probe, Fluorescence spectroscopy, Circular Dichroism (CD), MD-Simulation, and DFT studies were performed and studied in detail. Moreover, to check the potency of the real-time application of the developed nanoprobe, we have successfully determined the spiked concentration of progesterone levels in pharmaceutical and biological fluid samples with functional percentage recovery. Also, the stability and other competitive binding studies of the probe with the coexisting substances are performed to check the rationality of the sensing probe at physiological conditions.