Jul 2026· Journal of Diabetes and Metabolic Disorders· Vol 25· 0 citations· 27 references
Medicine
TL;DR
Cox proportional hazards analysis demonstrated an inverse relationship between serum FAI and all-cause mortality in the overall, postmenopausal and men (> 60 years) CKM subgroup, and a higher T: E ratio was inversely associated with all-cause mortality specifically in men aged > 60 years with CKM.
The regulation and secretion of hormones in the endocrine system change with aging. While these changes may influence age-related disease risks, the role of hypothalamic-pituitary-thyroid (HPT) axis sensitivity in metabolic and cardiovascular health remains unclear.
This study enrolled 13,646 participants (6,221 males, 7,425 females). Metabolic (BMI, SUA, FPG, lipoproteins) and cardiovascular (ECG, CK-MB, NT-proBNP) indices were measured. Multivariable logistic regression adjusted for age (per 10-year increment), sex, and outcome-specific confounders. Nonlinear relationships between age and TFQI were analyzed using restricted cubic splines (RCS).
RCS analysis revealed a significant age-dependent decline in TFQI-fT3 values, with an inflection point at 48 years (p<0.001); TFQI-fT4 showed a similar but attenuated trend. For metabolic outcomes, increased fT3 sensitivity (TFQI-fT3 Q1) was associated with lower MetS risk in older adults (>48 years) (OR 0.79, 95% CI 0.65-0.97, p=0.023), whereas no significant association was observed in younger adults (≤48 years) (all p>0.05). For cardiovascular outcomes, higher fT3 sensitivity was associated with reduced risk of abnormal ST segments in both age groups (younger: OR 0.57, 95% CI 0.32-0.97, p=0.046; older: OR 0.68, 95% CI 0.48-0.95, p=0.027). Conversely, decreased fT4 sensitivity (TFQI-fT4 Q4) specifically increased abnormal ST-segment risk in older adults (OR 1.43, 95% CI 1.04-1.96, p=0.025), with no significant effect in younger adults (OR 1.11, 95% CI 0.65-1.82, p=0.693).
Enhanced HPT axis sensitivity to fT3 increased with age (inflection point at 48 years in this study) and was associated with a lower prevalence of metabolic syndrome (in >48-year-olds) and ST-segment abnormalities (all adults).
Lei Zhao, R. Mu, Xin Zhang et al.· Frontiers in Endocrinology· 0 citations
Aims: Sex differences in cardiac electrophysiology and cardiovascular (CV) risk are well established, but the extent to which circulating hormonal markers contribute to electrocardiogram (ECG) morphology remains unclear. We investigated whether hormone-related ECG components are associated with incident CV events and whether these associations differ by sex and menopausal status. Methods: In a prospective cohort (N=8,056 UK Biobank participants; median follow-up: 12.8 years), we first evaluated direct associations between sex hormones and incident CV disease. Based on initial risk signals, two-stage analyses focused on premenopausal females and males. Linear regressions evaluated associations between standardized hormonal markers and residualized lead-I ECG parameters after confounders adjustment. Cox proportional hazards models then tested whether the hormone-predicted ECG components were associated with incident CVD events. Results: In premenopausal females (N=980), higher free androgen index (FAI) was positively associated with QRS amplitude ({beta}=19.17V, p-value=0.038) and the FAI-predicted QRS amplitude component was associated with incident CVD (Hazard Ratio [HR]=1.41, p-value=0.02). In males (N=3,997), FAI was inversely associated with QTc duration ({beta}=-0.95ms, p-value=0.005), and its predicted component with increased CVD risk (HR=1.32, p-value<0.001). Conversely, higher sex hormone-binding globulin (SHBG) prolonged QTc, with its predicted component also conferring risk (HR=1.15, p-value=0.004). Additionally, FAI directly associated with ST segment deviation ({beta}=19.17V), whose predicted component was protective (HR=0.76, p-value<0.001). Conclusions: This study shows that SHBG and FAI subtly modulate specific depolarization and repolarization ECG parameters. Relative androgen excess in premenopausal females and lower androgenic status in males appear to be associated with subclinical electrophysiological variations linked to long-term CV risk.
A. Hernández, J. Madrid, C. Sánchez et al.· medRxiv· 0 citations
Background Endogenous sex steroid hormones are involved in numerous regulatory mechanisms of the cardiovascular system and their imbalances are frequently observed in patients with established cardiovascular disease (CVD). However, their prognostic significance for mortality remains unclear. This study aims to systematically synthesize existing research and quantify the association between endogenous sex steroid hormones, sex hormone binding globulin (SHBG), and the risk of all-cause and cardiovascular mortality in individuals with established CVD. Methods Six bibliographic databases were systematically searched. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model, comparing the highest versus lowest levels of sex hormones/SHBG. The risk of bias was evaluated using the ROBINS-E tool (Risk Of Bias In Non-randomized Studies - of Exposures). Results Twelve studies with a total of 5,981 patients with established CVD were included. No significant association was found between endogenous total testosterone and risk of all-cause ((HR (95%CI): 0.78 (0.56 to 1.09), n= 5 studies) or CVD (HR (95%CI): 1.30 (0.28 to 6.01), n= 3) mortality in men. Most studies (seven out of twelve studies) were classified as having a high risk of bias, particularly due to confounding. Conclusions We found no evidence for an association between endogenous sex hormones and mortality outcomes in patients with CVD. This study underscored the lack of sufficient evidence on this topic, especially concerning women. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42022329605, identifier CRD42022329605.
Mojgan Amiri, H. Raeisi-Dehkordi, S. Beigrezaei et al.· Frontiers in Endocrinology· 0 citations
Background Lower testosterone is often observed with abnormal glucose-lipid metabolism, but the clinical value of calculated testosterone fractions in metabolic assessment remains uncertain. This study evaluated cross-sectional associations of total testosterone (TT), calculated free testosterone (FT), free testosterone percentage (FT%), bioavailable testosterone (BioT), bioavailable testosterone percentage (BioT%), and sex hormone-binding globulin (SHBG) with glucose-lipid traits in male andrology outpatients. Methods This single-center retrospective cross-sectional analysis included 420 adult male andrology outpatients with complete records for TT, SHBG, albumin, glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Age-adjusted partial Spearman correlations, rank-standardized regression, SHBG-adjusted models, restricted cubic spline analysis, age-stratified interaction analysis, sensitivity analyses, and exploratory machine learning-assisted validation were performed. Results TT was inversely associated with glucose and TG and positively associated with HDL-C. FT% and BioT% were positively associated with TG and inversely associated with HDL-C, but these associations were markedly attenuated or reversed after additional adjustment for SHBG. Restricted cubic spline models supported approximately linear associations of TT with glucose, TG, and HDL-C. In machine learning-assisted validation, adverse glucose-lipid metabolic status was present in 285 participants (67.9%). The Age + TT + SHBG model and XGBoost showed modest discrimination, with AUCs of 0.691 and 0.688, respectively. SHAP analysis suggested SHBG and age were the strongest model contributors, but this ranking should be interpreted as exploratory because correlated predictors can affect SHAP-based importance estimates. Conclusions In male andrology outpatients, lower TT was associated with an adverse glucose-lipid profile, particularly higher glucose and TG and lower HDL-C. Percentage-based calculated testosterone indices appeared to reflect SHBG-dependent redistribution of circulating testosterone rather than an independent favorable androgen state. Machine learning-assisted validation further supported the interpretive importance of SHBG, although prediction performance remained exploratory. These findings should be interpreted within a single-center outpatient cohort and should not be generalized directly to the broader male population.
Miao-Miao Ma, Qi Zhang, Zu-Long Wang et al.· Frontiers in Endocrinology· 0 citations
Background The cardio-kidney-metabolic (CKM) syndrome, recently conceptualized by the American Heart Association (AHA) in 2023, integrates cardiovascular, renal, and metabolic dysfunction into a unified staging framework. To date, no study worldwide has examined the association between parity and CKM syndrome stages. Fertility history may influence long-term metabolic health through hormonal fluctuations, inflammatory responses, and cumulative physiological stress. This cross-sectional design cannot support causal inference. Methods We analyzed 4,814 women aged 45 years and older with complete blood biomarker data from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2018). CKM stages were classified using objective biomarkers including cystatin C-based estimated glomerular filtration rate (eGFR). Parity was categorized as 0, 1, 2 (reference), 3, 4–5, and 6 or more. Poisson regression with robust standard errors estimated adjusted prevalence ratios (aPR). Restricted cubic splines (RCS) assessed dose-response relationships. Exploratory factor analysis identified multimorbidity patterns. Multiple imputation by chained equations (MICE) addressed missing data. Results The prevalence of CKM Stage 2 or higher was 53.2%. Parity demonstrated a U-shaped association with CKM syndrome. Compared with parity = 2, aPRs were: parity = 1: 0.88 (95% CI: 0.75–1.02, P = 0.078); parity 6 or more: 0.87 (95% CI: 0.74–1.03, P = 0.110). RCS analysis confirmed a nonlinear dose-response with the nadir at parity = 2–3 (Wald P = 0.042). Factor analysis revealed three multimorbidity patterns: respiratory-cardio-arthritic (beta = + 0.026, P = 0.001), cardio-metabolic (beta approximately 0, P = 0.98), and digestive-arthritic-renal (beta = + 0.014, P = 0.020). MICE analysis (n = 7,236) confirmed directionally consistent findings. Conclusions Parity exhibits a U-shaped association with CKM syndrome in Chinese middle-aged and older women, suggesting a "healthy mother effect" with dual protective pathways. These findings support integrating fertility history into sex-specific CKM risk assessment.
Jia-Ping Lu, Heng Xu, Qiu-Lian Xu· Research Square· 0 citations
Abstract Introduction The cardiovascular effects of hormone replacement therapy (HRT) remain controversial. This study investigated HRT‐associated atherosclerotic cardiovascular disease (ASCVD) risk, focusing on reproductive characteristics. Material and Methods This prospective cohort study analyzed 170 250 women aged 40–69 years from UK Biobank (2006–2024). Cox proportional hazards regression models were employed to estimate ASCVD risk, with stratification by reproductive characteristics (age at menarche, age at menopause, and menopausal status) and age groups (≤45, 46–55, >55 years). Mediation analysis was conducted to examine potential biological pathways through sex hormones, inflammatory markers, and lipid profiles. All analyses were adjusted for demographic factors, socioeconomic status, lifestyle factors, and reproductive history. Results During follow‐up, 11 357 women (6.67%) developed ASCVD. HRT users demonstrated elevated ASCVD risk (adjusted HR 1.13, 95% CI 1.08–1.18, p < 0.001), primarily from increased ischemic stroke. Risk varied by reproductive characteristics: late menarche showed highest risk (HR 1.15, 95% CI 1.08–1.24), followed by late menopause (HR 1.25, 95% CI 1.01–1.54). Perimenopause demonstrated the most pronounced elevation (HR 1.28, 95% CI 1.12–1.46). Women ≤45 years had 77% higher ASCVD risk with HRT use. Dose–response relationships between HRT duration (≥5 years) and ASCVD risk were observed (p overall = 0.009, p nonlinear = 0.004). Mediation analysis revealed minimal indirect effects through traditional biomarkers (<2%), suggesting direct vascular mechanisms. Conclusions HRT increases ASCVD risk with substantial variation by reproductive characteristics. Findings support reproductive profile‐based cardiovascular risk assessment for personalized HRT prescribing.
Meng-Chun Wang, Can Zhang, Chunlai Yang et al.· Acta Obstetricia et Gynecolo...· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
