Search Results (93)

Background and Objectives: Ticagrelor reduces ischemic events in acute coronary syndrome (ACS) but increases bleeding risk. Clinical predictors of bleeding are well established; the contribution of cytochrome P450 polymorphisms involved in ticagrelor metabolism remains uncertain, with conflicting reports in the literature. We examined the association of CYP3A4* 22 (rs 35599367), CYP3A5* 3 (rs 776746), and CYP4F2 (rs3093135) with bleeding in a Serbian ACS cohort. Materials and Methods: This prospective, single- center observational study enrolled 105 consecutive ACS patients undergoing percutaneous coronary intervention (PCI) or medical management after coronary angiography and receiving dual antiplatelet therapy (DAPT) with acetylsalicylic acid and ticagrelor at the University Clinical Center Niš between January 2024 and the end of May 2025. Bleeding events occurring during the index hospitalization and the six-month follow-up were classified according to the Bleeding Academic Research Consortium (BARC) criteria. Genotyping used TaqMan assays. Associations with bleeding were assessed using Firth’s penalized logistic regression, with multivariable adjustment for age and renal function. Severity-stratified analyses and gradient-boosted machine learning (XGBoost with SHAP) were performed as exploratory analyses. Results: Thirteen patients (12.4%) experienced bleeding (nine minor [BARC 1/2], four major [BARC 3/5]). Age ≥ 75 years (univariable OR 7.62, p = 0.001) and eGFR < 60 mL/min/1. 73 m ² (OR 3.68, p = 0.006) were the strongest predictors. CYP3A5 *1 carrier status was univariably associated with bleeding (OR 4.16, p = 0.043) but did not remain significant after adjustment for age and renal function, and *1 carriers were significantly older and more likely to have impaired renal function. No genotype was associated with major (BARC 3/5) bleeding. The apparent effect was concentrated in minor bleeding (BARC 1/2 rate: 30.8% versus 5.5%), with no major events among *1 carriers. CYP 3 A 4* 22 (OR 1.37, p = 0.109) and CYP 4 F 2 (OR 1.17, p = 0.111) showed no association. Machine-learning analyses confirmed eGFR and age as the dominant predictors. Conclusions: In this Serbian ACS cohort, clinical factors—particularly advanced age and impaired renal function—dominated the prediction of bleeding risk. The CYP3A5 signal was largely explained by baseline imbalances in age and renal function. CYP 3 A 4* 22 and CYP 4 F 2 polymorphisms did not contribute additional predictive information. Preemptive genotyping for these variants is unlikely to materially improve bleeding-risk assessment beyond standard clinical evaluation in patients of this type. Full article

Background: Obesity is a chronic endocrine–metabolic disorder. The risk of comorbidities increases with a higher body mass index (BMI), particularly when BMI ≥ 35.0 kg/m². Common complications include insulin resistance, type 2 diabetes, dyslipidemia, and chronic low-grade inflammation, which collectively impair DNA stability by promoting the formation of genotoxic species. Methods: This non-randomised, quasi-experimental clinical intervention study included 53 participants (both sexes) with a BMI ≥ 35.0 kg/m², who were assigned to parallel experimental or control streams based on clinical needs and institutional eligibility. During a three-week intervention, the experimental group received a hospital-supervised very-low-calorie diet (VLCD; ~600 kcal/day) under continuous medical monitoring. Conversely, the control group followed a standard reduced-calorie diet (SRD) of 1500 kcal/day in a free-living home environment. Before and after the intervention, primary, oxidative, and permanent DNA damage were measured using alkaline, FPG-modified comet (peripheral blood mononuclear cells), and cytokinesis-block micronucleus cytome assays (phytohaemagglutinin-stimulated binucleated lymphocytes), alongside anthropometric and biochemical tracking. Results: Within-group evaluations revealed that both dietary regimens improved several metabolic health indicators, notably modulating insulin resistance, lipid profiles, and leukocyte counts. However, participants in the VLCD stream experienced significantly greater downward changes in body weight, BMI, and absolute lipid values. Crucially, the VLCD intervention was associated with a highly significant within-group reduction in parameters of permanent chromosomal damage, effectively halving the frequencies of micronuclei and nuclear buds, independent of baseline variations, in adjusted multivariate regression models. Conversely, the home-based SRD regimen demonstrated no measurable impact on permanent genomic damage. Neither diet induced a significant change in repairable primary or oxidative DNA lesions over this short timeframe. Conclusions: These exploratory findings suggest that strict calorie restriction can rapidly stabilise genome stability in advanced clinical settings, warranting future randomised controlled trials with long-term longitudinal follow-up to assess permanent risk reductions. Due to structural baseline variations in age, chronic comorbidities, and compliance environments between the cohorts, direct comparative superiority cannot be definitively established. Full article

Background: Type 1 diabetes mellitus (T1D) is associated with chronic inflammation, platelet-related alterations, and increased cardiovascular risk (CVR). The relationships between adipokines and platelet indices in long-standing T1D remain incompletely defined. Objective: To explore the relationships between adipokines (adiponectin and leptin), platelet indices, and inflammatory status in adults with long-standing T1D. Methods: This cross-sectional study included 124 adults with long-standing T1D and 59 non-diabetic controls. Platelet indices were obtained from automated blood count, and serum leptin (LEP), adiponectin (ADNC), and C-reactive protein (CRP) were measured using standardized assays. Associations were evaluated using correlation and multivariable regression analyses with adjustment for body mass index (BMI). Results: Platelet count (PLT) and plateletcrit (PCT) were higher in T1D compared with non-diabetic individuals (p = 0.003 for both), while mean platelet volume (MPV) and platelet distribution width (PDW) showed non-significant upward trends. ADNC levels were higher in T1D (p < 0.001), whereas LEP and the leptin–adiponectin ratio (LAR) did not differ between groups. In T1D, LEP correlated with PLT (rho = 0.235), PCT (rho = 0.263), and CRP (rho = 0.474), all p < 0.05. Similar associations were observed for LAR. No significant associations were found in non-diabetic controls. In multivariable analyses, PCT remained associated with LEP in T1D after adjustment for BMI, whereas in the control group, LEP was associated with BMI only. Conclusions: LEP and platelet-related indices were associated in individuals with long-standing T1D, whereas ADNC showed no such relationships. These findings suggest a distinct pattern of adipokine–platelet associations in long-standing T1D. Full article

Objective: To investigate maternal serum silent information regulator-2 protein 1 (SIRT1) levels in pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP) and evaluate their diagnostic performance. Methods: This prospective case–control study included 44 pregnant women with ICP and 44 healthy pregnant controls matched according to gestational age at blood sampling and maternal body mass index. Maternal serum SIRT1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Clinical, laboratory, and obstetric outcomes were compared between groups. Correlation, receiver operating characteristic (ROC) curve, and exploratory multivariable logistic regression analyses were performed. Results: Maternal serum SIRT1 levels were significantly lower in the ICP group compared with controls [1.06 (1.05) ng/mL vs. 1.54 (1.74) ng/mL, p = 0.005]. ROC analysis demonstrated modest discriminative performance of maternal serum SIRT1 alone for identifying ICP (AUC: 0.674, 95% CI: 0.559–0.788, p = 0.005). A SIRT1 cut-off value of ≤1.28 ng/mL yielded 63.6% sensitivity and 60.5% specificity. In contrast, ALT alone showed excellent discriminative performance (AUC: 0.927, 95% CI: 0.860–0.995, p < 0.001). Combined ROC analyses demonstrated further improvement with the ALT + albumin model (AUC: 0.962, 95% CI: 0.925–0.999), whereas addition of SIRT1 resulted in only a minimal incremental increase in AUC to 0.966 (95% CI: 0.933–0.998). Maternal serum SIRT1 concentrations were not independently associated with ICP after adjustment for laboratory parameters. Conclusions: Although maternal serum SIRT1 levels were significantly reduced in pregnancies complicated by ICP, their diagnostic performance was modest and provided minimal incremental value beyond conventional biochemical markers. Nevertheless, reduced maternal serum SIRT1 concentrations may support the involvement of inflammatory and oxidative stress-related pathways in ICP pathophysiology and warrant further mechanistic investigation. Full article

Background and Objectives: Psoriasis is a chronic immune-mediated inflammatory disease characterized by heterogeneous clinical presentation and variable response to biologic therapy. Genetic variation within the IL-23/Th17 inflammatory pathway may influence treatment outcomes. This study evaluated the association between IL12B rs3213094 and IL23R rs11209026 single-nucleotide polymorphisms (SNPs) and response to biologic therapy in patients with moderate-to-severe psoriasis. Materials and Methods: We conducted a multicenter observational study including 92 Romanian patients with moderate-to-severe psoriasis vulgaris receiving their first biologic therapy (anti-TNF, anti-IL-17, or anti-IL-23 monoclonal antibodies). Clinical response was assessed using the Psoriasis Area and Severity Index (PASI) at baseline and weeks 12, 24, 36, and 48. Early response was defined as achieving PASI75 at week 12. Patient-reported disease impact was assessed using the Dermatology Life Quality Index (DLQI) at the same time points. Genotyping of IL12B rs3213094 and IL23R rs11209026 was performed using TaqMan assays. Longitudinal PASI dynamics were analyzed using repeated-measures ANOVA, while multivariable logistic regression was used to identify independent predictors of PASI75 at week 12. Results: A significant reduction in PASI scores over time was observed (p < 0.001). The IL12B rs3213094 genotype was associated with differences in early response kinetics, with T-allele carriers showing significantly greater PASI improvement at week 12 compared with CC homozygotes (90.0% vs. 65.7%, p = 0.003). This effect was limited to early treatment and attenuated at later time points. In multivariable analysis, the IL12B rs3213094 CT + TT genotype was independently associated with PASI75 achievement at week 12 (OR = 4.285, 95% CI 1.500–12.239, p = 0.007). Treatment with anti-IL-17 agents was also an independent predictor of early response (OR = 3.946, 95% CI 1.416–10.998, p = 0.009). No significant association was observed between IL23R rs11209026 and treatment response. DLQI scores improved significantly over time (p < 0.001), without genotype-dependent differences. Conclusions: IL12B rs3213094 SNP is significantly associated with early biologic treatment response in psoriasis, supporting its potential role as a pharmacogenetic biomarker of treatment responsiveness. These findings may inform the integration of genetic markers into personalized therapeutic strategies, particularly in underrepresented populations such as those from Eastern Europe. Further studies in larger cohorts are warranted to validate these results. Full article

Objectives: Diminished ovarian reserve (DOR) significantly compromises in vitro fertilization (IVF) success. Although systemic markers such as anti-Müllerian hormone (AMH) serve as valuable clinical indicators of the ovarian reserve, they lack the sensitivity to reflect the qualitative deterioration of the follicular microenvironment. Therefore, in this study, we aimed to characterize the inflammatory proteome of follicular fluid (FF) to establish a high-performance auxiliary diagnostic model for DOR. Methods: Utilizing the ultra-sensitive Olink proximity extension assay, we quantified 92 inflammation-related proteins in the FF of 88 participants (67 with DOR and 21 normal controls). Differentially expressed proteins (DEPs) were identified, and their relationships with key clinical indices were evaluated. A robust predictive signature was refined through integrated Least Absolute Shrinkage and Selection Operator (LASSO) regression and Random Forest algorithms, with diagnostic performance assessed via 10-fold cross-validation. Results: Thirty-five DEPs were significantly dysregulated in the FF of patients with DOR, demonstrating strong associations with serum AMH and basal estradiol concentrations. A minimized diagnostic panel comprising four core proteins, adenosine deaminase (ADA), vascular endothelial growth factor A (VEGFA), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and matrix metalloproteinase-1 (MMP-1), was established. This multivariable model achieved an excellent area under the receiver operating characteristic curve (AUC) of 0.953. Conclusions: The identified four-protein signature reflects localized chronic inflammation and early pathophysiological shifts in the DOR follicular microenvironment. As a high-performance molecular index, this panel could complement conventional systemic assessments, provide a reliable means of evaluating follicular viability, and optimize individualized therapeutic strategies. Full article

Background and Objectives: Endothelial dysfunction is essential in the development and progression of coronary artery disease (CAD) and its complications. Galectin-3 mediates inflammation and organ fibrosis and promotes endothelial dysfunction. Meanwhile, the vascular reactivity index (VRI) reflects endothelial function. The purpose of this research was to evaluate the association between serum galectin-3 levels and VRI in patients diagnosed with CAD. Materials and Methods: One hundred and eighteen patients with CAD were enrolled. Endothelial function was noninvasively evaluated using digital thermal monitoring, and VRIs were obtained. According to VRI values, patients were classified into good (≥2.0), intermediate (1.0–1.9), and poor (<1.0) subgroups. Galectin-3 levels were quantified using an enzyme-linked immunosorbent assay. Results: Patients with poor vascular reactivity were older in age (p = 0.028) and had higher serum total cholesterol (p = 0.003), low-density lipoprotein cholesterol (p = 0.005), and galectin-3 (p < 0.001) levels. Multivariable stepwise linear regression analysis revealed galectin-3 as an independently associated factor of lower VRIs (β = −0.488; p < 0.001). Logistic regression model confirmed that galectin-3 independently was associated with higher odds of vascular reactivity dysfunction (odds ratio, 1.120; 95% confidence interval, 1.016–1.235; p = 0.023) or poor vascular reactivity (odds ratio, 1.445; 95% confidence interval, 1.179–1.772; p < 0.001). Conclusions: Serum galectin-3 is independently associated with reduced VRIs and endothelial dysfunction in patients with CAD. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with chronic low-grade inflammation. Interleukin-39 (IL-39), a newly identified cytokine, has been implicated in immune regulation; however, its role in PCOS remains unclear. This study aimed to evaluate serum IL-39 levels in patients with PCOS and its potential as an adjunctive inflammatory biomarker candidate. Methods: This case–control study included 44 patients with PCOS diagnosed according to the Rotterdam criteria and 44 age-matched in the control group. Serum IL-39 levels were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory parameters were recorded. Group comparisons were performed using appropriate parametric and non-parametric tests. Correlation analysis was conducted using Spearman’s coefficient. Multivariable logistic regression analysis was performed to identify independent predictors of PCOS. Receiver operating characteristic (ROC) analysis was used to assess discriminative performance. Results: Serum IL-39 levels were significantly higher in the PCOS group compared to control group (p < 0.001). No significant correlations were observed between IL-39 and other clinical or laboratory parameters. In multivariable analysis, IL-39 was independently associated with PCOS. ROC analysis showed that IL-39 had moderate discriminative ability (AUC = 0.74), with 68% sensitivity and 70% specificity. The combined model including IL-39, body mass index (BMI), luteinizing hormone (LH), and age demonstrated improved performance (AUC = 0.78), with higher sensitivity (86%) and negative predictive value (81%). Conclusions: IL-39 levels are elevated in PCOS and may represent a potential adjunctive inflammatory biomarker candidate. Its diagnostic performance improves when combined with other clinical parameters, supporting a multivariable approach in PCOS evaluation. Full article

Background: Gestational diabetes mellitus (GDM) is a common metabolic disorder characterized by glucose intolerance and associated with adverse maternal and fetal outcomes. Emerging evidence suggests that oxidative stress and hypoxia-related pathways may contribute to its pathophysiology. This study aimed to evaluate the diagnostic performance of serum sestrin-2 (SESN-2) and hypoxia-inducible factor-1alpha (HIF-1α) as potential biomarkers in GDM. Methods: In this case–control study, 100 pregnant women (50 with GDM and 50 controls) were enrolled. Serum SESN-2 and HIF-1α levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: Patients with GDM showed significantly higher body mass index, glucose levels, glycated hemoglobin (HbA1c), insulin, and C-reactive protein (CRP) (all p < 0.05). SESN-2 and HIF-1α levels were significantly elevated (both p < 0.0001). Receiver operating characteristic (ROC) analysis showed area-under-the-curve (AUC) values of 0.799 for SESN-2 and 0.769 for HIF-1α, which increased to 0.909 when combined. Both biomarkers were independently associated with GDM in multivariable analysis. Conclusions: SESN-2 and HIF-1α levels are elevated in GDM and are associated with its presence. These biomarkers demonstrated moderate diagnostic performance, and their combined use improved discrimination; however, they should be considered complementary rather than standalone diagnostic tools. Given the cross-sectional design, the findings reflect associations rather than predictive relationships, and further prospective studies are required to clarify their clinical utility. Full article

Objectives: CD93, an angiogenesis-related transmembrane glycoprotein, is transcriptomically downregulated in uterine corpus endometrial carcinoma, yet circulating protein levels have not been clinically evaluated. This study aimed to evaluate serum CD93 as a diagnostic biomarker for EC and to examine its association with clinicopathological parameters. Methods: In this single-center case–control study, serum CD93 concentrations were measured by enzyme-linked immunosorbent assay in 46 patients with histologically confirmed primary EC and 35 controls with histologically verified benign gynecological pathology. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. Results: Serum CD93 was significantly lower in EC patients than controls (median 4.55 [IQR 3.51–6.97] vs. 10.24 [7.18–12.14] ng/mL; p < 0.001). In multivariable analysis adjusted for age and body mass index, lower CD93 remained independently associated with EC (OR = 0.521; 95% CI 0.061–0.720; p < 0.001). ROC analysis yielded an area under the curve of 0.845 (95% CI 0.759–0.921), with 82.6% sensitivity and 74.3% specificity at a cut-off of 7.338 ng/mL. CD93 levels showed no significant association with histological subtype, grade, lymphovascular space invasion, nodal metastasis, or recurrence. Conclusions: Serum CD93 is significantly reduced in EC and demonstrates independent diagnostic performance, supporting its prospective validation as a non-invasive biomarker in larger multicenter cohorts. Full article

Background: Chronic viral hepatitis is a major global health problem associated with progressive liver injury and an increased risk of cirrhosis and hepatocellular carcinoma. The identification of novel biomarkers may improve disease monitoring and diagnostic accuracy. Methods: In this prospective case–control study, a total of 90 participants were included: 20 patients with chronic hepatitis B (CHB); 20 with chronic hepatitis C (CHC); 20 with HBeAg-negative chronic infection (HCI); and 30 age-, sex-, and body mass index-matched healthy controls. Serum irisin and nesfatin-1 levels were measured using enzyme-linked immunosorbent assays (ELISAs). Group comparisons were performed using multivariate analysis of variance (MANOVA) followed by Scheffé post hoc tests. Receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic performance. Results: Significant differences were observed among groups in terms of irisin, nesfatin-1, total bilirubin, and platelet counts (p ≤ 0.05). Nesfatin-1 levels were significantly higher in all patient groups compared with healthy controls (p < 0.001). Irisin levels were only significantly lower in the HCI group (p < 0.001). ROC analysis indicated that nesfatin-1 may have the potential to discriminate between infected patients and healthy individuals; however, the generalizability of this finding is limited by the study design and sample size. Conclusions: Nesfatin-1 may represent a potential biomarker for chronic viral hepatitis, whereas alterations in irisin levels may be more specific to the inactive carrier phase. Full article

Background/Objectives: Appetite-regulating hormones are bioactive components of human milk. We tested the associations of leptin and adiponectin with infant growth and eating behaviors to age 6 months. Methods: In a cohort of 70 healthy, full-term infants and their mothers, human milk adiponectin and leptin were assayed at age 2 months (m). At infant ages 2, 4, and 6 m, infant anthropometry was obtained, mothers reported feeding frequency, duration, and breastfeeding intensity and completed the Baby Eating Behavior Questionnaire (Enjoyment of Food, Food Responsiveness, and General Appetite), and infant sucking vigor using an artificial nipple (burst duration and sucking frequency) was measured. Mothers reported demographics, gestational diabetes and pre-pregnancy body mass index (BMI), gestational age, and infant birthweight. Multivariate models evaluated predictors of leptin and adiponectin, and associations of leptin and adiponectin with infant growth and eating behaviors. Results: Human milk leptin was predicted by maternal BMI (β = 0.02) and breastfeeding intensity (β = −0.32). Regarding infant growth, infant weight-for-age and weight-for-length z-scores at 6 m were predicted by leptin (β = 0.91 and β = 1.22, respectively) and adiponectin (β = 0.01 and β = 0.01, respectively). Regarding infant eating behaviors, feeding duration at 2 m and feeding frequency at 4 m were predicted by adiponectin (β = 0.03 and β = −0.02, respectively). Conclusions: Human milk leptin and adiponectin may contribute to weight gain in early infancy, but the effect does not appear to be mediated substantially by infant eating behaviors. Further investigation into the metabolic programming of early infant weight gain is warranted. Full article

Background and Objectives: Peripheral arterial disease (PAD) is highly prevalent in patients with end-stage renal disease and is associated with adverse cardiovascular outcomes. Although the ankle–brachial index (ABI) is widely used to identify PAD, it may not fully reflect the complex vascular pathophysiology in patients undergoing peritoneal dialysis (PD). Antibodies against oxidized low-density lipoprotein (anti-oxLDL Ab) have been implicated in atherogenesis; however, their clinical relevance in PD populations remains unclear. Materials and Methods: In this cross-sectional investigation, 90 patients receiving maintenance PD were included. PAD was defined by an ABI below 0.90, and serum anti-oxLDL antibody concentrations were quantified using an enzyme-linked immunosorbent assay. Results: Patients with PAD were older (p = 0.006), had a higher prevalence of diabetes (p = 0.010), and exhibited higher levels of triglycerides (p = 0.008), fasting glucose (p < 0.001), and C-reactive protein (CRP, p < 0.001), but lower anti-oxLDL Ab levels (p = 0.008). Multivariable logistic regression demonstrated that reduced anti-oxLDL Ab levels (per 10 mU/mL increase, odds ratio [OR]: 0.803, 95% confidence interval [CI]: 0.648–0.995, p = 0.045) and increased CRP levels (per 0.1 mg/dL increase, OR: 1.662, 95% CI: 1.152–2.398, p = 0.007) were independently associated with PAD, with consistent results across penalized regression models. Log-transformed anti-oxLDL Ab levels were positively correlated with both left and right ABI values (p = 0.005 and p = 0.017, respectively). Decision curve analysis indicated that the anti-oxLDL Ab-based model provided greater net benefit compared with the treat-all and treat-none strategies across a range of threshold probabilities. Conclusions: Reduced serum anti-oxLDL Ab levels are independently associated with PAD in patients undergoing PD. Serum anti-oxLDL Ab levels are positively associated with ABI values. These findings suggest that impaired immunity against oxidized LDL may contribute to vascular disease in PD patients. Full article

Background and Objectives: Although conventional semen analysis remains central in male infertility evaluation, the biological relationship between sperm morphology and genomic integrity remains incompletely defined. Sperm DNA fragmentation (SDF) has emerged as a clinically relevant marker of genomic instability; however, its relationship with composite morphological indices of spermatogenic dysfunction remains debated. This study aimed to evaluate the relationship between sperm DNA fragmentation assessed in the post-swim-up fraction and composite sperm morphological indices derived from raw semen, using a multivariable analytical framework that accounts for conventional semen parameters. Materials and Methods: This observational study included 183 semen samples from men undergoing fertility evaluation. SDF was assessed using a sperm chromatin dispersion (SCD)-based assay in the post-swim-up fraction. Sperm morphology was evaluated in raw semen according to World Health Organization criteria, and composite morphological indices, namely the Teratozoospermia Index (TZI), Sperm Deformity Index (SDI), and Multiple Anomalies Index (MAI), were calculated. Associations were examined using Spearman correlation and multivariable linear regression models adjusted for sperm concentration and progressive motility. Exploratory distributional analyses were performed across clinically defined SDF categories. Results: Bivariate analyses demonstrated weak, non-significant positive correlations between SDF and all composite morphological indices. None of the morphological indices independently predicted SDF after adjustment for sperm concentration and progressive motility in multivariable regression models. In contrast, sperm concentration showed a consistent inverse association with SDF. Distributional analyses revealed substantial overlap between morphological severity and SDF categories, indicating heterogeneity in the co-occurrence of structural abnormalities and DNA fragmentation at the individual sample level. Conclusions: Composite sperm morphological indices were not independently associated with sperm DNA fragmentation after adjusting for quantitative semen parameters in the present analytical framework. These findings suggest that structural abnormalities and genomic instability may capture complementary aspects of male infertility rather than representing interchangeable markers. SDF assessment may therefore provide complementary diagnostic information beyond morphology-based evaluation, particularly in assisted reproductive contexts. Full article

Background: This study aimed to investigate the relationship between serum neuroactive steroids (NAS) and oxytocin and craving and psychosocial functioning in men diagnosed with methamphetamine use disorder (MUD). Methods: In this observational cross-sectional study, 40 men with MUD (PG) and 41 non-substance-use-disorder controls (CG) completed measures of emotion dysregulation (DERS-16), attachment (ECR-R), aggression (BPAQ), and suicidal ideation (BSS). PG additionally completed the Substance Craving Scale (SCS) and Addiction Profile Index (API). Serum allopregnanolone (ALLO), DHEAS, testosterone, 17β-estradiol (E2), and oxytocin were assayed. Results: The results indicated that the PG exhibited significantly higher scores than the CG across all psychological measures. Robust adjusted group effects were observed for DERS-16 (Model 1: F = 35.507, p < 0.001; Model 2: F = 18.225, p < 0.001) and trait anger (Model 1: F = 41.104, p < 0.001; Model 2: F = 16.732, p < 0.001). Notably, serum levels of ALLO, DHEAS, testosterone, E2, and oxytocin did not differ significantly between groups. However, hormonal measures were strongly intercorrelated within both groups (r ≈ 0.877–0.936, all p < 0.001). In the PG, craving demonstrated positive correlations with DHEAS (r = 0.384, p = 0.014), testosterone (r = 0.415, p = 0.008), E2 (r = 0.360, p = 0.023), and oxytocin (r = 0.350, p = 0.027). A multivariable model analyzing craving was statistically significant (R² = 0.350; F(3,36) = 6.474, p = 0.001), with composite hormonal factor (B = 2.390, p = 0.016) serving as an independent predictor, while API Excluding Craving(API-EC) (p = 0.094) and DERS-16 did not emerge as a significant factor (p = 0.056). In hormone-specific models controlling for API-EC and DERS-16, DHEAS (p = 0.012), testosterone (p = 0.007), oxytocin (p = 0.023), and E2 (p = 0.023) retained significance after false discovery rate (FDR) correction; ALLO did not (p = 0.055). Conclusions: Despite the absence of significant differences in peripheral NAS and oxytocin levels between groups, men with MUD exhibited pronounced psychosocial impairments. The craving experienced during inpatient treatment was primarily elucidated by an integrated endocrine profile. These findings underscore the necessity for larger longitudinal studies incorporating repeated hormonal assessments to further explore these relationships. Full article