Search Results (1,732)

Background/Objectives: Adolescence is a critical period for the early detection of metabolic syndrome (MetS), a condition that increases the risk of cardiometabolic diseases in adulthood. Timely identification of at-risk adolescents enables targeted prevention strategies. This study aimed to analyze the discriminative capacity and accuracy of six biochemical and/or anthropometric indices related to lipid metabolism and adiposity for the early detection of MetS in a sample of Spanish adolescents. Methods: A cross-sectional study carried out according to the STROBE guidelines. A sample of 981 adolescents aged 11–16 years old were randomly recruited from schools in Southeastern Spain. The presence or absence of MetS was determined according to the International Diabetes Federation criteria. The following biochemical and/or anthropometric indices were evaluated: triglyceride glucose index, visceral adiposity index, logarithm children’s lipid accumulation product, triglyceride glucose-body mass index, triglyceride glucose-waist circumference, and triglyceride glucose-waist-to-hip ratio. Results: The triglyceride glucose-waist-to-hip ratio and triglyceride glucose-body mass index parameters were the strongest indicators associated with MetS in boys and girls, respectively, after adjusting for several factors. Moreover, all evaluated indices showed optimal AUC values, with the visceral adiposity index and triglyceride glucose-waist circumference index exhibiting the highest discriminative capacity in both genders. Conclusions: The evaluated biochemical and anthropometric indices—particularly visceral adiposity index and triglyceride-glucose-waist circumference—show promise as accessible biomarkers for identifying adolescents at metabolic risk. These indices may serve as practical tools in preventive health strategies aimed at improving metabolic health by screening adolescents at risk of MetS, thereby helping to reduce the future burden of non-communicable diseases. Full article

Background/Objectives: Frailty is a prevalent geriatric syndrome associated with impaired postural control and elevated fall risk. Although conventional exercise is a core strategy for frailty management, adherence remains limited. Virtual reality (VR)-based interventions have emerged as potentially engaging alternatives, but their effects on objective postural control and task-specific confidence in frail populations remain understudied. This study aimed to evaluate the effectiveness of a supervised VR training program using the Nintendo Ring Fit Plus™ on postural control, functional mobility, and balance confidence among frail community-dwelling older adults. Methods: Fifty-one adults aged ≥65 years classified as frail or prefrail were enrolled in a four-week trial. Participants were assigned to either a VR intervention group (n = 28) or control group (n = 23). Participants were non-randomly assigned based on availability and preference. Outcome measures were collected at baseline and post-intervention. Primary outcomes included center of pressure (CoP) metrics—sway area, mean velocity, and sway path. Secondary outcomes were the Timed Up and Go (TUG), Berg Balance Scale (BBS), Activities-specific Balance Confidence (ABC), and Falls Efficacy Scale–International (FES-I). Results: After adjusting for baseline values, age, and BMI, the intervention group showed significantly greater improvements than the control group across all postural control outcomes. Notably, reductions in sway area, mean velocity, and sway path were observed under both eyes-open and eyes-closed conditions, with effect sizes ranging from moderate to very large (Cohen’s d = 0.57 to 1.61). For secondary outcomes, significant between-group differences were found in functional mobility (TUG), balance performance (BBS), and balance confidence (ABC), with moderate-to-large effect sizes (Cohen’s d = 0.53 to 0.73). However, no significant improvement was observed in fear of falling (FES-I), despite a small-to-moderate effect size. Conclusions: A supervised VR program significantly enhanced postural control, mobility, and task-specific balance confidence in frail older adults. These findings support the feasibility and efficacy of VR-based training as a scalable strategy for mitigating frailty-related mobility impairments. Full article

Background: Polycystic ovary syndrome (PCOS) is a complex and multifactorial disorder affecting reproductive, endocrine, and metabolic functions in women of reproductive age. While environmental and lifestyle factors play a role, increasing evidence highlights the contribution of genetic and epigenetic mechanisms to its pathogenesis. Objective: This narrative review aims to provide an updated overview of the current evidence regarding the role of genetic variants, gene expression patterns, and epigenetic modifications in the etiopathogenesis of PCOS, with a focus on their impact on ovarian function, fertility, and systemic alterations. Methods: A comprehensive search was conducted across MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Library using MeSH terms including “PCOS”, “Genes involved in PCOS”, and “Etiopathogenesis of PCOS” from January 2015 to June 2025. The selection process followed the SANRA quality criteria for narrative reviews. Seventeen studies published in English were included, focusing on original data regarding gene expression, polymorphisms, and epigenetic changes associated with PCOS. Results: The studies analyzed revealed a wide array of molecular alterations in PCOS, including the dysregulation of SIRT and estrogen receptor genes, altered transcriptome profiles in cumulus cells, and the involvement of long non-coding RNAs and circular RNAs in granulosa cell function and endometrial receptivity. Epigenetic mechanisms such as the DNA methylation of TGF-β1 and inflammation-related signaling pathways (e.g., TLR4/NF-κB/NLRP3) were also implicated. Some genetic variants—particularly in DENND1A, THADA, and MTNR1B—exhibit signs of positive evolutionary selection, suggesting possible ancestral adaptive roles. Conclusions: PCOS is increasingly recognized as a syndrome with a strong genetic and epigenetic background. The identification of specific molecular signatures holds promise for the development of personalized diagnostic markers and therapeutic targets. Future research should focus on large-scale genomic studies and functional validation to better understand gene–environment interactions and their influence on phenotypic variability in PCOS. Full article

Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients. Full article

Cardiorenal syndrome (CRS) is a term used to describe the combined dysfunction of the heart and kidneys. This complex disorder is widely acknowledged to be challenging in both its diagnosis and management, and this is the case particularly in the elderly population, due to multi-morbidity, polypharmacy, and age-related physiological changes. Given advancements in medicine and more prolonged cumulative exposure to risk factors in the elderly population, it is likely that the prevalence of chronic kidney disease (CKD) and heart failure (HF) will continue to rise going forward. Hence, understanding the mechanisms involved in the development of CRS is paramount. There are five different CRS types—they are categorised depending on the primary organ involved the acuity of disease. The pathophysiological process behind CRS is complex, involving the interplay of many processes including hemodynamic changes, neurohormonal activation, inflammation, oxidative stress, and endothelial dysfunction and vascular stiffness. The numerous diagnostic and management challenges associated with CRS are significantly further exacerbated in an elderly population. Biomarkers used to aid the diagnosis of CRS, such as serum creatinine and brain natriuretic peptide (BNP), can be challenging to interpret in the elderly population due to age-related renal senescence and multiple comorbidities. Polypharmacy can contribute to the development of CRS and therefore, before initiating treatment, coordinating a patient-centred, multi-speciality, holistic review to assess potential risks versus benefits of prescribed treatments is crucial. The overall prognosis of CRS in the elderly remains poor. Treatments are primarily directed at addressing the sequelae of the underlying aetiology, which often involves the removal of fluid through diuretics or ultrafiltration. Careful considerations when managing elderly patients with CRS is essential due to the high prevalence of frailty and functional decline. As such, in these patients, early discussions around advance care planning should be prioritised. Full article

Sarcopenia, characterized by progressive skeletal muscle loss and functional decline, represents a major public heath challenge in aging populations. Despite increasing awareness, current management strategies—primarily resistance exercise and nutritional support—remain limited by accessibility, adherence, and inconsistent outcomes. This underscores the urgent need for novel, effective, and scalable therapeutics. Flavonoids, a diverse class of plant-derived polyphenolic compounds, have attracted attention for their muti-targeted biological activities, including anti-inflammatory, antioxidant, metabolic, and myogenic effects. This review aims to evaluate the anti-sarcopenic potential of selected flavonoids—quercetin, rutin, kaempferol glycosides, baicalin, genkwanin, isoschaftoside, naringin, eriocitrin, and puerarin—based on recent preclinical findings and mechanistic insights. These compounds modulate key pathways involved in muscle homeostasis, such as NF-κB and Nrf2 signaling, AMPK and PI3K/Akt activation, mitochondrial biogenesis, proteosomal degradation, and satellite cell function. Importantly, since muscle wasting also features prominently in cancer cachexia—a distinct but overlapping syndrome—understanding flavonoid action may offer broader therapeutic relevance. By targeting shared molecular axes, flavonoids may provide a promising, biologically grounded approach to mitigating sarcopenia and the related muscle-wasting conditions. Further translational studies and clinical trials are warranted to assess their efficacy and safety in human populations. Full article

Metabolic dysfunction-associated fatty liver disease (MASLD) is a chronic, non-communicable spectrum of diseases characterized by lipid accumulation. It is often asymptomatic, and its prevalence varies by region, age, gender, and economic status. It is estimated that 25% of the world’s population currently suffer from MAFLD, and 20 million patients will die from MAFLD-related diseases. In the last 20 years, tea and anti-obesity research have indicated that regularly consuming tea decreases the risk of cardiovascular disease, stroke, obesity, diabetes, and metabolic syndrome (MeS). In this review, we aimed to present studies concerning the influence of matcha extracts and epigallocatechin-3 gallate (EGCG) supplements on metabolic functions in the context of MAFLD in human and animal studies. The published data show promise. In both human and animal studies, the beneficial effects on body weight, cholesterol levels, and liver metabolism and function were noted, even in short-period experiments. The safety levels for EGCG and green tea extract consumption are marked. More experiments are needed to confirm the results observed in animal studies and to show the mechanisms by which green tea exerts its effects. The preliminary data from research concerning microbiota or epigenetic changes observed after polyphenols and green tea consumption need to be expanded. To improve the efficiency and availability of green tea or supplement consumption as a treatment for MAFLD patients, more research with larger groups and longer study durations is needed. Full article

Introduction: Congestive heart failure (CHF), a complex clinical syndrome characterized by the heart’s inability to pump blood effectively due to structural or functional impairments, is a growing public health concern, with profound implications for patients’ physical and emotional well-being. In India, the burden of CHF is rising due to aging demographics and increasing prevalence of lifestyle-related risk factors. Among the subtypes of CHF, heart failure with preserved ejection fraction (HFpEF), i.e., heart failure with left ventricular ejection fraction of ≥50% with evidence of spontaneous or provokable increased left ventricular filling pressure, and heart failure with reduced ejection fraction (HFrEF), i.e., heart failure with left ventricular ejection fraction of 40% or less and is accompanied by progressive left ventricular dilatation and adverse cardiac remodeling, may present differing impacts on health-related quality of life (HRQoL), i.e., an individual’s or a group’s perceived physical and mental health over time, yet comparative data remains limited. This study assesses HRQoL among CHF patients using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), one of the most widely used health-related quality of life questionnaires for patients with heart failure based on physical and emotional dimensions and identifies sociodemographic and clinical variables influencing these outcomes. Methods: A cross-sectional analytical study was conducted among 233 CHF patients receiving inpatient and outpatient care at the Department of Cardiology at a quaternary care teaching hospital in coastal Karnataka in India. Participants were enrolled using convenience sampling. HRQoL was evaluated through the MLHFQ, while sociodemographic and clinical characteristics were recorded via a structured proforma. Statistical analyses included descriptive measures, independent t-test, Spearman’s correlation and stepwise multivariable linear regression to identify associations and predictors. Results: The mean HRQoL score was 56.5 ± 6.05, reflecting a moderate to high symptom burden. Patients with HFpEF reported significantly worse HRQoL (mean score: 61.4 ± 3.94) than those with HFrEF (52.9 ± 4.64; p < 0.001, Cohen’s d = 1.95). A significant positive correlation was observed between HRQoL scores and age (r = 0.428; p < 0.001), indicating that older individuals experienced a higher burden of symptoms. HRQoL also varied significantly across NYHA functional classes (χ² = 69.9, p < 0.001, ε² = 0.301) and employment groups (χ² = 17.0, p < 0.001), with further differences noted by education level, gender and marital status (p < 0.05). Multivariable linear regression identified age (B = 0.311, p < 0.001) and gender (B = –4.591, p < 0.001) as significant predictors of poorer HRQoL. Discussion: The findings indicate that patients with HFpEF experience significantly poorer HRQoL than those with HFrEF. Older adults and female patients reported greater symptom burden, underscoring the importance of demographic-sensitive care approaches. These results highlight the need for routine integration of HRQoL assessment into clinical practice and the development of comprehensive, personalized interventions addressing both physical and emotional health dimensions, especially for vulnerable subgroups. Conclusions: CHF patients, especially those with HFpEF, face reduced HRQoL. Key factors include age, gender, education, employment, marital status, and NYHA class, underscoring the need for patient-centered care. Full article

Background: Aicardi-Goutières Syndrome (AGS) is a rare neuroinflammatory condition characterized by early-onset symptoms that extend outside the nervous system. Due to the rarity of the disease, the pathogenesis is not well understood, and its diagnosis and treatment remain elusive. We recently demonstrated mitochondrial abnormalities and increased reactive oxygen species (ROS) levels in lymphoblastoid cell lines (LCLs) derived from RNASEH2B- and RNASEH2A-mutated AGS patients. On this background, we turned our attention to metformin, the first-choice drug for type 2 diabetes, as a possible treatment acting on oxidative stress in RNASEH2-mutant AGS cells. Methods and Results: By means of flow cytometry, we found that metformin treatment significantly decreases ROS production in RNASEH2B- and RNASEH2A-mutated AGS LCLs. Of note, metformin treatment reduces the green JC-1 monomeric signal and, concurrently, increases the red JC-1 signal in both mutated LCLs, accounting for restoration of the mitochondrial membrane potential. Immunofluorescence staining shows a decrease in 8-oxoG levels only in RNASEH2B- mutated AGS LCLs. Finally, the significant upregulation of Forkhead Box O3 (FOXO3), cytochrome C somatic (CYCS), and superoxide dismutase 2 (SOD2) mRNA levels in RNASEH2B-mutated AGS LCLs after metformin treatment points to FOXO3 signaling as a possible mechanism to reduce oxidative stress. Conclusions: In conclusion, even if these pilot results need to be confirmed on a larger cohort, we shed light on metformin treatment as a valid approach to ameliorate oxidative stress-related inflammation in AGS patients. Full article

Familial dysbetalipoproteinemia (FD) is a prevalent and highly atherogenic hyperlipoproteinemia associated with the ε2/ε2 APOE genotype or rare APOE variants. The contributions of additional genetic and clinical factors to the FD phenotype remain unclear. We investigated these factors in both autosomal recessive and autosomal dominant forms of FD. Targeted (n = 4666) and exome (n = 194) sequencing were used to identify the ε2/ε2 APOE genotype or rare FD-causative APOE variants. Twenty-four lipid-related genes and forty variants included in a polygenic risk score for hypertriglyceridemia (HTG) were analyzed. FD was defined by the presence of FD variants and triglycerides (TG) ≥ 1.5 mmol/L (main study group). The comparison group consisted of patients with FD variants but TG < 1.5 mmol/L. Univariable and multivariable regression analyses were performed. A total of 71 unrelated subjects were identified (45.1% male, median age 50 years). FD was diagnosed in 52 patients, while 19 had FD variants only. Age (p = 0.019), elevated polygenic risk for HTG (p = 0.001), and the presence of metabolic syndrome components (p = 0.014) were independently associated with the FD phenotype. TG levels were significantly associated with polygenic burden (0.05 mmol/L per percentile), the presence of additional rare lipid-related variants (7.0 mmol/L), and glucose metabolism disorders (3.62 mmol/L), together explaining 30% of TG variance in cross-validated model. These results highlight the interplay of genetic and metabolic factors in FD development and support the integration of HTG genetic risk scores and metabolic control into personalized FD management. Full article

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Risk factors for EC include metabolic alterations (obesity, metabolic syndrome, insulin resistance), hormonal imbalance, age at menopause, reproductive factors, and inherited conditions, such as Lynch syndrome. For the inherited forms, several genes had been implicated in EC occurrence and development, such as POLE, MLH1, TP53, PTEN, PIK3CA, PIK3R1, CTNNB1, ARID1A, PPP2R1A, and FBXW7, all mutated at high frequency in EC patients. However, gene function impairment is not necessarily caused by mutations in the coding sequence of these and other genes. Gene function alteration may also occur through post-transcriptional control of messenger RNA translation, frequently caused by microRNA action, but transcriptional impairment also has a profound impact. Here, we review how chromatin modifications change the expression of genes whose impaired function is directly related to EC etiopathogenesis. Chromatin modification plays a central role in EC. The modification of chromatin structure alters the accessibility of genes to transcription factors and other regulatory proteins, thus altering the intracellular protein amount. Thus, DNA structural alterations may impair gene function as profoundly as mutations in the coding sequences. Hence, its central importance is in the diagnostic and prognostic evaluation of EC patients, with the caveat that chromatin alteration is often difficult to identify and needs investigations that are specific and not broadly used in common clinical practice. The different phases of the healthy endometrium menstrual cycle are characterized by differential gene expression, which, in turn, is also regulated through epigenetic mechanisms involving DNA methylation, histone post-translational modifications, and non-coding RNA action. From a medicolegal and policy-making perspective, the implications of using epigenetics in cancer care are briefly explored as well. Epigenetics in endometrial cancer is not only a topic of biomedical interest but also a crossroads between science, ethics, law, and public health, requiring integrated approaches and careful regulation. Full article

Background/Objectives: This study aims to uncover the variables related to the success of the intervention. Methods: A retrospective study was conducted on patients who underwent joint replacement surgery utilizing a customized alloplastic system between 2018 and 2023, comprising subjects with complete records for both the planning and follow-up phases. The Student’s t-test was applied with a significance threshold of p < 0.05. Results: Forty-eight subjects were admitted for initial analysis, and 31 subjects were evaluated with a minimum follow-up of 1 year and a maximum of 7 years, with a mean age of 36.37 ± 15.53. The TMJ diagnosis was mainly with degenerative TMJ disease, followed by ankylosis and craniofacial syndromes, and an average of 2.1 ± 1.2 previous surgeries were noted. Degenerative joint disease correlated with increased pain (p < 0.0001) and a higher prevalence of prior joint surgery (p < 0.0001). Thirty-one subjects were followed up with 47 prostheses installed; 74.4% underwent complementary surgery with other facial osteotomies. Significant improvements (p < 0.0001) were observed when comparing pain levels pre- and postoperatively, with a decrease from 5.5 (±2.3) to 2.2 (±0.4). Concerning the interincisal opening, there was a significant increase (p < 0001) from 25.85 (±10.2) mm to 35.93 (±4.2) mm in mouth opening. TMJ replacement treatment is efficient and effective, demonstrating stability in follow-up assessments for up to 7 years. Conclusions: The indications for replacement are diverse and may benefit patients who have not yet progressed to end-stage TMJ disease. Full article

Organ functions generally decline with age, but the ovary is a prototypical organ that undergoes functional loss over time. Autophagy plays a crucial role in maintaining organ homeostasis, and age-related upregulation of the autophagy inhibitor protein, Rubicon, has been linked to cellular and tissue dysfunction. This review describes how granulosa cell autophagy supports follicular growth and oocyte selection and maturation by regulating cellular energy metabolism and protein quality control. We then introduce the role of selective autophagy, including mitophagy or lipophagy, in steroidogenesis and cellular remodeling during luteinization. In aged ovaries, Rubicon accumulation suppresses autophagic flux, leading to diminished oxidative-stress resilience and enhanced DNA damage. Moreover, impaired autophagy drives the accumulation of ATP citrate lyase, which correlates with poor oocyte quality and reduced ovarian reserve. Following fertilization, oocytes further upregulate autophagy to provide the energy required for blastocyst transition. Conversely, in infertility-related disorders, such as premature ovarian insufficiency, endometriosis, and polycystic ovary syndrome, either deficient or excessive autophagy contributes to disease pathogenesis. Both autophagy inhibitors (e.g., Rubicon) and activators (e.g., Beclin1) could be emerging as promising biomarkers for assessing ovarian autophagy status. Therapeutically, Rubicon inhibition by trehalose in aged ovaries and autophagy suppression by agents such as hydroxychloroquine in polycystic ovary syndrome and endometriosis hold potential. Establishing robust methods to evaluate ovarian autophagy will be essential for translating these insights into targeted treatments. Full article

This narrative review examines the effects of caffeine on brain health in older adults, with particular attention to its potential for dependence—an often-overlooked issue in geriatric care. Caffeine acts on central adenosine, dopamine, and glutamate systems, producing both stimulating and rewarding effects that can foster tolerance and habitual use. Age-related pharmacokinetic and pharmacodynamic changes prolong caffeine’s half-life and increase physiological sensitivity in the elderly. While moderate consumption may enhance alertness, attention, and possibly offer neuroprotective effects—especially in Parkinson’s disease and Lewy body dementia—excessive or prolonged use may lead to anxiety, sleep disturbances, and cognitive or motor impairment. Chronic exposure induces neuroadaptive changes, such as adenosine receptor down-regulation, resulting in tolerance and withdrawal symptoms, including headache, irritability, and fatigue. These symptoms, often mistaken for typical aging complaints, may reflect a substance use disorder yet remain under-recognized due to caffeine’s cultural acceptance. The review explores caffeine’s mixed role in neurological disorders, being beneficial in some and potentially harmful in others, such as restless legs syndrome and frontotemporal dementia. Given the variability in individual responses and the underestimated risk of dependence, personalized caffeine intake guidelines are warranted. Future research should focus on the long-term cognitive effects and the clinical significance of caffeine use disorder in older populations. Full article

Background: The most common female endocrinopathy is polycystic ovary syndrome (PCOS), affecting 10–20% of women of reproductive age. It is associated with a wide range of hormonal and biochemical abnormalities and long-term metabolic and cardiovascular risks. It is characterized by infertility due to chronic anovulation, hyperandrogenism, polycystic ovarian morphology, and is often associated with insulin resistance (IR) and obesity. Hyperinsulinemia further increases androgen production and reduces sex hormone-binding globulin (SHBG) levels, thereby aggravating symptoms. In addition, vitamin D deficiency is often present in PCOS patients, and increasing evidence suggests that it may also be associated with insulin resistance and hyperandrogenism. Objective: This study aimed to evaluate the relationships between insulin resistance, vitamin D deficiency, body mass index (BMI), and androgen levels in women with PCOS. Method: A cross-sectional study was conducted in which data from 195 women diagnosed with PCOS and not yet receiving therapy at a gynecologic endocrinology unit of a university-based tertiary clinical center, between 2019 and 2024, were analyzed. The parameters recorded were age, body mass index (BMI), 25(OH) vitamin D levels, androgen hormone levels (testosterone, androstenedione), glucose-insulin responses during a 3-point oral glucose tolerance test (OGTT). Statistical analyses, including linear regression, Pearson, and Spearman correlation tests were used to assess associations between variables. Results: The mean age of the patients was 24.8 years (18–42), and the mean BMI was 30.6 kg/m² (17–51). Vitamin D deficiency was observed in 84.1% of patients, hyperandrogenism in 45.8%, and insulin resistance in 44.5%. A significant inverse correlation was found between BMI and vitamin D levels (r = −0.31, p =< 0.01) indicating that higher BMI is associated with lower vitamin D status. Similarly, BMI also showed a significant negative correlation with SHBG levels (r = –0.45, p < 0.01), suggesting that increasing body weight is linked to reduced SHBG concentrations. In addition, BMI was significantly positively correlated with 2 h insulin levels (r = 0.43, p =< 0.01) and with testosterone levels (r = 0.21, p = 0.01). These findings suggest that increased adiposity intensifies insulin resistance and is linked to both vitamin D deficiency and elevated androgen levels. Moreover, the combination of hyperinsulinemia and low vitamin D further disrupts hormonal balance by promoting ovarian androgen production and decreasing SHBG levels, thereby increasing the bioavailability of testosterone. A significant inverse correlation was found between vitamin D levels and 2 h insulin levels (r = −0.28, p =< 0.01), indicating that lower vitamin D status is associated with increased insulin resistance. Furthermore, 2 h insulin levels showed a significant positive correlation with testosterone levels (r = 0.32, p =< 0.01), suggesting that greater insulin resistance is linked to higher androgen production. Additionally, vitamin D levels were inversely correlated with testosterone (r = −0.18, p = 0.02), demonstrating that a lower vitamin D status may further contribute to the hyperandrogenic environment. Vitamin D levels also showed a significant positive correlation with SHBG concentrations (r = 0.29, p < 0.01), indicating that a higher vitamin D status may be associated with increased SHBG levels. In contrast, 2 h insulin levels were inversely correlated with SHBG (r = −0.43, p < 0.01), reflecting the suppressive effect of hyperinsulinemia on SHBG production. Conclusions: Insulin resistance, BMI, and vitamin D deficiency are closely related to each other and to the severity of PCOS, which is confirmed by the correlations with androgen levels. The revealed relationships draw attention to the special importance of vitamin D supplementation and the correction of carbohydrate metabolism in alleviating the symptoms of the disease and reducing long-term health risks. Full article