Search Results (1,349)

Peripheral nerves provide a direct connection between the brain and the tumor microenvironment. This connection allows the nervous system to influence processes associated with the development, progression, and metastasis of different tumor types. Therefore, tumor innervation by peripheral nerve fibers is currently emerging as a characteristic that contributes to multiple hallmarks of cancer. Several experimental studies have shown that cancer progression involves actively inducing the ingrowth of autonomic and sensory nerve fibers into tumor tissue. In this process, known as neoaxonogenesis, cancer and other cells in the tumor microenvironment play an important role by synthesizing and releasing neurotrophic factors (e.g., nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor), axonal guidance molecules (netrins, semaphorins, ephrins, slits), exosomes (containing microRNA and axonal guidance molecules), and other molecules present in the tumor microenvironment (e.g., granulocyte colony-stimulating factor, leukemia inhibitory factor), which modulate the ingrowth of nerve fibers into the tumor. This results in an increased nerve supply to tumor tissue, which is primarily linked to its growth. However, there are also studies demonstrating the protective effects of increased nerve fiber density against processes associated with cancer progression in certain types of cancer. The findings from these studies contribute to the complexity of neuro-cancer interactions, which is probably based on the type of cancer and the physiological specializations of the nerve fibers in a given organ. Despite contrasting findings, the stimulatory effects of nerve fibers on cancer growth are supported by several studies that described reducing the negative impact of nerve fibers on tumors and thus inhibiting cancer progression. The most significant approaches to reducing neural effects appear to be denervation, the administration of neurotransmitter receptor antagonists, the administration of local anesthetics, and the administration of antibodies against neurotrophic factors. Other significant approaches include methods that improve quality of life, such as psychotherapy and heart rate variability biofeedback. Despite their therapeutic potential, there are several limitations to using approaches that manipulate cancer innervation in clinical practice. These limitations include impaired normal tissue function and nervous system function, as well as the problematic direct application of the therapeutic agent to the tumor site, dosage-dependent, cancer type-dependent, cancer stage-dependent, duration-dependent, and timing-dependent effects. Procedures that modify neoaxonogenesis and nerve fiber signaling appear to be a promising new therapeutic approach in oncology. However, more research is needed to better understand their effects on cancer progression. In the future, the assessment of the presence and density of nerve fibers in tumors, as well as the evaluation of approaches aimed at reducing their negative impact, could be part of personalized anticancer therapy. As part of this therapy, a fresh tumor sample would be collected from the patient to generate patient-derived organoid models to test and consider the possibility of using supportive therapy and to predict its efficacy. Based on these results, it would be possible to evaluate the applicability of nerve-fiber-targeted therapy for a given patient. This review article summarizes and describes the current knowledge concerning the significance of nerve fibers in cancer progression, with a particular emphasis on neoaxonogenesis in tumors and the various factors that influence this process. Full article

Backgrounds: The aim of this pilot study was to evaluate the hierarchical contribution of individual genetic polymorphisms to the variability of autonomic regulation parameters and respiratory function in athletes of different sport specializations using Classification and Regression Tree (CRT) analysis. Methods: The study included athletes divided into two groups: hockey players (n = 48) and martial artists (n = 43). Heart rate variability (LF, HF) parameters and spirometric indices (FEV₁) were assessed. Genetic analysis included 8 single nucleotide polymorphisms (SNPs): IL6 rs1800795, VDR rs731236, KCNJ11 rs5219, ADRB2 rs1042713, ADRB2 rs1042714, TRHR rs16892496, MSTN rs1805086, UCP3 rs1800849. Results: In martial artists, the main predictors were genes responsible for adrenoreceptor sensitivity (ADRB2) and neuroimmune interactions (IL6). In hockey players, the most significant predictors were genes involved in muscle growth (MSTN), energy metabolism (UCP3), and neuroendocrine regulation (TRHR). These findings indicate that similar resting HRV parameters in athletes from different sports may be associated with different genetic polymorphisms, reflecting sport-specific physiological adaptations to training loads. Conclusions: The results highlight the sport-specific nature of genetic determinants of autonomic regulation. In martial artists, genes related to the immuno-adrenergic axis (IL6, ADRB2) appear to play a dominant role, whereas in hockey players neuroendocrine, muscle-metabolic, and mitochondrial factors (TRHR, MSTN, UCP3) demonstrate greater influence. The observed interactions between genotypes and FEV₁ emphasize the importance of transitioning from generalized approaches toward personalized monitoring strategies in sports science. Full article

Heart rate variability (HRV) is a key physiological marker for autonomic nervous system function and cardiovascular health. Photoplethysmography (PPG) is commonly used to derive HRV metrics in wearable and low-cost monitoring systems. This study presents a comparative assessment of basic HRV metrics obtained from a MAX30102 optical sensor and a custom analog circuitry with an ADS1115 analog-to-digital converter (ADC). Both measurement pathways were carefully aligned using analog high-pass and low-pass filters and a consistent digital filtering pipeline, ensuring that the frequency bands relevant to HRV were preserved. PPG signals were recorded simultaneously, and inter-beat intervals were extracted to calculate the Standard Deviation of NN intervals (SDNN), Root Mean Square of Successive Differences (RMSSD), and Percentage of successive NN intervals >50 ms (pNN50) across multiple 30-s windows. Bland–Altman analysis was employed to evaluate agreement between the two methods. Results indicate that the analog circuit with an ADS1115 achieves comparable HRV basic metrics to the MAX30102 sensor, with improved Signal-to-Noise Ratio (SNR) due to high-resolution ADC and low-noise analog amplification. These findings demonstrate that a carefully designed analog acquisition system can reliably reproduce HRV basic parameters from PPG signals, providing an alternative approach for low-cost, flexible biosensing platforms. Full article

Heart rate variability (HRV) has emerged as a key biomarker for assessing autonomic nervous system activity, stress, fatigue, and emotional states. With the rapid development of wearable sensor technologies, HRV analysis has expanded from clinical environments to real-world, continuous monitoring. This review summarizes current applications of HRV metrics in wearable devices, including fitness tracking, mental stress assessment, sleep quality evaluation, and early detection of physiological or psychological disorders. Recent advances in photoplethysmography (PPG)-based HRV estimation have enabled noninvasive and user-friendly measurement, though challenges remain in accuracy under motion and variable environmental conditions. We also discuss methodological considerations, such as artifact correction, data segmentation, and the integration of HRV with other biosignals for multimodal analysis. Emerging research suggests that combining HRV with metrics such as respiration rate, skin conductance, and accelerometry can enhance robustness and interpretability in dynamic settings. Finally, future directions are proposed toward personalized health analytics, emotion-aware computing, and real-time adaptive feedback systems. This review highlights the growing potential of wearable HRV analysis as a foundation for preventive healthcare and human–machine symbiosis. Full article

This study examined the within-session (same-day) test–retest reliability of heart rate (HR) and parasympathetic modulation, assessed using the root mean square of successive differences (RMSSD), across exercise and recovery phases in trained soccer players. Twenty-seven male soccer players (age: 24.9 ± 3.7 years) completed a standardized soccer training session. HR and RMSSD were recorded using an ECG-based chest-strap monitor at rest, pre-exercise, and at ~10–20 min, 1 h, and 3 h post-exercise. At each time point, two consecutive 5 min seated recordings were obtained under identical conditions. Test–retest reliability was evaluated using intraclass correlation coefficients (ICC_(3,1)), standard error of measurement (SEM), coefficient of variation (CV%), minimal detectable change (MDC₉₅), paired-samples t-tests, and Hedges’ g effect sizes. HR demonstrated excellent reliability across all time points (ICC = 0.980–0.994; SEM = 0.87–1.25 bpm; CV% = 1.33–3.70%). RMSSD showed excellent reliability at rest (ICC = 0.944) and pre-exercise (ICC = 0.918), moderate reliability during early recovery (~10–20 min; ICC = 0.551), and good reliability at 1 h (ICC = 0.826) and 3 h post-exercise (ICC = 0.873). No significant systematic differences were observed between test and retest measurements (all p > 0.05), and effect sizes were trivial. These findings indicate that within-session reliability of HR remains consistently high across exercise and recovery phases, whereas RMSSD reliability varies according to measurement timing, particularly during early recovery. Full article

Background/Objectives: Constipation is a common gastrointestinal problem in older adults and is associated with reduced quality of life, functional decline, frailty, and an increased risk of delirium and cognitive impairment. Its pathogenesis is multifactorial, involving age-related changes in gastrointestinal motility, neural regulation, comorbidities, and polypharmacy. However, this condition has traditionally been regarded as a localized gastrointestinal disorder, which may not fully reflect its systemic clinical significance in older populations. While prior narrative reviews have described multifactorial contributors to constipation, none have formally applied a geriatric syndrome framework to integrate these dimensions. This review proposes a three-criterion operational definition—multifactorial pathogenesis, association with functional decline and frailty, and contribution to adverse systemic outcomes—to characterize constipation in older adults as a “systemic geriatric syndrome,” and evaluates available evidence against each criterion. Methods: A narrative literature search was conducted using PubMed to identify relevant studies published between 1 January 2023, and 31 December 2025. MeSH terms included “Constipation” [Major Topic] and “Aged” [MeSH Terms]. Eligible articles included English-language original studies, systematic reviews, and clinical or epidemiological studies involving individuals aged ≥65 years. Results: Diagnosis in older adults is often complicated by secondary causes, including medications and neurological disorders, as well as atypical symptom presentations in individuals with cognitive impairment. Key pathophysiological mechanisms include reductions in interstitial cells of Cajal, impaired smooth muscle contractility, dysfunction of the enteric and autonomic nervous systems, and gut microbiota dysbiosis, which may promote chronic low-grade inflammation. Major contributing factors include physical inactivity, sarcopenia, dehydration, inappropriate defecation posture, and polypharmacy, particularly opioids and anticholinergic agents. Importantly, these factors interact through the brain–gut–microbiota axis, contributing not only to gastrointestinal dysfunction but also to systemic outcomes such as frailty, cognitive decline, and increased healthcare burden, thereby supporting a multidimensional disease framework. Conclusions: The available evidence collectively supports the plausibility of framing constipation in older adults as a systemic geriatric syndrome, though formal validation of this classification requires further longitudinal and mechanistic research. Comprehensive and individualized management strategies, extending beyond simple laxative use, are essential to reduce complications and preserve functional health in aging populations. Further studies are required to validate this framework. Full article

Background and Objectives: Fibromyalgia syndrome (FMS) is frequently accompanied by autonomic symptoms and autonomic dysregulation, which may influence ocular blood flow regulation. The choroid is a densely vascular, autonomically innervated tissue, and optical coherence tomography (OCT)-derived markers have been used to explore potential ocular microvascular changes in FMS, with inconsistent findings. The choroidal vascularity index (CVI), defined as the proportion of luminal area within the total choroidal area, has been proposed as a potentially more robust marker of choroidal vascular status than thickness alone. We aimed to compare CVI and choroidal thickness between patients with FMS and healthy controls and examine the association between autonomic symptom burden and CVI in FMS. Materials and Methods: This single-centre observational cross-sectional case–control study enrolled adults aged 18–65 years. Swept-source OCT was performed; low-quality scans were excluded, and only right eyes were analysed. CVI, subfoveal maximum and mean choroidal thickness were obtained using an artificial intelligence-assisted analysis platform. Autonomic symptom burden, fibromyalgia impact, and central sensitization-related symptoms were assessed using the Composite Autonomic Symptom Score-31 (COMPASS-31), the Revised Fibromyalgia Impact Questionnaire (FIQ-R), and the Central Sensitization Inventory (CSI), respectively. Group comparisons, Spearman correlations, and multivariable linear regression were performed. Results: COMPASS-31, FIQ-R, and CSI scores were higher in the FMS group (all p < 0.001). CVI and choroidal thickness did not differ significantly between groups (CVI p = 0.124; maximum thickness p = 0.136; mean thickness p = 0.097). CVI was not correlated with COMPASS-31, FIQ-R, or CSI within either group. In adjusted models, age was independently associated with CVI (p < 0.001), whereas FMS status and COMPASS-31 total score were not. Conclusions: CVI and choroidal thickness were similar in FMS and controls, and CVI was not associated with self-reported autonomic symptom burden in FMS. Studies incorporating objective autonomic testing and dynamic vascular imaging paradigms are warranted. Full article

Chronic inflammation contributes to bladder cancer (BC) development and progression through dysregulated cytokine signaling and tumor–immune interactions. This case–control study investigated associations between IL6 rs1800795, TNF rs1800629, CCL2 rs1024611, and VEGFA rs699947 polymorphisms, circulating cytokine levels, clinicopathological characteristics, and autonomic nervous system balance assessed by heart rate variability (HRV) in 73 BC patients and 88 controls. Genotyping was performed using PCR–RFLP, serum cytokine levels were measured by ELISA, and associations were evaluated using logistic, linear regression, and survival analyses. No significant associations with BC risk were observed for IL6, TNF, or VEGFA variants. However, the CCL2 rs1024611 GG genotype was associated with increased BC risk (recessive model: OR = 5.82, p = 0.026). Stratified analyses showed a lower frequency of the IL6 rs1800795 C allele and TNF rs1800629 GA genotype in high-grade and muscle-invasive tumors, suggesting potential associations with reduced tumor aggressiveness. No polymorphism was associated with serum cytokine levels or disease-free survival. In BC patients, the TNF rs1800629 A allele was associated with higher parasympathetic-related HRV indices and lower sympathetic parameters, whereas no such associations were observed in controls. These findings indicate that genetic variation within inflammatory pathways may contribute to BC susceptibility and tumor phenotype and may also modulate neuroimmune interactions. Full article

Background: Benign prostatic hyperplasia (BPH) can be associated with lower urinary tract symptoms (LUTS) and potential avlterations in autonomic nervous system function, as reflected by heart rate variability (HRV). This observational study was designed to generate hypotheses regarding the differential impacts of surgical de-obstruction versus uroselective pharmacological blockade on autonomic nervous system equilibrium, HRV restoration, and symptomatic outcomes in men with BPH and bladder outlet obstruction. Methods: Data from a prospective cohort of 242 men undergoing TURP and 210 men receiving tamsulosin were analyzed. HRV parameters (standard deviation of normal-to-normal intervals [SDNN], low-frequency/high-frequency [LF/HF] ratio, total power [TP], very low frequency [VLF]) and International Prostate Symptom Score (IPSS) was assessed at baseline and 12 weeks. Propensity score matching (PSM) was used to address baseline differences in age, prostate volume, IPSS, and baseline SDNN. Inter-group comparisons used ANCOVA with baseline as a covariate. Results: After TURP, SDNN increased by 14.70 ms (40%; 36.97 ± 22.80 to 51.67 ± 27.59 ms; p = 0.032; paired Cohen’s d = 0.58), LF/HF decreased by 0.90 (55%; 1.63 ± 1.60 to 0.73 ± 0.52; p = 0.028; d = −0.76), TP increased by 1303 ms² (95%; 1367 ± 820 to 2670 ± 1420 ms²; p = 0.025; d = 1.12), and VLF increased by 810 ms² (85%; 950 ± 560 to 1760 ± 980 ms²; p = 0.030; d = 1.01). For tamsulosin, SDNN increased by 6.73 ms (18%; 38.12 ± 12.50 to 44.85 ± 11.20 ms; p = 0.004; d = 0.57), LF/HF decreased by 0.16 (8%; 1.95 ± 0.65 to 1.79 ± 0.55; p = 0.012; d = −0.27), TP increased by 559 ms² (39%; 1453 ± 620 to 2012 ± 580 ms²; p = 0.006; d = 0.93), and VLF increased by 355 ms² (35%; 1020 ± 450 to 1375 ± 420 ms²; p = 0.010; d = 0.82). Secondary p-values (LF/HF, TP, VLF) were adjusted via the Benjamini–Hochberg method; adjusted p > 0.05 was used for some. Inter-group differences in changes were significant (ANCOVA p < 0.01; partial η² = 0.12–0.22 for group factor). TURP was associated with greater IPSS reduction (−10.2 points; 18.5 ± 6.2 to 8.3 ± 4.1; p < 0.001) compared to tamsulosin (−5.3 points; 15.8 ± 5.6 to 10.5 ± 4.8; p < 0.001; d = −1.02; inter-group p < 0.001). PSM confirmed these associations with p < 0.01 for HRV changes. Change in SDNN was associated with IPSS improvement in multivariate regression (standardized β = −0.42, p < 0.01). Conclusions: In this observational study, TURP was associated with greater changes in HRV parameters and symptomatic improvement compared to tamsulosin. These findings are hypothesis-generating and require confirmation in long-term randomized trials. Full article

Background: Dental treatment often requires prolonged mouth opening. This may compromise comfort during spontaneous nasal breathing and saliva swallowing, leading to stress or anxiety. A high-flow nasal cannula (HFNC) delivers warmed and humidified air at high flow rates and may improve breathing comfort; however, the feasibility of its routine use during dental treatment has not been established. Objectives: The primary objective of this pilot study is to evaluate the feasibility of conducting a definitive clinical trial to investigate the use of a HFNC during dental treatment. The secondary objective is to explore preliminary patient-centered outcomes related to stress and comfort to inform the design of future clinical trials. Methods: This single-center, open-label pilot feasibility study will be conducted at Nagasaki University Hospital, with adult patients undergoing routine full-mouth periodontal treatment participating in two treatment sessions, one without a HFNC and one with a HFNC, separated by at least four weeks. The primary feasibility outcomes include recruitment and retention rates, patient tolerance and acceptability of the HFNC, completeness of data collection, and device-related adverse events. The secondary outcomes are exploratory and include physiological stress-related parameters (pulse rate, respiratory rate, autonomic nervous system indices, and electroencephalographic alpha wave activity) and patient-reported comfort assessed using a questionnaire. Conclusions: This pilot study was designed to assess the feasibility and safety of HFNC use during full-mouth periodontal treatment and to inform the design of future definitive clinical trials. In particular, the resultant exploratory patient-centered outcomes and preliminary data may be used to guide outcome selection and sample size estimation. Full article

Motion sickness (MS), or kinetosis, is a condition experienced by some individuals in response to rhythmic or irregular body motion. Multiple studies have explored its neurobiological mechanisms and countermeasures, with the sensory-conflict hypothesis remaining the most accepted explanation. Heart-rate variability (HRV) and electrocardiography provide complementary autonomic nervous system perspectives that may support MS assessments. From an applied viewpoint, reliable HRV markers could enable the early detection and continuous monitoring of MS in real-world contexts, such as autonomous vehicles, where passenger comfort and safety are critical, motivating contact-free cardiac sensing for unobtrusive monitoring. This systematic review examines the value of HRV indices in MS, conducted under PRISMA guidelines across PubMed, Scopus, and the Web of Science. The included studies were grouped into four categories based on the methods used to induce MS: mechanical stimulus, real trip, visual stimulus, and virtual reality. Aggregated findings indicate that frequency–domain metrics, particularly the low frequency (LF)/high frequency (HF) ratio, HF power, and mean heart rate (mHR), are most frequently reported in relation to MS. Overall, autonomic dysregulation likely contributes to MS susceptibility, but standardized protocols are needed to validate HRV as a reliable marker. Full article

Background/Objectives: Poincaré plot analysis represents a nonlinear approach to heart rate variability (HRV) assessment, but the physiological meaning of several derived parameters remains unclear. This study aimed to evaluate associations between selected Poincaré plot-derived parameters, conventional HRV indices, and cardiovascular autonomic reflex tests in a real-world clinical population. Methods: This observational study included 269 adult patients referred for evaluation of suspected autonomic dysfunction. All participants underwent short-term resting ECG, cardiovascular autonomic reflex testing, and 24 h Holter ECG monitoring. Poincaré plot-derived parameters were analyzed in relation to short- and long-term HRV measures using the Spearman correlation with false discovery rate correction, and group comparisons were performed based on reflex test results. Results: Several Poincaré plot-derived parameters showed strong correlations with long-term HRV indices. VLI and LA were primarily associated with global and long-term autonomic variability, whereas VAI and SA were more closely related to parasympathetic modulation. Associations with short-term HRV were generally weak. Lower values of selected parameters were observed in patients with abnormal parasympathetic reflex tests, while no significant differences were found in relation to orthostatic hypotension. Conclusions: Poincaré plot-derived parameters capture complementary aspects of autonomic regulation beyond conventional HRV indices and may enhance autonomic phenotyping in clinical settings. Full article

Objective: This study aimed to investigate the acute effects of intermittent high-intensity badminton court exercise on cardiac autonomic modulation in male non-elite badminton players. Methods: This study employed a single-arm, repeated-measures experimental design, recruiting 25 healthy male collegiate badminton players. Participants completed five sets of high-intensity intermittent court tests until exhaustion, followed by calculation of stress index (SI), time-domain (RMSSD and SDNN), and frequency-domain (LF, HF, and LF/HF ratio) parameters at rest using a certified heart rate variability (HRV) analyzer. Repeated-measures ANOVA and effect size (partial η² and Hedges’ g) were used to assess changes and recovery trends of HRV parameters across time points: pre-test, immediate, 15 min, 24 h, and 48 h post-exercise. Results: (1) Stress index: The overall temporal trend showed statistical significance (p < 0.001, partial η² = 0.236, large effect size). Compared to pre-test, immediate and 15 min post-exercise increases were 8.24 (95% CI: 0.63–15.85) and 9.84 (95% CI: 3.07–16.61) respectively, with Hedges’ g values of 0.77 and 0.99 (p < 0.001, large effect sizes). Values returned to pre-test levels at 24 and 48 h with no significant differences (p > 0.05). (2) Time-domain parameters: The overall temporal trend was statistically significant (p < 0.001, partial η² = 0.553 for RMSSD and 0.586 for SDNN, both large effect sizes). Immediate post-exercise decreases in RMSSD and SDNN were 35.44 (95% CI: 21.95, 48.93) and 48.44 (95% CI: 32.49, 64.38) respectively, with Hedges’ g values of 2.31 and 2.78 (p < 0.001, large effect sizes). At 15 min, decreases were 31.64 (17.85, 45.42) and 41.48 (26.23, 56.72) respectively, with Hedges’ g values of 1.99 and 2.25 (p < 0.001, large effect sizes). Values returned to pre-test levels at 24 and 48 h with no significant differences (p > 0.05). (3) Frequency-domain parameters: Compared to pre-test, differences in LF, HF, and LF/HF were not statistically significant at any time point (all p > 0.05). Conclusions: Following high-intensity exercise leading to peripheral fatigue, cardiac autonomic function demonstrates a “suppression–recovery” dynamic pattern: cardiac stress levels increase significantly within 15 min post-exercise, with decreased overall HRV regulatory capacity and strong inhibition of parasympathetic activity; HRV status may return to baseline levels after 24 h. However, the frequency-domain indices of HRV showed no significant changes in response to the acute effects of high-intensity exercise. Full article

Complex regional pain syndrome (CRPS) is a heterogeneous and disabling chronic pain condition characterized by maladaptive neuroplasticity involving persistent peripheral nociceptive input, autonomic dysregulation, and central sensitization. Despite increasing clinical use, the role of botulinum toxin in CRPS remains controversial, with inconsistent outcomes reported across studies. This review synthesizes mechanistic, translational, and clinical evidence suggesting that these apparent inconsistencies may be partly explained by heterogeneity in anatomical targeting and route of administration rather than absence of biological efficacy. Available evidence suggests that botulinum toxin may exhibit its most consistent therapeutic signal when delivered to neural structures directly implicated in dominant CRPS pathophysiology, particularly the sympathetic nervous system and proximal somatic afferents, whereas superficial or non-specific delivery strategies appear to yield more variable responses. Importantly, differences across anatomical targets should not be interpreted as evidence of comparative effectiveness, as observed variation may reflect phenotype selection, procedural heterogeneity, confounding, and differences in outcome reporting. By integrating experimental data, randomized trials, and case-based clinical evidence, an anatomy-informed, route-specific neuromodulation framework is proposed to reconcile existing findings and inform future research. This mechanism-informed perspective is intended to guide rational trial design and phenotype-aligned clinical application of botulinum toxin in CRPS, rather than to provide a definitive evidence-closing synthesis. Full article

The menstrual cycle represents a dynamic infradian rhythm characterized by coordinated fluctuations in ovarian steroids that extend beyond reproductive function and influence systemic metabolism. This narrative review synthesizes current evidence on how menstrual cycle phase modulates energy balance, macronutrient metabolism, micronutrient handling, and responses to dietary bioactive compounds. Across phases, small-to-moderate but consistent differences emerge in energy intake, resting energy expenditure, substrate utilization, and protein turnover, with a tendency toward increased energy intake and lipid oxidation during the mid-luteal phase compared with the early follicular and peri-ovulatory phases. Emerging metabolomics data further reveal coordinated cyclical variation in amino acids, B vitamins, and lipid species, suggesting temporally sensitive windows in which low energy availability or micronutrient insufficiency may more readily impair performance, recovery, or symptom burden. Importantly, menstrual cycle-related metabolic variability reflects not only estradiol and progesterone oscillations but also integrated adaptations across the hypothalamic–pituitary–adrenal axis, autonomic nervous system, immune signaling, and gut microbiota. These interconnected systems contribute to inter- and intra-individual heterogeneity in metabolic phenotype. From a clinical and applied perspective, the evidence supports “cycle-aware” but non-dogmatic nutritional strategies, particularly in contexts of metabolic dysfunction, high training loads, or reproductive disorders. Future research should systematically verify cycle phase, incorporate multi-system biomarkers, and adopt sex-specific analytical frameworks to improve translational relevance. Recognizing the menstrual cycle as a biologically meaningful metabolic variable may enhance precision nutrition, exercise prescription, and metabolic risk assessment in women. Full article