Search Results (249)

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

Menopause is a natural biological transition marked by the cessation of regular menstrual cycles and is associated with significant endocrine, hormonal, and metabolic changes. Sleep disturbances are among the most common and distressing symptoms during this period, affecting approximately 40–60% of women in the menopausal transition and postmenopause. Vasomotor symptoms, including hot flushes and night sweats, often occur alongside fatigue, anxiety, and mood disturbances. These symptoms frequently coexist with sleep disorders such as insomnia, early morning awakenings, fragmented sleep, obstructive sleep apnea, restless legs syndrome, and circadian rhythm disruptions. Evidence from animal models, translational research, and clinical studies highlights the complex interaction between hormonal fluctuations, neuroendocrine dysregulation, metabolic changes, and circadian rhythm disruption. These factors contribute to altered sleep regulation, appetite control, and weight gain during the menopausal transition. This review summarizes current evidence on the mechanisms of underlying sleep disturbances in menopause, their clinical manifestations, diagnostic approaches, and available therapeutic strategies. Improving the management of sleep disorders during this stage may substantially enhance overall health and quality of life in menopausal women. We discuss presentation of different sleep disorders in menopause, their current management and future direction of research for development of precision-based algorithm of treatment considering the endocrine and hormonal profile of the women. Full article

Background/Objectives: Primary dysmenorrhea is a common gynecological disorder characterized by painful uterine contractions. Danggui Buxue Decoction (DBD) is used to treat menstrual irregularities, but its mechanism in primary dysmenorrhea remains unclear. This study investigated the efficacy of DBD against dysmenorrhea and its calcium signaling-related mechanism. Methods: DBD components were analyzed by UPLC–Orbitrap MS. Isolated uterine muscle strips precontracted with oxytocin (OT, 50 ng/mL) or KCl (60 mM) were used to assess the effects of DBD and its active compounds (Quercetin, Formononetin, Ononin, Ferulic acid, Senkyunolide I, Calycosin, Ligustilide, Calycosin-7-O-β-D-glucoside). Ca²⁺-dependent experiments, intracellular calcium release assays, and inhibitor treatments (Nifedipine, 2-APB) were performed to evaluate the involvement of L-type calcium channels and the IP₃R pathway. A primary dysmenorrhea model induced by estradiol benzoate and oxytocin was used to assess the analgesic effects, histopathology, inflammatory factors, and IP₃/Ca²⁺-related proteins and genes following DBD and Quercetin treatment. Results: A total of 161 compounds were identified in DBD. DBD and its eight active constituents relaxed OT (50 ng/mL) or KCl (60 mM)-induced uterine contractions, with Quercetin, Calycosin, and Ligustilide showing particularly prominent relaxant activity. These three compounds suppressed extracellular calcium influx and intracellular calcium release through the blockade of L-type calcium channels and IP₃R. In vivo, DBD and Quercetin alleviated pain, reduced inflammation, and decreased uterine Ca²⁺ and IP₃ levels in dysmenorrhea mice. Conclusions: DBD and its active component Quercetin promote uterine relaxation by lowering Ca²⁺ levels, which is achieved through suppression of L-type calcium channels and the IP₃/Ca²⁺ pathway. This contributes to their therapeutic action against primary dysmenorrhea. Full article

Backgrounds: Premature ovarian insufficiency (POI) is a clinical syndrome characterized by premature ovarian dysfunction, amenorrhea, and infertility. Ferulic acid (FA) is a prominent bioactive phenolic compound derived from traditional Chinese herbs Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort. These herbs are commonly used to treat gynecological disorders including menstrual irregularities and infertility, and are known to modulate endoplasmic reticulum (ER) stress. However, the therapeutic potential and molecular mechanisms of FA in the context of POI remain largely unexplored. This study aimed to investigate the protective effects of FA against POI and to elucidate the underlying pharmacological mechanisms. Methods: In vivo, a mouse model of POI was established via a single intraperitoneal injection of cyclophosphamide (CTX; 120 mg/kg), and using FA for 28 days of continuous gavage to observe its therapeutic effect. Ovarian function and pathological changes were assessed by hormone levels, follicle development and oxidative stress (OS) level. In vitro, the effects of FA were examined using 4-hydroperoxy cyclophosphamide (4-OHCP)-treated KGN granulosa cells. Transcriptome sequencing, molecular docking, and molecular dynamics simulations were employed to identify potential targets of FA. Results: Our findings demonstrated that FA administration helped preserve regular estrous cycles, promoted follicle development and hormone secretion, and attenuated OS in both ovarian tissue and granulosa cells (GCs). Transcriptomic profiling combined with molecular docking and molecular dynamics simulations suggested that FA potentially targets key ER stress proteins, specifically Grp78 and Perk. Further in vivo and in vitro experiments confirmed that FA alleviates ER stress by inhibiting the overactivation of the Perk/eIF2α/ATF4/CHOP signaling pathway. Notably, the protective effects of FA were comparable to those of the ER stress inhibitor 4-Phenylbutyric acid (4-PBA) and were reversed by the ER stress activator tunicamycin (TM). Additionally, FA downregulates ERO1α expression, further blocking secondary oxidative damage triggered by ER stress. In KGN cells, FA significantly inhibits 4-OHCP-induced apoptosis and upregulates the anti-apoptotic proteins BCL-2 and BCL-xL, exhibiting efficacy similar to 4-PBA. Conclusions: FA improves ovarian function in CTX-induced POI by coordinately regulating OS and ER stress, inhibiting the Perk/eIF2α/ATF4/CHOP pathway, and suppressing GC apoptosis. These findings provide experimental evidence supporting FA as a potential therapeutic candidate for POI. Full article

Background and Objectives: Adenomyosis is increasingly being recognized as a heterogeneous uterine disorder with variable clinical expressions. Current ultrasound-based classifications do not consistently align structural severity with symptom burden. Given its role in angiogenesis, inflammation, and endometrial remodeling, vascular endothelial growth factor (VEGF) signaling may influence both morphological features and clinical manifestations. This study evaluated the association between three VEGF polymorphisms (−2578C/A, −634G/C, −936C/T) and adenomyosis presence, ultrasound-based severity, and symptoms in infertile women undergoing in vitro fertilization (IVF). Materials and Methods: In this prospective cohort study, 85 infertile women were assessed for adenomyosis using MUSA criteria and Exacoustos grading. VEGF genotyping was performed by PCR-RFLP. Clinical data included menstrual bleeding status scores and dysmenorrhea intensity. Results: Under a dominant model, the variant genotypes (AA+CA) of the VEGF–2578C/A polymorphism −2578 A showed increased odds of adenomyosis versus CC (adjusted OR = 4.00, 95% CI: 1.48–10.84; p = 0.0037). The A allele frequency was higher in women with adenomyosis (57.14% vs. 33%), which was consistent with increased susceptibility (OR = 2.71, 95% CI: 1.44–5.09; p = 0.003). The AA + CA genotypes were more frequent with higher ultrasound-based severity (p = 0.0029; 50% vs. 72% vs. 100% across increasing severity strata); however, among women with adenomyosis, AA + CA carriers had lower odds of clinically relevant dysmenorrhea (adjusted OR = 0.18, 95% CI: 0.06–0.55; p = 0.0017), which remained significant after correction for multiple testing (adjusted p = 0.0051). No significant associations were identified for −936C/T or −634G/C across adenomyosis presence, ultrasound-based severity, number of sonographic features, dysmenorrhea, or heavy menstrual bleeding (all p > 0.05). Conclusions: These preliminary findings suggest divergent associations of VEGF −2578C/A with structural severity versus symptom expression, supporting a partial dissociation between ultrasound-defined severity and clinical phenotype in adenomyosis. Full article

Background: For decades, the ketogenic diet has been successfully used for the treatment of obesity, metabolic syndrome, and type 2 diabetes. The mechanisms through which it affects metabolism are not fully understood, but the hormonal changes that occur during ketogenic nutrition are likely to play an important role. Objectives: To investigate the effect of the ketogenic diet on various hormones associated with obesity and the accompanying metabolic disorders in childhood. Methods: One hundred children aged 8–18 years with obesity were enrolled. After baseline anthropometric, biochemical, and hormonal testing, they followed a 4-month “well-formulated ketogenic diet.” Fifty-eight of them successfully completed the study with follow-up assessments. Among them, 8 girls had polycystic ovary syndrome (PCOS) and 7 children had Hashimoto’s autoimmune thyroiditis. Results: At the end of the 4-month period, there was a significant decrease in basal insulinemia (p < 0.0001) and in mean morning cortisol levels (p = 0.04), as well as an increase in adiponectin levels (p = 0.04). All girls with PCOS experienced spontaneous menstrual cycles, accompanied by a reduction in testosterone levels. TSH levels showed no change for the whole group (p = 0.13), but there was a significant decrease in T3 (p < 0.0001) and a mild increase in T4 (p = 0.05). Among patients with Hashimoto’s thyroiditis, TSH levels were significantly higher at the end of the study. Conclusions: A short-term, well-formulated ketogenic diet in children with obesity is associated with hormonal changes that support weight loss and improve insulin sensitivity. The diet shows particularly beneficial effects in girls with PCOS and may be considered as part of a comprehensive therapeutic approach in these patients. Monitoring thyroid function during ketogenic nutrition is advisable in patients with hypothyroidism and thyroid disorders. Full article

This systematic review examined the influence of menstrual cycle phases on lower-limb muscle activation patterns in eumenorrheic women. Following the PRISMA guidelines, a comprehensive search was conducted in PubMed, Web of Science, and SPORTDiscus using the keywords: (menstrual cycle OR menstrual phase* OR menstruation) AND (neuromuscular activation OR muscle activation OR muscle activity OR neuromuscular control patterns) AND (electromyography OR EMG). Inclusion criteria required participants to be eumenorrheic women with regular menstrual cycles, verified through blood analysis and other physiological confirmation methods, and without menstrual disorders or hormonal contraceptive use. Additionally, eligible studies had to assess lower-limb muscle activation using electromyography. Seven studies met the criteria, comprising a total of 116 eumenorrheic women. Most studies reported no statistically significant differences in muscle activation patterns across menstrual cycle phases. Overall, hormonal fluctuations may influence muscle activation depending on the nature of the task performed (dynamic vs. static; fatiguing vs. non-fatiguing). Future research should incorporate larger sample sizes, longer monitoring periods, and more standardized methodological approaches. Full article

The ovaries are crucial reproductive organs that regulate the menstrual cycle and support pregnancy through the production of steroid hormones. They are highly susceptible to various environmental pollutants, which can lead to ovarian disorders. Luteal phase defect (LPD) and premature ovarian failure (POF) are common ovarian disorders in women. In this study, we integrate network toxicology with molecular docking and molecular dynamics simulations to elucidate the toxicological mechanisms of Benzo(a)pyrene (BaP), a widespread endocrine disruptor, in LPD and POF. Through systematic data mining of the GeneCards and OMIM databases, we identified 1336 targets associated with LPD and 2066 targets related to POF, as well as 220 BaP targets. Venn diagram analysis revealed 36 potential targets for BaP-induced LPD and 43 for BaP-induced POF. GO and KEGG enrichment analyses suggest that BaP-induced LPD and POF may share toxicological mechanisms. PPI network visualization indicated that EGFR, ESR1, and STAT3 are critical common targets for BaP-induced LPD and POF. Molecular docking and molecular dynamics simulations revealed that BaP exhibits strong binding affinity with all three core genes. In KGN cells modeling LPD and POF phenotypes, cellular experiments confirmed that BaP downregulated EGFR and ESR1 expression while upregulating STAT3 expression, thereby supporting the reliability of these targets in BaP-induced ovarian dysfunction. These findings provide insights into BaP-induced reproductive toxicity and offer a foundation for targeted clinical interventions to mitigate the effects of environmental pollutants on women’s reproductive health. Full article

Physiological hypoxia is a defining feature of early pregnancy, coordinating menstrual repair, implantation, decidualization, placental development, and fetoplacental adaptation. Hypoxia-inducible factors, HIF-1α and HIF-2α, act as master regulators of these processes by sensing oxygen tension and orchestrating cellular responses in metabolism, angiogenesis, immune regulation, and tissue remodeling. Although structurally related, HIF-1α and HIF-2α exhibit distinct spatial and temporal functions across reproductive stages. Embryonic HIF-1α is primarily involved in early embryonic development, whereas embryonic HIF-2α is required for later developmental stages. Furthermore, maternal HIF-1α acts early in pregnancy, coordinating metabolic adaptation, endometrial regeneration, decidualization, angiogenic expansion, placental organization, and maternal immune tolerance. In contrast, maternal HIF-2α regulates epithelial breakdown, trophoblast invasion, implantation mechanics, and vesicle-mediated trafficking. Mouse genetics demonstrate that disruption of either isoform leads to non-redundant defects in reproductive success, from failed implantation to placental insufficiency and fetal lethality. Pathological hypoxia or aberrant HIF signaling drives pregnancy disorders including preeclampsia, fetal growth restriction, recurrent pregnancy loss, and heavy menstrual bleeding. Defining the distinct roles of HIF-1α and HIF-2α supports the development of therapies targeting hypoxia-responsive pathways in infertility and obstetric disease. Full article

Endometriosis is a chronic inflammatory disorder affecting about 190 million women of reproductive age worldwide. It represents a major health challenge due to its broad impact on physical, reproductive, and psychological well-being and is clinically characterized by pelvic pain, menstrual irregularities, and infertility. This narrative review synthesized current evidence on the relationship between adiposity, metabolic and inflammatory markers, and endometriosis from a biopsychosocial and intersectional perspective. A comprehensive search was conducted in PubMed, Scopus, and Web of Science for peer-reviewed studies published in English over the past decade.: Results pointed out that endometriosis significantly affects inflammatory activity within adipose tissue, especially in visceral adipose tissue. Studies also reported reduced adipocyte size and altered adipose tissue function. The endometriosis cytokine profile exhibited a pattern of systemic and tissue-specific inflammatory activation (i.e., elevated levels of interleukin-6 and monocyte chemoattractant protein-1). Sociodemographic factors (i.e., age, race/ethnicity, socioeconomic status, and educational level) also play a significant role in differences in symptomatology, disease course, and healthcare access. To sum up, endometriosis need to be considered as a multisystem condition related to metabolic, inflammatory, and psychosocial factors. It is necessary to adopt a biopsychosocial and intersectional perspective to improve diagnosis and support more equitable and personalized therapeutic approaches. Full article

Women exhibit a higher prevalence of depression, anxiety, stress-related disorders, and autoimmune conditions compared to men, yet the biological mechanisms underlying this sex difference remain incompletely understood. Growing evidence identifies neuroinflammation as a central mediator of psychiatric vulnerability in women, shaped by interactions between sex hormones, immune activation, and neural circuit regulation. Throughout the female lifespan, fluctuations in estrogen and progesterone, such as those occurring during puberty, the menstrual cycle, pregnancy, postpartum, and perimenopause, modulate microglial activity, cytokine release, and neuroimmune signaling. These hormonal transitions create windows of heightened sensitivity in key brain regions involved in affect regulation, including the amygdala, hippocampus, and prefrontal cortex. Parallel variations in systemic inflammation, mitochondrial function, and hypothalamic–pituitary–adrenal (HPA) axis responsivity amplify stress reactivity and autonomic imbalance, contributing to increased risk for mood and anxiety disorders in women. Emerging data also highlight sex-specific interactions between the immune system and monoaminergic neurotransmission, gut–brain pathways, endothelial function, and neuroplasticity. This review synthesizes current neuroscientific evidence on the sex-dependent neuroinflammatory mechanisms that bridge hormonal dynamics, brain function, and psychiatric outcomes in women. We identify critical periods of vulnerability, summarize converging molecular pathways, and discuss novel therapeutic targets including anti-inflammatory strategies, estrogen-modulating treatments, lifestyle interventions, and biomarkers for personalized psychiatry. Understanding neuroinflammation as a sex-specific process offers a transformative perspective for improving diagnosis, prevention, and treatment of psychiatric disorders in women. Full article

Background: Eating disorders are increasingly diagnosed in young women, particularly during adolescence. The recently described Anorexic Readiness Syndrome (ARS) is more common than full-blown anorexia. It has been identified in female athletes engaging in disciplines focusing on the aesthetics of the body, in women involved in recreational exercise and in those who are not physically active but strive to achieve the “perfect” figure. The study aimed to assess the severity and prevalence of ARS in women regularly engaging in body-shaping physical activity. Methods: The study included 659 women aged ≥ 14 years who engaged in regular body-shaping physical activity, provided informed consent to participate in the study (in the case of minors, also the consent of a parent or legal guardian), and had no diagnosed chronic diseases. The level of ARS was assessed using a questionnaire measuring attitudes toward food, supplemented with a specially designed survey consisting of 32 questions and a personal data form. Based on the frequency of body-shaping physical activity, participants were divided into two groups: the study group comprised women exercising ≥ 3 times per week (n = 301), while women exercising < 3 times per week constituted the control group (n = 358). The analyses examined the relationships between ARS, frequency of body-shaping physical activity, BMI, and menstrual irregularities. Results: Medium or high ARS level was identified in over 96% (n = 637) of the respondents. The level of ARS was significantly related to the allocation into the group (p = 0.034) and the weekly hours of physical activity (p = 0.011 in the control group; p = 0.020 in the study group). There was a correlation between ARS and menstrual irregularities (p = 0.001). Weak but significant correlations were identified for awareness of eating disorders (V = 0.20; p = 0.001), adherence to a special diet (V = 0.18; p < 0.001) and self-assessed health (V = 0.18; p < 0.001). Conclusions: Higher ARS levels were observed in women reporting greater weekly physical activity. No significant associations were found between ARS and body mass index or body weight. Medium and high ARS levels were significantly associated with self-reported menstrual disturbances, while most participants with elevated ARS were unaware of disordered eating risk. Full article

Background: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, and an increased prevalence of metabolic syndrome. Clusterin (CLU), a chaperone protein induced by cellular stress and known to play roles in inflammation, oxidative stress, and lipid metabolism, may be associated with the metabolic abnormalities observed in patients with PCOS. The purpose of this current study is to investigate serum CLU levels and their link with endocrine, biochemical, and metabolic parameters, such as metabolic syndrome, among women with PCOS. Methods: This cross-sectional study included 40 women aged 18–30 with PCOS diagnosed according to the Rotterdam criteria and 40 age- and BMI-matched healthy controls. Demographic data, Ferriman–Gallwey scores, hormonal and metabolic parameters (including TSH, prolactin, 17-OH progesterone, total testosterone, insulin, AMH, HOMA-IR, and serum CLU levels), and ultrasonographic ovarian morphology were assessed. Statistical analyses, including ROC and logistic regression, were performed. Results: Women with PCOS had higher follicle counts, Ferriman–Gallwey scores, LH/FSH ratios, fasting insulin levels, HOMA-IR, triglycerides, and systolic blood pressure than controls, whereas menstrual cycle frequency and HDL levels were lower (all p < 0.05). Serum CLU concentrations were markedly higher in the PCOS cohort. In the PCOS population, CLU showed positive relationships with the Ferriman–Gallwey score, fasting glucose, fasting insulin, HOMA-IR, and triglycerides, and a negative correlation with HDL. CLU levels were significantly higher in women with metabolic syndrome in the PCOS cohort compared to those without. In logistic regression analysis, CLU, AMH, and the LH/FSH ratio emerged as independent predictors of PCOS. Furthermore, CLU remained an independent predictor of metabolic syndrome in the PCOS cohort. In ROC analysis, CLU demonstrated strong diagnostic efficacy in detecting both PCOS (AUC = 0.834) and metabolic syndrome in patients with PCOS (AUC = 0.804). Conclusions: Our results show that serum CLU is higher in women with PCOS and is associated with the clinical and metabolic features peculiar to patients with PCOS. CLU was found to distinguish between patients with PCOS and healthy women and demonstrated a strong association with the presence of metabolic syndrome within the PCOS group. Overall, these findings suggest that CLU may be a valuable auxiliary biomarker for detecting women with PCOS at risk for metabolic disturbances. Full article

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder linked to impaired cognition and altered dopamine neurotransmission. Emerging evidence suggests that women with ADHD experience pronounced hormone-related difficulties, with menstrual cycle-related changes in mood and cognition interfering with daily functioning and diminishing treatment efficacy. This review examines the influence of hormonal fluctuations during the menstrual cycle on cognitive functioning and ADHD symptomatology in women. A comprehensive literature search of Ovid EmBase identified studies published between 2015 and 2025 examining cognitive performance, including attention, executive functioning, working memory, and inhibitory control, across menstrual cycle phases in women with or without ADHD. Twenty-nine studies met inclusion criteria. Neurobiological measurements included hormonal assays, neuroimaging, and neurotransmitter models. Seven studies in non-clinical populations suggested that attentional processing was enhanced during the mid-luteal phase, which may be linked to higher progesterone levels. By contrast, four studies in women with ADHD and six studies in women with mood-related disorders, such as PMS or PMDD, consistently observed impairments in attention, executive function, and impulsivity during the mid-luteal and pre-menstrual phases. These objective findings parallel subjective reports of worsened cognition, heightened mood symptoms, and diminished medication efficacy during the luteal phase. Current evidence indicates that ADHD-related cognitive functioning fluctuates with the menstrual cycle, with impairments particularly evident in women with ADHD and/or comorbid mood disorders. These changes may reflect increased sensitivity to allopregnanolone, peri-menstrual oestrogen withdrawal, and the absence of compensatory neural adaptations observed in non-clinical populations. However, findings remain preliminary and sometimes contradictory due to methodological heterogeneity and small sample sizes. Further research is needed to clarify these mechanisms and, importantly, to translate theoretical insights into clinical application through female-specific diagnostic procedures and treatment strategies. Full article

Mespilus germanica L. is one of the two species of the genus Mespilus L., and is distributed in several regions, including Southeastern Europe, Anatolia, the Caucasus, and parts of the Middle East. The fruits of the plant are consumed as food, and the fruits, leaves, and stem bark are traditionally used for various systemic disorders, including gastrointestinal, respiratory, urinary tract, and skin conditions, as well as menstrual irregularities. In our study, the anti-inflammatory potential and antimicrobial activities of aqueous-methanolic extracts prepared from ripe (MGRF) and unripe fruits (MGUF), leaves (MGL), and stem bark (MGB) of M. germanica were evaluated in vitro. Quercetin, catechin, epicatechin, ellagic acid, chlorogenic acid, and caffeic acid were analyzed using high-performance liquid chromatography. MGL exhibited the strongest activity against Staphylococcus aureus (MIC = 8 µg/mL), while MGB was most active against Enterococcus faecalis (MIC = 4 µg/mL), and fruit extracts were effective against resistant Acinetobacter baumannii (MIC = 16–32 µg/mL). Membrane-protective effects were more pronounced in MGUF and MGB, whereas MGL demonstrated the highest protein stabilization activity. Leaves also contained the highest levels of chlorogenic acid and epicatechin. These findings support the traditional use of M. germanica, though further studies are required to explore its therapeutic potential. Full article