Gynecological Endocrinology最新文献

Objective: To conduct a comprehensive assessment of physical, functional, emotional, cognitive, nutritional, metabolic, and sexual health in mid-aged women.

Methods: This cross-sectional study was conducted at the Universidad Espíritu Santo Clinic (UEES Clinic), Ecuador, as part of a multidisciplinary integrated health initiative. Women aged 40-60 years were recruited through social media outreach by the UEES Research Center and Clinic between 1 October 2024 and 1 October 2025. Interested participants scheduled a clinical evaluation by telephone. Assessments included laboratory tests (complete blood count, FSH, estradiol, HDL-C, triglycerides, glucose, and thyroid hormones [T3, T4]); validated surveys: Menopause Rating Scale (MRS) for climacteric symptoms and quality of life; Center for Epidemiologic Studies Depression Scale, 10-item version (CESD-10) for depressive mood; short Everyday Memory Questionnaire-Revised (EMQ-R) for cognition; and FSFI-6 for sexual function. Participants also underwent anthropometric measurements, body composition analysis, muscle strength testing, and dietary assessment.

Discussion: This methods paper describes a multidisciplinary approach for the comprehensive health evaluation of mid-aged women. It enables early identification of factors affecting quality of life and provides a replicable framework relevant to both local and broader Latin American contexts, serving as a model for similar initiatives across the region.

Women's reproductive life encompasses dynamic phases, including menarche, menstrual cycles, pregnancy, lactation, and menopause, as well as transitional periods of variable duration. These stages drive physiological changes that influence both physical and mental well-being and may modulate susceptibility to autoimmunity. The interplay between autoimmunity and reproductive milestones is bidirectional: reproductive stages can affect disease onset and progression, while autoimmune disorders influence fertility, pregnancy outcomes, and the timing of menopause. Persistent challenges in detecting autoimmune diseases, particularly within rheumatology and gastroenterology, underscore the need for targeted screening, multidisciplinary collaboration, and patient-centered strategies. Fertility preservation, preconception counseling, and individualized pregnancy management are essential to safeguard reproductive rights and optimize maternal and neonatal outcomes. Post-reproductive life, especially the menopause transition, represents a vulnerable period in which immune, hormonal, and metabolic changes converge. This manuscript highlights the importance of a comprehensive, lifespan-oriented approach to reproductive well-being in women with autoimmune diseases, integrating preventive, diagnostic, and therapeutic strategies across all stages of reproduction.

Objective: To analyze the effects of melatonin on angiogenesis in cultured granulosa cells from women undergoing in vitro fertilization, comparing those with female-factor versus male-factor infertility.

Methods: Granulosa cells were obtained from 47 women undergoing in vitro fertilization treatment, including 31 women with female-factor (FFG) and 16 women with male-factor infertility (MFG). Cells from both groups were cultured and divided into four treatment conditions for 96 h: a) control (culture medium without melatonin); b) vehicle (melatonin diluent-ethanol); c) 0.1 µM melatonin; and d) 10 µM melatonin. Expression of 84 genes involved in angiogenesis signaling pathway was analyzed by real-time PCR.

Results: Cultured granulosa cells from both groups expressed aromatase and melatonin receptors. In both groups, cell proliferation peaked at 72 h when exposed to 10 µM melatonin. Of the 84 analyzed genes, three showed significant differential mRNA expression. In the MFG, melatonin at 10 µM upregulated VEGF-B mRNA expression in granulosa cells but downregulated PDGFA and HGF mRNA expression, in contrast to the higher expression of these genes in the FFG under identical conditions.

Conclusion: Melatonin differentially modulates angiogenesis-related gene expression in granulosa cells, indicating that its effects may depend on infertility type and melatonin dose in women undergoing in vitro fertilization.

Objective: This study investigates serum metabolic profiles in breast cancer to identify diagnostic biomarkers and stage-specific metabolites, offering insights for clinical practice.

Methods: Gas chromatography‒mass spectrometry (GC‒MS)-based metabolomics analyzed serum from healthy controls, patients with benign breast lesions, and malignant breast cancer cohorts. Orthogonal partial least squares discriminant analysis (OPLS-DA) modeling differentiated metabolic signatures between groups, while Spearman's correlation assessed metabolite-stage relationships. Diagnostic performance was assessed through receiver operating characteristic (ROC) analysis.

Results: Amino acid metabolism alterations, particularly in alanine, aspartate, and glutamate metabolism, characterized breast cancer. Malignant cases showed elevated glutamic acid and lactic acid but reduced fructose compared to benign lesions, achieving significant diagnostic discrimination (AUC = 0.9757 for glutamic acid, AUC = 0.9583 for lactic acid, AUC = 1.000 for fructose). Glutamic acid demonstrated progressive elevation across health-to-disease continuum (healthy-benign-early-stage-advanced), strongly correlating with the malignancy stage (ρ = 0.934, p < 0.001) and effectively distinguishing early/late-stage cancers (AUC = 0.9500).

Conclusions: Serum metabolomics identified glutamic acid as a dynamic biomarker for breast cancer detection and staging, warranting further mechanistic studies.

Objective: To investigate the associations of the neutrophil/albumin ratio (NAR) with type 2 diabetes mellitus (T2DM) in women with a history of gestational diabetes mellitus (GDM).

Methods: We conducted a cross-sectional study involving 782 participants from the National Health and Nutrition Examination Survey. Logistic regression analyses were performed to explore the relationship between NAR and T2DM, adjusting for various confounding factors across different models. Interaction analyses examined the modifying effects of socio-demographic characteristics on the relationship between NAR and T2DM. Mediation analyses were utilized to investigate whether key laboratory indicators and insulin resistance indices mediated the association between NAR and T2DM.

Results: Higher NAR levels were positively associated with T2DM risk. (OR[95%CI]:1.649[1.181,2.309], p = 0.003). Mediation analyses revealed that the effect of NAR on T2DM was entirely mediated through the regulation of red cell distribution width (RDW Coefficient[95%CI]: 0.009[0.001,0.024], p = 0.020) and high-density lipoprotein cholesterol (HDL-C Coefficient[95%CI]: 0.038[0.017,0.067], p < 0.001). Besides, significant interactions and differences were observed in the relationship between NAR and T2DM risk based on body mass index (BMI) (NAR*BMI: interaction coefficient: -0.651, interaction p = 0.027). In individuals with 25 kg/m² ≤ BMI < 30 kg/m², NAR increased the risk of T2DM by regulating the insulin resistance index (HOMA-R) (β[95%CI]: 2.220[0.653,3.787], p = 0.007).

Conclusion: This study revealed that among women with GDM history, NAR may influence the risk of T2DM through the modulation of RDW and HDL-C. Furthermore, NAR and BMI had a significant interaction affecting T2DM risk, particularly prominent in women with 25 kg/m² ≤ BMI < 30 kg/m². Within this subgroup, NAR elevated the risk of T2DM via HOMA-R.

Background: Endometriosis (EMs) is a common gynecological disorder associated with infertility. EMs patients often require assisted reproductive technology (ART) but exhibit lower success rates. This study aimed to characterize the follicular fluid microbiome in EMs patients undergoing in vitro fertilization (IVF) and provide insights into mechanisms underlying lower pregnancy rates.

Methods: Follicular fluid samples were collected from EMs patients and control subjectsundergoing IVF. Microbial DNA was subjected to 16S rRNA gene sequencing. Bioinformatic analyses, including alpha and beta diversity analysis, microbial composition profiling and biomarker identification, were performed.

Results: The follicular fluid microbiome in EMs patients exhibited altered alpha and beta diversity compared to controls. Distinct microbial compositions were observed at various taxonomic levels. Differentially abundant taxa were identified as potential biomarkers for EMs. Microbial profiles were associated with clinical parameters such as oocyte quality and fertilization rates. Models based on microbial profiles were constructed to elucidate the relationship between EMs and IVF outcomes. Functional predictions suggested alterations in metabolic pathways in the follicular fluid microbiome of EMs patients.

Conclusions: This study revealed significant alterations in the follicular fluid microbiome of EMs patients, providing a basis for further research into the role of the microbiome in EMs-related infertility.

Objective: This study aimed to investigate the mechanism of the involvement of USP33 in autophagic ferroptosis in endometriosis (EMs).

Methods: Endometrial stromal cells (ESCs) were isolated from 15 healthy controls and 30 patients with EMs, which were designated NESCs and EESCs, respectively. Real-time PCR and Western blotting were utilized to determine USP33 expression as well as GPX4, LC3II/LC3I, NCOA4, FTH1, LAST1, p-LAST1, YAP, and p-YAP levels. Immunofluorescence was used to detect the colocalization of ferritin and LAMP2, as well as that of LC3 and ferritin. The levels of ROS, Fe²⁺, MDA, and GSH were measured to assess ferroptosis. An LDH assay was performed to evaluate cell death. A co-IP assay was implemented to identify the interaction between USP33 and LAST1 and detect the level of LAST1 ubiquitination. The stability of the protein was also detected via a cycloheximide (CHX) assay.

Results: USP33 was underexpressed in EMs patients. Loss of USP33 conferred resistance to ferroptosis in EESCs, as evidenced by increased proliferation; decreased levels of ROS, Fe²⁺, and MDA; elevated levels of GPX4 and GSH; and reduced cell death. In addition, USP33, which is localized in autophagosomes, was suggested to promote the degradation of ferritin in autophagosomes. Furthermore, USP33 repressed the Hippo-YAP pathway by suppressing LATS1 ubiquitination, thereby contributing to the reduced resistance of EESCs to ferroptosis.

Conclusion: USP33 impedes the ubiquitination of LAST1 and represses the Hippo/YAP pathway, thus facilitating ferritinophagy and ferroptosis in EMs.

Objective: The purpose of this systematic review and meta-analysis is to assess the association of handgrip strength (HGS) in subjects with high-normal or mildly elevated and low-normal serum uric acid (SUA) reported by quartiles.

Methods: The research protocol was registered at PROSPERO (CRD420251050351). We searched four databases to obtain relevant articles reporting HGS by SUA quartiles in subjects without gout. Outcomes were compared by combining the third and fourth SUA (higher) quartiles versus the first and second (low) quartiles. The risk of bias was assessed using the Newcastle‒Ottawa Scale, and heterogeneity with the I² test. The results are reported as the mean difference (MD), standardized MD (SMD), or odds ratio (OR).

Results: Seven cross-sectional studies, including 18,765 adult subjects with higher SUA quartiles showed significant higher HGS (SMD: 0.21, 95% confidence interval [CI]: 0.03, 0.39), body mass index (MD: 1.02 kg/m², 95% CI: 0.48, 1.55), total cholesterol (SMD: 0.14, 95% CI: 0.05, 0.24), LDL-cholesterol SMD: 0.13, 95% CI: 0.09, 0.17), and triglycerides (SMD: 0.26, 95% CI: 0.11, 0.41) than those with lower SUA quartiles. HDL-cholesterol was significantly reduced in subjects with higher SUA (SMD: -0.13, 95% CI: -0.20, -0.07). High SUA levels were associated with a drinking history (OR: 1.21, 95% CI: 1.10, 1.34) and hypertension (OR: 1.51, 95% CI: 1.15, 1.99).

Conclusions: Subjects with higher normal SUA levels showed higher HGS compared to those with lower normal levels.

Background: Astrocytes, once regarded as passive support cells, are recognized as active regulators of synaptic organization and neuronal integration. Through extension or retraction of their processes, astrocytes influence synapse formation and elimination. Astrocytes express estrogen receptors, and animal studies have shown that estradiol modifies astrocytic morphology in relation to synaptic density.

Objective: To examine the effects of estradiol and two clinically available selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene on astrocyte processes in human brain tissue.

Methods: Human temporal lobe cortical slices were incubated for 60 min with estradiol (10 nM), tamoxifen (1.0 µM), or raloxifene (1.0 µM), and the results were compared with untreated control slices. Astrocytes were visualized by immunostaining for the glial cytoskeletal marker glial fibrillary acidic protein (GFAP). Light microscopy image analysis was used to quantify astrocytic process thickness and branching, using Neurolucida® software.

Results: Control slices exhibited astrocytic branch extension and thinning during the incubation period. Similar morphological changes were observed in the tamoxifen-treated slices. In contrast, raloxifene treatment was associated with a significant reduction in astrocyte branching and thinning compared with controls (p = 0.01 for primary processes). Estradiol treatment resulted in intermediate reductions in astroglial process measures that did not reach statistical significance.

Conclusions: Estradiol, tamoxifen, and raloxifene - widely used hormonal agents - were associated with distinct effects on astrocyte morphology in human cortical tissue. These findings support a role for estrogen receptor modulation in astroglial structural regulation and suggest a potential cellular mechanism contributing to central nervous system symptoms reported in clinical settings.