OBJECTIVE: Diabetes mellitus profoundly impairs female reproductive health by inducing uterine atrophy, follicular loss, and hormonal dysregulation. Oxidative stress and profibrotic signaling, particularly transforming g...OBJECTIVE: Diabetes mellitus profoundly impairs female reproductive health by inducing uterine atrophy, follicular loss, and hormonal dysregulation. Oxidative stress and profibrotic signaling, particularly transforming growth factor-β (TGF-β), are central to this pathology, while the role of heat shock protein 70 (HSP70) remains insufficiently characterized. Alpha-lipoic acid (ALA), a mitochondrial cofactor and potent antioxidant, has shown efficacy against diabetic complications; however, its protective effects on reproductive tissues in type 1 diabetes are not well established. METHODS: Thirty adult female Wistar rats were allocated into control, diabetic, and diabetic + ALA groups ( = 10 each). Diabetes was induced by a single intraperitoneal injection of streptozotocin (60 mg/kg). ALA was administered orally (200 mg/kg/day) for four weeks. Histopathological evaluation focused on uterine gland degeneration, stromal fibrosis, and ovarian follicular integrity. Plasma anti-Müllerian hormone (AMH), uterine TGF-β, and ovarian HSP70 levels were quantified using ELISA. RESULTS: Streptozotocin-induced diabetes caused significant uterine gland degeneration, stromal fibrosis, ovarian follicular loss, reduced AMH, and elevated TGF-β and HSP70 ( < 0.001). ALA treatment attenuated glandular and stromal injury, reduced fibrosis, and improved follicular morphology. Biochemically, ALA increased AMH, decreased uterine TGF-β, and further upregulated ovarian HSP70, indicating activation of cytoprotective pathways. Although glucose levels remained elevated, partial glycemic reduction was observed. CONCLUSION: ALA exerts antifibrotic and cytoprotective effects in diabetic reproductive tissues, mitigating uterine and ovarian damage through modulation of TGF-β and HSP70 pathways.
The ACTH stimulation test is the gold standard for diagnosing NCAH. However, this test has a human and material cost. While some teams perform it as a second-line test, others use it as a first-line test to avoid false n...The ACTH stimulation test is the gold standard for diagnosing NCAH. However, this test has a human and material cost. While some teams perform it as a second-line test, others use it as a first-line test to avoid false negatives associated with single basal 17-hydroxyprogesterone (17-OHP) serum levels. In this prospective, single-center, cross-sectional observational study, we included 210 women aged from 15 to 41 who were referred for oligoanovulation and/or hyperandrogenism from November 2022 to June 2024. In this population, we determined the proportion of false negatives for NCAH using basal 17-OHP serum levels by performing ACTH stimulation tests. Among the 210 patients included, no NCAH was diagnosed, and no false negatives of basal 17-OHP serum levels were identified. Basal 17-OHP serum levels were significantly higher in PCOS patients but remained below the 2 ng/ml threshold and were significantly correlated with hormonal and ultrasound markers of PCOS. Consequently, the systematic use of the ACTH stimulation test in women with hyperandrogenism and/or oligoanovulation does not appear to be a cost-effective diagnostic strategy.
OBJECTIVE: To evaluate the clinical efficacy and safety of a once-daily oral fixed-dose combination of relugolix 40 mg, estradiol 1 mg, and norethisterone acetate 0.5 mg in women with symptomatic adenomyosis coexisting w...OBJECTIVE: To evaluate the clinical efficacy and safety of a once-daily oral fixed-dose combination of relugolix 40 mg, estradiol 1 mg, and norethisterone acetate 0.5 mg in women with symptomatic adenomyosis coexisting with uterine fibroids. METHODS: This case series included six women with uterine fibroids and concomitant adenomyosis, diagnosed by transvaginal ultrasound according to MUSA criteria. All patients received continuous treatment for 12 months. Clinical outcomes included changes in dysmenorrhea and pelvic pain assessed by the Visual Analogue Scale (VAS), menstrual blood loss evaluated through the Pictorial Blood Assessment Chart (PBAC), and hemoglobin levels. Ultrasonographic assessment measured uterine volume and adenomyosis-related features before and after treatment. RESULTS: All patients achieved complete resolution of dysmenorrhea and chronic pelvic pain, with VAS scores reduced to zero. Menstrual bleeding ceased in all cases (PBAC = 0), and hemoglobin levels improved after 12 months. Ultrasound examination demonstrated a reduction in uterine volume ranging from 8.6% to 58.3%, along with partial regression of direct adenomyotic features. No adverse events or treatment discontinuations were reported during follow-up. CONCLUSIONS: Relugolix/estradiol/norethisterone acetate combination therapy was effective, well-tolerated, and associated with consistent clinical and sonographic improvement in women with adenomyosis and coexisting fibroids. Future larger-scale, controlled studies with extended follow-up are warranted to validate these findings.
OBJECTIVE: This review comprehensively explores the potential relationship between the microbiota and adenomyosis, aiming to identify specific microbial biomarkers, elucidate the molecular mechanisms underlying the invol...OBJECTIVE: This review comprehensively explores the potential relationship between the microbiota and adenomyosis, aiming to identify specific microbial biomarkers, elucidate the molecular mechanisms underlying the involvement of the microbiota in the disease, and provide insights into more precise and personalized therapeutic strategies for patients with adenomyosis. METHODS: This article adopts the narrative review method to comprehensively analyze the literature on the relationship between the microbiota and adenomyosis. A comprehensive literature search was conducted in PubMed, Embase and Web of Science databases. A total of 8 articles were included, among which one was an animal experiment. This review focuses on analyzing the differences in the composition of the microbiota between patients with adenomyosis and healthy control groups, as well as the potential molecular mechanisms by which the microbiota participates in the development of adenomyosis. RESULTS: Studies have demonstrated that the composition of the microbiota in women with adenomyosis differs significantly from that in healthy controls.The potential mechanisms by which microbiota may be involved in adenomyosis are closely associated with immune-inflammatory responses and estrogen regulation, which further affect the progression of adenomyosis. CONCLUSIONS: Microbiota may play an important role in the pathogenesis of adenomyosis. Elucidating the specific microbial biomarkers and the underlying molecular mechanisms of microbiota in adenomyosis is crucial for developing novel, precise, and personalized therapeutic strategies, which may provide new options for the treatment of adenomyosis.
OBJECTIVES: This study aims to investigate the therapeutic effects of the Bushen Huatan (BSHT) Formula on non-obese polycystic ovary syndrome (PCOS) rats, and to explore its potential mechanisms of action. METHODS: A PCO...OBJECTIVES: This study aims to investigate the therapeutic effects of the Bushen Huatan (BSHT) Formula on non-obese polycystic ovary syndrome (PCOS) rats, and to explore its potential mechanisms of action. METHODS: A PCOS model was induced in rats via letrozole, a high-fat/high-sucrose diet, and a PEPD inhibitor for 35 days; estrous cyclicity, fasting glucose, and glycated hemoglobin were monitored. After modeling, the animals underwent 28 days of assigned treatment, followed by an oral glucose tolerance test (OGTT) and assays for sex steroids and lipids. Ovarian and hepatic histology and hepatic steatosis were evaluated. Adipose-derived exosomes were characterized for size, concentration, and surface markers (TSG101, HSP70, CD63). Detect the expression levels of adipose tissue-derived exosomal microRNA-27a-3p (AT-EXO-miR-27a-3p) and ovarian mRNA. Ovarian PPARG, P-AKT, GLUT4, INSR and IRS-1 proteins were quantified. RESULTS: Compared with the model control group, BSHT lowered serum testosterone, elevated E₂ and FSH, ameliorated glucose intolerance, and improved lipid profiles by decreasing TC and TG and increasing HDL-C. Polycystic ovarian morphology and hepatic lipid accumulation were also attenuated. BSHT down-regulated AT-EXO-miR-27a-3p expression (mean ± SD: 5.13 ± 0.27 vs 17.91 ± 1.19; < 0.001) and up-regulated both mRNA (0.38 ± 0.03 vs 0.08 ± 0.002; < 0.001) and protein (0.37 ± 0.10 vs 0.12 ± 0.02; = 0.001), while markedly increasing INSR protein abundance (1.50 ± 0.11 vs 0.37 ± 0.04; < 0.001). CONCLUSIONS: This study demonstrates that the BSHT prescription may alleviate reproductive endocrine disorders in PCOS rats by mitigating the inhibitory effects of fat-derived exosomal miR-27a-3p on PPARG.
OBJECTIVES: This retrospective study compares pregnancy outcomes in polycystic ovary syndrome (PCOS) patients across different controlled ovarian stimulation (COS) protocols-specifically GnRH antagonist and GnRH agonist...OBJECTIVES: This retrospective study compares pregnancy outcomes in polycystic ovary syndrome (PCOS) patients across different controlled ovarian stimulation (COS) protocols-specifically GnRH antagonist and GnRH agonist cycles-combined with various frozen embryo transfer(FET) preparation methods, such as hormone replacement therapy (HRT) and ovulatory cycles. Despite the known variations in COS and FET protocols, the optimal combination for improving pregnancy outcomes in this population remains unclear. METHODS: We analyzed the first FET cycles of 2510 patients with PCOS at our center between January 2017 and September 2024. Baseline characteristics and pregnancy outcomes were compared using the Kruskal‒Wallis test, the chi-square (χ²) statistic, the Bonferroni correction for multiple comparisons, and inverse probability of treatment weighting (IPTW) adjustment. RESULTS: After IPTW adjustment, no significant differences were observed in live birth rates or other key reproductive outcomes among the four protocol combinations (all > 0.05). Exploratory analyses revealed nonsignificant trends, suggesting two patterns: 1) GnRH agonist (vs. antagonist) COS protocols were associated with lower point estimates for the risks of preterm PROM and HDP; 2) ovulation (vs. HRT) cycles for FET preparation were similarly associated with lower point estimates for these risks. CONCLUSIONS: For PCOS patients, live birth success is equivalent regardless of COS/FET protocol combination, supporting flexible treatment personalization. Clinical decision-making involves a critical trade-off: GnRH agonist protocols and ovulation FET cycles may be associated with a trend toward lower obstetric morbidity, potentially linked to the promotion of a more physiological ovulatory milieu. This balance between immediate iatrogenic risk and long-term pregnancy health warrants further study.
OBJECTIVE: To review the mechanism of action, epidemiology, clinical efficacy, factors influencing treatment outcomes, and limitations of clomiphene citrate (CC). METHODS: A systematic literature search was conducted usi...OBJECTIVE: To review the mechanism of action, epidemiology, clinical efficacy, factors influencing treatment outcomes, and limitations of clomiphene citrate (CC). METHODS: A systematic literature search was conducted using electronic databases. The search strategy employed a combination of relevant MeSH terms and keywords. The final selection was limited to complete, peer-reviewed articles. RESULTS: Clomiphene citrate (CC) is the first-line oral ovulation induction agent for WHO Group II anovulation, most commonly polycystic ovary syndrome. It acts primarily at the hypothalamus, depleting estrogen receptors to increase gonadotropin-releasing hormone pulsatility and stimulate gonadotropin release. Although effective in restoring ovulation in approximately 73% of treated women, pregnancy rates remain significantly lower (~36%), highlighting a pronounced ovulation‒pregnancy gap. This discrepancy is largely attributed to CC's peripheral anti-estrogenic effects, which can cause endometrial suppression and hostile cervical mucus, thereby impairing implantation. Treatment success is influenced by factors such as obesity, insulin resistance, and hyperandrogenism, which are key predictors of CC resistance. While generally well-tolerated, side effects include hot flashes, mood swings, headaches, visual disturbances, and a notable risk of multiple pregnancies (8%-10%). CONCLUSIONS: While CC remains a cornerstone for inducing ovulation, its peripheral anti-estrogenic effects and significant rate of resistance necessitate adjunctive strategies, careful patient selection, and a transition to advanced therapies when needed to improve live birth outcomes.
BACKGROUND: Although assisted reproductive technology (ART) may increase the incidence of ectopic pregnancy (EP), the risk of EP and its associated risk factors in polycystic ovary syndrome (PCOS) patients, one of the ta...BACKGROUND: Although assisted reproductive technology (ART) may increase the incidence of ectopic pregnancy (EP), the risk of EP and its associated risk factors in polycystic ovary syndrome (PCOS) patients, one of the target populations for ART, remain poorly understood. METHODS: This retrospective study analyzed 377 PCOS patients undergoing IVF/ICSI (2010-2017). Standard ART protocols were applied, including controlled ovarian stimulation, oocyte retrieval, and embryo transfer. LASSO regression with 10-fold cross-validation selected 13 predictive features from 26 variables. Univariate and multivariate logistic regression analyses were performed for the overall cohort. A predictive nomogram was developed and internally validated using bootstrap resampling. RESULTS: Among 377 PCOS patients analyzed, LASSO regression identified 13 potential predictors including age, IVF cycles, and endometrial thickness (EMT). In women <35 years ( = 333), multivariate analysis revealed three independent EP predictors: increased IVF cycle number (aOR = 4.592, 95%CI 1.48-14.21, = 0.008), thinner EMT (aOR = 0.587, 95%CI 0.40-0.86, = 0.007), and frozen embryo transfer (aOR = 0.044, 95%CI 0.01-0.22, < 0.001). The developed nomogram incorporating these factors showed good discrimination (AUC 0.82) and calibration. Notably, clinical factors like abortion history and prolactin levels, while significant in univariate analysis, lost predictive value after multivariate adjustment in younger women. CONCLUSION: This study identifies three key predictors of ectopic pregnancy in younger PCOS (<35 year) patients undergoing ART: IVF cycle number, endometrial thickness, and frozen embryo transfer. The developed nomogram provides a validated assessment tool, particularly for younger patients. These findings highlight the need for personalized risk stratification and further research into underlying mechanism.
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 Univer...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 chan...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.
BACKGROUND: Genitourinary syndrome of menopause (GSM) is characterized by vulvovaginal dryness, irritation, dyspareunia, and elevated vaginal pH due to estrogen deficiency-related changes of the lower genital tract. Non-...BACKGROUND: Genitourinary syndrome of menopause (GSM) is characterized by vulvovaginal dryness, irritation, dyspareunia, and elevated vaginal pH due to estrogen deficiency-related changes of the lower genital tract. Non-hormonal therapies, including hyaluronic acid (HA)-based vaginal gels, are increasingly used to improve local tissue hydration and symptoms. OBJECTIVE: To assess short-term clinical outcomes and local tolerability associated with a hyaluronic acid-based vaginal gel (Gynexelle Hyalo-Duo) in women with GSM. METHODS: This retrospective, single-center observational study included 60 women aged 18-65 years (30 reproductive-age and 30 postmenopausal) managed at Studio Medico Capasso, Naples, Italy. The gel was applied daily for 7 days, followed by three applications per week for 3 weeks. Outcomes included the Vaginal Health Index (VHI), Vulvar Health Index (VuHI), Subjective Evaluation of Specific Symptoms (SESS), and vaginal pH, assessed at baseline (T₀), after 1 week (T₁), and after 4 weeks of treatment (T₂). RESULTS: At T₂, mean VHI increased from 12.7 ± 3.3 to 19.3 ± 4.0 (< 0.001), VuHI decreased from 5.3 ± 3.8 to 2.5 ± 3.5 (< 0.001), and SESS improved from 11.8 ± 3.3 to 2.4 ± 3.9 (< 0.001). Vaginal pH decreased from 6.1 ± 1.0 to 4.7 ± 0.8 (< 0.001). Improvements were observed in both reproductive-age and postmenopausal women. No adverse events were documented. CONCLUSION: Short-term use of a hyaluronic acid-based vaginal gel was associated with improvements in vulvovaginal symptoms and vaginal health parameters, with good local tolerability, in a real-world observational setting.
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 spe...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 ( = 0.934, < 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: This study aimed to determine if there was a change in serum G protein-coupled receptor 120 (GPR120) level and develop a nomogram model that accurately predicted the risk of preeclampsia (PE) in the first trim...OBJECTIVE: This study aimed to determine if there was a change in serum G protein-coupled receptor 120 (GPR120) level and develop a nomogram model that accurately predicted the risk of preeclampsia (PE) in the first trimester. METHODS: A total of 250 pregnant women were included in our prospective cohort study from January 2023 to July 2024. We measured the level of GPR120, and maternal demographics and clinical features were retrieved. Optimization of variable selection was achieved. We developed a nomogram based on multivariate logistic regression to predict the risk of pulmonary embolism (PE), incorporating eight selected predictive indicators. The AUC and calibration plots were utilized to assess the discrimination and calibration of the nomogram. For assessing the clinical advantages and usefulness of the two prediction models, the DCA, IDI, and NRI were utilized. RESULTS: The GPR120 expression level in the first trimester was significantly elevated in women who later developed PE (< 0.001). The nomogram demonstrated excellent discriminatory power in predicting PE in both the training and validation cohort. Calibration of the nomogram remained satisfactory in both the training and validation cohorts. The NRI values and IDI demonstrated that the performance of the developed nomogram was remarkably superior to that of the Model 2 ( < 0.05). The nomogram's clinical usefulness was validated by the DCA. CONCLUSIONS: GPR120 expression is significantly increased in early pregnancy of PE patients. The nomogram exhibited predictive capability for PE development but needs larger, multicenter cohorts for validation.
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 influe...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 ( = 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.