Search Results (61)

Objectives: Equol, a gut-derived metabolite of soy isoflavones with estrogenic activity, may influence bladder aging. However, the association between overactive bladder (OAB), which is closely linked to bladder aging, and the estrogenic effects of equol remains unknown. Therefore, this study investigated the association between endogenous equol production and onset and severity of OAB in postmenopausal women. Methods: The study included 128 postmenopausal women, newly diagnosed with OAB, who were categorized into equol- and non-equol-producing groups based on urinary equol levels as measured by enzyme-linked immunosorbent assay. Patient clinical characteristics, OAB Symptom Score (OABSS), and urodynamic parameters were assessed. Propensity score matching was performed to minimize confounding factors related to the timing of lower urinary tract symptom (LUTS) onset. Results: Equol producers exhibited a significantly later onset of LUTS than non-producers (68.7 ± 10.9 vs. 62.7 ± 10.7 years, p = 0.002). Equol producers were more prevalent in the late-onset group (58.6% vs. 31.0%, p = 0.002), which had significantly higher urinary equol concentrations than the early-onset group (p = 0.014). No significant differences were observed in total OABSS or subscale scores between the groups, suggesting that equol did not affect symptom severity. Propensity score-matched analysis (n = 104) confirmed that equol non-production was an independent risk factor for early-onset LUTS (OR, 1.930; 95% CI, 1.248–4.049; p = 0.014). Conclusions: Endogenous equol production was significantly associated with the delayed onset of OAB in postmenopausal women. Thus, equol may serve as a protective factor and non-invasive biomarker to guide individualized prevention and early intervention strategies in urological care for women. Full article

Background: Urinary steroid profiling plays a key role in the diagnosis of inherited and acquired endocrine disorders. Despite the proven diagnostic value of gas chromatography–mass spectrometry (GC-MS), standardized and clinically validated protocols for extended steroid panels remain limited. Methods: We developed and validated a GC-MS method for the quantification of 32 urinary steroid metabolites, including androgens, estrogens, progestins, glucocorticoids, and mineralocorticoids. Sample preparation involved solid-phase extraction, enzymatic hydrolysis, and dual derivatization, followed by chromatographic separation and mass detection under full scan mode. Validation followed ICH M10 guidelines. Results: The method demonstrated high selectivity, accuracy (within ±15%), and precision (CV% < 15%) across three QC levels. Limits of Quantification were estimated using the Hubaux–Vos approach and were suitable for detecting both physiological and pathological steroid concentrations. Robustness and matrix effect tests confirmed the method’s reliability and reproducibility. Conclusions: This GC-MS protocol enables comprehensive urinary steroid profiling and calculation of diagnostic ratios for inborn errors of steroid metabolism and endocrine disorders. The method is suitable for clinical application and future integration into personalized medicine workflows. Full article

Background: Preeclampsia (PE) is a critical complication of pregnancy that affects 3% to 5% of all pregnancies and has been linked to aberrant placentation, causing severe maternal and fetal illness and death. Objectives: This systematic review aims to elucidate the association of in-utero endocrine-disrupting chemical (EDC) exposure and microRNAs and their imprinted genes from prenatal and maternal circulation of PE patients. Methods: Databases such as PubMed, PubMed Central, ScienceDirect, the Comparative Toxicogenomics Database (CTD), ProQuest, EBSCOhost, and Google Scholar were utilized to search for articles that investigate the relationships between selected EDCs and epigenetic events such as DNA methylation and microRNAs that are associated with PE. Results: A total of 29 studies were included in the database search. Altered expression of microRNAs (miR-15a-5p, miR-142-3p, and miR-185) in the placenta of PE patients was positively associated with the urinary concentration of phthalates and phenols in the development of the disease in the first trimester. EDCs such as phenols, phthalates, perfluoroalkyl substances (PFOAs), polybrominated diphenyl ethers (PBDEs), and organochlorine phosphates (OCPs) have been reported to be associated with hypertensive disorders in pregnancy. miRNA-31, miRNA-144, miRNA-145, miRNA-210, placental specific clusters (C14MC, and C19MC) may be used as possible targets for PE because of their potential roles in the onset and progression of PE. Conclusions: Prenatal EDC exposure, including exposure to BPA, showed association with signaling pathways including estrogen, sFlt-1/PlGF, ErbB, MAPK/ERK, and cholesterol mechanisms with placental hemodynamics. Even low EDC exposures leave altered epigenetic marks throughout gestation, which might cause PE complications. Full article

Background and Objectives: Stress urinary incontinence (SUI) impacts 4–50% of adult women, frequently resulting in embarrassment, diminished self-esteem, and social withdrawal, significantly affecting quality of life. The aim of our study is to cross-culturally adapt and validate the Urinary Incontinence Outcome Questionnaire (IOQ) for the Serbian population and to assess the multifaceted impact of SUI on the quality of life among women. Materials and Methods: A cross-sectional study involved a total of 150 women: 100 undergoing surgical management for SUI (ST group) and 50 receiving non-surgical treatments, including vaginal estrogen, pessaries, electrical stimulation, or collagen fillers (NST group). The participants completed questionnaires on demographics, fatigue (MFI), anxiety and depression (HADS), and quality of life (SF-36), as well as the IOQ. Results: The ST group had a mean age of 60.0 ± 10.0 years, with 65% married, 65% with secondary education, 62% non-smokers, and 78% with comorbid conditions, primarily cardiovascular disease (59%). The NST group showed similar characteristics, with a significant difference in cardiovascular comorbidity (p = 0.049). All IOQ subscales demonstrated good internal consistency (Cronbach alpha > 0.7), except for the subscale Complications (Cronbach alpha = 0.440). The IOQ score for “Symptoms pre-operative” had the highest mean value (62.8 ± 18.6), while “Hospital Re-admission” had the lowest (303 ± 17.1). A comparison of the SF-36 scores showed significant differences in the Energy (p = 0.025) and Emotional well-being (p = 0.015) domains between the ST and NST groups. Conclusions: The Serbian version of the IOQ has been validated, demonstrating psychometric features that endorse its application in clinical and research contexts. This study highlights the significant impact of SUI on quality of life and the need for a comprehensive approach to treatment. The results emphasize the importance of addressing both the physical and psychological aspects of SUI to improve the lives of affected women. Full article

Recurrent urinary tract infection (rUTI) is a significant public health problem in women. General measures to prevent recurrence include behavioral changes and increased fluid intake, cranberry ingest, use of methenamine hippurate, antibiotic prophylaxis, D-mannose, probiotics, or vaccines. We conducted a literature review of the latest updates on preventing rUTI in December 2024. The search concluded with 27 articles that fulfilled our inclusion criteria. Our review demonstrated that behavioral changes such as correct genital hygiene, avoiding postponing micturition or defecation, urinating after sexual intercourse, and ingesting 1.5–2 L of water could prevent rUTI. The ingestion of cranberries reduces the risk of symptomatic, culture-verified urinary tract infections in women with rUTIs. Methenamine hippurate is an alternative to antibiotics to avoid rUTI. Estrogen reduces rUTI in women with hypoestrogenism. Limited evidence supports using D-mannose, probiotics, and vaccines to prevent rUTI. In conclusion, after successful treatment of the acute episode, preventative measures are needed to reduce rUTI frequency and morbidity according to each patient’s characteristics and preferences. Full article

Worldwide, urinary tract infections (UTIs) have an increased incidence, especially in women. Recurrent UTIs (rUTIs) appear in less than three months in 80% of the cases, being associated with age, sexual activity, or diabetes mellitus. Antibiotics represent the first line of treatment for rUTIs after the diagnosis based on a positive mid-stream urine (MSU) culture. Alternative therapies including low-dose antibiotic treatment, immunoprophylaxis, cranberry extracts, probiotics, D-mannose, intravesical instillations, methenamine, and estrogens may reduce the recurrence of UTIs in female patients. Multimodal therapy seems to be the future in preventing and treating rUTIs. The main aim of this narrative review is to present the actual therapeutic challenges and the most efficient prophylaxis options in women diagnosed with rUTIs. Full article

Urinary tract infections (UTIs) represent a prevalent health concern among the female population, with anatomical and physiological determinants such as a shorter urethra and its proximity to the rectum augmenting vulnerability. The presence of Escherichia coli and various other pathogens plays a significant role in the etiology of these infections, which can be aggravated by sexual intercourse and disturbances to the vaginal microbiome. The physiological alterations associated with pregnancy further elevate the likelihood of UTIs, with untreated cases potentially leading to severe complications such as pyelonephritis, preterm labor, and stillbirth. Furthermore, postmenopausal women encounter an augmented risk of UTIs attributable to estrogen deficiency and vaginal atrophy, as well as conditions including pelvic organ prolapse (POP) and urinary incontinence (UI), which hinder optimal bladder functionality. The aforementioned factors, in conjunction with the rising prevalence of cesarean deliveries and catheterization, complicate the management of UTIs. While precise diagnosis is paramount, it remains a formidable challenge, notwithstanding advancements in molecular diagnostic techniques. Management strategies encompass antibiotic-sparing therapies; however, the increasing incidence of multidrug resistance represents an alarming trend. Diverse guidelines from various medical specialties endeavor to standardize treatment approaches, yet significant inconsistencies continue to exist. This study systematically appraises the extant guidelines, evaluating the quality of evidence while identifying areas of agreement and discord to supply practitioners with effective strategies for UTI management. Full article

Endometriosis afflicts 10% of women in their reproductive years and nearly half of women with infertility, and its etiology is not yet clear. Pharmacological therapy is generally based on progestins like progestogen. This drug binds to progesterone receptors with many known side effects. Here, we describe the case of a 33-year-old woman surgically treated for endometriosis who continued with drug therapy based on estradiol valerate and dienogest. Approximately 21 months after treatment, she reported ocular symptoms with vision alteration, diplopia, and metamorphopsia related to central serous chorioretinopathy (CSC). After the discontinuation of combined progestin-based treatment, the CSC fully subsided. Semeiological, clinical, and laboratory approaches were adopted, and urinary steroids were measured. A slight increase in prolactinemia in the absence of macro-prolactinemia was reported. The steroidal profile appeared without abnormalities, although a slight alteration of estrogen balance was noted. Considering the pharmacodynamics of dienogest versus selective progesterone receptor modulators, it can be assumed that patients’ clinical events are related to specific site response to steroids that bind the progesterone receptor. Dienogest may have induced the CSC as a not yet characterized side effect of the drug. Undoubtedly, further specific studies are needed concerning the metabolic and pharmacodynamic aspects that cannot be exhaustively covered here. Full article

Background: This is a prospective study. Atrophic vulvovaginitis (VVA), a prevalent condition resulting from estrogen deficiency after the menopause, is characterized by symptoms such as vaginal dryness, itching, burning, dyspareunia, and urinary discomfort. Standard treatment involves systemic estrogen replacement therapy (HRT) and localized estrogen treatments, such as estriol. However, many women with moderate-to-severe VVA may not fully benefit from estrogen therapy alone. Non-hormonal adjunctive treatments, such as pelvic floor exercises (e.g., Kegel exercises), are being explored to enhance clinical outcomes. Objectives: This study investigates the combined effect of local estriol therapy and Kegel exercises in improving VVA symptoms in postmenopausal women. Methods: Fifty postmenopausal women diagnosed with VVA were enrolled and divided into three severity groups: mild, moderate, and severe. All participants received estriol therapy (0.5 mg vaginal tablets daily for 10 days each month) for the first three months. Following this, Kegel exercises were introduced for an additional three-month period, alongside continued estriol therapy. Symptom improvement was evaluated after six months, with outcomes categorized as complete remission, partial remission, or no remission. Results: Significant improvements in symptom remission were observed, particularly in the moderate and severe groups. In the mild VVA group, 81.82% achieved complete remission with combined therapy compared to 68.18% with estriol alone. In the severe group, complete remission was observed in 40% of patients receiving combined therapy compared to 20% with estriol therapy alone. These findings suggest that Kegel exercises enhance the effectiveness of estriol by improving local blood circulation, which facilitates better estrogen absorption and distribution. Conclusions: The addition of Kegel exercises to local estriol therapy significantly improves symptom remission rates, especially in moderate and severe VVA cases. This approach offers a promising strategy for managing postmenopausal VVA, particularly in cases that do not fully respond to estrogen therapy alone. Full article

Background: Genitourinary Syndrome of Menopause (GSM) is a prevalent condition in postmenopausal women characterized by symptoms such as vaginal dryness, itching, and urinary tract issues due to declining estrogen levels. Despite its widespread impact on quality of life, GSM often remains underdiagnosed and without effective treatment. Methods: This study assessed the long-term efficacy of fractional CO₂ laser treatment in alleviating GSM symptoms in perimenopausal women. The study involved 125 participants, with clinical evaluations conducted using vaginal pH, the Vaginal Health Index Score (VHIS), the Vaginal Maturation Index (VMI), and the Female Sexual Function Index (FSFI). Results: Results indicated significant improvements in these parameters, with pH levels decreasing, VHIS scores rising, and notable gains in VMI and FSFI observed up to 12 months post-treatment. This improvement has been validated through both subjective and objective assessments of GSM. Conclusions: The findings indicate that this method is effective and safe, with no significant side effects reported. However, conducting a long-term observational study on eventual longer protocol for maintaining the positive effect of this therapy should be conducted. Full article

Genitourinary syndrome of menopause (GSM) affects a significant percentage of postmenopausal women and manifests as vaginal dryness, irritation, and urinary discomfort, typically treated with vaginal estrogens. Hydrogels are preferred over creams due to their superior comfort and mucoadhesive properties. This study introduces a novel vaginal gel formulation containing hydroxyethyl cellulose (HEC) and estriol-hydroxypropyl-β-cyclodextrin complex (E3-HPBCD) for the treatment of GSM. The estriol (E3) release profile of the gel was evaluated using a Franz diffusion cell system, and its permeability was tested on reconstructed human vaginal epithelium. Biocompatibility was assessed using (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) (MTT), lactate dehydrogenase (LDH) assays, and real-time cell analysis (RTCA) on human skin keratinocyte (HaCaT) cells, which showed increased cell viability and no obvious cytotoxicity. The results indicated that efficient E3 release and satisfactory epithelial permeability with HPBCD provide the bioavailability of E3. These results suggest the potential of the gel as a biocompatible and effective alternative for the treatment of GSM. Further studies are required to assess the long-term safety and clinical efficacy. Full article

Background/Objectives: Carcinoembryonic antigen (CEA) is a cell-surface glycoprotein serving as a drug target, diagnostic marker, and serum marker for cancer monitoring. However, prevalence data on CEA expression in cancer tissues vary considerably. This study was designed to determine CEA expression in normal and neoplastic tissues. Methods: A tissue microarray containing 13,725 samples from 120 different tumor types, as well as 76 different normal tissue types, was analyzed by immunohistochemistry (IHC). Results: CEA was detectable in 65 (54.2%) of 120 tumor categories, including 49 (40.8%) tumor types with at least one strongly positive case. CEA positivity was most common in colorectal adenomas (100%) and carcinomas (98.7%), other gastrointestinal adenocarcinomas (61.1–80.3%), medullary carcinomas of the thyroid (96.3%), pulmonary adenocarcinoma (73.7%), mucinous carcinomas of the ovary (79.8%) and the breast (43.2%), small-cell carcinomas of the lung (64.3%), and urinary bladder (38.9%). CEA overexpression was linked to high tumor grade and invasive growth (p < 0.0001 each) in urinary bladder cancer, and estrogen and HER2 receptor positivity (p ≤ 0.0158) in invasive breast cancer of no special type. In colorectal adenocarcinomas, reduced CEA expression was associated with mismatch repair deficiency (p < 0.0001). Conclusions: The comprehensive list of CEA-positive human tumor types demonstrates that CEA is expressed in a broad range of epithelial neoplasms, many of which might benefit from CEA serum monitoring and anti-CEA therapies. Full article

This scoping review explores the therapeutic strategies available for managing genitourinary syndrome of menopause (GSM), a condition often underdiagnosed and undertreated despite significantly affecting women’s quality of life. GSM results from decreased estrogen levels during menopause, leading to a range of symptoms including vulvovaginal atrophy and urinary tract issues. Material and Methods: we screened the literature for original studies with “menopause”, “hormonal therapy”, “vulvovaginal atrophy”, “urinary incontinence”, “urinary infections”, “genitourinary syndrome”. Results: A total of 451 relevant articles were retrieved. After screening, 19 articles were included in this scoping review. Discussion: First-line treatments typically include lubricants and moisturizers for short-term symptom relief, while unresolved or severe cases may warrant hormonal treatment. Topical hormonal treatments often have fewer side effects than systemic alternatives. Special attention is given to selective estrogen receptor modulators like ospemifene and steroid hormones like dehydroepiandrosterone (DHEA), which have shown beneficial effects on GSM symptoms. Moreover, innovative therapeutic approaches, such as laser treatment, are discussed in the context of their efficacy and accessibility. The safety of GSM hormonal therapy in women with a history or risk of cancer is also addressed, noting the need for more definitive research in this area. While there is a growing demand for tailored therapy, this scoping review emphasizes the importance of effective communication and counseling to allow women to make informed decisions about their treatment. Overall, this review underscores the need for increased awareness and further research into effective treatment options for GSM. Full article

Lower urinary tract symptoms (LUTS) are common in postmenopausal women. These symptoms are often linked to decreased estrogen levels following menopause. This study investigated the relationship between estrogen levels, alterations in bladder tissue structure, bladder function, and the incidence of urinary frequency. An age-appropriate bilateral ovariectomized mouse model (OVX) was developed to simulate conditions of estrogen deficiency. Mice were divided into three groups: a sham-operated control group, OVX, and an estradiol-treated group. The assessments included estrogen level measurement, urination frequency, cystometry, histological analysis, immunofluorescence staining, and real-time quantitative PCR. Additionally, we quantified the expression of the mechanosensitive channel proteins Piezo1 and TRPV4 in mouse bladder tissues. Lower estrogen levels were linked to increased voiding episodes and structural changes in mouse bladder tissues, notably a significant increase in Collagen III fiber deposition. There was a detectable negative relationship between estrogen levels and the expression of Piezo1 and TRPV4, mechanosensitive proteins in mouse bladder tissues, which may influence voiding frequency and nocturia. Estrogen treatment could improve bladder function, decrease urination frequency, and reduce collagen deposition in the bladder tissues. This study explored the connection between estrogen levels and urinary frequency, potentially setting the stage for novel methods to address frequent urination symptoms in postmenopausal women. Full article

Metformin plasma exposure is increased in rats with thioacetamide (TAA)-induced liver failure. The absorption, distribution, and excretion process of metformin is mainly mediated by organic cation transporters (OCTs) and multidrug and toxin extrusion transporters (MATEs). To investigate the mechanisms of the increase in TAA-induced metformin plasma exposure, we employed intestinal perfusion and urinary excretion assays to evaluate the changes in the absorption and excretion of metformin and used Western blotting to investigate the metformin-related transport proteins’ expression changes and mechanisms. The results showed that neither intestinal OCT2 expression nor metformin intestinal absorption were significantly altered by TAA-induced liver failure, while significantly decreased expression and function of renal OCT2 and MATE1 as well as impaired metformin excretion were observed in TAA rats. HK-2 cells were used as an in vitro model to explore the mechanism of liver-failure-mediated downregulation in renal OCT2 and MATE1. The results demonstrated that among numerous abnormal substances that changed in acute liver failure, elevated estrogen levels and tumor necrosis factor-α were the main factors mediating the downregulation of OCT2 and MATE1. In conclusion, this study highlights the downregulation of renal OCT2 and MATE1 in liver injury and its regulatory mechanism and reveals its roles in the increase in TAA-mediated metformin plasma exposure. Full article