Search Results (260)

Background: The incidence of endometrial cancer (EC) is rising globally across all age groups. Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion that may progress to EC if untreated. A clinical model is needed to efficiently identify women requiring prompt evaluation while avoiding unnecessary invasive procedures. Obesity is a major risk factor, but whether Asian women require a lower body mass index (BMI) cutoff than the World Health Organization (WHO) definition remains debated. This study aimed to develop a multivariable risk prediction model to guide biopsy decisions and determine an appropriate BMI cutoff for predicting EIN/EC risk among Asian women. Methods: This study retrospectively reviewed 1192 women aged ≥18 years who underwent hysteroscopy between 2010 and 2023 at a tertiary hospital. Candidate predictors included patient age, parity, BMI, postmenopausal status, symptom of abnormal uterine bleeding (AUB), diabetes mellitus, hypertension, polycystic ovary syndrome (PCOS), use of oral contraceptives, intrauterine devices, or menopausal hormone therapy, tamoxifen treatment, presence of multiple polyps, and endometrial thickness (EMT) measured by transvaginal ultrasonography. Multivariable logistic regression with stepwise selection identified independent predictors, and model stability and calibration were assessed using 1000 bootstrap resamples. Results: EIN/EC was diagnosed in 55 patients (4.6%). Six independent predictors were identified: postmenopausal status (adjusted odds ratio [aOR] 5.93, 95% CI 2.92–12.04), AUB (aOR 4.07, 1.51–10.97), multiple polyps (aOR 2.49, 1.33–4.66), PCOS (aOR 2.37, 1.08–5.22), BMI (aOR 1.13 per kg/m²; 1.84 per +5 kg/m²), and EMT (aOR 1.07 per mm, 1.02–1.11). When using categorical cutoffs, Obese II (BMI ≥ 30 kg/m²) and markedly increased EMT (≥20 mm) remained significant. Predicted probabilities ranged from 0.3% with no risk factors to 90.9% with all six risk factors present. The final model demonstrated good discrimination (AUC 0.79, 95% CI 0.73–0.86) and excellent calibration on bootstrap validation (mean absolute error 0.005). Conclusions: This six-factor clinical model stratifies individual EIN/EC risk using readily available variables and may guide timely, risk-based biopsy decisions by identifying high-risk patients while minimizing unnecessary procedures in low-risk cases. BMI ≥ 30 kg/m² (WHO obesity threshold) was confirmed as a meaningful cutoff, but external validation is warranted to confirm its generalizability and clinical applicability. Full article

Combined oral contraceptives (COCs) remain one of the most popular reversible contraceptive methods worldwide. Still, regardless of the drug composition and duration of therapy, almost all COCs are associated with the risk of venous thrombosis. This review highlights the main pathogenetic mechanisms of thrombosis development during oral contraceptive use. Increase the production of certain clotting factors; a decrease in antithrombin and protein S levels; acquired resistance to activated protein C; a reduction in tissue factor pathway inhibitor (TFPI); indirect endothelial activation; inhibition of endogenous fibrinolysis; regulation of tissue factor by estradiol-sensitive microRNA; homocysteine imbalance caused by decreased intestinal reabsorption of folates and vitamin B-12; reduced bioavailability of nitric oxide (NO) due to high homocysteine levels; higher blood pressure, water retention, insulin resistance, increased levels of pro-inflammatory C-reactive protein (CRP) and uric acid, and antifibrinolytic (plasminogen activator inhibitor 1 type, PAI-1) biomarkers as consequences of NO deficiency; increased platelet adhesiveness and ADP-induced aggregation, which promote fibrinogen binding; and increased expression of pro-inflammatory cytokines are the main thrombotic effects of COCs use. Clinicians should carefully evaluate each patient’s individual risk factors when prescribing COCs and conduct regular monitoring to reduce the risk of complications. Full article

The oral microbiome may be an indicator of oral pathologies and hormonal fluctuations. Consequently, the proper identification of methods for studying microbial factors is essential. Because more than half of the components of the oral microbiome belong to species that are very difficult or even impossible to cultivate in the laboratory, the assessment of the oral microbiome nowadays is based on genetic sequencing, using techniques such as DNA hybridization, 16S rRNA sequencing, and metagenomics, mainly analyzing saliva and subgingival plaque. Variations in results may be caused by differences in sample type, analysis methods, accuracy in determining cycle phases, and biases introduced by DNA extraction techniques and technical variations. Choosing the right primers for the 16S rRNA gene and reference databases (like HOMD, Greengenes2) is essential for accurately identifying microorganisms. Metagenomic sequencing offers greater taxonomic and functional detail, but it is costlier and presents bioinformatics challenges, including contamination with human DNA. When the patients under study are women, we have to take into consideration the cyclical changes in the menstrual cycle. Studies suggest that estrogen influences local immune and inflammatory responses and can worsen existing gingival inflammation. Certain oral bacteria can even utilize estradiol and progesterone as growth factors. The composition of the oral microbiome is also affected by hormonal contraceptives, carbohydrate intake, smoking, age, body mass index, genetics, and oral hygiene—all factors that need to be controlled for in future studies. Interpreting the biological significance of the reported cyclic changes requires careful examination of the specific methods used in each study. Full article

Background/Objectives: Tubo-ovarian high-grade serous carcinoma (HGSC) is a highly lethal malignancy, usually diagnosed at an advanced stage due to the lack of early symptoms and biomarkers. Contraceptive hormone use is associated with a reduced risk of HGSC, but the relative contributions of natural versus synthetic progestins, and their interaction with estrogens, are poorly understood. Methods: We evaluated the chemo-preventive efficacy of a synthetic progestin medroxyprogesterone acetate (MPA), progesterone (P4), and combined 17β-estradiol-progesterone (E2 + P4) in a well-characterized genetically engineered mouse model (GEMM) of oviductal HGSC based on the conditional inactivation of one or both alleles of the Brca1, Trp53, Rb1, and Nf1 tumor suppressor genes (BPRN-het and BPRN-homo mice, respectively). Mice received hormones or placebo via slow-release pellets implanted subcutaneously. After induction of tumor formation, the mice were monitored for tumor development, progression, and survival. Tumor incidence was assessed histologically, and hormone effects were further explored via RNA-seq analysis of oviductal tissues. Results: MPA significantly reduced HGSC incidence and delayed tumor progression compared to the placebo, P4, and P4 + E2 in both BPRN-homo and BPRN-het mice, with up to 78% tumor-free survival in the MPA-treated BPRN-het cohort. P4 monotherapy did not provide significant protection vs. the placebo, but the effects of P4 could have been impacted by a failure to achieve sustained release of the hormone beyond 4–8 weeks. The E2 + P4 combination accelerated tumorigenesis and reduced survival (p < 0.0001 in BPRN-homo and p = 0.0004 in BPRN-het mice). MPA did not affect tumorigenesis in a colon cancer GEMM, or the growth of mouse HGSC-derived cells in vivo, suggesting the role of MPA in the early stages of HGSC development. Gene expression analyses showed that P4 and MPA downregulated cholesterol homeostasis, early and late estrogen response, and epithelial–mesenchymal transition pathways, though only MPA afforded tumor protection. Conclusions: These findings demonstrate that a synthetic progestin, specifically MPA, confers robust protection against HGSC development, while a combination including E2 (E2 + P4) increases risk. This work also illustrates how HGSC GEMMs can be used to compare the chemo-preventive effects of various synthetic progestins on HGSC development in order to prioritize the most effective ones for use in preventing HGSC in both general and high-risk populations. Full article

Introduction: Ductal carcinoma in situ (DCIS) is a non-invasive precursor of breast cancer, usually detected on mammography as clustered microcalcifications. Many cases, however, lack calcifications and require complementary imaging. This study aimed to describe the multimodal imaging features of DCIS and evaluate the radiology–pathology correlation. Methods: We retrospectively reviewed 75 women (aged 36–52 years) with biopsy-proven DCIS (January 2023–June 2025). All underwent mammography, targeted ultrasound, and dynamic contrast-enhanced 1.5T MRI. Imaging findings were correlated with histopathology, and logistic regression was used to explore predictors of MRI kinetics. Results: Mammography detected microcalcifications in 53.8% of patients, while 46.2% showed no calcifications. Ultrasound frequently revealed non-mass, duct-oriented hypoechoic abnormalities in non-calcified cases. MRI consistently demonstrated non-mass enhancement, with weak or persistent kinetics without washout in 69.2% and washout in 30.8%. A moderate correlation between MRI and histological extent was found (r = 0.62, p < 0.001), with MRI tending to overestimate lesion size. Oral contraceptive use was common (61.5%) but not significantly associated with kinetic pattern or grade. Conclusions: Mammography remains essential for calcified DCIS, whereas MRI enhances detection of non-calcified lesions. Persistent kinetics without washout may represent a typical imaging feature of DCIS. However, moderate radiology–pathology concordance and frequent overestimation highlight the need for careful interpretation. These findings support a multimodal diagnostic approach that can improve detection accuracy and assist in more tailored surgical planning. Full article

Polycystic ovary syndrome (PCOS) represents one of the most prevalent endocrine–metabolic disorder in women of reproductive age, which includes but not restricted to reproductive disruptions, insulin resistance (IR), hyperandrogenism, and chronic low-grade inflammation. Its heterogeneous pathophysiology arises from the interplay of metabolic, endocrine, and immune factors, including dysregulated adipokine secretion, cytokine-mediated inflammation, oxidative stress (OS), and mitochondrial dysfunction. Current pharmacological therapies, such as metformin, clomiphene, and oral contraceptives, often provide partial benefits and are limited by side effects, necessitating the exploration of safer, multi-target strategies. Flavonoids, a structurally diverse class of plant-derived polyphenols, have gained attention as promising therapeutic candidates in PCOS due to their antioxidant, anti-inflammatory, insulin-sensitizing, and hormone-modulating properties. Preclinical studies in rodent PCOS models consistently demonstrate improvements in insulin sensitivity, normalization of ovarian morphology, restoration of ovulation, and reduction in hyperandrogenism. Human clinical studies, though limited in scale and heterogeneity, report favorable effects of flavonoids such as quercetin, isoflavones, and catechins on glucose metabolism, adipokine balance, inflammatory markers, and reproductive functions. This evidence-based study critically synthesizes mechanistic insights into how flavonoids modulate insulin signaling, adipokine–cytokine crosstalk, OS, and androgen excess, while highlighting translational evidence and emerging delivery systems aimed at overcoming bioavailability barriers. Collectively, flavonoids represent a promising class of nutraceuticals and adjuncts to conventional therapies, offering an integrative strategy for the management of PCOS. Full article

Objectives: The aim of this study was to review the importance of peritoneal fluid steroid hormone concentrations to understand the mechanism of hormonal medical treatment of endometriosis-associated pain. Design: The study included a PubMed search and a pilot trial in 8 adolescents. Results: Oral contraceptives (OCs) were designed to inhibit ovulation in all women, and doses are much higher than the mean ovulation-inhibiting dose. Therefore, in most women, half a dose and in some women, even less is sufficient to inhibit ovulation. The inhibition of ovarian function and ovulation decreases estrogen and progesterone concentrations in plasma and peritoneal fluid. Surprisingly, the effect on peritoneal fluid steroid hormone concentrations has not been considered to explain the impact on endometriosis-associated pain. The lowering of the high estrogen concentrations in peritoneal fluid is sufficient to explain the pain decrease in superficial and ovarian endometriosis. A direct progesterone effect is unlikely, given the high progesterone concentrations in the peritoneal fluid of ovulatory women. In 8 adolescents, half an OC dose resulted in an apparently similar pain relief as a full dose (personal observation). Conclusions: The decrease in ovarian and superficial pelvic endometriosis-associated pain with OCs can be explained by lowering the intra-ovarian and the high estrogen concentrations in peritoneal fluid after ovulation. A direct progesterone effect is unlikely. Since OCs are severely overdosed in most women, half a dose is sufficient in most with fewer side effects, permitting individualization of therapy in women not requiring contraception. Understanding peritoneal fluid also explains that hormone replacement therapy is not contraindicated in most women with a history of endometriosis. Since the mechanisms of medical therapy of endometriosis-associated pain and the prevention of progression might be different, the growth of lesions must be monitored during treatment. Full article

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic inflammatory breast condition that poses diagnostic and therapeutic challenges. While corticosteroids are standard first-line therapy, some patients require additional immunomodulation, such as methotrexate. Predictive factors for step-up therapy remain poorly characterized. This study aimed to identify clinical, imaging, and pathological factors predictive of step-up therapy in IGM and evaluate associations between treatment approach and outcomes. Methods: A retrospective cohort study of women diagnosed with IGM was conducted between May 2022 and June 2024 at a tertiary center in Singapore. Data on demographics, clinical presentation, imaging, histopathology, and treatment were extracted. Step-up therapy was defined as methotrexate use following corticosteroids. Primary outcome was predictors of step-up therapy; secondary outcomes included treatment success, relapse, surgery, and time to remission. Statistical analyses included chi-square/Fisher’s exact tests, Cox models, and Kaplan-Meier analysis. Results: Fifty-two women (median age 39 years) were included; 26 (50%) required step-up therapy. Predictors included oral contraceptive (OCP) use (RR 1.92; 95% CI 1.45–2.53; p < 0.001), smoking (RR 2.00; 95% CI 1.49–2.69; p < 0.001), flares (RR 2.33; 95% CI 1.44–3.79; p = 0.002), and percutaneous aspiration (RR 2.10; 95% CI 1.53–2.88; p = 0.025). Patients receiving methotrexate had lower relapse rates (RR 1.23; 95% CI 1.12–1.36; p < 0.001) but longer time to remission (adjusted HR 0.09; 95% CI 0.02–0.46; p = 0.004). Conclusions: OCP use, smoking, flares, and aspiration need may predict step-up therapy in IGM. Early identification could guide a more personalized, potentially top-down treatment. Full article

Primary care providers are increasingly tasked with providing basic gynecologic care, including contraceptive therapy, to their patients. In the United States, oral contraceptive pills are the most frequently prescribed form of contraception; thus, it is critical that primary care providers are well versed in addressing common patient questions. Well-documented concerns relating to oral contraception initiation include changes in weight, mood, cancer risk, libido, acne, and infertility. Herein, we provide a clinical case example of a patient with these common concerns, review the related evidence, and suggest appropriate counseling with the goal of helping primary care clinicians provide the highest level of evidence-based oral contraceptive care. Full article

Background/Objectives: Medroxyprogesterone acetate (MPA) is a synthetic contraceptive that can be used orally or as a once-every-three-month injection (i.e., depot MPA [dMPA]). Prior research has reported an increased association between dMPA and cerebral meningioma but has been limited in generalizability to meningioma cases treated with surgery or cases derived from an administrative database of commercial insurance enrollees. The current study builds upon prior research by examining the association among public insurance enrollees utilizing both a non-active and active comparator. Methods: Utilizing Alabama Medicaid data, cases of cerebral meningioma were matched to up to ten controls based on age and year of Medicaid enrollment. A conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the association between MPA and dMPA exposure and cerebral meningioma were compared to both an active and non-active comparator. Results: Among 469 cases and 4690 matched controls, there was no association between oral MPA and cerebral meningioma. Associations for dMPA exposure were similar when using a non-active (OR 1.87, 95% CI 1.16–3.00) or active comparator (OR 1.93, 95% CI 01.01–3.69). These associations were strongest for prolonged exposure compared to a non-active (OR 3.80, 95% CI 1.88–7.68) and active comparator (OR 3.67, 95% CI 1.09–12.29). Conclusion: The current results are consistent with the prior literature that dMPA exposure is associated with an increased likelihood of meningioma for prolonged use. More research is needed to examine whether the association is limited to a certain histology or grade of meningioma. Clinicians should consider discussing with patients these reported associations prior to using dMPA. Full article

Background: Endometrial proliferative lesions are common in the menopausal transition and carry a measurable risk of carcinoma. Early risk stratification may guide evaluation and follow-up. Methods: We performed a single-center retrospective study of 315 women aged 45–55 years (May 2021–May 2024) at a private clinic in Bucharest. Lesions were classified per WHO 2014 as hyperplasia without atypia, atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN), or adenocarcinoma; “advanced pathology” was defined as AH/EIN or adenocarcinoma. Clinical comorbidities and transvaginal ultrasound endometrial thickness were recorded. Associations were tested with χ²; odds were estimated with multivariable logistic regression (adjusted ORs), with a modified Poisson sensitivity analysis for adjusted relative risk. Thickness differences were compared by one-way ANOVA, and severity correlations by Spearman’s ρ. Internal validation used 1000-bootstrap resampling. Results: Hyperplasia without atypia comprised 74.6% of cases, AH/EIN 20.0%, and adenocarcinoma 5.4% (advanced pathology 25.4%). Diabetes was independently associated with advanced pathology (aOR 2.75; 95% CI 1.14–6.61; p = 0.0237), while a history of non-atypical hyperplasia was inversely associated (aOR 0.31; 95% CI 0.13–0.72; p = 0.0068). Obesity showed a borderline association (aOR 1.79; 95% CI 0.98–3.26; p = 0.058), and long-term oral contraceptive use also approached significance (aOR 0.42; 95% CI 0.18–1.00; p = 0.051). Endometrial thickness increased stepwise with histopathological severity (ANOVA p < 0.0001; η² = 0.44) and correlated with ordered severity (ρ = 0.634). The multivariable model showed moderate discrimination (AUC 0.68; optimism-corrected 0.66) with acceptable calibration (slope 0.92; Hosmer–Lemeshow p = 0.052) and overall accuracy (Brier 0.18). Conclusions: In perimenopausal abnormal bleeding, metabolic comorbidities—especially diabetes—together with increased endometrial thickness identify women at higher risk of AH/EIN or carcinoma. Histopathology remains the diagnostic reference. The model can aid clinical prioritization but requires external validation and should not be used as the sole basis for decisions. Full article

This review aims to explore the implications of climate change for breast cancer management and prevention, with a focus on global strategies and interventions that can be applied in various contexts, including South Africa. Climate change has emerged as a significant global health concern, with far-reaching implications for various diseases, including cancer. This systematic review aims to synthesise epidemiological research examining the relationship between climate change and the incidence of breast cancer. We conducted a comprehensive literature search using main search terms, including “breast cancer,” “climate change,” “air pollution,” “water pollution,” “global warming,” and “greenhouse effect,” supplemented by the general term “breast” cancer across multiple databases. Our analysis identified studies that link environmental changes—such as rising temperatures, altered precipitation patterns, and increased exposure to pollutants—with breast cancer risk. Our findings highlight a potential association between climate-related factors, including heat stress, air and water pollution, endocrine-disrupting chemicals, and lifestyle changes influenced by environmental shifts, and the epidemiology of breast cancer. This review underscores the need for an integrated approach that incorporates climate science into public health strategies to mitigate breast cancer risk. By elucidating these connections, we aim to inform policymakers and healthcare professionals about the importance of addressing climate change not just as an environmental issue, but as a pressing determinant of health that may exacerbate cancer incidence, particularly in vulnerable populations. Further research is warranted to elucidate the underlying biological mechanisms and to develop targeted interventions that can address both climate change and its potential health impacts. Full article

Background/Objectives: This study examined how reproductive factors—such as oral contraceptive (OC) use, age at menarche, number of pregnancies, and age at first delivery—are related to the risk of metabolic syndrome (MetS) in Korean women aged 30–69, based on their menopausal status. Methods: Data from the Korea National Health and Nutrition Examination Survey 2010–2023 were analyzed, including 31,178 women with complete data. Survey-weighted logistic regression and restricted cubic spline analyses were conducted, adjusting for sociodemographic, lifestyle, and reproductive covariates. Results: OC use was associated with higher MetS risk in both pre-menopausal (adjusted OR 1.40, 95% CI 1.13–1.72) and post-menopausal women (adjusted OR 1.16, 95% CI 1.03–1.29). This association was observed primarily in relation to elevated blood pressure in both groups and high triglycerides in post-menopausal women. Other reproductive factors, including age at menarche, number of pregnancies, and age at first delivery, showed no significant associations with MetS risk. Conclusions: OC use was associated with higher MetS risk in this cross-sectional study of Korean women. These observational findings suggest a potential relationship that warrants further investigation through longitudinal studies to establish temporal relationships and explore underlying mechanisms. Full article

Background/Objectives: Hormonal contraceptives are widely used, but their effects on respiratory health remain underexplored. This systematic review examined the impact of oral contraceptive pills (OCPs) on pulmonary function, with an emphasis on asthma-related outcomes and underlying mechanisms. Methods: MEDLINE (PubMed), EMBASE (Ovid), CINAHL, AMED, SPORTDiscus, and PEDro were searched from January 2000 to December 2024. Pulmonary outcomes assessed included PEFR, FEV₁, airway hyperresponsiveness, and exhaled nitric oxide levels. Results: Twelve peer-reviewed studies were included. Most studies reported that OCPs do not impair lung function and may even improve respiratory parameters. Women using OCPs showed enhanced peak expiratory flow and reduced symptom variability, particularly in asthma and cystic fibrosis. Potential mechanisms include the stabilization of airway reactivity and modulation of inflammatory pathways. Heterogeneity across study populations and contraceptive types limited a meta-analysis, and few studies stratified outcomes by hormonal composition or comorbidities. Conclusions: Hormonal contraceptives may provide protective or regulatory effects on pulmonary function in specific populations. Larger precision-based studies are needed to clarify mechanisms and guide contraceptive counseling for women with respiratory conditions. Full article

The use of hormonal contraceptives is essential to ensure effective and safe contraception. However, factors such as inadequate prescription, poor adherence, or lack of information can lead to drug-related problems (DRPs) and negative outcomes associated with medication (NOMs). Methods: An observational, descriptive, cross-sectional study was conducted between January and June 2024 in two community pharmacies in Tenerife. It included 316 users of hormonal contraceptives over the age of 18. The main instrument was a structured questionnaire, administered through individual interviews conducted in the Personalized Care Area (PCA). Results: Combined Oral Contraceptives (COCs) were the most frequently used method (72.2%). Adverse reactions were reported by 47.2% of participants, mainly psychiatric disorders (28.1%). Emergency contraception had been used at least once by 43.8% of the respondents. Among COC users, 68.9% reported difficulties with daily adherence, and only 36.7% had adequate knowledge in case of missed doses. Conclusions: Community pharmacists may play a key role in reproductive health by providing personalized counselling, referring patients to other levels of care, and promoting the rational and safe use of hormonal contraceptives. Full article