Search Results (506)

Background/Objectives: Early detection of breast cancer (BC) substantially improves outcomes, with a 5-year survival rate of 99% for early-stage disease. Risk-based screening, which tailors recommendations according to individual clinical, personal, and lifestyle factors, is a promising strategy to enhance early detection. However, previous studies have reported inconsistent evidence of association with BC risk for several modifiable lifestyle factors including premenopausal adiposity, sedentary behaviour, oral contraceptive use. To address these uncertainties, we investigated the association between clinical, personal, and modifiable lifestyle factors and BC risk in the Prevention, Imaging, Network, Knowledge (P.I.N.K.) project. P.I.N.K. generated real-world evidence by integrating clinical data with information collected through a structured questionnaire evaluating the associations between BC and clinical, personal, and lifestyle factors in 27,123 Italian women aged ≥ 40 years, who underwent integrated breast imaging diagnostics. Methods: Characteristics of women with and without BC were compared. Adjusted logistic regression, Least Absolute Shrinkage and Selection Operator (LASSO), and Random Forest models were applied to identify relevant predictors. Variables selected by at least two methods were included in a multivariate logistic regression model, with BC diagnosis as the outcome. Results: Accordingly with previous studies a consistent association was found for high breast density, late menopause, overweight, abdominal adiposity, cardiovascular-cerebrovascular and oncological comorbidities and smoking. Greater consumption of plant-based foods, lower intake of red and processed meat, and regular physical activity were associated with lower odds of BC as well. Conversely, an unexpected inverse association was assessed for menstrual irregularities, hyperlipidaemia, and oral contraceptive use. Conclusions: The integration of multiple sources of information both clinical and self-reported data collected directly from women adds to the growing evidence on the role of modifiable lifestyle factors in BC risk in supporting more targeted prevention strategies. Future prospective studies should further investigate the long-term effects of lifetime physical activity trajectories, different oral contraceptive formulations, and detailed reproductive history, including menstrual cycle characteristics and menopausal timing, to refine individualized BC risk prediction. Full article

Background/Objectives: Mat Pilates is widely recommended for middle-aged women, but whether baseline obesity modifies its effects remains unclear. This study compared responses to a 12-week mat Pilates programme between non-obese and obese middle-aged women across body-composition, cardiovascular, blood-metabolic, haemorheological and autonomic endpoints. Methods: In an exploratory secondary analysis of a completed, uncontrolled single-arm intervention cohort, de-identified pre- and post-intervention data from 32 premenopausal women (47.5 ± 7.6 years) were stratified by BMI into non-obese (NOG; <25 kg/m²; n = 14) and obese (OG; ≥25 kg/m²; n = 18) groups using WHO Asia-Pacific criteria. All completed identical 60 min sessions three times weekly for 12 weeks, with intensity progressed every four weeks. Outcomes were analysed with mixed-design ANOVA and Bonferroni-corrected paired t-tests. Results: Group × time interactions were significant for body weight, fat mass and percent body fat (p < 0.05). Flow-mediated dilation rose in both groups (NOG +15.6%, OG +29.7%; p < 0.05). Group × time interactions were non-significant for blood pressure, lipids and haemorheology; obesity-dependent claims are therefore restricted to the outcomes with significant interactions (body weight, fat mass, percent body fat). For the remaining outcomes, within-group changes reached significance only in the OG (total cholesterol, LDL-cholesterol, aggregation index, critical shear stress) or only in the NOG (diastolic and mean arterial pressure) but did not differ significantly between groups. Conclusions: Following the programme, endothelial function improved in both groups, whereas body-composition responses differed significantly by obesity status. Because this uncontrolled secondary analysis lacked a non-exercising control group, these associations cannot be attributed causally to mat Pilates. The apparent BMI dependence was not reproduced when adiposity was modelled continuously (baseline BMI, percent body fat or fat mass), so all between-group contrasts are hypothesis-generating. Adequately powered randomised controlled trials with a non-exercising comparator and objective monitoring of diet, non-exercise activity, sleep and menstrual-cycle phase are needed before BMI-dependent adaptations to mat Pilates can be considered established. Full article

Background: Opportunistic salpingectomy is widely used in gynecological surgery as a preventive measure against ovarian carcinoma. Questions have been raised about the potential impact of salpingectomy on ovarian function, given the possibility of ovarian vascularity disruption through the utero-ovarian arch located in the mesosalpinx. The aim of this study was to evaluate the short-term effects of bilateral salpingectomy on ovarian reserve. Methods: This prospective cohort study included forty premenopausal women, aged 34–50 years, who underwent hysterectomy with bilateral salpingectomy and ovarian preservation for benign uterine conditions. Ovarian reserve was evaluated before surgery and three months postoperatively, using serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and antral follicle count (AFC). Health-related quality of life was assessed using the Women’s Health Questionnaire (WHQ). Results: Serum FSH levels increased significantly after surgery, while AMH levels decreased significantly (both p < 0.05). No significant postoperative changes were observed in AFC. The overall WHQ score increased significantly, indicating a mild deterioration in health-related quality of life. The greatest postoperative changes were observed in the depressive, somatic and sexual domains, where menstrual symptoms improved following surgery. No significant correlation was found between WHQ scores and hormonal or ultrasonographic markers of ovarian reserve. Conclusions: Bilateral salpingectomy performed during hysterectomy was associated with significant short-term hormonal changes, while AFC remained stable. Although patient-reported quality of life slightly worsened after surgery, these changes were not correlated with hormonal or ultrasonographic markers of ovarian reserve. Larger controlled studies with longer follow-up are required to determine the long-term clinical significance of these findings. Full article

Background: Endometrial cancer (EC) is one of the most prevalent cancers in women globally, which has recently gained attention as an increase has been noted among premenopausal women. Improving fertility-sparing treatments is crucial to assist women in completing their family planning. Methods: This study aims to explore the current evidence on the mechanisms of action and correlation between Glucagon-like Peptide-1 (GLP-1) and its agonists with EC, as well as the potential application in the conservative therapy for early-stage EC. A narrative review of the worldwide literature was conducted according to Scale for the Assessment of Narrative Review Articles (SANRA) principles, intending to analyze the correlation of GLP-1 receptor agonists (GLP-1RAs) with EC and their precise effect in the fertility-sparing treatment in women with atypical endometrial hyperplasia (AEH) or early-stage EC. Results: Preclinical studies indicate that GLP-1 receptor (GLP-1R) expression on healthy and malignant endometrial tissues of models regulates apoptosis via the AMPK-mTOR pathway. Observational and early clinical studies conclude that their role in the improvement of metabolic and hormonal imbalance increases the risk for the development of EC, as well as anti-tumour and anti-inflammatory effects. Conclusions: GLP-1RAs represent a potentially promising addition to the conservative management of AEH and early-stage EC in premenopausal women; however, further extensive clinical trials are required to ensure their safety and efficacy in future treatment algorithms and preconception exposure. Full article

With a lifetime risk estimated to be 1 in 8 in industrialized countries, breast cancer is the most frequent type of cancer among women worldwide and the second leading cause of cancer deaths in women. More importantly, current evidence suggests that in women aged <45 years, breast cancer is unquestionably the leading cause of cancer-related deaths. Hormonal therapy has an established role in the treatment of breast cancer. Hormonal therapy aims at preventing the stimulation of mitogenic estrogen-dependent pathways. Hormonal therapy can be performed through blocking the production of estrogens or through blocking the action of estrogens upon tumor cells. The action of estrogens upon tumor cells can be blocked through selective estrogen receptor modulators (SERMs) or through selective estrogen receptor downregulators (SERDs). Estrogen receptor mutation (ESR1 mutation) is one of the common mechanisms by which breast cancer becomes resistant to additional therapies from SERMs or aromatase inhibitors. Fulvestrant, an injectable anti-estrogen, is the SERD commonly used. Fulvestrant has no agonistic activity and causes degradation of the estrogen receptor. This agent is more active in postmenopause than premenopause and is indicated in the treatment of advanced breast cancer in case of disease progression during or after tamoxifen. Oral SERDs are being rapidly developed to replace fulvestrant with the potential of higher efficacy and lower toxicities. Novel agents such as complete estrogen receptor antagonists (CERANs), proteolysis targeting chimeras (PROTACs), and selective estrogen receptor covalent antagonists (SERCAs) are also promising therapies. This manuscript focuses on recent advances in the development of drugs targeting the estrogen receptor. Full article

Background: Lipedema is a chronic disorder that predominantly affects women and is characterized by abnormal subcutaneous adipose tissue accumulation, pain, and vascular dysfunction. However, reliable circulating biomarkers that reflect disease-specific pathophysiology are still lacking. This study investigated serum markers associated with adipose tissue, inflammation, and angiogenesis to further elucidate the pathophysiology of lipedema. Methods: In this cross-sectional observational study, fasting serum levels of adiponectin, chemerin, lipopolysaccharide-binding protein (LBP), proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble CD163 (sCD163), and soluble CD137 (sCD137)—proteins associated with obesity and inflammation—were measured in 23 premenopausal women with lipedema and 23 age-matched healthy premenopausal controls. Serum endostatin levels, an angiogenesis inhibitor, and insulin-like growth factor binding protein 2 (IGFBP2), a potent proangiogenic factor, were also assessed. Results: Patients with lipedema and obese controls had comparable body mass index, glucose, and serum lipid profiles. No significant differences were observed between groups in circulating levels of adiponectin, chemerin, LBP, PCSK9, sCD163, sCD137 and IGFBP2. In contrast, serum endostatin levels were significantly reduced in patients with lipedema (p = 0.038). Additional analyses demonstrated markedly higher endostatin expression in human subcutaneous adipose tissue than in the liver, suggesting that circulating endostatin levels may be related to adipose tissue mass. However, serum endostatin levels were lower in obese compared with normal-weight women (p < 0.001). Conclusion: Lipedema was not associated with altered circulating levels of adiponectin, chemerin, LBP, PCSK9, sCD163, sCD137 or IGFBP2. Reduced serum endostatin levels support a potential role for vascular dysfunction in the pathophysiology of lipedema. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is increasingly recognized as a condition associated with cardiometabolic risk, yet its relationship with subclinical atherosclerosis in premenopausal women remains unclear. This systematic review aimed to synthesize and critically appraise the available evidence on the association between PCOS and markers of subclinical atherosclerosis. Methods: A systematic search of PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library was conducted for studies published between January 2021 and January 2026. Eligible studies included premenopausal women with PCOS and assessed direct vascular markers or validated surrogate indicators of subclinical atherosclerosis. Data were synthesized narratively following PRISMA guidelines. Results: Nine studies were included, comprising five human clinical studies and four bioinformatics analyses. Evidence from imaging-based studies demonstrated increased carotid intima-media thickness, reduced wall shear stress, and a higher prevalence of subclinical vascular abnormalities in women with PCOS, particularly in some hyperandrogenic phenotypes. In contrast, adolescent populations showed predominantly metabolic and inflammatory alterations without clear structural vascular changes. Biochemical studies reported adverse lipid profiles and elevated atherogenic markers, while mechanistic studies highlighted inflammatory and mitochondrial pathways. Conclusions: Current evidence suggests that PCOS may be associated with early vascular alterations in premenopausal women; however, findings are limited by heterogeneity and observational designs. Further large-scale, phenotype-stratified prospective studies using standardized vascular assessments are needed to clarify cardiovascular risk in this population. Full article

Coeliac disease is a chronic autoimmune enteropathy triggered by gluten consumption in genetically predisposed individuals. Given that lifelong adherence to a gluten-free diet (GFD) is the only effective treatment, the nutritional quality of commercially available gluten-free (GF) products is of particular importance. The aim of this study was to determine the nutritional content of selected GF products across multiple food categories available in the Greek market and compare them with their gluten-containing (GC) counterparts. In addition, the nutritional adequacy of a GFD for adults was assessed through an indicative 7-day dietary meal plan. A total of 228 food products (114 GF and 114 GC), categorized as charcuterie, starchy, bakery, confectionery, miscellaneous, meat-based, and plant-based, were included. Analysis of food label information revealed broadly comparable nutritional profiles with respect to energy, fat, saturated fat, carbohydrate, sugar, and sodium between GF and GC products. However, GF products contained less protein (7.31 ± 4.94 g vs. 9.86 ± 4.79 g, p < 0.001) and more dietary fibre (4.55 ± 3.05 g vs. 3.23 ± 2.21 g, p = 0.001). Analysis of the meal plan demonstrated that recommended intakes for all evaluated macronutrients and most micronutrients can be achieved while following a GFD with careful dietary planning. However, iron intake fell slightly below the recommended level for premenopausal women, while meeting vitamin D requirements remained challenging. Full article

Adaptogens are substances touted for their ability to promote resilience to stress. With more individuals reporting a greater degree of perceived stress, renewed attention has been focused on novel adaptogen complexes for stress reduction. Salidroside is a potent adaptogen found in the Rhodiola root, traditionally credited with increasing resistance to physical and mental stressors, while recent science has uncovered the neuroprotective effects of L-malic acid. The main objective of this study was to determine if daily supplementation of a novel salidroside and L-malic acid complex, across two dosing levels, could improve markers of perceived stress and its downstream effects, including anxiety and sleep disturbance. A 6-week randomized, double-blind, placebo-controlled, clinical study was conducted on individuals who subjectively reported a 30% room for improvement in perceived stress. Post hoc subgroup analysis was also conducted to determine if subpopulations experienced any enhanced benefits. Clinically meaningful improvements were reported in perceived stress and anxiety across the study population. Furthermore, men and non-premenopausal women saw enhanced benefits in emotional appraisal and sleep, suggesting hormonal interactions may be an underlying factor. SalidroPRO™ is a new dietary ingredient complex that may support rapid and sustained psychological well-being. Full article

Background: Menopause represents a critical physiological transition associated with hormonal changes that influence both metabolic health and quality of life (QoL). Metabolic dysfunction-associated steatotic liver disease (MASLD), a common metabolic condition, is closely linked to menopause; however, its independent contribution to QoL impairment remains unclear. This study aimed to investigate the interplay between menopausal status, metabolic dysfunction, MASLD, and QoL in midlife women. Methods: A cross-sectional observational study was conducted including 80 women aged 45–55 years, comprising both premenopausal and menopausal participants. Clinical, anthropometric, biochemical, and imaging data were collected. MASLD was diagnosed using magnetic resonance imaging in the presence of metabolic dysfunction. Metabolic assessment included glucose, insulin, liver enzymes, C-reactive protein, and indices of insulin resistance (HOMA-IR) and sensitivity (QUICKI). QoL was evaluated using the Utian Quality of Life (UQOL) scale. Associations were examined using univariate and multivariable linear regression models. Results: MASLD prevalence was significantly higher in menopausal women compared with non-menopausal women (61.9% vs. 15.8%, p < 0.001). Metabolic parameters, particularly insulin resistance and body mass index, were strongly associated with MASLD. The mean total UQOL score indicated moderate QoL. In multivariable analysis, menopausal status was the only independent predictor of reduced total QoL (b = −4.93, p = 0.01) and occupational health domain (b = −4.60, p = 0.001). MASLD and metabolic parameters were not independently associated with overall QoL. Correlation analyses revealed modest associations between metabolic markers and specific QoL domains, particularly occupational and physical health. Conclusions: Menopause is the primary determinant of reduced QoL in midlife women, particularly affecting functional domains, while MASLD does not independently impact QoL despite its strong association with metabolic dysfunction. These findings suggest that menopausal status may play a more prominent role in quality-of-life outcomes than MASLD in women undergoing the menopausal transition. However, the cross-sectional design does not allow conclusions regarding causal or mechanistic relationships. Full article

Background: The total vaginal hysterectomy (TVH) technique has been performed for many gynecological surgeries but is less used than total abdominal hysterectomy (TAH). The purpose of this study was to analyze the outcomes in patients who underwent either TVH or TAH for enlarged diffuse uterine adenomyosis (ADS). Methods: In this retrospective study, 160 hysterectomies with bilateral adnexectomy were scheduled for premenopausal women with diffuse ADS between 2020 and 2024 at a tertiary care center in Romania. The diagnosis was established based on clinical symptomatology, color Doppler transvaginal ultrasound, transabdominal ultrasonography and magnetic resonance imaging with histopathological confirmation of diffuse uterine ADS post-operatively from the hysterectomy specimen. All surgical procedures were performed by the same surgeon. The patients were divided into two groups: the TVH group (n = 80) and the TAH group (n = 80). Patient characteristics, including age, uterine weight, body mass index (BMI), parity, operative time, intraoperative blood loss, length of hospital stay, medical history, surgical history, intra- and postoperative complications, and the presence of adhesions, were evaluated. Results: No differences were observed between the two groups with regard to uterine weight, BMI, or parity. However, the TVH group was associated with significantly younger age, shorter operative time, lower intraoperative blood loss, and a reduced length of hospital stay (p < 0.001). Additionally, both medical and surgical histories were more frequently observed in the TAH group than in the TVH group. However, intra- (i.e., 3.75%) and postoperative complications (i.e., 13.75% vs. 3.75%) were slightly more frequent in the TAH group, as well as adhesions (i.e., 17.50% vs. 8.75%). Uterine hemisection, tactical myomectomy, or morcellation were frequently employed in the TVH group, being required in 77.5% of cases. Conclusions: In our cohort of patients with enlarged diffuse uterine ADS, TVH was associated with younger age, shorter operative time, reduced intraoperative blood loss, and a shorter length hospital stay compared with TAH, without an observed increase in perioperative complications. These results support the use of TVH as a feasible surgical approach for selected enlarged diffuse uterine ADS. Full article

Breast cancer (BC) is associated with metabolic factors that may influence circulating lipids and apolipoproteins. We performed a cross-sectional observational study including 198 women with infiltrating ductal breast carcinoma and 78 cancer-free controls. In the analyzed data, the breast cancer cohort included 39 premenopausal and 44 postmenopausal women without neoadjuvant chemotherapy (NACT), and 35 premenopausal and 54 postmenopausal women exposed to NACT; controls included 63 premenopausal and 52 postmenopausal women. Serum ApoA1 and ApoB were measured by ELISA, and HDL and LDL cholesterol were measured by enzymatic methods. Analyses included two-way ANOVA, Tukey post hoc testing, false-discovery-rate correction, and multivariable linear models adjusted for age and BMI, with HC3 robust sensitivity analyses. In cancer patients, HDL was lower in women exposed to NACT (adjusted β = −8.16, 95% CI −12.61 to −3.71), and ApoA1 differed by menopausal status. Subtype-aware analyses in the available subset did not show independent molecular subtype effects after multiplicity correction. These findings support cross-sectional associations between menopausal status, treatment exposure, and lipid/apolipoprotein profiles, but do not establish causality or prognostic value. Prospective longitudinal studies are required. Full article

Introduction: Breast cancer is the most common malignancy in women of reproductive age, and treatment advances have heightened the importance of fertility preservation (FP) for young patients. Despite heterogeneity across subtypes—hormone receptor-positive (HR+), HER2-positive, triple-negative (TNBC), and BRCA1/2-associated—existing guidelines lack subtype-specific FP guidance. Methods: This systematic review compared FP strategies across subtypes, identified subtype-specific challenges, and proposed pathways toward precision oncofertility care. PubMed, Scopus, and Web of Science were searched following PRISMA guidelines for English-language studies from 2004 to 2024. Results: After screening 1837 records, 19 studies met eligibility criteria (2 RCTs, 17 cohort studies); 11 of 17 non-randomized studies were at low overall risk of bias, and 6 at moderate risk due to confounding. Discussion: COS using letrozole- or tamoxifen-modified protocols was feasible, yielding 8–14 mature oocytes per cycle with reduced estradiol exposure suitable for HR+ disease. Evidence was strongest for HR+ patients; TNBC and HER2+ data were more limited, with some studies noting reduced ovarian reserve. GnRH agonists during chemotherapy reduced ovarian failure rates and improved post-treatment recovery, most consistently in hormone receptor-negative disease. BRCA1/2 carriers showed broadly comparable FP outcomes to non-carriers, though BRCA1-positive patients had modestly reduced oocyte yields in some studies with inconsistent results. Conclusions: Among studies with medium-term follow-up (3–5.5 years), no significant increase in recurrence or mortality attributable to FP was identified; long-term data beyond 5 years remain sparse. Substantial heterogeneity precluded meta-analysis; all synthesis is narrative. Standardized outco reporting and larger prospective subtype-stratified studies are required to establish precision oncofertility recommendations. Full article

Background: Smooth muscle tumors of uncertain malignant potential (STUMPs) are rare uterine neoplasms occupying the diagnostic continuum between benign leiomyoma and overtly malignant leiomyosarcoma. Their preoperative identification remains beyond the capability of current imaging modalities, and the diagnosis is almost invariably established through postoperative histopathological examination. The natural history of STUMP is highly variable, with recurrence rates ranging from approximately 7–27% and a documented potential for malignant transformation, underscoring the need for accurate pathological classification and long-term surveillance. Case Presentation: A 40-year-old woman with a history of hypertension presented with a 5-month history of progressive lower abdominal distension, urinary frequency, and menorrhagia. Transabdominal ultrasonography identified a large uterine fundal mass measuring approximately 10.89 × 8.96 cm. Preoperative laboratory findings demonstrated microcytic anemia. She underwent laparo-endoscopic single-site supracervical hysterectomy with bilateral salpingectomy. Histopathological examination revealed spindle cells with bland to mildly atypical nuclei, a mitotic count of <10/10 high-power fields, and focal necrosis, consistent with a diagnosis of STUMP. The patient remained free of recurrence over a 2-year follow-up period. Conclusions: This case illustrates the diagnostic challenge posed by STUMP in the preoperative setting and highlights the critical importance of thorough histopathological evaluation of all uterine smooth muscle tumor specimens. Minimally invasive hysterectomy with in-bag morcellation represents a feasible surgical approach, and long-term oncological surveillance is warranted given the risk of late recurrence and malignant transformation. Clinicians should maintain a heightened index of suspicion for borderline smooth muscle tumors when evaluating large or symptomatic uterine masses in premenopausal women. Full article

Background/Objectives: The benefits of vitamin K are well established in skeletal and cardiovascular health through activation of vitamin K-dependent proteins, including osteocalcin and matrix Gla protein. Emerging evidence also links vitamin K to pathways that influence body composition, including insulin sensitivity, adiponectin regulation, lipid oxidation, and inflammation. Vitamin K deficiency is linked to adverse health outcomes. We therefore evaluated whether menaquinone-7 (MK-7) supplementation alters body composition in adults with low vitamin K status. Methods: A total of 243 participants (166 women and 77 men) with low vitamin K status received 180 mcg of menaquinone-7 (MK-7), a form of Vitamin K, daily for one year. Changes in body mass index (BMI), body weight, fat mass, lean mass, and visceral adipose tissue (VAT) were assessed. Results: At baseline, higher dp-ucMGP, indicating lower vitamin K status, was positively associated with BMI (r = 0.223; p < 0.01), fat mass index (r = 0.200; p < 0.01), and VAT (r = 0.286; p < 0.001). After one year of supplementation, the total cohort showed a small but significant BMI reduction (−0.66%; p = 0.041). Responders (≥183 pmol/L dp-ucMGP drop) showed improvements in fat mass (−1.93%, p = 0.039), waist-to-hip ratio (−1.43%, p = 0.012), BMI (−1.37% ± 3.21, p = 0.004), and weight (−1.25%, p = 0.008), while non-responders exhibited an increase in VAT (+7.28%, p = 0.002). Women, especially premenopausal ones, experienced greater reductions in BMI, fat mass, and weight. dp-ucMGP levels significantly decreased in 90.9% of women (p < 0.001), whereas in men, although 77.8% showed a decrease, the change was not statistically significant. Among high responders (≥183 pmol/L dp-ucMGP reduction), both sexes demonstrated improvement, albeit significant body composition changes were seen only in women. Conclusions: Lower vitamin K status was associated with higher BMI, fat mass, and visceral adipose tissue. After one year of MK-7 supplementation, a modest reduction in BMI was observed, with more pronounced improvements in body composition among women. While these sex related differences may suggest that men require higher doses to achieve comparable responses, the current evidence remains preliminary. Further studies with larger cohorts are needed to clarify these findings. Full article