Search Results (434)

Osteoporosis is a common disease characterized by a reduction in bone mineral density (BMD), leading to an increased risk of pathological fractures and even mortality. Although menopause is a major risk factor, osteoporosis can also occur in premenopausal women. The aim of this study was to identify genetic variants associated with the development of osteoporosis in Korean premenopausal women. Subjects were recruited from the Anseong and Ansan cohorts of the Korean Genome and Epidemiology Study (KoGES). Clinical and epidemiological characteristics were assessed, and participants were classified based on BMD values measured at the distal radius and mid-shaft tibia. Individuals with confounding risk factors such as low body weight, smoking, high alcohol consumption, steroid/hormone therapy, or relevant medical history were excluded. A total of 247 healthy controls and 57 osteoporosis patients were included. Genotyping was performed using the Illumina Infinium HumanExome BeadChip and the Affymetrix Axiom Exome Array. Data were analyzed using the SNP and Variation Suite and PLINK, with quality control thresholds set at MAF ≥ 0.05 and HWE p ≥ 0.01. Functional annotation and protein structure predictions were performed using PolyPhen-2, SIFT, and PROVEAN. Genome-wide association analyses identified 113 single-nucleotide polymorphisms (SNPs) in 69 genes significantly associated with osteoporosis (p < 0.05) in both platforms, with 18 SNPs showing high cross-platform consistency (p < 0.01). Several of these genes were implicated in bone metabolism (e.g., ESRRG, PECAM1, COL6A5), vitamin D metabolism (e.g., NADSYN1, EFTUD1), skeletal muscle function (e.g., PACSIN2, ESRRG), and reproductive processes (e.g., CPEB1, EFCAB6, ASXL3). Notably, the CPEB1 rs783540 SNP exhibited the strongest association (p < 0.001) in both analyses. Our findings suggest that genetic polymorphisms in pathways related to bone metabolism, vitamin D signaling, muscle–bone interaction, and reproductive hormone regulation may contribute to the development of osteoporosis in Korean premenopausal women. These results provide a genetic basis for early identification of at-risk individuals and warrant further functional studies to elucidate the underlying mechanisms. Full article

Background and Objectives: This study aims to investigate female sexual dysfunction (FSD) and the clinical, pathological, and social factors affecting it in women diagnosed with non-metastatic breast cancer. Materials and Methods: The study included patients over the age of 18 who were followed up between January 2020 and December 2024, diagnosed with breast cancer at least 12 months previously, and treated. The Female Sexual Function Index (FSFI) and its six subheadings (desire, arousal, lubrication, orgasm, satisfaction, and pain) were used to assess sexual dysfunction, and the Hospital Anxiety and Depression Scale (HADs) was used to assess depression. Results: FSD was identified in 86.6% of the 217 patients (mean FSFI score: 20.38). Among women undergoing breast cancer treatment, being over 45 years of age (p = 0.003) and the use of luteinizing hormone-releasing hormone (LHRH) agonists (p < 0.001) were significantly associated with reduced sexual desire. Conversely, premenopausal status (p = 0.012) was associated with increased sexual satisfaction. Independent risk factors for FSD included age, menopausal status, use of LHRH agonists, income level, and axillary dissection. Furthermore, depression was found to have a significant negative impact on sexual desire, lubrication, and orgasm. Conclusions: This study demonstrates that sexual dysfunction is common among women undergoing treatment for breast cancer and is influenced by numerous clinical and social factors. These findings highlight the need for strategic interventions to reduce the adverse effects of treatment processes on the sexual health of women with breast cancer. Full article

Objectives: The objective of this study was to evaluate the safety of postoperative in vitro fertilization (IVF) for atypical endometriosis (AE) in terms of ovarian endometrioma recurrence and development of endometriosis-related ovarian cancer (EAOC). Methods: Premenopausal women with AE who had undergone ovarian surgery between 2008 and 2022 and had attended follow-up appointments for at least 3 months were included in this retrospective study. The recurrence of endometriosis, postoperative pregnancy rate, occurrence of postoperative EAOC in cases of AE, and independent risk factors of AE recurrence were analyzed. Results: A total of 105 patients were included in the study with a median age of 33 years (range, 16–50 years) and a median follow-up duration of 29.0 months (range, 3–143 months). Most of the patients were treated with cyst enucleation (96.2%). Recurrent ovarian endometrioma was detected in 19 patients (18.1%), 4 of whom (19.0%) underwent reoperation, and there were no cases of EAOC. The cumulative recurrence rate at 12, 24, and 50 months was 7.4, 15.8, and 26.3%, respectively. Among the 105 patients, 36 wanted to become pregnant; of these, 12 underwent IVF, which, according to a univariable analysis, did not increase their risk of recurrent ovarian endometrioma. According to a subsequent multivariable analysis, previous history of ovarian endometrioma operation was the sole significant risk factor for AE recurrence (HR, 4.246; 95% CI, 1.262–14.285; p = 0.020). Conclusions: IVF trials for pregnancy did not represent a risk factor for recurrence, as treated AE showed a low possibility of malignant transformation, and IVF was not a risk factor for recurrence. Full article

Although evidence suggests adiposity as a modifiable risk factor for postmenopausal breast cancer (BC), its association with premenopausal BC remains uncertain. This potential differential relationship for menopausal status has been insufficiently investigated in the Moroccan population due to limited data. This study aims to assess the relationship between various indicators of adiposity and the risk of BC among Moroccan women by menopausal status. A multicenter case-control study was conducted in Morocco between December 2019 and August 2023, including 1400 incident BC cases and 1400 matched controls. Detailed measures of adiposity and self-reported measures from different life stages were collected. Unconditional logistic regression analyses were conducted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between body size indicators and the risk of BC, adjusting for a range of known risk factors for BC. Higher waist circumference (WC) and hip circumference (HC) were associated with an increased risk of BC in both pre- (p-trend < 0.001 for both WC and HC) and post-menopausal women (p-trend < 0.001 for WC, 0.002 for HC). Current body mass index (BMI) ≥30 kg/m² increased the risk of postmenopausal BC (p-trend = 0.012). Among postmenopausal women, higher weight at age 20 was positively associated with BC risk (p-trend < 0.001), while, weight at age 30 was significantly associated with increased BC risk in both pre- (p-trend = 0.008) and post-menopausal women (p-trend = 0.028). Interestingly, weight gain since age 20 was inversely associated with BC risk in postmenopausal women in the adjusted model (p-trend = 0.006). Young-adult BMI observed a significant increased trend with BC risk in both pre- (p-trend = 0.008) and post-menopausal women (p-trend < 0.001). In premenopausal women, larger body shape during childhood and early adulthood was positively associated with BC risk (p-trend = 0.01 and = 0.011, respectively). In postmenopausal women, larger childhood and adolescent body silhouettes were also associated with increased BC risk (p-trend = 0.045 and 0.047, respectively). These results suggest that anthropometric factors may have different associations with pre- and post-menopausal BC among Moroccan women. This underscores the importance of conducting large prospective studies to better understand these findings and explore their links to different molecular subtypes of BC. Full article

Background: Endometrial cancer (EC) is the most common gynecological malignancy, increasingly affecting premenopausal women. While hysterectomy is the standard treatment, it eliminates reproductive potential, highlighting the need for effective fertility-sparing alternatives. Current ESHRE/ESGO/ESGE guidelines recommend progestin-based therapies, often with hysteroscopic resection. However, these are based on limited pharmacological options and moderate to low-quality evidence. Novel and combination therapies have shown promise but remain absent from current clinical guidelines. This review aims to evaluate the efficacy and safety of fertility-preserving treatments for early-stage EC, emphasizing the need to update current strategies based on emerging data. Methods: A systematic review and meta-analysis will follow PRISMA guidelines and the Cochrane Handbook. Eligible studies, including randomized and non-randomized designs, will assess fertility-preserving treatments for early-stage EC. Data will be extracted on complete response, recurrence, and long-term fertility outcomes. The GRADE system will assess evidence certainty. Risk of bias will be evaluated using RoB 2 for RCTs and ROBINS-I for non-randomized studies. Meta-analysis will be performed if sufficient data are available. Conclusions: This review will provide a comprehensive analysis of fertility-sparing treatments for early-stage EC, support personalized strategies, identify evidence gaps, and guide future research. Trial registration—Prospero: CRD420251032161. Full article

Background and Objectives: The objective of this review is to evaluate the current evidence regarding hormone treatments for both premenopausal and postmenopausal women with early-stage hormone receptor (HR) positive breast cancer. Materials and Methods: An in-depth exploration of the existing literature was conducted, with landmark clinical trials such as TEXT, SOFT, ATLAS, and aTTom serving as primary references. Results: Through an extensive review of the literature, our findings indicate that for premenopausal women with HR-positive, HER2-negative BC with a low risk of recurrence, standard 5-year monotherapy with tamoxifen represents the optimal therapeutic management, given its favorable clinical outcomes and lower associated toxicity. In contrast, for premenopausal women with an intermediate to high risk of recurrence with the same tumor characteristics, the most effective approach stated in the literature is a combination of ovarian suppression therapy (chemical/surgical) and an aromatase inhibitor/selective estrogen receptor modulator (tamoxifen), with a possible extension of the standard therapeutic period. In postmenopausal patients with HR-positive, HER2-negative breast cancer with a low recurrence risk, the first line of treatment is usually a standard 5-year period of treatment with aromatase inhibitors (AIs)(letrozole, anastrozole, or exemestane). On the other hand, in postmenopausal women with an intermediate to high risk, combination therapy might be needed, as well as an extension of the standard therapeutic time. Conclusions: Treatment consensus depends on pre- vs. postmenopausal status and recurrence risk. Full article

Uterine fibroids (leiomyomas) are benign tumors whose growth is influenced by estrogen and progesterone. This study aimed to compare the profiles of differentially expressed long non-coding RNAs (lncRNAs) in fibroids from postmenopausal and premenopausal women to identify hormone-responsive lncRNAs. RNA sequencing was performed on six pairs of fibroid (Fib) and adjacent myometrium (Myo) tissues from postmenopausal women. Out of 7876 normalized lncRNAs, 3684 were differentially expressed (≥1.5-fold), with 1702 upregulated and 1982 downregulated in Fib. Comparative analysis with a previously published premenopausal dataset identified 741 lncRNAs that were altered based on their menopausal status, including 62 lncRNAs that were uniquely dysregulated in postmenopausal samples. Overall, 9 lncRNAs were selected for validation by PCR in an expanded cohort of 31 postmenopausal and 84 premenopausal paired samples. Several lncRNAs, including LINC02433, LINC01449, SNHG12, H19, and HOTTIP, were upregulated in premenopausal Fib but not in postmenopausal ones, while ZEB2-AS1 displayed the opposite pattern. CASC15 and MIAT were elevated in Fib from both groups, although the increase was less pronounced in the postmenopausal group. LINC01117 was significantly downregulated in postmenopausal Fib, with no change observed in premenopausal samples. Additionally, analysis based on MED12 mutation status revealed that lncRNAs such as LINC01449, CASC15, and MIAT showed limited or reduced differential expression (mutation-positive vs. mutation-negative) in postmenopausal patients compared to the premenopausal group. These findings indicate that lncRNA expression in fibroids is modulated by menopausal status, likely reflecting hormonal influence. Hormone-responsive lncRNAs may play key roles in fibroid pathogenesis and represent potential targets for therapeutic intervention. Full article

Background/Objectives: Bisphosphonates may influence vascular calcification and atheroma formation via farnesyl pyrophosphate synthase inhibition in the mevalonate pathway regulating bone and lipid metabolism. However, the clinical impact of NCB use on cardiovascular outcomes remains uncertain, largely due to methodological heterogeneity in prior studies. We aimed to evaluate the association between nitrogen-containing bisphosphonate (NCB) therapy and coronary artery calcium (CAC) progression, as well as the incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) events. Methods: From 6814 participants in MESA Exam 1, we excluded males (insufficient male NCB users in the MESA cohort), pre-menopausal women, baseline NCB users, and users of hormone replacement therapy, raloxifene, or calcitonin. Among 166 NCB initiators and 1571 non-users with available CAC measurements, propensity score matching was performed using the available components of FRAX, namely age, race, BMI, LDL cholesterol, alcohol, smoking, and steroid use, and baseline CAC yielded 165 NCB initiators matched to 473 non-users (1:3 ratio). Linear mixed-effects models evaluated CAC progression, and Cox models analyzed incident CVD and CHD events. Results: In the overall cohort, NCB use was not significantly associated with CAC progression (annual change: −0.01 log Agatston units; 95% CI: −0.05 to 0.01). However, among participants with a baseline estimated glomerular filtration rate (eGFR) < 65 mL/min/1.73 m², NCB use was associated with attenuated CAC progression compared with non-users (−0.06 log Agatston units/year; 95% CI: −0.12 to −0.007). No significant association was observed between NCB use and incident CVD events in the overall cohort (HR: 0.90; 95% CI: 0.60−1.36) or within kidney function subgroups. Conclusions: Incident NCB use among postmenopausal women with mild or no CAC at baseline was associated with reduced CAC progression only in women with impaired kidney function. However, this association did not correspond to a decreased risk of subsequent cardiovascular events, suggesting that the observed imaging benefit may not translate into meaningful clinical association. Full article

Women have a lower age-matched cardiovascular risk than men, largely due to estrogen’s protective role in endothelial function. While exercise improves vascular health, acute vascular responses are influenced by factors such as age, fitness level, metabolic status, and exercise modality. In premenopausal women, fluctuations in estrogen levels during the menstrual cycle may further affect vascular reactivity. Here, we review current evidence on acute exercise-induced vascular responses in women, emphasizing menstrual phase influences and key biomarkers such as flow-mediated dilation (FMD), along with others including vascular conductance and pulse wave velocity (PWV). Despite limited and heterogeneous evidence, shear-induced vascular responses, (including FMD) following acute exercise, appear to be relatively stable across menstrual cycle phase, suggesting that strict phasic control may not always be necessary. However, future high-quality studies are needed to further clarify this response. In contrast, other vascular assessments that rely more heavily on neural components—such as vascular conductance and PWV—show greater estrogen sensitivity. Nonetheless, the inconsistencies between studies again underscore the need for future research with hormonal verification. Morever, adequate sample sizes, and standardized exercise protocols will improve both consistency and help develop and promote the inclusion of women in vascular research. Full article

Background: Ovarian cancer remains the deadliest and leading cause of gynecological cancer-associated mortality in the US. The aim of this study was to characterize the trends in the incidence of ovarian cancer between premenopausal and postmenopausal women to inform future targeted interventions. Methods: This population-based cross-sectional study analyzed data from the US Cancer Statistics (USCS) database, which covered the whole of the US population between 2001 and 2021. Joinpoint regression was used to compute the average annual percentage change (APC) with 95% confidence interval (CI) and age-standardized incidence rates per 1,000,000 population. Results: The results showed that the IR of ovarian cancer declined between 2001 and 2021. Postmenopausal women had greater decreases in the IR of ovarian cancer compared to premenopausal women who showed a small decline. When stratified by race/ethnicity, non-Hispanic American Indian/Alaska Native women aged 20–49 years experienced an increase in the IR of ovarian cancer (APC = 2.4; 95% CI 0.9 to 4.1) compared to other racial/ethnic groups which showed a decline. Joinpoint trend analyses identified one inflection point in localized ovarian cancer incidence trends among all three age groups: an initial decline from 2001 to 2011 among women 20–49 years old and 65+ years old, and from 2001 to 2012 among women 50–64 years old, followed by an upward trend thereafter to 2021. Similarly, there was one inflection point in the IR of ovarian cancer for the clear cell and endometrioid types among women aged 20–49 years old. Conclusions: The IR of ovarian cancer in the US declined significantly among postmenopausal compared to premenopausal women, for whom the IR of ovarian cancer decreased only slightly. Although encouraging, these findings show a need for continued efforts to improve early detection and prevention strategies to mitigate the burden of this deadly disease. Full article

Introduction: The purpose of this study was to evaluate effects of post-exercise protein supplementation with combined resistance and interval training on total insulin-like growth factor-1 (IGF-1) concentration, strength (3RM), and body composition (DXA) in untrained pre-menopausal women. Methods: Twenty-seven women (33.6 ± 9.2 years, 69.4 ± 12.4 kg, 25.5 ± 3.7 kg/m²) were randomised into a control (CON) or moderate protein group (PRO) (3 g, 24 g, resp.) and completed twelve weeks of upper-body resistance (2×/week) and high-intensity interval cycle training (3×/week). Linear mixed-effects model analyses were conducted. Results: PRO had a greater daily protein intake (5.0 ± 16.6 g, 20.5 ± 13.9 g, CON, PRO, resp., p = 0.025), with no change in IGF-1 (−6.0 ± 27.7 µg/L, −2.1 ± 27.8 µg/L, CON, PRO, resp., p = 0.920). Total lean mass increased (0.84 ± 0.80 kg, 0.56 ± 1.4 kg, CON, PRO, resp., p = 0.009), and all strength measures increased in both groups (19–113%, p < 0.05). Conclusions: Untrained women can increase strength and lean mass over twelve weeks of combined resistance and interval training. Post-exercise protein supplementation had little effect, despite increasing protein intake by ~20 g/day in the PRO group. IGF-1 was not associated with any outcome measure. Full article

Background: The diagnostic accuracy of the exercise treadmill test (ETT) remains suboptimal in premenopausal women. Menstrual cycle phases display hormonal variations and biological effects in premenopausal women. The early and late follicular phases of the menstrual cycle demonstrate nearly four-fold differences in estrogen levels. Methods: This study assessed the variability in ETT results between the early and late follicular phases in premenopausal women. This study included premenopausal females with regular menstrual cycles and chest pain. As per the study protocol, patients underwent two separate ETTs at the early and late follicular phases of the menstrual cycle. Hormones and high-sensitivity cardiac troponin T (hs-cTnT) were measured. The primary endpoint was the ST segment/heart rate (HR) index. The secondary endpoints were maximum ST/HR slope, ST segment depression, HR and blood pressure (BP) response, exercise capacity, and hs-cTnT change after ETT. Results: False-positive ETT results were common in premenopausal women. The early follicular phase displayed significantly higher hs-cTnT and BP responses to ETT compared to the late follicular phase. This study reports that ETT results are similar between the early and late follicular phases of the menstrual cycle in premenopausal women. Biological variability is observed in the BP and hs-cTnT response to ETT between the two phases. Conclusions: The menstrual cycle phase (early versus late follicular phase) did not affect the ETT results. The consideration of estrogen and hormonal status when evaluating the diagnostic test results can improve our understanding of cardiovascular disease in women. Full article

To elucidate the changes in gas exchange across the life course, we estimated the age trajectories of O₂ saturation, CO₂ (as either end-tidal or serum bicarbonate), resting heart rate, and resting respiratory rate from age 2 yr onward in female and male patients separately. We utilized two sources’ data: electronic health records (EHR) representing ambulatory visits of approximately 53,000 individuals and sleep clinic polysomnogram (PSG) records representing an additional ~21,000. We used linear regression to estimate age-group-specific mean response levels for women and men. We compared estimated female–male differences between pre- and post-pubertal children and between pre- and post-menopausal periods among adults. Women between 15 and 45 years had higher O₂ saturation and lower serum bicarbonate levels or end-tidal CO₂ levels than men of similar ages. For O₂ saturation and for both measures of CO₂, the female–male difference was larger on average among adults at pre-menopausal ages than those at post-menopausal ages. Women had higher O₂ saturation throughout their lives than men; however, the difference disappeared in the elderly. Women between menarche and menopause had significantly lower end-tidal CO₂ and serum bicarbonate than men of similar ages. After menopause, however, women appeared to have higher mean levels of both end-tidal CO₂ and serum bicarbonate than men. Full article

Cystic mucinous neoplasms (MCNs) of the pancreas are rare cystic tumors, accounting for approximately 2–5% of all pancreatic neoplasms. They predominantly occur in premenopausal women and are typically located in the body or tail of the pancreas. Due to their potential for malignant transformation, especially in cases associated with invasive carcinoma such as pancreatic ductal adenocarcinoma, early detection, complete surgical resection, and rigorous postoperative surveillance are essential. The occurrence of MCNs in male patients is exceedingly rare, comprising only about 2% of reported cases, and often resulting in preoperative diagnostic challenges. Molecular analyses have identified a strong association between KRAS mutations and disease progression in MCNs, underscoring their potential role as prognostic markers despite limited diagnostic utility. In this report, we present two additional cases of MCNs in male patients, highlighting their histopathological features and the ancillary investigations undertaken to support diagnosis. Full article

The vaginal microbiota, a critical determinant of women’s health, is influenced by hormonal and metabolic parameters across the lifespan. While Lactobacillus species are beneficial markers of vaginal health, microbial composition undergoes pronounced alterations after menopause. This study aimed to elucidate the associations between vaginal microbiota composition, vaginal pH, menopausal status, and metabolic parameters in Asian women. Vaginal secretion samples were collected from 40 women (20 premenopausal, 20 postmenopausal). Full-length 16S rRNA gene sequencing was used to characterize the microbiota, categorized into Community State Types (CSTs): CST-I + II (Lactobacillus crispatus/gasseri, protective), CST-III (Lactobacillus iners, neutral), and CST-IV (anaerobic bacteria, harmful). Vaginal pH and clinical data were assessed in relation to microbial profiles. CST distribution differed significantly by menopausal status and vaginal pH. Harmful-type CST-IV was more prevalent in postmenopausal women (70% vs. 40%, p < 0.05), while CST-III was dominant in premenopausal women (45% vs. 5%). CST-IV was associated with elevated pH (median 6.00, p = 0.026) and increased abundance of anaerobes including Bacteroides, Fusobacterium, Porphyromonas, Prevotella, and Streptococcus. Oral antibiotic use reduced both beneficial and harmful CSTs, shifting toward neutral CST-III (75%, p = 0.048). Use of sodium–glucose cotransporter-2 (SGLT2) inhibitors in postmenopausal women was associated with a higher prevalence of protective CST-I + II (57.14% vs. 8.33%, p < 0.05), though no significant impact on pathogen presence was observed. This study highlights the dynamic interplay between menopausal status, metabolic interventions, and vaginal microbiota composition. Findings may inform targeted strategies to maintain vaginal health in aging populations. Full article