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Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.

Background: Chemo-endocrine therapy can lead to various side effects associated with ovarian dysfunction. Predicting menstrual recovery is necessary to discuss the treatment-related issues regarding fertility and premature menopause with patients. Methods: In the ASTRRA trial, patients who resumed ovarian function within 2 years after chemotherapy were randomized to receive tamoxifen for 5 years or OFS with tamoxifen for 2 years. With these 1298 patients, we developed a model that predicts when menstrual recovery will occur within a 3-year period after chemotherapy using variables including age, body mass index, chemotherapy regimen and duration, and serum estradiol and follicle-stimulating hormone levels. Results: The data of 957 patients were used to develop the prediction model, and those of 341 patients were used for validation. In the development group, menstruation resumed in 450 patients (47.0%) within 5 years. In multivariable analysis, younger age (< 35 vs. 45, HR 7.85, 95% CI 4.63–13.30, p < 0.0001), anthracycline-based chemotherapy without taxane (vs. with taxane, HR 1.81, 95% CI 1.37–2.38, p < 0.0001), and chemotherapy duration (≤ 90 days vs. > 90 days, HR 1.32, 95% CI 1.01–1.72, p = 0.045) correlated with menstrual recovery. Using combined age, regimen, and duration of chemotherapy, we developed a simplified scoring system to estimate recovery chances and used a concordance index of 0.679 overall and 0.744 at 3 years for validation. Conclusion: This model predicted timing and probability of menstrual recovery, based on their individual age, type and duration of chemotherapy in premenopausal women diagnosed with breast cancer who received tamoxifen after chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives It is not clear whether the association between younger age at menopause and increased risk of dementia is modified by type of menopause. We examined the association of age at menopause or hysterectomy with dementia risk in three groups of women: those with natural menopause, premenopausal bilateral oophorectomy (surgical menopause) or premenopausal hysterectomy (without bilateral oophorectomy). Study design Individual-level data from 233 802 women in five prospective cohort studies (from four countries) were harmonized and pooled. Cox proportional hazards models were used to assess the associations of age at natural menopause, surgical menopause or premenopausal hysterectomy, with age at dementia, death (where available) or end of follow-up, whichever came first. Results The study followed women to the median age of 72 years (quartiles 67, 76 years). The median follow-up time was 13 years, with 3262 dementia cases during this period. Compared with women with menopause at 50–52 years, women with menopause <40 years had a higher risk of dementia (adjusted hazard ratio (aHR): 1.47, 95% confidence interval (CI): 1.39, 1.56). This level of risk was comparable to that of current smoking and stroke, which are well-established risk factors for dementia. Increased risk of dementia associated with surgical menopause or premenopausal hysterectomy (compared to natural menopause) was not apparent after adjustment for age at menopause (aHR 0.99, 95% CI: 0.93, 1.04 and aHR 0.97, 95% CI: 0.95, 1.00, respectively). Conclusion Women who experience menopause before the age of 40 years have a higher risk of dementia irrespective of type of menopause. [ABSTRACT FROM AUTHOR]

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Background: Hormone fluctuations in women are accompanied by an increase in obesity. Although obesity has various causes, the interaction between obesity and menopausal status remains unclear. Objectives: This study aimed to investigate the interaction between lifestyle physical activities (PAs), such as occupational and household activities, and purposeful exercise, such as sports, with appetite and their correlation with body composition during the menopausal transition (MT) and postmenopausal (PM) phases. Design: This was a descriptive cross-sectional design. Methods: Women aged 42–62 years, in the MT or PM phases, were included. PA and appetite were measured using the validated Beacke questionnaire and the Simplified Nutritional Appetite Questionnaire, respectively. Body weight, height, waist circumference, and hip circumference were measured to estimate the body mass index (BMI) and waist-to-hip ratio (WHR). Results: A total of 101 women were included in the study. A significant positive relationship was found between appetite and PA in the MT group (r = 0.55, p < 0.001). In the MT group, PA (β = −0.38, p = 0.009) and appetite (β = 0.42, p = 0.004) predicted 16% of the BMI, while PA and appetite predicted 16% of the WHR. Only PA contributed significantly to the prediction of WHR (β = −0.33, p = 0.0.02). In the PM group, PA and appetite predicted 15% of the WHR (p = 0.030), and PA was a significant predictor of the WHR (β = −0.29, p = 0.0.03). There was no significant difference between the BMI and WHR in active women who regularly performed purposeful exercise compared to inactive women during the PM phase (p > 0.05). However, the appetite of active women was higher than of inactive women (p = 0.003). Conclusions: Menopausal status was effective on obesity indices, appetite, and PA. Lifestyle PA was superior to appetite in predicting obesity indices during the MT and PM phases, and particularly during PM; hence, PA was more important than exercise in determining obesity. Plain language summary: Exploring the impact of physical activity and appetite on obesity in women during menopause and after This study looked at how physical activity (PA) and appetite affect obesity in women going through menopause and after. Hormonal changes during menopause can lead to weight gain, but how this relates to activity levels and appetite is not well understood. Researchers included 101 women aged 42 to 62 who were either in the menopausal transition (MT) or postmenopausal (PM). They assessed the participants' levels of physical activity and appetite using questionnaires and measured body weight and measurements to calculate body mass index (BMI) and waist-to-hip ratio (WHR). The results showed a strong link between appetite and physical activity in women going through menopause. Both PA and appetite were found to influence BMI and WHR in these women. Interestingly, while both factors predicted obesity measures, it was mainly physical activity that played a key role in affecting the waist-to-hip ratio. In the postmenopausal group, physical activity and appetite also influenced waist-to-hip ratio, but there was no significant difference in BMI and WHR between women who exercised and those who did not. However, active women reported a higher level of appetite compared to inactive women. In conclusion, the study found that menopausal status impacts body composition and appetite. Lifestyle physical activity was more influential than appetite in predicting obesity during both the menopausal transition and after menopause, highlighting the importance of staying active rather than just focusing on exercise in managing body weight [ABSTRACT FROM AUTHOR]

Abstract Background Chemo-endocrine therapy can lead to various side effects associated with ovarian dysfunction. Predicting menstrual recovery is necessary to discuss the treatment-related issues regarding fertility and premature menopause with patients. Methods In the ASTRRA trial, patients who resumed ovarian function within 2 years after chemotherapy were randomized to receive tamoxifen for 5 years or OFS with tamoxifen for 2 years. With these 1298 patients, we developed a model that predicts when menstrual recovery will occur within a 3-year period after chemotherapy using variables including age, body mass index, chemotherapy regimen and duration, and serum estradiol and follicle-stimulating hormone levels. Results The data of 957 patients were used to develop the prediction model, and those of 341 patients were used for validation. In the development group, menstruation resumed in 450 patients (47.0%) within 5 years. In multivariable analysis, younger age ( 90 days, HR 1.32, 95% CI 1.01–1.72, p = 0.045) correlated with menstrual recovery. Using combined age, regimen, and duration of chemotherapy, we developed a simplified scoring system to estimate recovery chances and used a concordance index of 0.679 overall and 0.744 at 3 years for validation. Conclusion This model predicted timing and probability of menstrual recovery, based on their individual age, type and duration of chemotherapy in premenopausal women diagnosed with breast cancer who received tamoxifen after chemotherapy.

Abstract Background The transition to menopause is a significant event affecting health, well-being, and quality of life. Menopause typically occurs between the ages of 44–57, accompanied by symptoms such as hot flashes, mood changes, and sleep disturbances. Being postmenopausal also increases the risk of cardiovascular disease, stroke, and osteoporosis. Despite its importance, menopause is under-researched and under-discussed, particularly concerning the impact of chronic psychosocial stress. Methods A scoping review of qualitative, quantitative, and mixed methods research was conducted to map existing literature on the transition to menopause among populations experiencing chronic psychosocial stress in the United States. The review followed the PRISMA-ScR methodology, systematically searching literature in PubMed and SCOPUS databases using MeSH terms. Studies were included which focused on menopausal symptoms and psychosocial stressors. Data extraction and charting were performed using Covidence software. Results Fifteen studies were included, highlighting relationships between socioeconomic status, intimate partner violence, childhood abuse, and racial disparities which influenced menopausal experiences. Lower- income, higher perceived stress, and negative attitudes towards menopause were associated with increased psychological and somatic symptoms and early onset of menopause (prior to age 45). African American women were found to experience earlier onset and more severe vasomotor symptoms compared to their White counterparts. Women veterans used hormone therapy more frequently than the general population, particularly those with mood or anxiety disorders. The review also identified a geographic bias, with most studies conducted in the Northeast, Midwest, and Western regions of the United States. Conclusions This review underscores the necessity of considering social, cultural, and environmental factors in understanding menopausal experiences and addressing health disparities. Future research should aim to include diverse populations and adopt longitudinal and qualitative study designs to capture the dynamic nature of menopausal experiences. Policies and interventions directed at improving the well-being of women experiencing menopause in the context of chronic psychosocial stress are warranted. Trial Registration N/A.

Background: Premenopause syndrome triggers more severe physical and psychological problems and the emergence of various diseases. The limited research on the factors causing the severity of Premenopause syndrome has resulted in a lack of efforts to address the causative factors. Purpose: This study aims to explore factors that influence the severity of premenopause syndrome. Method: This is an analytic observational study with a cross-sectional design. Eighty-eight women aged 40-45 years were included in this study. The knowledge, attitude, age of menarche, use of hormonal contraceptives, and symptoms of premenopause syndrome observed in this study—data analysis using chi-square and multiple logistic regression. Results: Factors that influence the severity of premenopause syndrome are knowledge, attitude, age of menarche, and use of hormonal contraceptives (p

Background: The transition to menopause is a significant event affecting health, well-being, and quality of life. Menopause typically occurs between the ages of 44–57, accompanied by symptoms such as hot flashes, mood changes, and sleep disturbances. Being postmenopausal also increases the risk of cardiovascular disease, stroke, and osteoporosis. Despite its importance, menopause is under-researched and under-discussed, particularly concerning the impact of chronic psychosocial stress. Methods: A scoping review of qualitative, quantitative, and mixed methods research was conducted to map existing literature on the transition to menopause among populations experiencing chronic psychosocial stress in the United States. The review followed the PRISMA-ScR methodology, systematically searching literature in PubMed and SCOPUS databases using MeSH terms. Studies were included which focused on menopausal symptoms and psychosocial stressors. Data extraction and charting were performed using Covidence software. Results: Fifteen studies were included, highlighting relationships between socioeconomic status, intimate partner violence, childhood abuse, and racial disparities which influenced menopausal experiences. Lower- income, higher perceived stress, and negative attitudes towards menopause were associated with increased psychological and somatic symptoms and early onset of menopause (prior to age 45). African American women were found to experience earlier onset and more severe vasomotor symptoms compared to their White counterparts. Women veterans used hormone therapy more frequently than the general population, particularly those with mood or anxiety disorders. The review also identified a geographic bias, with most studies conducted in the Northeast, Midwest, and Western regions of the United States. Conclusions: This review underscores the necessity of considering social, cultural, and environmental factors in understanding menopausal experiences and addressing health disparities. Future research should aim to include diverse populations and adopt longitudinal and qualitative study designs to capture the dynamic nature of menopausal experiences. Policies and interventions directed at improving the well-being of women experiencing menopause in the context of chronic psychosocial stress are warranted. Trial Registration: N/A. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Ovarian hyperthecosis (OH) is a benign pathology, less common in premenopause. Literature is poor on its ultrasound (US) characteristics. We suggest that a heterogeneous ovary at US, with a central vascularisation and follicles to the periphery, with or without hyperandrogenism, should lead to consider OH in the hands of experts. [ABSTRACT FROM AUTHOR]

Background: Overactive bladder syndrome affects millions globally. It can intermittently cause urinary incontinence, which can significantly diminish the quality of life. This study investigated overactive bladder symptoms in premenopausal and postmenopausal individuals by analyzing the influence of demographic, gynecological, and obstetric factors. Methods: This single-center prospective cross-sectional study was conducted between September 1 and November 1, 2023, among premenopausal and postmenopausal women. In total, 244 patients meeting the inclusion criteria were selected using a simple random method. Participants were asked to complete an information collection form, and the Turkish version of the Overactive Bladder-V8 questionnaire was administered. A significance level of p < 0.05 was considered. Results: Individuals with an overactive bladder were older (mean age, 46.14 ± 14.56) and had a higher body mass index (mean, 28.47 ± 6.02) than healthy individuals (p = 0.013, p < 0.001, respectively). No significant difference in menopausal status was found (p = 0.091). Urinary incontinence was significantly higher in the overactive bladder group (63.6% vs. 17.4%, p < 0.001). The number of vaginal deliveries and prior gynecologic surgeries differed significantly between the groups (p = 0.030, p = 0.001, respectively). Conclusions: Age, higher body mass index, vaginal childbirth, and history of gynecological surgeries are associated with overactive bladder frequency, whereas menopausal status did not exert a significant effect. [ABSTRACT FROM AUTHOR]

Menopause is a phase of physiological alteration in women that leads to changes in both systemic and oral health. Buccal smears were collected from 28 premenopausal women and 28 early postmenopausal women who visited the outpatient Department of Oral medicine and radiology of our college. The Oral changes were observed and the patients were asked about complaints of their menstrual history, dry mouth, systemic conditions, signs of inflammation, focal infections, ulceration, white and red lesions, and periodontal diseases. The results were obtained by correlating the changes observed in premenopausal and early postmenopausal women by the influence of hormones on oral health using oral exfoliative cytology. The results of the study were then correlated with various other similar studies and revealed that there is a high chance that the early postmenopausal women are more prone to oral discomfort than the premenopausal women. The data obtained from this study will be used to plan preventive health care programs (creating awareness about oral hygiene maintenance, measures to improve salivary parameters) for the menopausal and early postmenopausal women to improve their oral health related quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Menopausal symptoms in women are influenced by personality traits as well as physical and psychological characteristics. The effects of coronavirus disease 2019 (COVID-19) phobia on personality traits and menopausal symptoms in premenopausal and postmenopausal women were examined in this study. Material and methods: The study was conducted in a cross-sectional and descriptive design with 410 women. The data were collected using a descriptive data form, the COVID-19 phobia scale, the menopause rating scale, and the Cervantes personality scale. Results: In this study, 46.8% of the women were premenopausal and 53.2% were postmenopausal. The mean age was 42.9 ±1.97 years in premenopausal women and 50.9 ±2.94 years in postmenopausal women. The psychological, social, and total COVID-19 phobia scores were found to be higher in postmenopausal women than premenopausal women. Postmenopausal women showed more introverted personality traits than pre- menopausal women. COVID-19 phobia affected postmenopausal women more than premenopausal women in terms of psychological, social and all menopausal symptoms. As COVID-19 phobia increased, neurotic per- sonality traits increased in premenopausal women, and introverted and neurotic personality traits increased in postmenopausal women (p < 0.05). Menopausal symptoms increased with neurotic personality traits in premenopausal women and with introverted personality traits in postmenopausal women (p < 0.001). Conclusions: COVID-19 phobia affected both groups in terms of menopausal symptoms and personality traits. For the management of menopausal symptoms, it is recommended to consider neurotic personality traits in premenopausal women and introverted personality traits in postmenopausal women. [ABSTRACT FROM AUTHOR]

Objective was to present detailed menstrual cramps information in normally ovulatory versus anovulatory cycles from a single-cycle cohort study during the SARS-CoV-2 Pandemic. Secondly, we reviewed the literature for cohort studies documenting both menstrual cramps and ovulation. Participants and Methods: The Menstruation and Ovulation Study 2 recruited 108 women ages 19– 35 years to a prospective, observational single-cycle study, recording cramps daily (0– 4 scale) in the Menstrual Cycle Diary© and assessing normal ovulation (luteal length ≥ 10 days) by the validated Quantitative Basal Temperature© (Mean Temperature Method). We searched databases for « primary dysmenorrhea » / » menstrual cramps »; « menstrual cycles »; « anovulation », finding four valid publications. Results: In 75 women/cycles during the Pandemic, mean age was 28.5, body mass index 23.5, and higher education (16 years); 40 normally ovulatory and 35 anovulatory cycles had similar lengths (29.5– 30.0 days), respectively (P= 0.571). However, anovulatory cycles recorded significantly worse menstrual cramps versus normally ovulatory cycles; anovulatory median intensity was 1.9 versus 1.6, and Cramp Score was 8 versus 6 in normally ovulatory cycles (P=0.017). Four publications in 273 women (991 cycles) showed cramps in both anovulatory and ovulatory cycles; three were in adolescent/young adult women, one of which documented a significantly greater percentage of cramps in ovulatory cycles. The 694 cycles in premenopausal women (20– 41 years) showed similar percentages of symptomatic cramps in cycles of both ovulatory types. Meta-analysis documented significantly higher cramp prevalence in ovulatory cycles (OR 2.10; 95% CI 1.31, 3.37; P=0.002). Conclusion: This is the first documentation of more intense and frequent cramps in anovulatory cycles. However, meta-analysis showing the presence of symptomatic cramps in both ovulatory and anovulatory cycles documented they were twice as prevalent in ovulatory menstrual cycles. Plain Language Summary: "Worse Menstrual Cramps in Anovulatory Cycles". Medicine has long believed that menstrual cramps only occur in ovulatory menstrual cycles that release an egg and have high progesterone levels that decrease before the next period. The notion was that dropping progesterone levels triggered release of prostaglandins that cause the pain and uterus muscle contractions of menstrual cramps. This research studied 75 community women aged 19– 35 years for a single cycle during COVID-19. Forty women had normally ovulatory cycles and 35 had anovulatory cycles with a similar mean cycle length of 29.7 days. Women in both groups were similar in age, weight, education and other reproductive characteristics. Women recorded Menstrual Cycle Diary© daily experiences for cramp presence and intensity (scored 0– 4). Ovulation was documented by daily first morning temperatures analyzed by the valid Quantitative Basal Temperature© method. Results showed menstrual cramps occurred in both normally ovulatory and anovulatory cycles. Surprisingly, anovulatory compared with ovulatory cycles had cramps that lasted longer (4 rather than 3 days), were more intense (1.9 versus 1.6) and with significantly higher Cramp Scores (of 8 versus 6). We also found four other published studies showing cramps occurred in both anovulatory and ovulatory cycles. A meta-analysis of these, however, showed that cramps were twice as frequent in ovulatory cycles. These results matter because they stimulate the search for more accurate understandings of why menstrual cramps occur. They will likely stimulate more effective therapies for the rare, intense menstrual cramps that currently are not effectively treated by anti-inflammatory medicines such as ibuprofen. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study is to evaluate plasma homocysteine level and its relation with serum estrogen in pre and postmenopausal women as a risk factor in coronary artery disease (CAD). Materials and Methods: A cross-sectional study was conducted among premenopausal (n = 50) and postmenopausal women (n = 50) with an estimation of plasma homocysteine (Hcy) and serum estradiol (E2). Postmenopausal women based on their angiographic status were sub-grouped into A (with normal coronaries) and B (with CAD). Results: The levels of Hcy, 21.98 (20.89-24.05) μmol/L, increased significantly (P < 0.0001) and that of E2, 3.05 (2.32-3.6) pg/mL, decreased significantly (P = 0.0001) in the postmenopausal group when compared to Hcy, 6.11 (4.94-8.27) μmol/L and E2, 26.37 (25.3-29) pg/mL in premenopausal group. The levels of Hcy were elevated (24.7 ± 3.92 μmol/L) in postmenopausal Group B in comparison with postmenopausal Group A (21.37 ± 3.31 μmol/L), P = 0.002. Logistic regression analysis showed Hcy and body mass index to be independent predictors of CAD. Plasma Hcy showed an area under curve (AUC) of 1.00 with sensitivity and specificity of 100% at cutoff >12.6 μmol/L between pre and postmenopausal groups and AUC of 0.722 with 60% sensitivity and 84% specificity at cutoff >23.7 μmol/L between postmenopausal Groups A and B. Conclusion: We observed low E2 and high Hcy levels in postmenopausal women in comparison with premenopausal women. Among postmenopausal women, those with CAD had higher Hcy levels. Assessing Hcy levels routinely in postmenopausal women will help in better risk prediction of CAD and may also help in conjunction with other risk factors to decide the initiation of hormone replacement therapy. [ABSTRACT FROM AUTHOR]

Background We conducted a systematic review and meta-analysis to examine outcomes of patients with endometrial intraepithelial neoplasia treated with oral progestins or a levonorgestrel-releasing intrauterine device (IUD). Methods We conducted a systematic review across 5 databases to examine outcomes of progestational treatment (oral progestins or levonorgestrel-releasing IUD) for patients with endometrial intraepithelial neoplasia. The primary outcome was the best complete response rate within 12 months of primary progestational treatment. Sensitivity analyses were performed by removing studies with extreme effect sizes. Secondary outcomes included the pooled pregnancy rate. Results We identified 21 eligible studies, including 824 premenopausal patients with endometrial intraepithelial neoplasia, for our meta-analysis. Among these, 459 patients received oral progestin, and 365 patients received levonorgestrel-releasing IUD as a primary progestational treatment. The pooled best complete response proportion within 12 months was 82% (95% confidence interval [CI] = 69% to 91%) following oral progestin treatment and 95% (95% CI = 81% to 99%) following levonorgestrel-releasing IUD treatment. After removing outlier studies, the pooled proportion was 86% (95% CI = 75% to 92%) for the oral progestin group and 96% (95% CI = 91% to 99%) for the levonorgestrel-releasing IUD group, with reduced heterogeneity. The pooled pregnancy rate was 50% (95% CI = 35% to 65%) after oral progestin and 35% (95% CI = 23% to 49%) after levonorgestrel-releasing IUD treatment. Conclusions This meta-analysis provides data on the effectiveness of oral progestins and levonorgestrel-releasing IUD treatment within 12 months of treatment among premenopausal patients with endometrial intraepithelial neoplasia. Although based on small numbers, the rate of pregnancy after treatment is modest. These data may be beneficial for selecting progestational therapies that allow fertility preservation for patients with endometrial intraepithelial neoplasia. [ABSTRACT FROM AUTHOR]

Background Vasospastic angina (VSA) is uncommon in premenopausal women who have less chronic endothelial injury causing vascular remodelling, considered to play a primary role in the pathogenesis for coronary vasospasms. Furthermore, vasospasms rarely occur in the bilateral coronary ostia. Isolated coronary ostial stenosis (ICOS), which often causes severe effort angina and requires surgical intervention, is more commonly reported in middle-aged women, with causes including fibromuscular dysplasia (FMD) and large-vessel vasculitis. However, ICOS associated with VSA is extremely rare. Case summary A 50-year-old premenopausal Japanese woman presented with a complaint of typical chest pain due to angina during light exertion daily in the early morning hours since 3 years. Coronary angiography (CAG) revealed bilateral mild-to-moderate ICOS in addition to multi-vessel spasms involving the bilateral coronary ostia confirmed by the vasospasm provocation test using intracoronary acetylcholine injection. Tests to determine the cause of ICOS did not identify FMD or any other disease. The angina attacks alleviated after calcium channel blocker (CCB) administration without intervention for bilateral ICOS for 24 years since the first presentation. Moreover, coronary computed tomography angiography (CTA) performed 24 years after the first presentation showed no ICOS. Discussion In our patient with typical and frequent VSA symptoms, CAG revealed both mild-to-moderate ICOS and the vasospasms in the bilateral coronary ostia. Fibromuscular dysplasia or large-vessel vasculitis was ruled out as the causes of ICOS. Vasospastic angina rarely occurred after the prescription of CCB, and coronary CTA 24 years after the first presentation showed no ICOS. Bilateral ICOS in our patient might be VSA related. [ABSTRACT FROM AUTHOR]

Endometrial polyp (EP) is a common lesion of the endometrium, which can be classified as premenopausal EP, postmenopausal EP, and Tamoxifen (TAM)-associated EP. Different types of EP have different clinical features and treatment. Ageing, menopause, and the use of TAM are high-risk factors for the development and malignancy of EP. The expression of steroid hormone receptors varies among the three types of EP due to the influence of different factors such as hormone levels in women. Premenopausal EP usually exhibits the classic pathological features of EP, postmenopausal EP has a richer mesenchymal stroma, and TAM-associated EP may be accompanied by atypical hyperplasia and carcinoma. Premenopausal EP is usually a homogeneous hypoechoic mass on ultrasound, while postmenopausal EP often shows multiple cystic foci of varying sizes, and TAM-associated EP often shows densely distributed honeycomb-like liquid dark areas. The treatment approaches for different types of EP are not entirely the same and should be personalized based on factors such as whether the patient is menopausal or not, with or without symptoms and fertility requirements, and risk of malignancy. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer incidence is higher in men, and a protective hormone-related effect in women is postulated. We aimed to investigate and quantify the relationship in the Stomach cancer Pooling (StoP) Project consortium. Methods: A total of 2,084 cases and 7,102 controls from 11 studies in seven countries were included. Summary odds ratios (ORs) and 95% confidence intervals (CIs) assessing associations of key reproductive factors and menopausal hormone therapy (MHT) with gastric cancer were estimated by pooling study-specific ORs using random-effects meta-analysis. Results: A duration of fertility of ≥ 40 years (vs. < 20), was associated with a 25% lower risk of gastric cancer (OR = 0.75; 95% CI: 0.58–0.96). Compared with never use, ever, 5–9 years and ≥ 10 years use of MHT in postmenopausal women, showed ORs of 0.73 (95% CI: 0.58–0.92), 0.53 (95% CI: 0.34–0.84) and 0.71 (95% CI: 0.50–1.00), respectively. The associations were generally similar for anatomical and histologic subtypes. Conclusion: Our results support the hypothesis that reproductive factors and MHT use may lower the risk of gastric cancer in women, regardless of anatomical or histologic subtypes. Given the variation in hormones over the lifespan, studies should address their effects in premenopausal and postmenopausal women. Furthermore, mechanistic studies may inform potential biological processes. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate the relationship of neoadjuvant therapy with HALP score, menopausal status and pathological response in patients with luminal A and luminal B breast cancer. Methods: In this retrospective study, the files of patients who applied to Ondokuz Mayıs University Medical Oncology department between January 2016 and January 2023 were scanned and a total of 150 patients, 60 premenopausal and 90 postmenopausal, who received neoadjuvant chemotherapy were included. Results: The median age of premenopausal patients was 40.67±6.35 (min 25-max 50), and postmenopausal patients was 57.67±7.48 (min 43-max 78). There was no relationship between overall survival and menopausal status (p=0.33). HALP score was significant only in postmenopausal patients (p=0.008). There was a significant association with complete pathological response (Miller&Payne 5) and PFS in the entire population (p=0.003). HALP score was lower in patients with PR level below 50% (p=0.039). There was no statistical significant between Ki67 and cerbB2, menopausal status and HALP score (p=0.106, p=0.064, respectively). Conclusion: As a result, we did not detect the relationship between HALP score and pathological response in Luminal A and B patients receiving neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Key Clinical Message Ovarian hyperthecosis (OH) is a benign pathology, less common in premenopause. Literature is poor on its ultrasound (US) characteristics. We suggest that a heterogeneous ovary at US, with a central vascularisation and follicles to the periphery, with or without hyperandrogenism, should lead to consider OH in the hands of experts.

PURPOSE: To assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer. METHODS: Secondary analysis of the Stockholm trial (STO-5, 1990-1997) randomly assigning 924 premenopausal patients to 2 years of goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 mg orally once daily), combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is performed. Random assignment was stratified by lymph node status; lymph node-positive patients (n = 459) were allocated to standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil). Primary tumor immunohistochemistry (n = 731) and gene expression profiling (n = 586) were conducted in 2020. The 70-gene signature identified genomic low-risk and high-risk patients. Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and multivariable time-varying flexible parametric modeling assessed the long-term distant recurrence-free interval (DRFI). Swedish high-quality registries allowed a complete follow-up of 20 years. RESULTS: In estrogen receptor-positive patients (n = 584, median age 47 years), goserelin, tamoxifen, and the combination significantly improved long-term distant recurrence-free interval compared with control (multivariable hazard ratio [HR], 0.49; 95% CI, 0.32 to 0.75, HR, 0.57; 95% CI, 0.38 to 0.87, and HR, 0.63; 95% CI, 0.42 to 0.94, respectively). Significant goserelin-tamoxifen interaction was observed (P = .016). Genomic low-risk patients (n = 305) significantly benefitted from tamoxifen (HR, 0.24; 95% CI, 0.10 to 0.60), and genomic high-risk patients (n = 158) from goserelin (HR, 0.24; 95% CI, 0.10 to 0.54). Increased risk from the addition of tamoxifen to goserelin was seen in genomic high-risk patients (HR, 3.36; 95% CI, 1.39 to 8.07). Moreover, long-lasting 20-year tamoxifen benefit was seen in genomic low-risk patients, whereas genomic high-risk patients had early goserelin benefit. CONCLUSION: This study shows 20-year benefit from 2 years of adjuvant endocrine therapy in estrogen receptor-positive premenopausal patients and suggests differential treatment benefit on the basis of tumor genomic characteristics. Combined goserelin and tamoxifen therapy showed no benefit over single treatment. Long-term follow-up to assess treatment benefit is critical.

Objectives of the study: to evaluate the effectiveness of the progestogens for the treatment of uterine fibroids (UF) in women in the premenopausal period. Materials and methods. 42 patients aged 45–50 years with UF were examined. The diagnosis of UF was verified according to clinical and instrumental research methods. The effectiveness of the therapy was evaluated according to clinical and ultrasound examination data before and during the course of treatment. All patients with diagnosed symptomatic UF received progestogen dienogest 2 mg ones a day continuously for a year, with clinical and sonographic control every 3 months. Results. UF was symptomatic in all examined patients. According to the International Federation of Gynecology and Obstetrics (FIGO) classification system for UF, 42.8% (18) of women had type III–IV nodes, 54.8% (23) had type II–V nodes, and 2.4% (1) of women had type VI nodes. In all patients were 2 or more nodes. Already after 6 months of therapy, bleeding complaints decreased by more than 8 times, moderate pain syndrome and urination disorders were noted in only one (2.4%) patient. After 12 months, pelvic pain and bladder dysfunction were absent in 100% of cases. One (2.4%) patient had spotting bleeding for 2 days during the 8th month of treatment. After 6 and 12 months of treatment, the size of the endometrium decreased significantly to 3.6–7 and 3.2–4.6 mm, respectively. The total volume of the uterus also underwent positive changes: it decreased by 10–40% in each patient during the course of treatment. Conclusions. It should be preferred progestogens in the treatment of UF in women aged 45–50 years who wish to preserve the uterus. Therapy with dienogest in a continuous long-term regimen showed high clinical effectiveness, confirmed the active antiproliferative, antiovulatory effect of the drug in the absence of estrogen deficiency symptoms, which is important for this age group of patients.

Rheumatoid arthritis is associated with systemic bone mass loss due to stimulation of osteoclastogenesis and suppression of osteoblastogenesis through inhibition of Wingless (Wnt)/ß catenin canonical and bone morphogenetic proteins (BMP) pathways by sclerostin. Our study assessed the correlation between tumor necrosis factor (TNF)-a and sclerostin with bone resorption markers C-terminal telopeptides of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) in pre-menopausal rheumatoid arthritis patients. This cross-sectional study involved 38 premenopausal women with RA. Serum TNF-a, sclerostin, P1NP, and CTX level were examined by ELISA method. This study revealed high level of serum CTX (mean 2.74 ng/mL) and a low level of P1NP (median 34.04 pg/mL). There was a significant negative correlation (r = -0.388) between TNF-a and sclerostin levels (p = 0.016), as well as a significant positive correlation (r = 0.362) between TNF-a and P1NP levels (p = 0.026). There was a significant negative correlation between TNF-a and sclerostin, and also a significant positive correlation between TNF-a and P1NP in our study. [ABSTRACT FROM AUTHOR]

Background: The decline of estrogen levels during menopause impacts weight, mood, and overall health, both orally and systemically. This study assessed salivary levels of tumor necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6), IL‐10, and IL‐7 in postmenopausal (PMW) and regularly menstruating premenopausal (RMPW) women, while considering serum cytokine levels, body mass index (BMI), periodontal health, and self‐reported physical and emotional well‐being. Methods: In this study, 75 PMW and 71 RMPW were included. Clinical and periodontal parameters were evaluated, and perceived health was assessed with the Women's Health Questionnaire (WHQ). Cytokine levels in both saliva and serum were quantified by enzyme‐linked immunosorbent assay (ELISA). Covariate evaluations of salivary cytokines were conducted using hierarchical linear regression modeling. Results: Cytokines were detectable in saliva from 71 PMW and 67 RMPW. In the initial unadjusted model, IL‐7, IL‐10, and TNF‐α exibited significant differences between RMPW and PMW. However, these differences became non‐significant (p > 0.05) in the final model after adjusting for age, which implies a negligible effect of the investigated covariates on salivary cytokine levels when age was considered. Lower levels of IL‐6 in PMW, which initially showed no significant difference, became borderline (p = 0.054) in the final model after adjusting for age. Conclusions: After adjusting for multiple factors, no significant difference was found in the salivary levels of the investigated cytokines between RMPW and PMW. Factors such as BMI, perceived health, serum cytokine levels, and periodontal parameters seem to minimally influence these levels in PMW. However, age may be a stronger confounding factor. [ABSTRACT FROM AUTHOR]

Background and purpose: The association between overweight/obesity and postmenopausal breast cancer has been proven. However, uncertainty exists regarding the association between physical weight statuses and premenopausal breast cancer subtypes. This study aimed to explore the association of body weight statuses with molecular subtypes of premenopausal breast cancer. Method: A systematic search of Medline, PubMed, Embase, and Web of Science was performed. The Newcastle–Ottawa Scale (NOS) and the Joanna Briggs Institute (JBI) Critical Appraisal tools were used to evaluate the quality of the literature. STATA and R software were used to analyze the extracted data. Result: The meta-analysis included 35 observational studies with a total of 41,049 premenopausal breast cancer patients. The study showed that the proportion of underweight patients was 4.8% (95% CI = 3.9–5.8%, P = 0.01), overweight was 29% (95%CI = 27.1–30.9%, P < 0.01), obesity was 17.8% (95% CI = 14.9–21.2%, P < 0.0001), and normal weight was 51.6% (95% CI = 46.7–56.5%, P < 0.0001). The pooled results showed that in comparison to the normal weight group, being physically underweight is related to a 1.44-fold risk (OR = 1.44, 95%CI = 1.28–1.63, P < 0.0001) of HER2 + breast cancer. Overweight is related to a 1.16-fold risk (OR = 1.16, 95%CI = 1.06–1.26, P = 0.002) of TNBC and a 16% lower risk (OR = 0.84, 95%CI = 0.75–0.93, P = 0.001) of ER + breast cancer. When compared to underweight/normal weight populations, both overweight (OR = 0.74, 95%CI = 0.56–0.97, P = 0.032) and obesity (OR = 0.70, 95%CI = 0.50–0.98, P = 0.037) can reduce the risk of ER + PR + breast cancer. Conclusion: In the premenopausal breast cancer population, the distribution of patients' numbers with different weight statuses was significantly distinct among the various breast cancer subtypes. Additionally, the associations between physical weight statuses and the risk of premenopausal breast cancer subtypes are divergent. [ABSTRACT FROM AUTHOR]

In this study, we conducted a comparative analysis of demographic, histopathological, and sonographic characteristics between pre- and postmenopausal women diagnosed with endometrial cancer, while also examining sonographic and anthropometric features in 'low' and 'intermediate/high-risk' cases, stratified by menopausal status. Our analysis, based on data from the International Endometrial Tumor Analysis (IETA) 4 cohort comprising 1538 women (161 premenopausal, 1377 postmenopausal) with biopsy-confirmed endometrial cancer, revealed that premenopausal women, compared to their postmenopausal counterparts, exhibited lower parity (median 1, IQR 0–2 vs. 1, IQR 1–2, p = 0.001), a higher family history of colon cancer (16% vs. 7%, p = 0.001), and smaller waist circumferences (median 92 cm, IQR 82–108 cm vs. 98 cm, IQR 87–112 cm, p = 0.002). Premenopausal women more often had a regular endometrial–myometrial border (39% vs. 23%, p < 0.001), a visible endometrial midline (23% vs. 11%, p < 0.001), and undefined tumor (73% vs. 84%, p = 0.001). Notably, despite experiencing a longer duration of abnormal uterine bleeding (median 5 months, IQR 3–12 vs. 3 months, 2–6, p < 0.001), premenopausal women more often had 'low' risk disease (78% vs. 46%, p < 0.001). Among sonographic and anthropometric features, only an irregular endometrial–myometrial border was associated with 'intermediate/high' risk in premenopausal women. Conversely, in postmenopausal women, multiple features correlated with 'intermediate/high' risk disease. Our findings emphasize the importance of considering menopausal status when evaluating sonographic features in women with endometrial cancer. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: To investigate the relationship between fasting blood glucose (FBG) and carotid intima-media thickness (IMT) in premenopausal and postmenopausal women. Subjects and methods: The study enrolled 2,959 women seen at the Maanshan People's Hospital of Anhui Province from December 2013 to December 2018. Carotid IMT was measured using Doppler ultrasound. Linear regression and R smoothing curves were used to analyze the relationship between blood glucose level and carotid IMT in the premenopausal and postmenopausal groups. Results: Postmenopausal compared with premenopausal women had higher mean IMT (mIMT; 0.81 ± 0.23 mm versus 0.70 ± 0.14 mm, respectively, p < 0.001) and maximum IMT (maxIMT; 0.86 ± 0.35 mm versus 0.74 ± 0.16 mm, respectively, p < 0.001) values. On linear regression analysis, mIMT values increased with increasing FBG values when FBG level was ≤ 7 mmol/L, but no significance was found between FBG and maxIMT. After stratification by menopausal status, mIMT and maxIMT increased with increasing FBG when FBG was ≤ 7 mmol/L in the premenopausal group. In the postmenopausal group, mIMT and maxIMT increased with increasing FBG. After adjustment for covariate factors, the relationship between FBG and mIMT remained the same as before the adjustment, but when FBG was ≤ 11 mmol/L, the maxIMT increased with increasing FBG. In the stratification analysis, maxIMT increased with increasing FBG when FBG was ≤ 7 mmol/L in the premenopausal group, while both mIMT and maxIMT increased with increasing FBG when FBG was > 10 mmol/L in the postmenopausal group. Conclusion: Levels of FBG contributed more to increased IMT in postmenopausal than premenopausal women. The influence of FBG was greater on maxIMT than mIMT. Additionally, FBG was helpful in assessing focal thickening of the carotid intima.

PurposeWe investigated the relationship between obesity, menopausal status, and invasive lobular carcinoma (ILC), the second most common histological subtype of breast cancer. Specifically, we evaluated the association between body mass index (BMI), metabolic syndrome, the 21-gene Oncotype Recurrence Score (Oncotype RS), and pathological features in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor-2-negative ILC.MethodsThe study cohort included 491 patients from a prospectively maintained institutional database consisting of patients with stage I-III, HR-positive ILC who underwent surgical treatment between 1996 and 2019.ResultsContrary to our expectations, we found that lower BMI was significantly associated with having higher Oncotype RS (18.9% versus 4.8%, p = 0.028) in post-menopausal patients, but was not related to tumor characteristics in pre-menopausal patients. Multivariate network analyses suggested a strong relationship between post-menopausal status itself and tumor characteristics, with lesser influence of BMI.ConclusionThese findings provide further insight into the recently appreciated heterogeneity within ILC and support the need for further investigation into the drivers of this disease and tailored treatment strategies.

BackgroundIn MONARCH 2, abemaciclib plus fulvestrant significantly improved median progression-free survival (PFS, 16.4 vs 9.3 months, hazard ratio [HR] 0.553) and overall survival (OS, 46.7 vs 37.3 months; HR 0.757) compared with placebo plus fulvestrant in hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer (ABC) patients who were endocrine therapy (ET) resistant, regardless of menopausal status. Here, we report findings in the premenopausal subgroup of the MONARCH 2 trial.MethodsThe premenopausal subgroup included patients with natural menstrual bleeding who received a gonadotropin-releasing hormone agonist at least 4 weeks prior to study treatment start date and for the entire study duration. Of the 669 patients enrolled in the MONARCH 2 trial, 114 were premenopausal (abemaciclib plus fulvestrant, n = 72; placebo plus fulvestrant, n = 42), and were included in this analysis. The primary objective was investigator-assessed PFS and secondary objectives were OS, objective response rate, and safety and tolerability. Exploratory analyses included time to second disease progression (PFS2), time to chemotherapy (TTC), and chemotherapy-free survival (CFS).ResultsAt the primary objective cutoff (February 14, 2017), median PFS was not reached for the abemaciclib plus fulvestrant arm versus 10.52 months for the placebo plus fulvestrant arm (HR 0.415; 95% CI 0.246-0.698). At the pre-specified OS interim cutoff (20-June-2019), median PFS was 28.6 months in the abemaciclib plus fulvestrant arm compared with 10.26 months in the placebo plus fulvestrant arm (HR 0.477; 95% CI 0.302-0.755). A numerical OS benefit was observed with abemaciclib plus fulvestrant compared to fulvestrant alone (HR 0.689; 95% CI 0.379-1.252, median, not reached vs 47.3 months). Improvements were also observed for the exploratory outcomes of PFS2 (HR 0.599), TTC (HR 0.674), and CFS (HR 0.642) with the addition of abemaciclib to fulvestrant. The safety profile was generally consistent with results disclosed previously.ConclusionsResults of the premenopausal subgroup in the MONARCH 2 trial were consistent with the improved clinical outcomes observed in the intent-to-treat population. The analysis provides support for the use of abemaciclib plus fulvestrant (with ovarian suppression) as an effective treatment option for premenopausal patients with HR+, HER2- ABC who are ET-resistant.Clinical trial registrationNCT02107703. Registered April 08, 2014- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02107703 .

PurposeThis analysis evaluated the genomic landscape of premenopausal patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer and the association of genetic alterations with response to ribociclib in the phase III MONALEESA-7 trial.MethodsPremenopausal patients were randomly assigned 1:1 to receive endocrine therapy plus ribociclib or placebo. Plasma collected at baseline was sequenced using targeted next-generation sequencing for approximately 600 relevant cancer genes. The association of circulating tumor DNA alterations with progression-free survival (PFS) was evaluated to identify biomarkers of response and resistance to ribociclib.ResultsBaseline circulating tumor DNA was sequenced in 565 patients; 489 had evidence of ≥ 1 alteration. The most frequent alterations included PIK3CA (28%), TP53 (19%), CCND1 (10%), MYC (8%), GATA3 (8%), receptor tyrosine kinases (17%), and the Chr8p11.23 locus (12%). A treatment benefit of ribociclib was seen with wild-type (hazard ratio [HR] 0.45 [95% CI, 0.33 to 0.62]) and altered (HR 0.57 [95% CI, 0.36 to 0.9]) PIK3CA. Overall, patients with altered CCND1 had shorter PFS regardless of treatment, suggesting CCND1 as a potential prognostic biomarker. Benefit with ribociclib was seen in patients with altered (HR 0.21 [95% CI, 0.08 to 0.54]) or wild-type (HR 0.52 [95% CI, 0.39 to 0.68]) CCND1, but greater benefit was observed with altered, suggesting predictive potential of CCND1. Alterations in TP53, MYC, Chr8p11.23 locus, and receptor tyrosine kinases were associated with worse PFS, but ribociclib benefit was independent of alteration status.ConclusionIn this study-to our knowledge, the first large study of premenopausal patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer-multiple genomic alterations were associated with poor outcome. A PFS benefit of ribociclib was observed regardless of gene alteration status, although in this exploratory analysis, a magnitude of benefits varied by alteration.

PURPOSE: The etiology of young-onset breast cancer (BC) is poorly understood, despite its greater likelihood of being hormone receptor-negative with a worse prognosis and persistent racial and socioeconomic inequities. We conducted a population-based case-control study of BC among young Black and White women and here discuss the theory that informed our study, exposures collected, study methods, and operational results. METHODS: Cases were non-Hispanic Black (NHB) and White (NHW) women age 20-49 years with invasive BC in metropolitan Detroit and Los Angeles County SEER registries 2010-2015. Controls were identified through area-based sampling from the U.S. census and frequency matched to cases on study site, race, and age. An eco-social theory of health informed life-course exposures collected from in-person interviews, including socioeconomic, reproductive, and energy balance factors. Measured anthropometry, blood (or saliva), and among cases SEER tumor characteristics and tumor tissue (from a subset of cases) were also collected. RESULTS: Of 5,309 identified potentially eligible cases, 2,720 sampled participants were screened and 1,812 completed interviews (682 NHB, 1140 NHW; response rate (RR): 60%). Of 24,612 sampled control households 18,612 were rostered, 2,716 participants were sampled and screened, and 1,381 completed interviews (665 NHB, 716 NHW; RR: 53%). Ninety-nine% of participants completed the main interview, 82% provided blood or saliva (75% blood only), and SEER tumor characteristics (including ER, PR and HER2 status) were obtained from 96% of cases. CONCLUSIONS: Results from the successfully established YWHHS should expand our understanding of young-onset BC etiology overall and by tumor type and identify sources of racial and socioeconomic inequities in BC.

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Observational studies in metastatic breast cancer (MBC) show that long-term overall survival (OS) is associated with limited tumor burden, or oligo-MBC (OMBC). However, a uniform definition of OMBC is lacking. In this real-world nationwide cohort, we aimed to define the optimal OMBC threshold and factors associated with survival in patients with OMBC. 3535 patients aged younger than 80 years at diagnosis of de novo MBC in the Netherlands between January 2000 and December 2007 were included. Detailed clinical, therapy, and outcome data were collected from medical records of a sample of the patients. Using inverse-sampling-probability weighting, the analysis cohort (n = 3447) was constructed. We assessed OS according to number of metastases at diagnosis to determine the optimal OMBC threshold. Next, we applied Cox regression models with inverse-sampling-probability weighting to study associations with OS and progression-free survival in OMBC. All statistical tests were 2-sided. Compared with more than 5 distant metastases, adjusted hazard ratios for OS (with 95% confidence interval [CI] based on robust standard errors) for 1, 2-3, and 4-5 metastases were 0.70 (95% CI = 0.52 to 0.96), 0.63 (95% CI = 0.45 to 0.89), and 0.91 (95% CI = 0.61 to 1.37), respectively. Ten-year OS estimates for patients with no more than 3 vs more than 3 metastases were 14.9% and 3.4% (P

BackgroundEpidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk.MethodsWe carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry.ResultsFor pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 × 10-18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 × 10-8).ConclusionsThe CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.

Rapid modernization in China has impacted the daily lives and health of women, including a rise in obesity. However, little is known about the impact of menopausal status, behavior, and psychosocial factors on the risk of obesity for rural women in China. The aim of this study is to identify risk factors, including demographic information (education, family history of T2DM, menopausal status), obesity-related behavior, and psychosocial factors associated with overweight/general obesity and abdominal obesity. In a cross-sectional study design, participants had their weight, height, and waist circumference measured and completed questionnaires regarding family demographics, obesity-related health behaviors (physical activity, diet, sleep), and psychosocial information (stress, social support, and self-efficacy related to physical activity and healthy diet). A total of 646 women were included in this study; 46.6% were overweight/generally obese, and 48% had abdominal obesity. Postmenopausal women had a higher prevalence of general and central obesity. Regular physical activity decreased the risk for overweight/general obesity and abdominal obesity (OR = .41 and .31, respectively, p = .04) in premenopausal women. Postmenopausal women who had not breastfed their infants and reported moderate/high-stress had a higher risk for overweight/general obesity (OR = 3.93, and 2, respectively) and those who reported less than 6 hours of sleep per day increased their risk for abdominal obesity (OR = 2.08). Different factors associated with obesity were found in Chinese women, depending on menopausal status. Future studies should examine the impact of menopause on a woman's risk for obesity, as well as develop tailored interventions to improve health, well-being and reduce the risk of obesity.

Introduction: The premenopausal and menopausal periods are natural processes that occur in women. Both of these periods bring about changes in physical, psychological, and social aspects. The symptoms and changes experienced in the body can make women feel fearful, anxious, and lead to changes in their quality of life. The research aims to determine the influence of premenopausal and menopausal women's demographic characteristics on anxiety and quality of life. Methods: This study employed a descriptive design with an analytical observational approach and a cross-sectional design. The study population consisted of community health Center Jagir cadres aged ≥35 years, selected through purposive sampling, with a sample size of 70 respondents. The analysis use the ordinal regression statistical test. Results: Demographic characteristics revealed that the majority were aged 46-55 years (46%), had a high level of education (83%), and were married (81%). The majority experienced mild anxiety (40%) and had good quality of life (67%). The demographic characteristics of women (age, education, and marital status) significantly influenced anxiety and quality of life with a p-value

Background. Schwannomas of the gastrointestinal tract are a rare type of spindle cell tumor of peripheral nerve. Commonly, schwannomas are discovered incidentally, as they are usually asymptomatic. Case. 46-year-old female patient, suffering from secondary amenorrhea and nonspecific intermittent pelvic pain associated with constipation. During gynecological visit an ultrasonographic systematic transvaginal examination was performed. At the sigmoid-rectal level an intraluminal solid mass was described and an urgent colonoscopy was prescribed. Endoscopic submucosal dissection was performed with en-bloc resection. On immunohistochemical analysis, S100 was strongly positive in tumor cells. Finally, a benign schwannoma of the sigmoid colon was diagnosed. Conclusion. Our case highlights the importance of an adequate transvaginal pelvic examination with the evaluation of all pelvic organs. It could be challenging to make diagnosis in an early stage on asymptomatic patients.

Background and Objectives: Obese premenopausal women are at high risk of developing insulin resistance (IR). Concurrent aerobic and strength training (CAST) has been shown to provide remarkable advantages, yet its effects, along with caloric restriction in such a high-risk population, are not yet established. This study aimed to investigate the impact of concurrent aerobic and strength training with caloric restriction (CAST-CR) on IR in obese premenopausal women. Materials and Methods: Forty-two obese premenopausal women with reported IR, aged 40–50 years, were randomly allocated to either the (CAST-CR) intervention group, who underwent CAST with caloric restriction, or the (AT-CR) control group, who received aerobic training in addition to caloric restriction. Both groups completed 12 weeks of controlled training with equivalent training time. Aerobic training began at 60% and gradually progressed to achieve 75% of the maximum heart rate, while strength training was executed at 50% to 70% of the one-repetition maximum (1RM). Anthropometric measures, abdominal adiposity, metabolic parameters, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) were evaluated prior to and following the intervention. Results: Both groups experienced a substantial enhancement in the selected parameters compared to the baseline (p < 0.001), with higher improvement within the CAST-CR group. The changes in HOMA-IR were −1.24 (95%CI, −1.37 to −1.12) in the CAST-CR group vs. −1.07 (95%CI, −1.19 to −0.94) in the AT-CR group. Conclusions: While AT-CR improved insulin sensitivity in premenopausal women who were obese and hyperinsulinemic, CAST with calorie restriction improved insulin sensitivity more significantly, suggesting it as a preferable alternative. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although irritable bowel syndrome (IBS) is more common in women, little is known about the role of hormonal changes and menopause in IBS. This study aimed to evaluate for differences in gastrointestinal (GI) and psychological symptoms between pre- and postmenopausal women with IBS compared to age-matched men with IBS. METHODS: Patients with Rome-positive IBS were identified. Premenopausal women were

RationaleNicotine patches may be less effective in female compared with male smokers. However, it is unknown if negative affect and physical symptoms influence transdermal nicotine patch-related effects on smoking behaviors.MethodsEighty-one acutely tobacco-abstinent premenopausal female smokers attended three counter-balanced experimental sessions across the menstrual cycle (early follicular, late follicular, and mid-luteal) and were randomized to patch condition (nicotine [21 mg] vs. placebo [0 mg] transdermal patch). Negative affect and physical symptoms were assessed prior to patch administration. The patch was removed 5 h post-administration, and participants completed a smoking reinstatement task. Multilevel linear models tested associations of patch condition, negative affect and physical symptoms, and their interaction on smoking behavior.ResultsThere was a significant patch condition × Negative Affect and Pain symptoms interaction on the number of cigarettes smoked (p

BackgroundIt is unclear if the relationship between depression and physical health problems in women is related to age, reproductive stage, obesity or socio-demographic risk factors.MethodsLongitudinal data were obtained every 6 months for 36 months in 264 midlife African American, Caucasian and Latina women who began the study as healthy regularly menstruating 40 to 50-year-olds; 75 transitioned to peri- or post-menopause by 36 months. Scores of 16 or higher on the Center for Epidemiologic Studies-Depression (CES-D) scale were used to estimate depression risk.ResultsDepression risk was 28% at study initiation and 25% at 36 months. Significantly more women at risk for depression were unemployed, obese, or hypertensive. Women at risk were more likely to become peri- or post-menopausal during the study period. A higher percentage (38%) of overweight and obese women had CES-D scores ≥ 16 compared to normal weight women (23%; p < .001). Over half (58%) of the 73 women at higher depression risk at the initial visit reported a health problem or chronic illness at 36 months, compared to only 36% of the 191 women with CES-D scores

ObjectiveOptical coherence tomography is a noninvasive technology that visualizes tissue microstructure with high spatial resolution. We designed a novel vaginal system that demonstrates a clear distinction between vaginal tissues planes. In this study, we sought to compare vaginal tomographic images of premenopausal, perimenopausal, and postmenopausal women, demonstrate feasibility of tracking vaginal tissue changes after treatment with fractional-pixel CO2 laser therapy, and obtain a histologic correlation of these findings.MethodsEnrolled subjects underwent imaging and were divided into 3 groups based on menopausal status. Women with genitourinary syndrome of menopause who received fractional-pixel CO2 laser therapy were assessed before and after treatment. A cadaveric vagina was used to obtain tomographic and histologic images to assess for accuracy. Our primary outcome was mean vaginal epithelial thickness. Statistical analysis was performed using analysis of variance and t tests, respectively.ResultsAmong 6 women, the mean vaginal epithelial thickness decreased with menopause (P < 0.01). Although change in epithelial thickness after fractional-pixel CO2 laser treatment varied between the 2 subjects evaluated, it increased significantly for the subject who reported improvement of vaginal symptoms (P < 0.01). Using a cadaveric specimen, optical biopsy was correlated to an hematoxylin and eosin-stained biopsy of the same vaginal site.ConclusionsThis study establishes feasibility of optical coherence tomography in providing an optical biopsy of the vaginal epithelium and lamina propria. In addition, it demonstrates vaginal changes as women enter menopause. This report is the initial phase of a longitudinal cohort study to evaluate changes in vaginal microstructure after energy-based treatment.

BACKGROUNDInflammation is implicated in many aging-related disorders. In animal models, menopause leads to increased gut permeability and inflammation. Our primary objective was to determine if gut permeability increases during the menopause transition (MT) in women. Our exploratory objectives were to examine whether greater gut permeability is associated with more inflammation and lower bone mineral density (BMD).METHODSWe included 65 women from the Study of Women's Health Across the Nation (SWAN). Key measures were markers of gut permeability (gut barrier dysfunction, fatty acid binding protein 2 [FABP2]) and immune activation secondary to gut microbial translocation (LPS binding protein [LBP], soluble CD14 [sCD14]), inflammation (high-sensitivity CRP), and lumbar spine (LS) or total hip (TH) BMD.RESULTSIn our primary analysis, FABP2, LBP, and sCD14 increased by 22.8% (P = 0.001), 3.7% (P = 0.05), and 8.9% (P = 0.0002), respectively, from pre- to postmenopause. In exploratory, repeated measures, mixed-effects linear regression (adjusted for BMI, age at the premenopausal visit, race/ethnicity, and study site), greater gut permeability was associated with greater inflammation, along with lower LS and TH BMD.CONCLUSIONGut permeability increases during the MT. Greater gut permeability is associated with more inflammation and lower BMD. Future studies should examine the longitudinal associations of gut permeability, inflammation, and BMD.FUNDINGFunding for this research was provided by NIH, Department of Health and Human Services, through the National Institute on Aging, National Institute of Nursing Research, and NIH Office of Research on Women's Health (U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, and U01AG012495).

The menstrual cycle is characterized by predictable patterns of physiological change across timescales. Although patterns of reproductive hormones across the menstrual cycle, particularly ultradian rhythms, are well described, monitoring these measures repeatedly to predict the preovulatory luteinizing hormone (LH) surge is not practical. In the present study, we explored whether non-invasive measures coupled to the reproductive system: high frequency distal body temperature (DBT), sleeping heart rate (HR), sleeping heart rate variability (HRV), and sleep timing, could be used to anticipate the preovulatory LH surge in women. To test this possibility, we used signal processing to examine these measures in 45 premenopausal and 10 perimenopausal cycles alongside dates of supra-surge threshold LH and menstruation. Additionally, urinary estradiol and progesterone metabolites were measured daily surrounding the LH surge in 20 cycles. Wavelet analysis revealed a consistent pattern of DBT and HRV ultradian rhythm (2-5 h) power that uniquely enabled anticipation of the LH surge at least 2 days prior to its onset in 100% of individuals. Together, the present findings reveal fluctuations in distal body temperature and heart rate variability that consistently anticipate the LH surge, suggesting that automated ultradian rhythm monitoring may provide a novel and convenient method for non-invasive fertility assessment.

Our primary aim was to estimate the magnitude of stage I endometrial cancer (EC) survivors that could benefit from hormonal therapy (HT). Our secondary aims were to assess EC incidence in women below 50 and below 60 over the years, and analyze the overall survival and any influencing factors. We analyzed the endometrioid EC data from the Surveillance, Epidemiology, and End Results (SEER) program according to women’s age, tumor stage, and grade. We analyzed the proportions of EC survivors below 50 and below 60 years of age and stratified those age groups by race. For age distribution and survival analysis SEER, 18 registries’ research data (2000–2018) were analyzed. We analyzed the SEER 12 registries’ research data (1992–2019) for incidence time trends. Our investigation found a 14% and 40% cumulative prevalence of stage I EC that occurs in women below 50 or 60 years, respectively. EC’s prevalence has progressively risen in recent decades, but cancer-specific mortality remains low. The increasing number of women affected by EC in premenopause or early postmenopause face an 18 years-survival rate of 96.86% and 95.73%, respectively. A significant proportion of low-grade EC survivors can potentially benefit from HT treatment, and this requires awareness of other aspects of their health or quality of life, in addition to cancer treatments.

Purpose: The intention of this systematic review was to analyze the literature on breast cancer (BC) and the use of the levonorgestrel-releasing intrauterine system (LNG-IUS). Methods: The literature was searched in Medline, Embase, Cochrane Library, CINAHL, Web of Science and ClinicalTrials.com and included search terms related to breast cancer and LNG-IUS. After elimination of duplicates, 326 studies could be identified and were assessed according to inclusion and exclusion criteria. In the end, 10 studies met the defined criteria and were included in the systematic review. Results: 6 out of the 10 selected studies were cohort studies, three were case–control studies and one a systematic review/meta-analysis. 6 found a positive association between BC and the use of LNG-IUS. One study only found an increased risk for invasive BC in the subgroup of women aged 40–45 years. In contrast, three studies showed no indication of a higher BC risk. Conclusion: The results imply an increased BC risk in LNG-IUS users, especially in postmenopausal women and with longer duration of use. Positive effects of the LNG-IUS such as reduced risks for other hormonal cancers have been observed, were, however, not focus of this systematic review. The heterogeneity of the analyzed studies and vast number of confounding factors call for further investigations in this issue. Patients should be advised according to their individual risk profile and hormone-free alternatives may be considered for women with a history of BC. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does exogenous estrogen use affect COVID-19-related mortality in women? SUMMARY ANSWER Menopausal hormone therapy (MHT) was associated with a lower likelihood of all-cause fatality related to COVID-19 in postmenopausal women (odds ratio (OR) 0.28, 95% CI 0.18, 0.44; 4 studies, 21 517 women) but the combined oral contraceptive pill in premenopausal women did not have a significant effect (OR 1.00, 95% CI 0.42–2.41; 2 studies, 5099 women). WHAT IS KNOWN ALREADY Men are much more likely to die from COVID-19 than women. STUDY DESIGN, SIZE, DURATION In this systematic meta-analysis, a literature search was conducted using the following search terms related toCOVID-19 and estrogen, sex hormones, hormonal replacement, menopause, or contraception. The PubMed, Scopus, Cochrane Library, and EMBASE databases were searched to identify relevant studies published between December 2019 and December 2021. We also searched MedRxiv as a preprint database and reviewed the reference lists of all included studies and clinical trial registries for ongoing clinical studies until December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS All comparative studies that compared the rates mortality and morbidity (hospitalization, intensive care unit (ICU) admission, and ventilation support) due to COVID-19 in women using exogenous estrogen to a control group of women (nonusers) were included. A review of the studies for inclusion, extraction of data, and assessment of the risk of bias was performed independently by two reviewers. The ROBINS-I tool and the RoB 2 tool were used for bias assessment of the included studies. Pooled odds ratios (ORs) with 95% CIs were calculated using Review Manager V5.4.1. The I 2 statistic was used to quantify heterogeneity. The quality of the evidence was assessed using GRADE criteria. MAIN RESULTS AND THE ROLE OF CHANCE After searching the databases, we identified a total of 5310 studies. After removing duplicate records, ineligible studies, and ongoing studies, a total of four cohort studies and one randomized controlled trial comprising 177 809 participants were included in this review. There was a moderate certainty of evidence that MHT was associated with a lower likelihood of all-cause fatality related to COVID-19 (OR 0.28, 95% CI 0.18, 0.44; I 2 = 0%; 4 studies, 21 517 women). The review indicated a low certainty of evidence for other outcomes. The mortality rate of premenopausal women in the combined oral contraceptive pill group did not differ significantly from the control group (OR 1.00, 95% CI 0.42–2.41; 2 studies, 5099 women). MHT marginally increased the rate of hospitalization and ICU admission (OR 1.37, 95% CI 1.18–1.61; 3 studies, 151 485 women), but there was no significant difference in the need for respiratory support between MHT users and nonusers (OR 0.91, 95% CI 0.52–1.59; 3 studies, 151 485 women). Overall, the tendency and magnitude of the effects of MHT in postmenopausal women with COVID-19 were consistent across the included studies. LIMITATIONS, REASONS FOR CAUTION The certainty of the evidence for other outcomes of this review may be limited, as all included studies were cohort studies. In addition, the dosages and durations of exogenous estrogen used by postmenopausal women varied from study to study, and combined progestogen administration may have had some effect on the outcomes. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study can aid in counseling postmenopausal women taking MHT when they are diagnosed with COVID, as they have a lower chance of death than those not taking MHT. STUDY FUNDING/COMPETING INTEREST(s) Khon Kaen University provided financial support for this review and had no involvement at any stage of the study. The authors have no conflicts of interest to declare. REGISTRATION NUMBER PROSPERO, CRD42021271882. [ABSTRACT FROM AUTHOR]