Association of physical weight statuses defined by body mass index (BMI) with molecular subtypes of premenopausal breast cancer: a systematic review and meta-analysis.

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.

Reproductive factors, hormonal interventions, and gastric cancer risk in the Stomach cancer Pooling (StoP) Project.

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.

Does Urodynamic Stress Incontinence Increase After the Menopause?: Results from 2,994 Urodynamic Studies in Australian Women.

INTRODUCTION AND HYPOTHESIS: Most studies attempting to estimate the age-related prevalence of urinary incontinence (UI) have used questionnaires. In the present study we analysed a consecutive series of urodynamic test results to determine the distribution of the different types of UI in pre- and post-menopausal women. We hypothesised that the prevalence of urodynamic stress incontinence (USI) would be significantly greater in pre-menopausal than in post-menopausal women. METHODS: All women from a large tertiary urogynaecology department, who underwent urodynamic tests during the years 2000-2015 were included. Patient history and test results were collected. A sample size of 1,475 was calculated, based on the hypothesis that the prevalence of USI will be 20% larger in the pre- versus the post-menopausal group. RESULTS: A total of 2,994 women with UI on urodynamics were available. There was a significant difference between pre- and post-menopausal status for each of the three diagnoses: USI 483 (59.3%) versus 912 (41.8%), detrusor overactivity (DO) 125 (15.4%) versus 399 (18.3%) and USI with concomitant DO 206 (25.3%) versus 869 (39.9%). A bimodal pattern of age was seen in women with USI, with a peak in the 46-50 and 61-65 age group, before decreasing with age. DO generally increased with age. USI with concomitant DO increased steadily after the menopause, becoming the predominant type after the age of 66. CONCLUSIONS: In this large cohort of women attending urodynamics, we have shown that USI is the predominant type of incontinence in pre-menopausal women; however, USI with concomitant DO increases after menopause, eventually predominating.

Experiences of menopausal transition among populations exposed to chronic psychosocial stress in the United States: a scoping review.

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.

Incidence of Breast Cancer in Younger Women: A Canadian Trend Analysis.

Purpose: Breast cancer (BC) incidence is increasing globally. Age-specific BC incidence trend analyses are lacking for women under age 50 in Canada. In this study, we evaluate the incidence trends in breast cancer in women under age 50 in Canada and compare them with corresponding trends among women 50 to 54. Methods: BC case counts were obtained from the National Cancer Incidence Reporting System (1984-1991) and the Canadian Cancer Registry (1992-2019) both housed at Statistics Canada. Population data were also obtained from Statistics Canada. Annual female BC age-specific incidence rates from 1984 to 2019 were derived for the following age groups: 20 to 29, 30 to 39, 40 to 49, 40 to 44, 45 to 49, and 50 to 54. Changes in trends in age-specific BC incidence rates, if any, and annual percent changes (APCs) for each identified trend, were determined using JoinPoint. Results: Statistically significant increasing trends in BC incidence rates were noted for almost all age groups: since 2001 for 20 to 29 (APC = 3.06%, P < .001); since 2009 for 30 to 39 (APC = 1.25%, P = .007); since 1984 for both 40 to 49 (APC = 0.26%, P < .001) and 40 to 44 (APC = 0.19%, P = .011), increased since 2015 for 40 to 49 (APC = 0.77%, P = .047); and since 2005 for 50 to 54 (APC = 0.38%, P = .022). Among women 45 to 49 there was a non-significant increase since 2005 (APC = 0.24, P = .058). Statistically significant average annualized increases in BC incidence rates were observed for each age group studied. Conclusions: Examining age-specific incidence rates formed a more complete picture of BC time trends with significant increasing trends in the incidence of BC among women in their 20s, 30s, 40s, and early 50s. A greater awareness regarding the increasing number of cases of BC in women younger than 50 is critical to allow for earlier diagnosis with its resultant reduced mortality and morbidity.

Endogenous testosterone concentrations and muscle mass, strength and performance in women, a systematic review of observational studies.

OBJECTIVE: To explore the associations between endogenous testosterone blood concentrations and muscle mass, strength and performance in community dwelling women. DESIGN, PATIENTS AND MEASUREMENTS: Online databases, including Ovid MEDLINE, EMBASE and Web of Science, were searched for observational studies, with at least 100 female participants, reporting associations between endogenous testosterone blood concentrations and muscle mass, strength and performance. The findings were synthesized in a narrative review. Heterogeneity in study design and analysis precluded a meta-analysis. RESULTS: Of the 36 articles retrieved for full-text review, 10 met the inclusion criteria. Eight studies were cross-sectional, 1 longitudinal and 1 provided both cross-sectional and longitudinal data. Testosterone was measured by liquid chromatography-tandem mass spectrometry in two studies and by immunoassay in 8. An association between total testosterone and muscle mass, strength or performance in women was not found. The studies of calculated free or bioavailable testosterone and lean muscle mass reported a positive association, but no association was reported for muscle strength or performance. Each included study was limited by a high risk of bias in at least one assessed domain. CONCLUSIONS: This review does not support an association between testosterone and muscle mass, strength or performance in women. This, together with the reported associations between free or bioavailable testosterone and muscle mass should be interpreted cautiously due to the predominant use of immunoassay and the inaccuracy of calculated variables. Additionally, biological significance of nonprotein bound testosterone has not been established. Further studies examining the relationship between precisely measured testosterone and muscle mass and function in women are required.

The effects of exogenous estrogen in women with SAR-CoV-2 infection: a systematic review and meta-analysis.

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 I2 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; I2 = 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.

In vivo assignment of methylmalonic acid in breast tissue using 2D MRS and relationship with breast density, menopausal status and cancer risk.

BACKGROUND: Methylmalonic acid (MMA) is linked to progression and aggressiveness of tumours. A recent study showed that high levels of circulatory MMA directed genetic programs promoting cancer progression. PURPOSE: To evaluate in vivo two-dimensional correlated spectroscopy (2D COSY) data from women at elevated risk of breast cancer to determine if resonances consistent with MMA are present, and if so to correlate levels with breast density, menopausal status and risk categories. MATERIALS AND METHODS: With institutional review board approval, 106 women at elevated risk (mean age 47), including 46 participants at medium risk, 43 at high risk with no known mutation and 17 BRCA-mutation carriers, were recruited. Breast density was assessed using a T2 sequence. A T1 sequence was used to place the voxel for the 2D COSY data. Peak volumes were normalized to the methylene peak at (1.30, 1.30) ppm. Chi-squared and Mann-Whitney tests were used. RESULTS: Two resonances are assigned on the diagonal at 3.15 ppm and 3.19 ppm consistent with and denoted MMA1 and MMA2 respectively. MMA1 and MMA2 increased in parallel with increased risk. BRCA-mutation carriers recorded an increase in mean MMA1 of 120% (p = 0.033) and MMA2 of 127% (p = 0.020) in comparison with participants with no known mutation. BRCA-mutation carriers with dense breasts recorded a significant increase in mean MMA1 of 137% (p = 0.002) and in mean MMA2 of 143% (p = 0.004) compared with BRCA-mutation participants with low-density breast tissue. MMA1 and MMA2 were higher in premenopausal women with dense breasts compared with those with low-density tissue. The highest values of MMA were recorded in BRCA-mutation carriers. CONCLUSION: Two tentative assignments are made for MMA in breast tissue of women at elevated risk for cancer. BRCA-mutation carriers exhibited higher values of MMA than those with no known mutation. Premenopausal women with BRCA mutation and dense breasts recorded the highest levels of MMA compared with other categories.

The alteration of apoptosis-related genes in female pelvic supportive tissues with regard to menopausal status.

PURPOSE: We aimed to compare the expression levels of anti-apoptotic and proapoptotic genes in the parametrium, sacrouterine and round ligaments with respect to menopausal status in women presenting without any indication of pelvic organ prolapse (POP). We hypothesized that apoptosis related gene expressions in female pelvic tissues may be altered during menopause. METHODS: The study groups consisted of pre-menopausal (n = 10) and menopausal (n = 10) females who did not have POP symptoms. Three different types of tissue samples (Parametrium, Round Ligament and Sacrouterine Ligament) were obtained and RNA was isolated from these tissues. After purifying and quantifying RNA samples, qPCR was used to determine the expression levels of anti-apoptotic and pro-apoptotic genes. RESULTS: BCL-2 gene expression levels were significantly lower in all the tissues of menopausal patients compared to those of premenopausal patients. In comparison to premenopausal patients, the sacrouterine ligament tissue BAD expression level was significantly high (p = 0.035), and the BCL-2/BAD ratio was significantly lower in menopausal patients (p = 0.006). CONCLUSION: Apoptosis-related protein levels change during menopause; pro-apoptotic gene expressions decrease and anti-apoptotic gene expressions increase. The significant alteration of BCL-2 and BAD expression in sacrouterine ligament with respect to menopausal status was observed and this suggested that when compared to other pelvic tissues, the sacrouterine ligament, which plays a crucial role for genital organs in restoring normal pelvic anatomy and providing support, could be affected more by menopause.

Influence of the levonorgestrel-releasing intrauterine system on the risk of breast cancer: a systematic review.

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.

Concurrent Aerobic and Strength Training with Caloric Restriction Reduces Insulin Resistance in Obese Premenopausal Women: A Randomized Controlled Trial.

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.

Insulin resistance and the development of breast cancer in premenopausal women: the Kangbuk Samsung Health Study.

PURPOSE: Research on the role of insulin resistance (IR) in breast cancer risk in premenopausal women is scarce. We aimed to investigate the relationship between IR and the development of breast cancer in premenopausal women. METHODS: We analyzed the prospective association of IR and incident breast cancer in premenopausal women without breast cancer at baseline using a subsample of the Kangbuk Samsung Health Study. RESULTS: Among 134,488 Korean premenopausal women, 696 women developed incident breast cancers during a median follow-up of 4.34 years. After adjustment for dense breast and other potential confounders, HR (95% CI) for incident breast cancer comparing HOMA-IR quintiles 2, 3, 4, and 5 to the first quintile was 0.91 (0.71-1.17), 0.89 (0.69-1.15), 0.75 (0.57-0.98), and 0.87 (0.65-1.16), respectively (P for trend = 0.117), while HR (95% CI) comparing insulin quintiles 2, 3, 4, and 5 to the first quintile was 1.02 (0.80-1.30), 0.90 (0.69-1.16), 0.72 (0.54-0.96), and 0.96 (0.72-1.28), respectively (P for trend = 0.151). This pattern did not significantly differ by obesity. These results were attenuated and no longer significant in time-dependent analyses where updated status of insulin and other covariates over time were treated as time-varying covariates. CONCLUSION: Our findings do not support the positive relationship of IR with the development of breast cancer in premenopausal women, unlike in postmenopausal women. Thus, the role of IR as a risk factor for breast cancer may differ by menopausal status.

Association between body mass index and incidence of breast cancer in premenopausal women: a Japanese nationwide database study.

PURPOSE: The association between body mass index (BMI) and the incidence of premenopausal breast cancer in the Asian population remains unclear. We investigated this association using data from a Japanese nationwide administrative database. METHODS: We retrospectively identified 785,703 females aged < 45 years with available health checkup data on BMI from January 2005 and April 2020 from a Japanese nationwide database. Cox proportional hazards model was used to estimate hazard ratios for breast cancer (total breast cancer, breast cancer with hormonal drug and trastuzumab administration, and breast cancer by age ≤ 45 years) associated with BMI recorded at the first health checkup. We conducted restricted cubic spline analysis without BMI categorization to investigate potential nonlinear associations with adjustment for backgrounds such as smoking and alcohol consumption. RESULTS: Overall, the median BMI was 20.5 (interquartile range [IQR], 18.9-22.7) kg/m2, and the median age was 37 (IQR, 29-41) years. Breast cancer occurred in 5597 participants (0.71%) at a median age of 44 (IQR, 42-46) years during a median follow-up of 1034 (IQR, 634-1779) days. A BMI of ≥ 22.0 kg/m2 was significantly associated with lower incidences of total breast cancer, breast cancer with hormonal drug administration, and breast cancer by age ≤ 45 years, whereas no significant associations were observed for breast cancer with trastuzumab administration. CONCLUSION: This study, which used a Japanese nationwide database, demonstrated that BMI was inversely associated with premenopausal breast cancer development in Japanese women, similar to that observed in Western women.

Lifetime personal cigarette smoking and risk of young-onset breast cancer by subtype among non-Hispanic Black and White women in the Young Women's Health History Study.

PURPOSE: To evaluate the association between lifetime personal cigarette smoking and young-onset breast cancer (YOBC; diagnosed <50 years of age) risk overall and by breast cancer (BC) subtype, and whether risk varies by race or socioeconomic position (SEP). METHODS: Data are from the Young Women's Health History Study (YWHHS), a population-based case-control study of non-Hispanic Black (NHB) and White (NHW) women, ages 20-49 years (n = 1812 cases, n = 1381 controls) in the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry areas, 2010-2015. Lifetime personal cigarette smoking characteristics and YOBC risk by subtype were examined using sample-weighted, multivariable-adjusted polytomous logistic regression. RESULTS: YOBC risk associated with ever versus never smoking differed by subtype (Pheterogeneity = 0.01) with risk significantly increased for Luminal A (adjusted odds ratio [aOR] 1.34; 95% confidence interval [CI] 1.06-1.68) and HER2-type (aOR 1.97; 95% CI 1.23-3.16), and no association with Luminal B or Triple Negative subtypes. Additionally, ≥30 years since smoking initiation (versus never) was statistically significantly associated with an increased risk of Luminal A (aOR 1.55; 95% CI 1.07-2.26) and HER2-type YOBC (aOR 2.77; 95% CI 1.32-5.79), but not other subtypes. In addition, among parous women, smoking initiated before first full-term pregnancy (versus never) was significantly associated with an increased risk of Luminal A YOBC (aOR 1.45; 95% CI 1.11-1.89). We observed little evidence for interactions by race and SEP. CONCLUSION: Findings confirm prior reports of a positive association between cigarette smoking and Luminal A YOBC and identify a novel association between smoking and HER2-type YOBC.

Challenges in the diagnosis and management of glucocorticoid-induced osteoporosis in younger and older adults.

OBJECTIVE: Glucocorticoids constitute a considerable risk for developing osteoporosis in both younger and older adults. However, currently available bone imaging modalities and fracture-risk assessment tools do not adequately capture the dramatic changes in bone microarchitecture, heterogeneity of glucocorticoid exposure, the impact of chronic disease and other osteoporosis risk factors on the assessment of osteoporosis in these individuals. DESIGN: A narrative review is presented, following a systematic search of the literature from 2000 to 2021. RESULTS: Our current appreciation of glucocorticoid-induced osteoporosis (GIO) is focused on older populations, with limited evidence to guide the investigation, risk assessment and treatment in premenopausal women and men less than 50 years. The impact of the underlying chronic disease on secondary osteoporosis in these younger adults is also poorly understood. CONCLUSION: Through this narrative review, we provide a comprehensive overview of and recommendations for optimising the management of this common cause of secondary osteoporosis younger and older adults.

Women's experiences in the transition to menopause: a qualitative research.

BACKGROUND: Around the time of transition to menopausal period, women experience mental, and psychological disorders that require adequate attention to these symptoms. This study aimed to explore the experiences of women in the face of premenopausal symptoms. METHODS: This qualitative study was conducted using a content analysis method in Javanrood, Iran, in 2020. The data were collected through in-depth semi-structured face to face interviews with 16 premenopausal using interview guide in a private room in comprehensive health centers. The women inclusion criteria were approaching menopause, having irregular menstruation, and having no disease or medication that affects menstruation. Furthermore, the exclusion criteria were the absence of menstruation for more than 12 months, and the women's refusal to continue the interview. The participants were selected using purposive sampling and sampling continued until data saturation. The collected data were analyzed with MAXQDA10 software following the multi-step method proposed by Graneheim and Lundman. RESULTS: The participants' mean age was 47 ± 2.98 years. The data analysis revealed 5 categories including: "menopause and aging", "life transformation", confrontation of fear and hope", "life adjustment", and "need to facilitate the transition time". CONCLUSION: This study suggested the women's experience of the transition to menopause was characterized by the fear of the future and its consequences and the need for reassurance about it. Besides, the women sought solutions to their problems in health care providers, peers, and the family.

Bone mass density in lean and overweight women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome is a condition characterized by hormonal and metabolic disturbances that may affect bone health. The purpose of this study was to investigate the effect of polycystic ovary syndrome on bone mineral density and to examine which clinical characteristics of the syndrome could influence bone mineral density. MATERIALS AND METHODS: We examined 183 premenopausal women: 158 women with polycystic ovary syndrome and 25 healthy age- and body mass index matched controls. Bone mineral density and body composition were investigated by whole-body dual energy X-ray absorption. Total and free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, estradiol, fasting insulin and glucose, parathyroid hormone, calcium and 25-OH-cholecalciferol were measured. The effect of polycystic ovary syndrome on bone mineral density was analyzed by statistical two-way analysis of variance tests and multiple linear regressions for investigating the connection between bone mineral density and selected clinical parameters. RESULTS: Women with polycystic ovary syndrome had significantly lower bone density in the lumbar vertebrae L1-L4 compared to healthy controls, independently of body mass index. We found that total lean body mass was the most important associating factor for bone mineral density and these were strongly correlated throughout all regression analyzes. We found no connection between lumbar bone density and androgen status, hyperinsulinemia, estradiol or calcium homeostasis. CONCLUSIONS: Premenopausal women with polycystic ovary syndrome have lower bone mineral density in the lumbar vertebrae L1-L4 compared to healthy controls. Total lean body mass and polycystic ovary syndrome are significantly associated to this finding.

Evaluation of a Standardized Questionnaire for Initial Assessment of Abnormal Uterine Bleeding in Premenopausal Women.

OBJECTIVE: To assess the effect of a standardized questionnaire for premenopausal women with abnormal uterine bleeding (AUB) on clinical information collection and duration of consultation. METHODS: We conducted a before and after study involving 100 premenopausal women undergoing consultation for AUB. During stage 1, 50 consultations were recorded on a consultation sheet with no specific template. During stage 2, 50 women completed a 26-item auto-administered standardized questionnaire before the consultation, which was then reviewed with the consultant and added to the medical record. The duration of consultation was assessed in subgroups of 27 women in each stage. Two independent evaluators assessed the quality and completeness of data collected in the medical records using a score sheet developed by experts. Outcomes from both stages were compared using the t test. RESULTS: The descriptive characteristics were similar in both groups. The mean global scores of the quality and completeness of data collected improved significantly between stages 1 and 2, from 67% ± 12% to 95% ± 5% (P < 0.0001), as did medical background scores (54% ± 29% vs. 85% ± 13%; P < 0.0001) and AUB-related symptoms scores (69% ± 13% vs. 97% ± 5%; P < 0.0001). A mean reduction in duration of consultation of nearly 4 minutes was observed (24.6 ± 4.3 min vs. 20.7 ± 4.8 min; P < 0.0001). CONCLUSION: The AUB-specific standardized questionnaire improves quality and completeness of data collected in medical records and reduces duration of consultation.

Endometrial Biopsy in Low-Risk Women: Are We Over-Investigating?

The appropriate age at which to perform endometrial biopsy for abnormal uterine bleeding (AUB) is controversial. This study aimed to determine the prevalence of malignant and premalignant pathologies in women aged 41-49 years with AUB and without risk factors for endometrial cancer. Records of women who had undergone a biopsy at the gynaecology clinic of the Centre hospitalier de l'Université de Montréal between 2014 and 2018 were reviewed. Of the 209 women included in the study, 2 had atypical hyperplasia, which resolved without treatment, and 3 had hyperplasia without atypia. The remaining women had benign results, showing that the prevalence of malignant and premalignant endometrial pathologies is low in this subgroup of patients.

Lifestage Sex-Specific Genetic Effects on Metabolic Disorders in an Adult Population in Korea: The Korean Genome and Epidemiology Study.

Although many genome-wide association studies (GWASs) have evaluated the association with metabolic disorders, the current study is the first attempt to analyze the genetic risk factors for various metabolic disorders according to sex and age groups of the life course in Korean adults. A total population of 50,808 people were included in this GWAS. The genetic traits for eight metabolic phenotypes were investigated in peri-, and postmenopausal women compared to a younger group or men of corresponding age groups. The metabolic phenotypes include general obesity, abdominal obesity, hypertension, type 2 diabetes, hypercholesterolemia, hypertriglyceridemia, hypo-high-density lipoprotein cholesterolemia, and metabolic syndrome. In the total participants, GWAS results for eight metabolic phenotypes found 101 significant loci. Of these, 15 loci were the first reported to be associated with the risk of metabolic disorder. Interestingly, some of the significant loci presented the association with the various phenotypes, which presented when there was a correlation between phenotypes. In addition, we analyzed divided by gender and age (young adult, peri-menopausal group, older adult), and specifically identified specific loci in peri-menopausal women. Meanwhile, several genetic factors associated with metabolic disorders were newly reported in our study. In particular, several genes were significantly associated with one of the metabolic phenotypes in only a single specific group. These findings suggest that menopausal transition rather than aging itself potentiates the influence of genetic risks on metabolic disorders. In addition, some genetic loci with low frequencies may play a role in the metabolic disturbances in a specific sex and age group. The genetic traits derived from our study may contribute to understanding the genetic risk factors for metabolic disorders in the Korean population.