Alcohol use at midlife and in menopause: a narrative review.

Alcohol use disorder stands as a prevalent global issue, contributing to 140,000 annual deaths in the United States and causing numerous adverse health and socioeconomic outcomes. Despite being a natural physiological process, menopause often leads to troublesome symptoms that affect women's quality of life and exposes them to increased health risks. Our review delves into the intricate relationship between alcohol use disorder and the menopausal experience. We examine the impact of heightened alcohol consumption on the onset, severity, and burden of menopausal symptoms, particularly vasomotor symptoms. Additionally, we explore its effects on commonly experienced menopausal symptoms such as mood disturbances, sleep problems, and sexual dysfunction. Considering the chronic health conditions associated with both menopause and alcohol use disorder, our study also investigates the influence of alcohol use disorder on bone density. This is especially important due to the elevated risks and mortality linked to bone mineral density loss in menopausal women.

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.

Serum Prolactin Levels as a Novel, Practical Marker for Predicting Malignant Diseases of the Breast.

Background and objective Prolactin (PRL) has a high specificity toward breast cancer (BC), making it a valuable marker in both diagnosis and prognosis. In this study, we aimed to compare serum PRL levels between pre- and post-menopausal women with BC, as well as normal reference values. We also investigated the association of various risk factors with PRL levels in women with BC. Methods The study involved adult women diagnosed with BC based on clinical features and tissue histopathology receiving treatment at a tertiary care center in Pune, India. General and demographic information, anthropometric measurements (height, weight, and BMI), menstrual status (age at menarche and menopausal state), clinical presentation (signs and symptoms), duration of symptoms, and parity were recorded by using a pre-tested proforma based on hospital records or in-person interviews. Serum PRL was measured by the RIA method (sandwich assay). Results A total of 67 women (average age: 47.5 ± 11.8 years; 33 of them post-menopausal) with BC were included in the study. The participants had an average BMI of 24.9 ± 3.5 kg/m2, and 26 (39%) of them were overweight. The majority of women had BC stage IIA disease, involvement of the right side or upper outer quadrant, and had attained menarche after 14 years of age; 47 women had a BC duration of >3 months. Seven women were nulliparous, and the remaining had given birth to their first child before the age of 26 years. The average serum PRL level among the participants was 9.27 ± 7.62 ng/mL, with higher levels found in post-menopausal women compared to pre-menopausal women (11.08 vs. 7.51 ng/mL, respectively; p=0.08). Women with a higher stage and greater duration of disease had significantly higher serum PRL levels (p<0.001 for both). When compared with reference values, pre-menopausal women showed significantly lower (6.25 vs. 10.9, respectively; p=0.001) and post-menopausal women showed significantly higher (8.55 vs. 5.95; p=0.004) serum PRL levels. A positive correlation was found between serum PRL and age at the time of birth of the first child (p=0.068). Conclusions Based on our findings, PRL is an important hormone in the development of BC in women. Therapeutic modulation of PRL may be a realistic and novel approach to curing human BC, either administered alone or in combination with conventional treatments.

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.

Androgenicity in Young Women and Development of Metabolic Syndrome Before Menopause: The CARDIA and CARDIA Women's Studies.

Context: There are no reported data from prospective long-term studies on the relation of androgen levels in young women with development of metabolic syndrome (MetS) before menopause. Objective: We investigated associations of androgens and SHBG with incident MetS during 23 years of follow-up. Methods: We included 366 White and 375 Black women ages 20 to 32 years participating in the CARDIA study and CARDIA Women's study, free of MetS at baseline examination (1987-1988), and premenopausal 23 years later. Androgens and SHBG were categorized into quartiles. MetS was defined according to the American Heart Association/National Heart, Lung, and Blood Institute 2009 Joint Scientific Statement. Cox proportional hazards models were used. Results: By year 23, 30% of women developed MetS. Adjusting for baseline age, race, and education, hazard ratios (95% CI) of developing MetS were 1.46 (1.02-2.10) and 2.22 (1.53-3.21) for women in the highest vs lowest total testosterone (T) and free T quartile, respectively. The hazards of developing MetS were 47%, 59%, and 53% lower for women with SHBG in the second, third, and fourth quartiles (vs lowest quartile), respectively. Associations were attenuated for total T with further adjustments for smoking, physical activity, menstrual status, oral contraceptive/hormone (OCHM) use, insulin level, oligomenorrhea, and age at menarche, but remained statistically significant for free T and SHBG. Associations were similar for both Blacks and Whites, and OCHM nonusers, but not for OCHM users. Conclusion: High androgenicity in young premenopausal women is associated with higher risk of future MetS, suggesting that early assessment of androgens may contribute to prevention.

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.

Self-Image in Women with Parkinson's Disease.

There is a fundamental gap in knowledge in how Parkinson's disease manifests and affects women throughout their hormonal life cycle, resulting in unmet needs and adversely impacting women's quality of life. A set of questionnaires was developed and deployed through Fox Insight (open access) to address these issues by gathering data. This is the data from the first survey. The data from the questions regarding self-image were striking. 61% of women report that their Parkinson's disease negatively impacts their self-image. Here we explore the negative impact of Parkinson's disease on women to begin to fill the gaps in knowledge.

Association of reproductive factors with cardiovascular disease risk in pre-menopausal women: nationwide population-based cohort study.

BACKGROUND: Although the morbidity and mortality of cardiovascular diseases (CVD) are rising in young women, the risk factors of CVD among Korean pre-menopausal women have not been intensively investigated. AIMS: To determine how age at menarche and other female reproductive factors are associated with the risk of CVD in pre-menopausal women. METHODS AND RESULTS: A total of 1 088 992 pre-menopausal women who participated in health screening in 2009 were included. The study outcomes were myocardial infarction (MI) and ischaemic stroke. Cox proportional hazards regression analysis was conducted with adjustment of traditional CVD risk factors and reproductive factors. RESULTS: Mean age was 43.8 ± 5.3 years (98.9%, < 55 years), 3.5% were current smokers, and 1.2% were heavy drinkers. During a mean follow-up of 8.3years [9 032 685.9 person-years (PY)], there were 10 876 CVD events (1.0 per 1000 PY).With later menarche, the risk of CVD increased; ≤12 years [adjusted hazard ratio (HR) 1.04, 95% confidence interval 0.93-1.16], 13 years (reference), 14 years (1.06, 0.98-1.14), 15 years (1.15, 1.07-1.24), 16 years (1.23, 1.14-1.34), and ≥17 years (1.33, 1.24-1.44). Compared with non-users, oral contraceptives (OC) users (≥1 year) had an increased risk of CVD (1.11, 1.01-1.22) (P for trend = 0.007). CONCLUSIONS: Later menarche than the mean age at menarche (13 years old) and the use of OC (≥1 year) were associated with a higher risk of CVD, after adjusting for traditional cardiovascular risk factors. This study suggests that female reproductive factors could be unique risk factors for CVD in pre-menopausal women.

Unraveling the Link: A Comprehensive Literature Review of Type 2 Diabetes and Menopause Onset.

Women with diabetes mellitus (DM), a metabolic endocrine illness, may experience a variety of reproductive problems. The age at menopause onset has been extensively studied as a major predictor of women's health in the future; however, its relationship to diabetes in Indian women has received less attention. This literature review looked at the consequences of diabetes in women as well as the association between diabetes and the age at which menopause begins. The average age at menopause onset among women with type 2 diabetes mellitus (T2DM) has decreased globally. According to one Indian study, the average menopause age dropped to 45 years for 26% of women with T2DM. In the current review, 10 studies indicated that women with T2DM displayed an imbalanced hormonal profile resulting in an extended anovulatory period. Two investigations highlighted the significance of altered body composition of women with T2DM, thereby suggesting obesity as the primary risk factor of ovarian aging and early climacteric symptoms. T2DM may lower the average age at menopause onset; however, further research on Indian women is necessary. There is a need of studies on T2DM in premenopausal women are needed to demonstrate how the changes in body composition impact the age at which menopause begins. Delaying the onset of menopause in women with T2DM necessitates diet and lifestyle interventions to minimize ovarian aging and hormonal imbalance.

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.

Low bone mineral density in pre-menopausal women one year after gastric bypass / Baixa densidade mineral óssea em mulheres pré-menopausadas um ano após bypass gástrico

Introduction: Nutritional deficiencies, hormonal changes and severe weight loss after Roux-en-Y Gastric Bypass (RYGB) can promote changes in bone metabolism which may lead to a reduction in bone mineral density (BMD). Objective: to investigate the prevalence of osteopenia/osteoporosis and factors associated with BMD in pre-menopausal women who underwent RYGB. Methodology: a cross-sectional study conducted with secondary data of patients followed-up in a specialized center for obesity treatment. Variables studied: biochemical and anthropometric data, body composition by multifrequency bioimpedance and BMD of the lumbar spine (LS), total femur (TF) and femur neck (FN) by dual-energy X-ray absorptiometry. For statistical analysis, the SPSS® software and a 5% significance level were utilized. Results: seventy-two (72) pre-menopausal women were evaluated. Mean age, BMI and mean post-surgery time was 38.7±6.5 years, 25.8±2.5 kg/m² and 13.1±1.7 months, respectively. The prevalence of osteopenia in at least one of the densitometry sites was 13.9%, with LS being the most frequent site. A lower LS BMD was associated with greater weight loss, higher percentage of body fat before surgery and lower post-surgery serum vitamin D levels. There was a positive correlation between skeletal muscle mass index adjusted for height in the pre-surgery period and LS BMD (r=0.361; p=0.010) and TF (r=0.404; p=0.004). Conclusion: a relevant prevalence of osteopenia was detected in pre-menopausal women after RYGB, mainly in the LS.

Introdução: o Bypass Gástrico em Y de Roux (BPGYR) pode promover mudanças no metabolismo ósseo decorrentes de deficiências nutricionais, alterações hormonais e perda severa de peso, podendo acarretar redução da Densidade Mineral Óssea (DMO). Objetivo: investigar a prevalência de osteopenia/osteoporose e fatores associados à DMO em mulheres pré-menopausadas submetidas à BPGYR. Metodologia: estudo transversal com dados secundários de pacientes acompanhadas em um serviço especializado no tratamento da obesidade. Variáveis estudadas: dados bioquímicos e antropométricos, composição corporal por bioimpedância multifrequencial e DMO de coluna lombar (CL), fêmur total (FT) e colo do fêmur (CF) por Absorciometria por Dupla Emissão de Raios X. Para análise estatística foi utilizado o programa SPSS®, com o nível de significância de 5%. Resultados: foram avaliadas 72 mulheres pré-menopausadas, com média de idade e de IMC de 38,7±6,5 anos e 25,8±2,5 kg/m², respectivamente, e tempo médio de pós-operatório de 13,1±1,7 meses. A prevalência de osteopenia em pelo menos um dos sítios densitométricos foi de 13,9%, sendo a CL o sítio mais frequente. Uma menor DMO na CL se associou a maior perda de peso, maior percentual de massa gorda antes da cirurgia e níveis séricos menores de vitamina D pós-operatória. Observou-se correlação positiva entre o índice de massa muscular esquelética ajustada pela altura no pré-operatório e a DMO da CL (r=0,361; p=0,010) e do FT (r=0,404; p= 0,004). Conclusão: detectou-se prevalência relevante de osteopenia em mulheres pré-menopausadas após BPGYR, principalmente na CL.

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.

High carbohydrate intakes may predict more inflammatory status than high fat intakes in pre-menopause women with overweight or obesity: a cross-sectional study.

OBJECTIVE: The associations between dietary carbohydrate, fat intake, and inflammation are controversial. Most existing data are from industrialized societies which low-carbohydrate and high-fat diet is common and so their attribution to other populations remains unclear. We evaluated the association of fat and carbohydrate intakes with inflammatory markers in pre-menopause women with overweight or obesity in Iran. RESULTS: Three hundred and sixty women with body mass index (BMI) ≥ 25 were included to this study. The levels of monocyte chemoattractant protein-1 (MCP-1) indicated a trend towards significance across tertiles of total dietary carbohydrate. We found that the levels of galectin-3 were negatively associated with dietary carbohydrate in adjusted model. In addition, the levels of MCP-1 and transforming growth factor beta (TGF-ß) were positively correlated to dietary carbohydrate. No significant relationship was demonstrated between inflammatory parameters and total fat intake). However, there was a borderline significant negative association between total fat intake and TGF-ß level in adjusted model. Therefore, a total dietary carbohydrate were related to elevated inflammation risk, while a total fat intake were not associated to higher inflammation. This study suggests reconsideration of applying global dietary guidelines in societies with high carbohydrate diet.

Oestrogen receptor activity in hormone-dependent breast cancer during chemotherapy.

BACKGROUND: Chemotherapy efficacy in early-stage hormone receptor-positive (HR+) breast cancer (BC) according to menopausal status needs a biological explanation. METHODS: We compared early-stage HR+ BC biological features before and after (neo)adjuvant chemotherapy or endocrine therapy (ET), and assessed oestrogen receptor (ER) pathway activity in both pre- and post-menopausal patients. The nCounter platform was used to detect gene expression levels. FINDINGS: In 106 post-menopausal patients with HR+/HER2-negative BC randomized to neoadjuvant chemotherapy or ET (letrozole+ribociclib), a total of 19 oestrogen-regulated genes, including progesterone receptor (PGR), were found downregulated in the ET-based arm-only. We confirmed this finding in an independent dataset of 20 letrozole-treated post-menopausal patients and found, conversely, an up-regulation of the same signature in HR+/HER2-negative MCF7 cell line treated with estradiol. PGR was found down-regulated by 2 weeks of ET+anti-HER2 therapy in pre-/post-menopausal patients with HR+/HER2-positive (HER2+) BC, while anti-HER2 therapy alone increased PGR expression in HR-negative/HER2+ BC. In 88 pre- and post-menopausal patients with newly diagnosed HR+/HER2-negative BC treated with chemotherapy, the 19 oestrogen-regulated genes were found significantly downregulated only in pre-menopausal patients. In progesterone receptor (PR)+/HER2-negative BC treated with neoadjuvant chemotherapy (n=40), tumours became PR-negative in 69.2% of pre-menopausal patients and 14.8% of post-menopausal patients (p=0.001). Finally, a mean decrease in PGR levels was only observed in pre-menopausal patients undergoing anti-HER2-based multi-agent chemotherapy. INTERPRETATION: Chemotherapy reduces the expression of ER-regulated genes in pre-menopausal women suffering from hormone-dependent BC by supressing ovarian function. Further studies should test the value of chemotherapy in this patient population when ovarian function is suppressed by other methods. FUNDING: Instituto de Salud Carlos III, Breast Cancer Now, the Breast Cancer Research Foundation, the American Association for Cancer Research, Fundació La Marató TV3, the European Union's Horizon 2020 Research and Innovation Programme, Pas a Pas, Save the Mama, Fundación Científica Asociación Española Contra el Cáncer, PhD4MDgrant of "Departament de Salut", exp SLT008/18/00122, Fundación SEOM and ESMO. Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the author(s).

Research Progress on Animal Models of Menopausal Syndrome： A Review / 中国实验方剂学杂志

In order to explore the pathological mechanism of perimenopausal syndrome and seek prevention and treatment measures， it is necessary to establish animal models that similar to human perimenopausal syndrome， so as to provide reference for drug research， new drug development and clinical application. In this paper， the keywords of "perimenopausal period" "perimenopausal syndrome" "menopause" "menopausal syndrome""menopausal period" "menopausal syndrome" and "animal" were searched in China National Knowledge Infrastructure （CNKI）， Chongqing Weipu， China Biomedical Literature Database （CBM） and Pubmed. In addition， the selection of domestic peripheral menopausal syndrome model animals in recent years and the advantages and disadvantages of corresponding models were summarized. A total of 673 studies were identified， of which 61 were included in the analysis. The most common animal model of perimenopausal syndrome is castration model， while the immunodeficiency model is less used. With the aging of the population and the rapid increase of psychosocial stress， the incidence of perimenopausal syndrome is high. Therefore， it is particularly important to explore the mechanism of perimenopausal syndrome. According to the experimental purpose， experimental period， experimental technology and other factors， the selection of appropriate model animals and modeling methods is the key of the success of the experiment of perimenopausal syndrome.

Age of Natural Menopause and Related Factors among the Tabari Cohort.

OBJECTIVES: The age of menopause is affected by several factors. In this study we aimed to identify the age of natural menopause and its related factors in a large-scale population-based cohort in Iran. METHODS: In this study, a subset of data collected during the enrollment phase of the Tabari cohort study was utilized. Reproductive history and other related data were collected using a structured questionnaire. Blood samples were obtained from all participants. Data were analyzed using chi-square test, independent t test, and ANOVA as well as a multivariate linear regression model. RESULTS: Among participants of the Tabari cohort, 2,753 were menopausal women. The mean age of natural and induced menopause was 49.2 ± 4.7 and 43.2 ± 6.4 years, respectively (P = 0.001). The number of pregnancies, duration of breastfeeding, level of education, residency, presence of thyroid disease, and body mass index affected the age of menopause. After adjustments for confounding variables, the number of pregnancies remained significantly associated with late menopause. CONCLUSIONS: The age of natural menopause in this study was similar to that in other studies, and the number of pregnancies was positively associated with the age of menopause after adjustments for confounding variables.

The incidence of breast cancer in Canada 1971-2015: trends in screening-eligible and young-onset age groups.

OBJECTIVES: Breast cancer incidence has fluctuated considerably in Canada, with recent reductions in rates among screening-eligible women. However, incidence of early-onset and pre-menopausal breast cancer is understudied. We examined age-specific trends in breast cancer incidence between 1971 and 2015, as well as possible trends by birth cohort. METHODS: Incidence data were collected from the National Cancer Incidence Reporting System and the Canadian Cancer Registry, and annual percent changes were estimated using the Joinpoint Regression Program. Five-year birth cohort models were fit using the National Cancer Institute's web tool. RESULTS: Breast cancer incidence among women under age 40 has increased since 2000, while incidence under 50 has remained stable. Rates of post-menopausal breast cancer declined sharply and have recently plateaued. More recent birth cohorts are at a non-significantly increased risk of breast cancer compared with the reference, with an increasing upward trend. CONCLUSIONS: Rates of breast cancer may be increasing among younger women, and there is suggestive evidence that more recent birth cohorts are at increased risk of the disease. More research is needed into the risk factors for pre-menopausal breast cancer to support primary prevention efforts in this area.

Changes in the PGC-1α and mtDNA copy number may play a role in the development of pelvic organ prolapse in pre-menopausal patients.

OBJECTIVE: The alternations of mtDNA may play an important role in the molecular pathogenesis and process of Pelvic Organ Prolapse (POP) formation in both pre-menopausal and post-menopausal women. The aim of the present study is to analyze the association between the mitochondrial biogenesis gene and development of POP in the uterosacral ligaments (UL) of pre-menopausal women. MATERIALS AND METHODS: Seventy one pre-menopausal women, all below 52 years of age, were enrolled in this study. UL biopsies were obtained from uterine specimens taken from 33 women with POP (n = 33, study group) and 38 myoma patients without POP (n = 38, control group). Quantitative Real-Time PCR was performed to measure mitochondrial DNA (mtDNA) copy number and mtDNA4977. Western blotting and immunohistochemistry were used to assess the protein expression of PGC-1α, TFAM, NRF-1 and NRF-2. Statistical analysis was performed using SPSS statistical software and the Mann-Whitney U test, and the continuous variables were analyzed using the Student's t-test in demographic data. RESULTS: There were no significant differences in the patient demographics between the two groups (p > 0.05). The mtDNA copy number in the UL of pre-menopausal patients with prolapse was significantly higher than that in the no prolapse group (p = 0.008). There were no significant differences between the mtDNA4977 of the POP and non-POP groups, but a significantly higher expression of PGC-1α in the POP group compared to the non-POP group (1.59 ± 1.30 v.s. 0.66 ± 0.53; p = 0.036). The expression of TFAM in the POP group was higher than in the non-POP group). There was no significant difference in the TFAM(p = 0.377), NRF-1 and NRF-2 expression between the POP and non-POP groups (p = 0.647; p = 0.682). CONCLUSIONS: Changes in the PGC-1α and mtDNA copy number may play a role in the development of Pelvic Organ Prolapse in pre-menopausal patients.

Relationship between bone density and abdominal visceral fat in premenopausal overweight and obese Iranian women aged 30-50 years.

AIM: The presence of a direct relationship between body mass index (BMI) and bone mineral density (BMD) is frequently reported. However, data on the relationship between visceral fat and bone density varies, with positive, negative or no relationship having been reported. This study aims to examine the relationship between abdominal visceral fat and BMD. METHODS: A cross sectional study was carried out on 95 premenopausal, overweight and obese women aged 30-50 years referred to Sina Hospital, Tehran, Iran in 2011-2012. Anthropometric indices and visceral fat levels were measured. RESULTS: Multiple linear regression analysis showed that proximal femur BMD (P = 0.856) and lumbar spine BMD (P = 0.558) were not significantly related to visceral fat level. However, BMI had a direct and significant positive relationship with proximal femur BMD (P = 0.001) and lumbar spine BMD (P = 0.031). Menarche age was negatively related to lumbar spine BMD (P = 0.003). CONCLUSIONS: In this study, after adjusting for fat-free mass, no significant relationship was found between MBD of the proximal femur and lumbar spine, and visceral fat level or visceral fat to total fat percentage ratio. Therefore, abdominal visceral fat may not affect BMD, independent of weight. It seems that the positive relationship between BMI and proximal femur and lumbar spine BMD is due to the mechanical effects of weight on bones.