Reproductive factors and risk of lung cancer among 300,000 Chinese female never-smokers: evidence from the China Kadoorie Biobank study.

BACKGROUND: Lung cancer is the leading cause of cancer mortality among Chinese females despite the low smoking prevalence among this population. This study assessed the roles of reproductive factors in lung cancer development among Chinese female never-smokers. METHODS: The prospective China Kadoorie Biobank (CKB) recruited over 0.5 million Chinese adults (0.3 million females) from 10 geographical areas in China in 2004-2008 when information on socio-demographic/lifestyle/environmental factors, physical measurements, medical history, and reproductive history collected through interviewer-administered questionnaires. Cox proportional hazard regression was used to estimate adjusted hazard ratios (HRs) of lung cancer by reproductive factors. Subgroup analyses by menopausal status, birth year, and geographical region were performed. RESULTS: During a median follow-up of 11 years, 2,284 incident lung cancers occurred among 282,558 female never-smokers. Ever oral contraceptive use was associated with a higher risk of lung cancer (HR = 1.16, 95% CI: 1.02-1.33) with a significant increasing trend associated with longer duration of use (p-trend = 0.03). Longer average breastfeeding duration per child was associated with a decreased risk (0.86, 0.78-0.95) for > 12 months compared with those who breastfed for 7-12 months. No statistically significant association was detected between other reproductive factors and lung cancer risk. CONCLUSION: Oral contraceptive use was associated with an increased risk of lung cancer in Chinese female never-smokers. Further studies are needed to assess lung cancer risk related to different types of oral contraceptives in similar populations.

Effects of donor age and reproductive history on developmental potential of ovum pickup oocytes in Japanese Black cattle (Wagyu).

The objectives of this study were to analyze the (1) effects of donor age and multiparity on development of in vitro fertilization (IVF) embryos after ovum pickup (OPU), (2) effects of repeated and consecutive OPU-IVF procedures on embryo development, and (3) embryo production from OPU-IVF in donors with differing embryo yields after multiple ovulation and embryo transfer technology (MOET) in Japanese Black cattle (Wagyu). Donors were pre-treated with low-dosage follicle-stimulating hormone (FSH; 200 IU total), and oocytes were collected via OPU and fertilized by IVF to generate blastocysts. The number of oocytes collected per OPU session per donor was lower in heifers (2-4 years old, 5.3 oocytes) than in primiparous and pluriparous cows (2-10 years old, 13.6-19.1 oocytes; P < 0.05). Rates of blastocyst development for oocytes from heifers (33.1%) were lower than for those from cows (2-10 years old, 44.1-54.3%; P < 0.05), and average blastocyst yield/OPU/animal was lower in heifers (3.7) than in 5-6 years old cows (10.1; P < 0.05). Donors undergoing five consecutive OPU-IVF sessions after low-dosage FSH showed similar oocyte retrieval (12.2-15.1 oocytes per OPU/animal), blastocyst development rates (35.6-45.0%), and embryo yield/OPU/animal (4.8-5.8; P > 0.05) across sessions. Additionally, embryo yield from OPU-IVF was significantly improved in animals with previous low embryo yield from MOET (5.9 vs. 2.6, respectively, P < 0.05). These results indicate that Wagyu cows with previous births can be more productive as OPU-IVF donors than heifers, and oocytes from donors undergoing to five consecutive OPU-IVF cycles are competent for embryo development without loss of embryo yield/OPU/animal. Moreover, OPU-IVF can be used for embryo production and breeding from all elite Japanese Black cattle, regardless of previous low embryo yield in routine MOET.

Pregnancy History at 40 Years of Age as a Marker of Cardiovascular Risk.

BACKGROUND: Individual pregnancy complications are associated with increased maternal risk of cardiovascular disease. We assessed the link between a woman's total pregnancy history at 40 years of age and her relative risk of dying from atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: This population-based prospective study combined several Norwegian registries covering the period 1967 to 2020. We identified 854 442 women born after 1944 or registered with a pregnancy in 1967 or later, and surviving to 40 years of age. The main outcome was the time to ASCVD mortality through age 69 years. The exposure was a woman's number of recorded pregnancies (0, 1, 2, 3, or 4) and the number of those with complications (preterm delivery <35 gestational weeks, preeclampsia, placental abruption, perinatal death, and term or near-term birth weight <2700 g). Cox models provided estimates of hazard ratios across exposure categories. The group with the lowest ASCVD mortality was that with 3 pregnancies and no complications, which served as the reference group. Among women reaching 40 years of age, risk of ASCVD mortality through 69 years of age increased with the number of complicated pregnancies in a strong dose-response fashion, reaching 23-fold increased risk (95% CI, 10-51) for women with 4 complicated pregnancies. Based on pregnancy history alone, 19% of women at 40 years of age (including nulliparous women) had an increased ASCVD mortality risk in the range of 2.5- to 5-fold. CONCLUSIONS: Pregnancy history at 40 years of age is strongly associated with ASCVD mortality. Further research should explore how much pregnancy history at 40 years of age adds to established cardiovascular disease risk factors in predicting cardiovascular disease mortality.

Heterogeneity in the risk of cardiovascular disease mortality after the hypertensive disorders of pregnancy across mothers' lifetime reproductive history.

BACKGROUND: Prior studies on maternal cardiovascular disease (CVD) mortality and hypertensive disorders of pregnancy (HDP) have focused only on a woman's first birth and have not accounted for successive affected pregnancies. OBJECTIVES: The objective of this study is to identify mothers' risk of CVD mortality considering lifetime reproductive history. METHODS: We used data from the Medical Birth Registry of Norway, the Norwegian Cause of Death Registry, and the Norwegian National Population Register to identify all mothers who gave birth from 1967 to 2020. Our outcome was mothers' CVD death before age 70. The primary exposure was the lifetime history of HDP. The secondary exposure was the order of HDP and gestational age at delivery of pregnancies with HDP. We used Cox regression models to estimate hazard ratio (HR) and 95% confidence interval (CI), adjusting for education, mother's age, and year of last birth. These models were stratified by the lifetime number of births. RESULTS: Among 987,378 mothers, 86,294 had HDP in at least one birth. The highest CVD mortality, relative to mothers without HDP, was among those with a pre-term HDP in their first two births, although this represented 1.0% of mothers with HDP (HR 5.12, 95% CI 2.66, 9.86). Multiparous mothers with term HDP in their first birth only had no increased risk of CVD relative to mothers without HDP (36.9% of all mothers with HDP; HR 1.12, 95% CI 0.95, 1.32). All other mothers with HDP had a 1.5- to 4-fold increased risk of CVD mortality. CONCLUSIONS: This study identified heterogeneity in the risk of CVD mortality among mothers with a history of HDP. A third of these mothers are not at higher risk compared to women without HDP, while some less common patterns of HDP history are associated with severe risk of CVD mortality.

Prevalence of anaemia among married women with recent birth history and high-risk fertility behaviour: secondary data analysis of the National Family Health Survey-India (2019-21).

OBJECTIVES: To describe the prevalence of anaemia among currently married women with high-risk fertility behaviour (HRFB) based on age, parity and birth spacing indicators. DESIGN: Cross-sectional study. SETTINGS AND PARTICIPANTS: Fifth round of the National Family Health Survey (NFHS) was conducted in India (2019-2021) and included a nationally representative sample of 724, 115 women in the reproductive age group (15-49). Our analysis focused exclusively on married women who had given birth in the preceding 5 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The prevalence of anaemia with HRFB was the primary outcome, and the likelihood of having anaemia due to HRFB was the secondary outcome. DATA AND METHODS: Secondary data analysis of the NFHS-5 (2019-2021) datasets was done using a weighted analysis to determine anaemia prevalence in different HRFB categories. Bivariate analysis was done using the χ2 test, and multiple binary logistic regression analyses were done to estimate the odds of having anaemia due to HRFB after adjusting for known confounders. A p value <0.05 was reported as statistically significant. RESULTS: The final analysis comprised 145,468 women, of whom 59.1% had anaemia. About 53.1% of women depicted 'No risk' fertility behaviour, and 34.6% and 12.3% had single and multiple HRFB. Women with 'no-risk,' single and multiple HRFB had anaemia prevalence rates of 58.1%, 59.4% and 63.1%, respectively. Women with 'Single risk' had an 18% higher likelihood (1.18; 1.13-1.22) of having anaemia after controlling for confounding variables, compared with the HRFB category with 'No risk.' Women with 'Multiple risks' showed a 6% higher likelihood (adjusted OR 1.06; 95% CI 1.03 to 1.08). CONCLUSIONS: Anaemia remains a prevalent issue in India, and HRFB is observed as a significant contributing factor. This vulnerable group can be targeted through multiple interventions and further our efforts to realise our anaemia-related goals.

Birth History and Cardiovascular Disease Risk Among Youth With Significant Obesity.

Children born prematurely have greater lifetime risk for hypertension. We aimed to determine (1) the association between prematurity and cardiovascular disease (CVD) risk factors among 90 children with obesity and elevated blood pressure and (2) if dietary sodium intake modified these associations. Multivariable regression analysis explored for associations between prematurity (<37 weeks gestation; early gestational age) and low birth weight (<2.5 kg) with hypertension, left ventricular mass index (LVMI), and left ventricular hypertrophy (LVH). Effect modification by dietary sodium intake was also explored. Patients were predominately male (60%), black (78%), adolescents (13.3 years), and with substantial obesity (body mass index: 36.5 kg/m2). Early gestational age/low birth weight was not an independent predictor for hypertension, LVMI, or LVH. There was no effect modification by sodium load. Our results suggest the increased CVD risk conferred by prematurity is less significant at certain cardiometabolic profiles. Promoting heart-healthy lifestyles to prevent pediatric obesity remains of utmost importance to foster cardiovascular health.

Impact of health-related behavioral factors on participation in a cervical cancer screening program: the lifelines population-based cohort.

BACKGROUND: Regular participation in cervical cancer screening is critical to reducing mortality. Although certain sociodemographic factors are known to be associated with one-time participation in screening, little is known about other factors that could be related to regular participation. Therefore, this study evaluated the association between health-related behavioral factors and regular participation in cervical cancer screening. METHODS: The Lifelines population-based cohort was linked to data for cervical cancer screening from the Dutch Nationwide Pathology Databank. We included women eligible for all four screening rounds between 2000 and 2019, classifying them as regular (4 attendances), irregular (1-3 attendances), and never participants. Multinomial logistic regression was performed to evaluate the association between behavioral factors and participation regularity, with adjustment made for sociodemographic factors. RESULTS: Of the 48,325 included women, 55.9%, 35.1%, and 9% were regular, irregular, and never screening participants. After adjustment for sociodemographic factors, the likelihood of irregular or never screening participation was increased by smoking, obesity, marginal or inadequate sleep duration, alcohol consumption and low physical activity, while it was decreased by hormonal contraception use. CONCLUSION: An association exists between unhealthy behavioral factors and never or irregular participation in cervical cancer screening.

Comparison of pregnancy and neonatal outcomes in a retrospective full pregnancy history survey versus population-based prospective records: a validation study in rural Sarlahi District, Nepal.

INTRODUCTION: Countries without complete civil registration and vital statistics systems rely on retrospective full pregnancy history surveys (FPH) to estimate incidence of pregnancy and mortality outcomes, including stillbirth and neonatal death. Yet surveys are subject to biases that impact demographic estimates, and few studies have quantified these effects. We compare data from an FPH vs. prospective records from a population-based cohort to estimate validity for maternal recall of live births, stillbirths, and neonatal deaths in a rural population in Sarlahi District, Nepal. METHODS: We used prospective data, collected through frequent visits of women from early pregnancy through the neonatal period, from a population-based randomized trial spanning 2010-2017. We randomly selected 76 trial participants from three pregnancy outcome groups: live birth (n = 26), stillbirth (n = 25), or neonatal death (n = 25). Data collectors administered the Nepal 2016 Demographic and Health Surveys (DHS)-VII pregnancy history survey between October 22, 2021, and November 18, 2021. We compared total pregnancy outcomes and numbers of pregnancy and neonatal outcomes between the two data sources. We matched pregnancy outcomes dates in the two sources within ± 30 days and calculated measures of validity for adverse outcomes. RESULTS: Among 76 participants, we recorded 122 pregnancy outcomes in the prospective data and 104 outcomes in the FPH within ± 30 days of each woman's total observation period in the trial. Among 226 outcomes, we observed 65 live births that survived to 28 days, 25 stillbirths, and 32 live births followed by neonatal death in the prospective data and participants reported 63 live births that survived to 28 days, 15 stillbirths, and 26 live births followed by neonatal death in the pregnancy history survey. Sixty-two FPH outcomes were matched by date within ± 30 days to an outcome in prospective data. Stillbirth, neonatal death, higher parity, and delivery at a health facility were associated with likelihood of a non-matched pregnancy outcome. CONCLUSIONS: Stillbirth and neonatal deaths were underestimated overall by the FPH, potentially underestimating the burden of mortality in this population. There is a need to develop tools to reduce or adjust for biases and errors in retrospective surveys to improve reporting of pregnancy and mortality outcomes.

Breast cancer risk factors based on reproductive and nonreproductive profiling of Pakistani women: A hospital based case control study.

Breast cancer (BC) is a global public health problem attributed to varying risk factors. The designing of a targeted screening program focused on at-risk women can be cost-effective in reducing its burden. A hospital based case control study was conducted on 138 cases of breast cancer and 169 healthy controls to investigate the reproductive and non-reproductive risk factors for breast cancer in Pakistani women. The odds ratios (ORs) and 95% confidence intervals (CIs) were computed with unconditional logistic regression. Almost all i.e. 97.83% of cases were married (OR=5.03),70.29% were illiterate (OR=1.88), 73.19% were aged >35 years (OR=0.632) and 81.16% belonged to the poor class(OR=1.81). Early age at menarche (OR, 2.55; 95% CI 1.50-4.31, P=0.0001), hormone replacement therapy (OR=2.057, 95% CI 1.283-3.295, P= 0.002) early pregnancy (OR,2.23, 95% CI 1.29-3.88, P=0.004), history of miscarriage (OR, 2.11, 95% CI 1.32-3.39,P=0.002) & oral contraceptive use (OR, 2.76, 95% CI 1.54-4.92, P= 0.006) were significantly associated with BC. The study highlights the dire need for effective public health programs for high-risk women to address this highly fatal disease.

Le cancer du sein (BC) est un problème de santé publique mondial attribué à divers facteurs de risque. La conception d'un programme de dépistage ciblé axé sur les femmes à risque peut s'avérer rentable pour réduire son fardeau. Une étude cas-témoins en milieu hospitalier a été menée sur 138 cas de cancer du sein et 169 témoins sains pour étudier les facteurs de risque reproductifs et non reproductifs du cancer du sein chez les femmes pakistanaises. Les rapports de cotes (OR) et les intervalles de confiance (IC) à 95 % ont été calculés par régression logistique inconditionnelle. La quasi-totalité soit 97,83% des cas étaient mariés (OR=5,03), 70,29% étaient analphabètes (OR=1,88), 73,19% étaient âgés de >35 ans (OR=0,632) et 81,16% appartenaient à la classe pauvre (OR=1,81). . Âge précoce aux premières règles (OR = 2,55 ; IC à 95 % 1,50-4,31, P = 0,0001), traitement hormonal substitutif (OR = 2,057, IC à 95 % 1,283-3,295, P = 0,002) grossesse précoce (OR , 2,23, IC à 95 % 1,29-3,88, P=0,004), les antécédents de fausse couche (OR, 2,11, IC à 95 % 1,32-3,39, P=0,002) et l'utilisation de contraceptifs oraux (OR, 2,76, IC à 95 % 1,54-4,92, P= 0,006) étaient significativement associé à la Colombie-Britannique. L'étude souligne le besoin urgent de programmes de santé publique efficaces destinés aux femmes à haut risque afin de lutter contre cette maladie hautement mortelle.

The association of female reproductive factors with risk of metabolic syndrome in women from NHANES 1999-2018.

BACKGROUND: Female reproductive factors such as age at first birth (AFB), age at last birth (ALB), number of pregnancies and live births play an essential role in women's health. However, few epidemiological studies have evaluated the association between female reproductive factors and metabolic syndrome (MetS). We therefore conducted a cross-sectional study to investigate the association between MetS risk and female reproductive factors. METHODS: We investigated the relationship between AFB, ALB, number of pregnancies and live births and the incidence of MetS using publicly available data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Weighted multivariable logistic regression analysis, restricted cubic spline (RCS) model, and subgroup analysis were used to evaluate the association between AFB and ALB and the risk of MetS in women. In addition, the relationship between the number of pregnancies, live births and MetS risk was also explored. RESULTS: A total of 15,404 women were included in the study, and 5,983 (38.8%) had MetS. RCS models showed an N-shaped relationship between AFB and MetS risk, whereas ALB, number of pregnancies, and live births were linearly associated with MetS. Weighted multivariable logistic regression analysis showed that the number of live births was associated with MetS risk, with ORs of 1.18 (95% CI: 1.04, 1.35) for women with ≥ 5 deliveries compared to women with ≤ 2 births. CONCLUSIONS: AFB was associated with the risk of MetS in an N-shaped curve in women. In addition, women with high live births have a higher incidence of MetS.

Comparison of Population-Based Census versus Birth History for the Estimation of Under-5 Mortality in Niger.

The WHO guidelines on mass distribution of azithromycin for child survival recommend monitoring of mortality to evaluate effectiveness. Trials that contributed evidence to these guidelines used a population-based census to monitor vital status, requiring census workers to visit each household biannually (twice yearly). Birth history is an alternative to the census approach that may be more feasible because it decreases the time and labor needed for mortality monitoring. This study aimed to compare the population-based census (reference standard) and birth history (index test) approaches to estimating mortality among children 1 to 59 months old using data from the Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial. Sixteen communities that received 5 years of biannual census in the MORDOR trial were selected randomly also to receive birth history surveys. The census approach recorded more participants and households than birth history, with correlations more than 0.94 for each. The correlation between number of deaths in each community was 0.84 (95% CI, 0.59-0.94). A comparison of the mortality incidence rate estimated from the census against the under-5 mortality rate estimated from the birth history resulted in a correlation of 0.60 (95% CI, 0.15-0.84). Of the 47% of children who were linked individually to compare vital status from each method, the death status of children had a sensitivity of 80% (95% CI, 73-89) and a specificity of 98% (95% CI, 98-99), comparing birth history to census. Overall birth histories were found to be a reasonable alternative to biannual census for tracking vital status.

The importance of female reproductive history on self-reported sleep quality, mood, and urogenital symptoms in midlife.

OBJECTIVE: This study investigated the importance of reproductive history on somatic and psychological symptoms in midlife women. METHODS: A total of 503 women from 39 to 65 years of age were recruited from different localities in Slovakia. These were interviewed about their reproductive and menstrual history, sociodemographic background, and lifestyle and health status after submitting pretested questionnaires. All variables were measured by self-reporting, and multivariable logistic and ordinal regression analyses tested the associations. RESULTS: Women who experienced miscarriage had a greater likelihood of waking early and then sleeping poorly, and they also felt unattractive in midlife. Moreover, women with two or more miscarriages were four times more likely to experience this sleep symptom than those without miscarriage (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.70-10.38; P = 0.002). In addition, women with one or two children suffered significantly less often with severe depressed mood and lack of enjoyment than women with three and more children (lack of enjoyment: with one child, the OR was 0.39 [95% CI, 0.16-0.96; P = 0.041]; with two children, the OR was 0.47 [95% CI, 0.23-0.97; P = 0.040]; depressed mood: with one child, the OR was 0.32 [95% CI, 0.12-0.84; P = 0.021]). Finally, the premenopausal and perimenopausal women were less likely to experience severe vaginal dryness than those in postmenopause. CONCLUSIONS: This cross-sectional pilot study suggests that women's reproductive history, as determined by parity and miscarriage, may be relevant to their midlife health and well-being. Future research is warranted.

Reproductive Factors and the Risk of Open Angle Glaucoma in Women.

PRCIS: There was a significant inverse linear relationship between age at menopause and open angle glaucoma (OAG). Late menarche (≥13 y) and a history of 5 or more deliveries were significantly associated with an increased risk of OAG. PURPOSE: To determine the association between reproductive factors including age at menarche, age at menopause, reproductive period, parity, and the risk of OAG in women. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched until February 9, 2022. Studies were included if they assessed the association between reproductive factors and OAG. The adjusted odds ratios (ORs) with relevant 95% CIs were extracted and pooled using fixed-effects models. Besides, we conducted dose-response analyses via the generalized least squares for trend method. RESULTS: Seven articles including 18,618 women were identified in this review. The pooled results indicated that late age at menarche (≥13 y) was significantly associated with an increased risk of OAG (OR=1.76, 95% CI: 1.28, 2.43). Early menopause (<45 y) also significantly elevated the risk of OAG (OR=1.89, 95% CI: 1.23, 2.90) in categorical meta-analyses, consistent with the inverse linear relationship between menopausal age and the risk of OAG in dose-response analyses ( P =0.002). In addition, women who had delivered at least 5 children were at significantly higher risk of OAG compared with those nulliparous (OR=2.35, 95% CI: 1.02, 5.39), and a J-shape relationship between parity and OAG was observed in dose-response analyses ( P <0.001). CONCLUSIONS: Late menarche (≥13 y), early menopause (<45 y), and a history of 5 or more parturitions are possible risk factors for OAG. Longitudinal studies are warranted to further examine the relationships between reproductive factors and the risk of OAG.

Reproductive Factors and Endometrial Cancer Risk Among Women.

Importance: Despite evidence of an association between reproductive factors and endometrial cancer risk, prospective studies have been conducted mainly in non-Asian countries. Objective: To assess the association between reproductive factors, such as number of deliveries, age at menarche, or menopause, and endometrial cancer risk. Design, Setting, and Participants: This cohort study used pooled individual data from 13 prospective cohort studies conducted between 1963 and 2014 in the Asia Cohort Consortium. Participants were Asian women. Data analysis was conducted from September 2019 to April 2023. Exposures: Reproductive factors were assessed using a questionnaire in each cohort. Main Outcomes and Measures: The main outcome was time to incidence of endometrial cancer. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% CIs. Results: A total of 1005 endometrial cancer cases were detected among 332 625 women (mean [SD] age, 54.3 [10.4] years) during a mean (SD) of 16.5 (6.4) years of follow-up. Increasing number of deliveries was associated with a decreased endometrial cancer risk in a dose-response manner (≥5 deliveries vs nulliparous [reference]: HR, 0.37; 95% CI, 0.26-0.53; P for trend < .001). Compared with menarche at younger than 13 years, menarche at 17 years or older had an HR of 0.64 (95% CI, 0.48-0.86; P for trend < .001). Late menopause (age ≥55 years) showed an HR of 2.84 (95% CI, 1.78-4.55; P for trend < .001) compared with the youngest age category for menopause (<45 years). Age at first delivery, hormone therapy, and breastfeeding were not associated with endometrial cancer risk. Conclusions and Relevance: This large pooled study of individual participant data found that late menarche, early menopause, and a higher number of deliveries were significantly associated with a lower risk of endometrial cancer. These convincing results from Asian prospective studies add to the growing body of evidence for the association between reproductive factors and endometrial cancer.

An evaluation of truncated birth histories for the rapid measurement of fertility and child survival.

BACKGROUND: Full birth histories (FBHs) are a key tool for estimating fertility and child mortality in low- and middle-income countries, but they are lengthy to collect. This is not desirable, especially for rapid turnaround surveys that ought to be short (e.g., mobile phone surveys). To reduce the length of the interview, some surveys resort to truncated birth histories (TBHs), where questions are asked only on recent births. METHODS: We used 32 Malaria Indicator Surveys that included TBHs from 18 countries in sub-Saharan Africa. Each set of TBHs was paired and compared to an overlapping set of FBHs (typically from a standard Demographic and Health Survey). We conducted a variety of data checks, including a comparison of the proportion of children reported in the reference period and a comparison of the fertility and mortality estimates. RESULTS: Fertility and mortality estimates from TBHs are lower than those based on FBHs. These differences are driven by the omission of events and the displacement of births backward and out of the reference period. CONCLUSIONS: TBHs are prone to misreporting errors that will bias both fertility and mortality estimates. While we find a few significant associations between outcomes measured and interviewer's characteristics, data quality markers correlate more consistently with respondent attributes, suggesting that truncation creates confusion among mothers being interviewed. Rigorous data quality checks should be put in place when collecting data through this instrument in future surveys.

Exposure to endogenous and exogenous sex hormones and reproductive history influence prognosis in women with ALS.

INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a higher incidence in men suggesting an influence of sex steroids. Our objective was to investigate past exposure to endogenous and synthetic steroids in female ALS patients and controls. METHODS: We administered a questionnaire to 158 postmenopausal women (75 ALS patients and 83 controls). We calculated reproductive time span (RTS), lifetime endogenous estrogen (LEE) and progesterone exposures (LPE), oral contraceptive pill (OCP) use, and reproductive history. RESULTS: ALS patients showed shorter LEE and LPE, a lower proportion of breast cancer, and 11% showed no history of pregnancies vs. 4% of controls. Odds ratios (ORs) showed that <17 y of LEE and a delayed menarche (>13 y) constitute risk factors for ALS [OR = 2.1 (95% confidence interval {CI}, 1.08-4.2); and OR = 2.4 (95% CI, 1.1-5.1) respectively]. According to Cox survival analysis, for each year the LEE increased over 17 y, it was independently associated with longer survival [hazard ratio (HR) = 0.37 (95% CI, 0.16-0.85)] after adjusting for smoking, age and site of onset. Multivariate regression analysis demonstrated that for each month using OCP for longer than 40 mo increased the risk of ALS [adjusted OR = 4.1 (95% CI, 1.2-13.8)]. DISCUSSION: Thus, longer exposure to endogenous female sex steroids increased survival and reduced ALS susceptibility. In contrast, longer exposure to synthetic sex steroids showed a negative impact by reducing the production of endogenous female sex steroids or due to crossover with other steroid receptors. Given the neuroprotective effects of sex steroids, we suggest that abnormalities of neuroendocrine components may alter motor function in women with ALS.

Association of reproductive risk factors and breast cancer molecular subtypes: a systematic review and meta-analysis.

BACKGROUND: Associations between reproductive factors and breast cancer (BC) risk vary by molecular subtype (i.e., luminal A, luminal B, HER2, and triple negative/basal-like [TNBC]). In this systematic review and meta-analysis, we summarized the associations between reproductive factors and BC subtypes. METHODS: Studies from 2000 to 2021 were included if BC subtype was examined in relation to one of 11 reproductive risk factors: age at menarche, age at menopause, age at first birth, menopausal status, parity, breastfeeding, oral contraceptive (OC) use, hormone replacement therapy (HRT), pregnancy, years since last birth and abortion. For each reproductive risk factor, BC subtype, and study design (case-control/cohort or case-case), random-effects models were used to estimate pooled relative risks and 95% confidence intervals. RESULTS: A total of 75 studies met the inclusion criteria for systematic review. Among the case-control/cohort studies, later age at menarche and breastfeeding were consistently associated with decreased risk of BC across all subtypes, while later age at menopause, later age of first childbirth, and nulliparity/low parity were associated with increased risk of luminal A, luminal B, and HER2 subtypes. In the case-only analysis, compared to luminal A, postmenopausal status increased the risk of HER2 and TNBC. Associations were less consistent across subtypes for OC and HRT use. CONCLUSION: Identifying common risk factors across BC subtypes can enhance the tailoring of prevention strategies, and risk stratification models can benefit from subtype specificity. Adding breastfeeding status to current BC risk prediction models can enhance predictive ability, given the consistency of the associations across subtypes.

Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. MATERIALS & METHODS: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. RESULTS: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use. CONCLUSION: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.