Intergenerational Occurrence of Premature Birth and Reproductive Health in Prematurely-Born Women in the Women's Health Initiative.

OBJECTIVE: To compare reproductive history and postmenopausal health by birth status (preterm vs. full term) in a U.S. longitudinal study of postmenopausal women. Birth status was examined according to region of residence, household, and neighborhood socioeconomic status (SES). METHODS: In the Women's Health Initiative Observational Study, 2271 women were born prematurely (< 37 weeks). ANOVA and Chi-square determined birth status differences of reproductive history, pregnancy, and postmenopausal health. Odds ratios were calculated using either binary logistic or multinomial logistic regression. SES and U.S. region of residence were examined as potential effect modifiers. RESULTS: Preterm-born women compared to term-born women had higher risk of delivering a premature infant (aOR 1.68, 95% CI [1.46, 1.93]), higher odds of later-age first pregnancy (aOR 1.27 95% CI [1.02, 1.58]), longer duration to become pregnant (> 1 year to pregnancy) (aOR 1.10 95% CI [1.01, 1.21]), more miscarriages (aOR 1.23 95% CI [1.11, 1.37]), and more pregnancy complications including hypertension (aOR 1.58 95% CI (1.13, 2.21)], preeclampsia (aOR 1.64 95% CI [1.24, 2.16]), and gestational diabetes (aOR 1.68 95% CI [1.11, 2.53]). Preterm-born women had higher odds of menopause before age 50 (aOR 1.09 95% CI [1.05, 1.14]). Post-menopause, they had higher rates of diabetes (p = .01), hypertension (p = .01), hysterectomy (p = .045), and higher Charlson Comorbidity Index scores (p = .01). CONCLUSIONS: Preterm-born women had higher reproductive and pregnancy risks which when coupled with early menopause, may indicate a shorter childbearing period than term-born women. Guidelines for integration of preterm history in women's health care across the life course are needed to identify and manage their higher risk.

Exploring the impact of women-specific reproductive factors on phenotypic aging and the role of life's essential 8.

BACKGROUND: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life's Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. RESULTS: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. CONCLUSION: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

Reproductive factors and risk of cardiovascular outcomes in women with ST-elevation myocardial infarction.

BACKGROUND: There are many sex-specific factors affecting myocardial infarction (MI) outcomes in males and females. This study aimed to evaluate the relationship between reproductive factors and cardiovascular outcomes in women after ST-elevation MI. METHOD: This retrospective cohort study was initiated in 2016-2017 at Chamran Hospital, Isfahan, Iran. One hundred eighty women with a diagnosis of ST-elevation MI were followed up for 3 years, and any occurrence of cardiovascular events (CVs) was recorded. All information regarding reproductive factors was recorded via questionnaire. This information was compared between women with cardiovascular events and women without adverse events using a sample t test, chi-square test, and multiple backward logistic regression analysis. SPSS version 24 was used to conduct all analyses. RESULT: Sixty-four women with a mean age of 65.81 ± 13.14 years experienced CV events, and 116 women with a mean age of 65.51 ± 10.88 years did not experience CV events. A history of ischemic heart disease and diabetes mellitus were more prevalent in women with CV events (P = 0.024 and P = 0.019). After adjusting for ischemic heart disease and diabetes mellitus, oral contraceptive pill (OCP) usage was more prevalent in women with CV events than in women without CV events (60.9% vs. 40.4%, P = 0.008). There was a greater chance of CV events in women with OCP usage (OR = 3.546, P = 0.038) and a lower chance of CV events in women with greater age at menarche (OR = 0.630, P = 0.009) and longer breastfeeding duration (OR = 0.798, P = 0.041) according to multiple backward logistic regression models. CONCLUSION: Based on this study, OCP consumption is a risk factor, while older age at menarche and longer duration of breastfeeding are protective factors for cardiovascular outcomes in women after STEMI.

Reproductive life factors and estro-progestin exposure in women with early-onset Parkinson's disease compared to late-onset disease and controls: A retrospective cohort study.

BACKGROUND: Parkinson's disease (PD) is more common in men than women. Although hormonal factors may partially explain this difference, there are no studies evaluating reproductive life factors and exogenous estroprogestin exposure in women with Early Onset Parkinson Disease (EOPD). OBJECTIVE: To compare reproductive life factors and exogenous estroprogestin exposure among female patients with EOPD, late-onset Parkinson's disease (LOPD), and EOPD-matched unaffected controls. METHODS: We identified female patients with EOPD from 1989 to 2021, defining EOPD as PD with motor-symptoms onset before age 50 and LOPD as PD with motor onset after 50. We paired EOPD patients to age-matched, unaffected controls. We reviewed medical records to determine demographic characteristics, clinical history, and reported reproductive menopausal history (reviewing medical records). RESULTS: We included 87 EOPD patients, 84 LOPD patients, and 91 unaffected controls with information about reproductive life factors and exogenous estroprogestin exposure in their medical records. There were no significant differences in race, ethnicity, or BMI between the three groups. EOPD patients were more likely to have used hormonal contraception than LOPD patients (23/49 (47 %) vs 0/84 (0 %), p < 0.001). LOPD patients had higher numbers of pelvic surgeries (48/84 [57 %] in LOPD, 23/87 [26 %] in EOPD, p < 0.001) and higher usage of perimenopausal hormonal therapy (52/84 [62 %] in LOPD, 10/87 [11 %] in EOPD, p < 0.001) in LOPD than EOPD. CONCLUSIONS: Our study reports no significant difference in reproductive life factors and exogenous estroprogestin exposure between controls and EOPD patients, except for higher exposure to hormonal contraception in EOPD. There was no apparent difference in reproductive life factors and exogenous estroprogestin exposure between EOPD and LOPD patients. Our findings therefore do not observe that hormonal exposure is different between earlier onset of female EOPD compared to female LOPD patients, or between female EOPD patients and unaffected female controls.

Reproductive factors, genetic susceptibility and risk of type 2 diabetes: A prospective cohort study.

AIM: To explore the relationships of multiple reproductive factors with type 2 diabetes mellitus (T2DM) risk and the joint effects of reproductive factors and genetic susceptibility. METHODS: We included 262,368 women without prevalent T2DM from the UK biobank. Cox proportional hazards regression models were employed to estimate the relationships of reproductive factors with T2DM risk and the joint effects of reproductive factors and genetic susceptibility. RESULTS: During a mean follow-up of 12.2 years, 8,996 T2DM cases were identified. Early menarche (<12 years, hazard ratio (HR) 1.08 [95 % confidence interval (CI) 1.02;1.13]), late menarche (≥15 years, HR 1.11 [1.04;1.17]), early menopause (<45 years, HR 1.20 [1.12;1.29]), short reproductive lifespan (<30 years, HR 1.25 [1.16;1.35]), hysterectomy (1.31, HR [1.23;1.40]), oophorectomy (HR 1.28 [1.20;1.36]), high parity (≥4, HR 1.25 [1.17;1.34]), early age at first live birth (<20 years, HR 1.23 [1.16;1.31]), miscarriage (HR 1.13 [1.07;1.19]), stillbirth (HR 1.14 [1.03;1.27]), and ever used hormonal replacement therapy (HR 1.19 [1.14;1.24]) were related to a higher T2DM risk, while ever used oral contraceptives (HR 0.93 [0.89;0.98]) was related to a lower T2DM risk. Furthermore, women with reproductive risk factors and high genetic risk had the highest T2DM risk compared to those with low genetic risk and without reproductive risk factors. CONCLUSION: Our findings show that multiple reproductive factors are related to T2DM risk, particularly in women with high genetic risk.

Reproductive history is associated with functional disabilities and symptoms in women with knee osteoarthritis: a case-control study.

OBJECTIVES: Studies that have examined the correlation between reproductive history and knee osteoarthritis (KOA) have had heterogeneous findings. We aimed to investigate the reproductive history and its relationship with pain and physical dysfunction in women with KOA. This case-control study, comprising 204 women aged 50 and older with and without KOA recruited through random cluster sampling, was executed from February 2018 to October 2018 in the health centers of Tabriz City. The reproductive history questionnaire was completed for the subjects in two groups. Pain intensity and functional dysfunction caused by KOA were evaluated using the Visual analogue scale and the Western Ontario and McMaster index, respectively. RESULTS: The women's age of menarche in the case group was significantly lower (p = 0.031), and the number of pregnancies (p = 0.017) and the average duration of breastfeeding (p = 0.039) were substantially higher than those of the control group. Older age at the first menstruation (OR = 0.851) was a protective factor, and higher parity (OR = 8.726) was a risk factor for KOA. In the women with KOA, the younger age of the mother at the birth of the first alive baby and the longer duration of breastfeeding were associated with higher pain intensity and functional disorders.

Reproductive characteristics, menopausal status, race and ethnicity, and risk of breast cancer subtypes defined by ER, PR and HER2 status: the Breast Cancer Etiology in Minorities study.

BACKGROUND: Associations between reproductive factors and risk of breast cancer differ by subtype defined by joint estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status. Racial and ethnic differences in the incidence of breast cancer subtypes suggest etiologic heterogeneity, yet data are limited because most studies have included non-Hispanic White women only. METHODS: We analyzed harmonized data for 2,794 breast cancer cases and 4,579 controls, of whom 90% self-identified as African American, Asian American or Hispanic. Questionnaire data were pooled from three population-based studies conducted in California and data on tumor characteristics were obtained from the California Cancer Registry. The study sample included 1,530 luminal A (ER-positive and/or PR-positive, HER2-negative), 442 luminal B (ER-positive and/or PR-positive, HER2-positive), 578 triple-negative (TN; ER-negative, PR-negative, HER2-negative), and 244 HER2-enriched (ER-negative, PR-negative, HER2-positive) cases. We used multivariable unconditional logistic regression models to estimate subtype-specific ORs and 95% confidence intervals associated with parity, breast-feeding, and other reproductive characteristics by menopausal status and race and ethnicity. RESULTS: Subtype-specific associations with reproductive factors revealed some notable differences by menopausal status and race and ethnicity. Specifically, higher parity without breast-feeding was associated with higher risk of luminal A and TN subtypes among premenopausal African American women. In contrast, among Asian American and Hispanic women, regardless of menopausal status, higher parity with a breast-feeding history was associated with lower risk of luminal A subtype. Among premenopausal women only, luminal A subtype was associated with older age at first full-term pregnancy (FTP), longer interval between menarche and first FTP, and shorter interval since last FTP, with similar OR estimates across the three racial and ethnic groups. CONCLUSIONS: Subtype-specific associations with reproductive factors overall and by menopausal status, and race and ethnicity, showed some differences, underscoring that understanding etiologic heterogeneity in racially and ethnically diverse study samples is essential. Breast-feeding is likely the only reproductive factor that is potentially modifiable. Targeted efforts to promote and facilitate breast-feeding could help mitigate the adverse effects of higher parity among premenopausal African American women.

The association between reproductive history and abdominal adipose tissue among postmenopausal women: results from the Women's Health Initiative.

STUDY QUESTION: What is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women? SUMMARY ANSWER: Higher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity. WHAT IS KNOWN ALREADY: Postmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI. STUDY DESIGN, SIZE, DURATION: This study is a secondary analysis of data collected from the baseline visit of the Women's Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: Women who reported early menarche (<10 years) or early menopause (<40 years) had the highest levels of VAT. Adjusted multivariable linear regression results demonstrate women who experienced menarche >15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause <40 years, menopause at 50-55 years was associated with 19.3 cm2 (95% CI: -25.4, -13.3) less VAT and 27.4 cm2 (-29.6, 10.3) less SAT. High parity (>3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies. LIMITATIONS, REASONS FOR CAUTION: The WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention. STUDY FUNDING/COMPETING INTEREST(S): HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from 'ACSM'S Body Composition Assessment Book' and consulting fees from the WHI. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Longitudinal associations of reproductive factors and exogeneous estrogens with neuroimaging biomarkers of Alzheimer's disease and cerebrovascular disease.

INTRODUCTION: Female-specific reproductive factors and exogeneous estrogen use are associated with cognition in later life. However, the underlying mechanisms are not understood. The present study aimed to investigate the effect of reproductive factors on neuroimaging biomarkers of Alzheimer's disease (AD) and cerebrovascular pathologies. METHODS: We evaluated 389 females (median age of 71.7 years) enrolled in the Mayo Clinic Study of Aging with reproductive history data and longitudinal magnetic resonance imaging (MRI) scans. We used linear mixed effect models to examine the associations between reproductive factors and changes in neuroimaging measures. RESULTS: Ever hormonal contraception (HC) use was longitudinally associated with higher fractional anisotropy across the corpus callosum, lower white matter hyperintensity (WMH) volume, and greater cortical thickness in an AD meta-region of interest (ROI). The initiation of menopausal hormone therapy (MHT) > 5 years post menopause was associated with higher WMH volume. DISCUSSION: HC use and initiation of MHT >5 years post menopause were generally associated with neuroimaging biomarkers of cerebrovascular pathologies. HIGHLIGHTS: Hormonal contraception use was associated with better brain white matter (WM) integrity. Initiation of menopausal hormone therapy >5 years post menopause was associated with worsening brain WM integrity. Hormonal contraception use was associated with greater cortical thickness. Ages at menarche and menopause and number of pregnancies were not associated with imaging measures. There were few associations between reproductive factors or exogenous estrogens and amyloid or tau PET.

The association of female reproductive factors with history of cardiovascular disease: a large cross-sectional study.

BACKGROUND: This study aimed to explore the association of female reproductive factors (age at first birth (AFB), age at last birth (ALB), number of pregnancies, and live births) with history of cardiovascular disease (CVD). METHODS: A total of 15,715 women aged 20 years or over from the National Health and Nutrition Examination Surveys from 1999 to 2018 were included in our analysis. Weighted multivariable logistic regression analysis and restricted cubic spline (RCS) model were used to evaluate the association of AFB and ALB with history of CVD in women. Additionally, the relationship between the number of pregnancies, and live births and history of CVD was also explored. RESULTS: After adjusting for potential confounding factors, the RCS plot showed a U-curve relationship between AFB, ALB and history of CVD. Among them, AFB was associated with congestive heart failure (CHF), heart attack, and stroke in a U-shaped curve. Additionally, this U-shaped correlation also exists between ALB and CHF and stroke. However, the number of pregnancies and live births was liner positive associated with history of CVD, including coronary heart disease, CHF, angina pectoris, heart attack, and stroke. CONCLUSIONS: Women with younger or later AFB and ALB have higher odds of CVD in later life. Further study is warranted to verify the underlying mechanisms of this association.

Reproductive Factors and Thyroid Cancer Risk: The Multiethnic Cohort Study.

Background: Women are three times more likely to be diagnosed with thyroid cancer than men, with incidence rates per 100,000 in the United States of 20.2 for women and 7.4 for men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and menopausal hormone therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods: Risk factors for thyroid cancer were evaluated among female participants (n = 118,344) of the Multiethnic Cohort Study. The cohort was linked to Surveillance, Epidemiology, and End Results cancer incidence and statewide death certificate files in Hawaii and California, with 373 incident papillary thyroid cancer cases identified. Exposures investigated include age at menarche, parity, first pregnancy outcome, birth control use, and menopausal status and type. Multivariable Cox proportional hazards models were used to obtain relative risk (RR) of papillary thyroid cancer and their 95% confidence intervals (CI). Covariates included age, race and ethnicity, reproductive history, body size, smoking, and alcohol consumption. Results: We observed a statistically significant increased risk of papillary thyroid cancer for oophorectomy (adjusted RR 1.58, 95% CI: 1.26, 1.99), hysterectomy (adjusted RR 1.65, 95% CI: 1.33, 2.04), and surgical menopause (adjusted RR 1.55, 95% CI: 1.22, 1.97), and decreased risk for first live birth at ≤20 years of age versus nulliparity (adjusted RR 0.66, 95% CI: 0.46, 0.93). These associations did not vary by race and ethnicity (p het > 0.44). Conclusion: The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in all racial and ethnic groups in our multiethnic population, which validates uniform obstetric and gynecological practice.

Reproductive factors and cardiovascular health in post-menopausal women: a special focus on natural menopause.

Female-specific reproductive factors might contribute to increased risk of cardiovascular disease, and the American Heart Association (AHA) recently proposed Life's Essential 8 (LE8) score to quantify cardiovascular health (CVH). The study aimed to examine the relationships between reproductive factors and the LE8 score among post-menopause women in the United States. We enrolled 3223 post-menopause women from National Health and Nutrition Examination Survey (NHANES). CVH groups based on LE8 score were low (0-49), moderate (50-79), and high good CVH levels (80-100). Multivariate ordinal logistic regressions were applied to estimate the associations between reproductive factors and the LE8 score. In multivariate model, early menarche (OR: 0.69, 95 percent CI: 0.51-0.93) and early menopause (OR: 0.57, 95 percent CI: 0.43-0.77) were associated with LE8 score compared with normal menarche and menopause; Meanwhile, ages at menarche and menopause were positively correlated with LE8 score. The number of pregnancies and full-term pregnancies were negatively associated with LE8 (OR for per pregnancy increase and 95 percent CI, 0.93 (0.88, 0.98), 0.93 (0.87, 0.99), separately). Overall, natural menopausal women with early age at menarche and menopause, and a higher number of pregnancies may have a high risk of lower CVH, and need to focus on their CVH.

Leukocyte telomere length in multiple sclerosis: relationship between disability severity and pregnancy history.

BACKGROUND: Aging-related processes contribute to neurodegeneration and disability in multiple sclerosis (MS). Biomarkers of biological aging such as leukocyte telomere length (LTL) could help personalise prognosis. Pregnancy has been shown to be protective against disability accumulation in women with MS, though it is unclear if this effect relates to aging mechanisms or LTL. OBJECTIVES: This study aimed to cross-sectionally characterise LTL in a cohort of individuals with MS, and to correlate LTL with disability severity and pregnancy history. METHODS: We extracted DNA from the whole blood of 501 people with MS in Melbourne, Australia. Expanded Disability Status Scale (EDSS) score and demographic data, as well as pregnancy history for 197 females, were obtained at sample collection. Additional data were extracted from the MSBase Registry. LTL was determined in base pairs (bp) using real-time quantitative polymerase chain reaction. RESULTS: A relationship between EDSS score and shorter LTL was robust to multivariable adjustment for demographic and clinical factors including chronological age, with an adjusted LTL reduction per 1.0 increase in EDSS of 97.1 bp (95 % CI = 9.7-184.5 bp, p = 0.030). Adjusted mediation analysis found chronological age accounted for 33.6 % of the relationship between LTL and EDSS score (p = 0.018). In females with pregnancy data, history of pregnancy was associated with older age (median 49.7 vs 33.0 years, p < 0.001). There were no significant relationships between adjusted LTL and any history of pregnancy (LTL increase of 65.3 bp, 95 % CI = -471.0-601.5 bp, p = 0.81) or number of completed pregnancies (LTL increase of 14.6 bp per pregnancy, 95 % CI = -170.3-199.6 bp, p = 0.87). CONCLUSIONS: The correlation between LTL and disability independent of chronological age and other factors points to a link between neurological reserve in MS and biological aging, and a potential research target for pathophysiological and therapeutic mechanisms. Although LTL did not significantly differ by pregnancy history, longitudinal analyses could help identify interactions with prospectively captured pregnancy effects.

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.

Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium.

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.

Reproductive Factors Related to Childbearing and a Novel Automated Mammographic Measure, V.

BACKGROUND: We investigated the associations between several reproductive factors related to childbearing and the variation (V) measure (a novel, objective, single summary measure of breast image intensity) by menopausal status. METHODS: Our study included 3,814 cancer-free women within the Nurses' Health Study (NHS) and NHSII cohorts. The data on reproductive variables and covariates were obtained from biennial questionnaires closest to the mammogram date. V-measures were obtained from mammographic images using a previously developed algorithm capturing the standard deviation of pixel values. We used multivariate linear regression to examine the associations of parity, age at first birth, time between menarche and first birth, time since last pregnancy, and lifetime breastfeeding duration with V-measure, adjusting for breast cancer risk factors, including the percentage of mammographic density (PMD). We further examined whether these associations were statistically accounted for (mediated) by PMD. RESULTS: Among premenopausal women, none of the reproductive factors were associated with V. Among postmenopausal women, inverse associations of parity and positive associations of age at first birth with V were mediated by PMD (percent mediated: nulliparity: 66.7%, P < 0.0001; parity: 50.5%, P < 0.01; age at first birth 76.1%, P < 0.001) and were no longer significant in PMD-adjusted models. Lifetime duration of breastfeeding was positively associated with V [>36 vs. 0 ≤1 months ß = 0.29; 95% confidence interval (CI) 0.07; 0.52, Ptrend < 0.01], independent of PMD. CONCLUSIONS: Parity, age at first birth, and breastfeeding were associated with postmenopausal V. IMPACT: This study highlights associations of reproductive factors with mammographic image intensity.

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.