BACKGROUND: Women\'s reproduction requires increased energy demands, which consequently may lead to cellular damage and aging. Hence, Telomere Length (TL), a biomarker of biological aging and health status may possibly serve as a biomarker of reproductive effort. The aim of this systematic review is to evaluate telomere dynamics throughout pregnancy and the association between parity and TL.
METHODS: A systematic search was conducted across seven databases including CINAHL, Cochrane, PsycINFO, Proquest, PubMed; Scopus; and Web of Science, using keywords and MeSH descriptors of parity and TL. Predefined inclusion and exclusion criteria were used to screen abstracts and titles. After the removal of duplicates, 3431 articles were included in the primary screening, narrowed to 194 articles included in the full-text screening. Consensus was reached for the 14 studies that were included in the final review, and the Newcastle-Ottawa scale (NOS) was utilized to assess the quality of the selected studies. A mini meta-analysis utilized JASP 0.17.3 software and included 4 applicable studies, comprising a total of 2564 participants to quantitatively assess the estimated effect size of parity on TL.
RESULTS: Of the 11 studies reviewed on parity and TL, four demonstrated a negative correlation; one - a positive correlation and six -found no correlation. Studies demonstrating a negative correlation encompassed rigorous methodological practices possibly suggesting having more children is associated with enhanced telomere attrition. Of the four longitudinal studies assessing telomere dynamics throughout pregnancy, most found no change in TL from early pregnancy to postpartum suggesting pregnancy does not affect TL from early pregnancy to early postpartum. The meta-analysis revealed a negative, yet, non-significant effect, of the estimated effect size of parity on TL(ES = -0.009, p = 0.126, CI -0.021, 0.03).
CONCLUSIONS: Studies assessing pregnancy, parity and TL yielded mixed results, most likely due to the different research methods utilized in each study. Improvements in study design to better understand the short-term effects of pregnancy on TL and the effect of parity on TL over time, include precise definitions of parity, comparisons of different age groups, inclusion of reproductive lifespan and statistically adjusting for potential confounders in the parity and TL relationship.

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.
CONCLUSIONS: 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.

Cancer is a leading cause of death worldwide. In Korea, it is also a major public health problem. Cancer burden may increase significantly due to ageing population and changes in lifestyle. The features of reproductive factors have changed, which include increased age at first childbirth and decreased breastfeeding duration. This study aims to systematically summarise the association between modifiable reproductive factors and cancer incidence and mortality to provide evidence for planning strategies aimed at reducing cancer incidence and mortality in women.
A literature search was performed using the EMBASE, MEDLINE, Cochrane Library and Korean databases such as the Korean Studies Information Service System, Research Information Sharing Service, KoreaMED, Korean Medical Database, National Assembly Library and Korea Institute from their inception to 24 August 2022. We will include cohort studies addressing the associations between at least one of the reproductive factors and the incidence and mortality of all or specific cancers among Korean women. Two reviewers will screen the references, extract the data, and assess the risk of bias independently and in duplicates. Discrepancies will be resolved through discussion or consultation with a third-party reviewer. We will use the Grading of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence. We will summarise the findings of the included systematic reviews through quantitative or narrative syntheses and present the summarised findings in tables.
Ethical approval is not required, since we will use only the published data. We will disseminate the study findings in peer-reviewed publications.
CRD42022356085.

UNASSIGNED: Breast cancer (BC) is the most frequent cancer in Iranian females. Due to the changes in lifestyle and reproductive risk factors, the BC incidence rate has been rapidly increasing. Knowing risk factors of BC could significantly contribute to improve preventive behaviors. To investigate the relationship between menstrual and reproductive factors and BC in Iranian female population.
UNASSIGNED: Web of Science, PubMed, Scopus, and SID as well as references of included studies were searched. Among relevant published observational studies, 27 studies met the inclusion criteria. Pooled risk estimates for the risk factors were determined using random-effects models due to the presence of substantial heterogeneity (P < 0.05).
UNASSIGNED: All of the selected studies had case-control design. There was a positive relationship between maternal age at first pregnancy and risk of BC (OR = 1.79 95% CI: 1.36-2.35). Also, menopausal status was associated with higher risk of BC (OR = 1.60 95% CI: 1.18-2.17), whereas, there was no association between menarche age and increased risk of BC (OR = 0.55 95% CI: 0.29-1.03). History of abortion (OR = 1.21 95% CI: 0.97-1.5), nulliparity (OR = 1.43 95% CI: 0.89-2.31), and breastfeeding history (OR = 0.68 95% CI: 0.42-1.09) were not associated with BC risk.
UNASSIGNED: Our findings suggest that age at the first pregnancy and menopausal status were significantly associated with BC risk among Iranian women, whereas menarche age, nulliparity, and history of breastfeeding were not. In regard to the history of abortion, our findings revealed no association with BC, but in high-quality studies, this relationship was significant.

Previous reviews have found that menstrual and reproductive factors are associated with lung cancer risk, but evidence on a possible association with age at menopause is inconsistent. This review aimed to determine the association of early and late menopause with lung cancer risk. Publications were reviewed and obtained through PubMed, EMBASE and Scopus database search up to March 2021. The pooled relative risks (RRs) or odds ratios (ORs) and corresponding 95% CIs were estimated using a random-effects meta-analysis. Twenty-eight studies were included in at least one meta-analysis, of age at menopause (lowest vs highest; n=26), early menopause (≤45 vs ≥50/51 years or middle; n=11), late menopause (≥55 vs <50 years or middle; n=6), or continuous (per additional year; n=6). We found that early menopause was associated with lung cancer in both cohort studies (RR 1.26, 1.10-1.41; n=6) and case-control studies (OR 1.38, 1.11-1.66; n=5). Three large cohort studies showed that the increased risk was primarily evident among smokers (RR 1.38, 1.10-1.66) but not among non-smokers (RR 1.02, 0.63-1.40). Four case-control studies found that late menopause was also associated with lung cancer (OR 1.29, 1.08-1.51); conversely, the association was mainly observed among non-smokers (OR 1.35, 1.11-1.59) but not among smokers (OR 1.05, 0.75-1.36). In conclusion, evidence from this review indicates an increased risk of lung cancer in women who experience early menopause (≤45 years), although this risk is primarily among smokers. Large prospective cohort studies are needed to confirm the association between late menopause (≥55 years) and lung cancer risk among non-smokers. PROSPERO registration: CRD42020205429.

Results of this work may provide some guidance for subsequent ovarian cancer screening in women with preeclampsia and provide new directions for future studies.
This study investigated the difference in cancer risk between women with preeclampsia and women with a normal pregnancy.
Electronic databases, namely PubMed, Embase, and the Cochrane Library, were searched for relevant studies from database inception to February 4, 2021. The results are expressed as risk ratios (RRs).
The study included 13 cohort studies comprising 5,254,150 participants. The difference in the total cancer risk between the control and preeclampsia groups was statistically nonsignificant. However, breast cancer (BC) risk was lower in the preeclampsia group (RR = 0.88, 95% confidence interval (CI) = 0.83-0.93; I2 = 57.2%). A subgroup analysis stratified by reproductive factors demonstrated that BC risk in the preeclampsia population decreased in parous women (RR = 0.79, 95% CI = 0.72-0.87; I2 = 0%), women with full-term pregnancies (RR = 0.79, 95% CI = 0.75-0.84; I2 = 0%), and women with increasing parity. Furthermore, BC risk reduced in women with preeclampsia regardless of their menopausal status and the sex of their offspring.
Overall, women with preeclampsia have a decreased BC risk and increased ovarian cancer risk compared with the normal population. A subgroup analysis stratified by reproductive factors demonstrated that BC risk decreased in the preeclampsia population in parous women, women with full-term pregnancies, and women with increasing parity regardless of their menopausal status and the sex of their offspring.

Non-melanoma skin cancers (NMSC) are more frequent among men, but women (especially those aged < 40 years) have experienced steeper growth in their incidence rates in recent years. Hormonal factors were hypothesized to be playing a role in modulating NMSC risk, but the studies published to date provided conflicting results. We systematically reviewed and meta-analysed the studies focusing on the association between hormone-related characteristics (use of exogenous sex hormones, and aspects of menstrual and reproductive history) and the risk of NMSC among women. We included observational and experimental studies published in PubMed and EMBASE until February 2020. We calculated summary relative risk (SRR) and 95% confidence intervals (CI) by applying random effects models with maximum likelihood estimation, and used the I2 statistics to quantify the degree of heterogeneity of risk estimates across studies. Eleven independent studies encompassing a total of over 30,000 NMSC cases were included in quantitative analyses. No evidence of an increased NMSC risk emerged among ever vs. never users of oral contraceptives (SRR 1.13, 95% CI 0.88-1.45) or hormones for menopause (SRR 1.09, 95% CI 0.87-1.37). Likewise, age at menarche or at menopause and parity were not associated with NMSC risk. Heterogeneity across studies was low, and pooled results were comparable between NMSC subtypes. We found no evidence that hormonal factors play a role in the pathogenesis of NMSC among women.

OBJECTIVE: A systematic review and meta-analysis were conducted to quantitatively synthesize the current evidence regarding the risk of developing metabolic syndrome (MetS) in women with a personal history of gestational diabetes mellitus (GDM), without pre-existing diabetes, compared with those without a history of GDM.
METHODS: Four electronic databases [MEDLINE (via PubMed), Scopus, Cochrane Library, PROSPERO] were searched for relevant literature until July 29th 2020. Cochran\'s Q test was applied for the assessment of heterogeneity. The random-effects model was applied by calculating the odds ratio (OR) and 95% confidence interval (CI) for each study. Publication bias was estimated with Egger\'s linear regression test.
RESULTS: The results from 23 studies (10,230 pregnant women; 5169 cases, 5061 controls), indicated that women with a history of GDM had a higher risk of developing MetS compared with those without such a history (OR 3.45; 95% CI 2.80-4.25, p < 0.0001). This risk remained higher, independently of maternal age and ethnicity (although the risk was not as high in Asians; OR 2.11; 95% CI 1.27-3.52). The risk of developing MetS was even higher in studies where women with GDM had increased body mass index (BMI) compared with the controls (OR 4.14; 95% CI 3.18-5.38).
CONCLUSIONS: The risk for developing MetS following delivery is higher in women with a history of GDM compared with women without such a history. Timely recognition and appropriate intervention are critical to halt progression to MetS and its associated morbidity.

BACKGROUND: A number of studies have investigated the association between reproductive factors and lung cancer risk, however findings are inconsistent. This meta-analysis aimed to evaluate the association between female reproductive factors and lung cancer risk.
METHODS: We conducted a comprehensive systematic search to identify relevant and eligible studies published before 18th December 2019. Inter-study heterogeneity was assessed using the Q test and I2 statistic. Based on the heterogeneity of each reproductive factor, fixed or random effects models were used to calculate the summary odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses by study design, lung cancer subtypes, smoking status, and ethnicity were also performed.
RESULTS: A total of 66 studies with 20 distinct reproductive factors were included in this meta-analysis. Comparing the highest and lowest categories (reference) of each reproductive factor, parity (OR = 0.83, 95% CI = 0.72-0.96), menstrual cycle length (OR = 0.79, 95% CI = 0.65-0.96), and age at first birth (OR = 0.85, 95% CI = 0.74-0.98), were significantly associated with a lower risk of overall lung cancer. On the contrary, non-natural menopause was significantly associated with higher lung cancer risk (OR = 1.52, 95% CI = 1.25-1.86). Among never-smokers, a significant negative association was found between parity and lung cancer risk. Both parity and non-natural menopause were statistically significant in case-control studies.
CONCLUSIONS: These results suggest that certain reproductive factors may be associated with lung cancer risk. Future studies should further validate the associations, and investigate the underlying mechanisms.

OBJECTIVE: The risk of being diagnosed with contralateral breast cancer (CBC) is an important health issue among breast cancer survivors. There is an increasing interest in the effect of lifestyle and reproductive factors on CBC risk, since these factors may partly be modifiable. We performed a systematic review and meta-analysis and aimed to evaluate the impact of lifestyle and reproductive factors on CBC risk in population-based breast cancer studies.
METHODS: The PubMed electronic database was searched up to 2nd November 2019, for relevant publications. Of the included studies, a meta-analysis per lifestyle or reproductive factor was performed.
RESULTS: Thirteen out of 784 publications were used for the meta-analysis. Body mass index (≥ 25 vs. < 25 kg/m2; RR = 1.22; 95% CI 1.01-1.47) was associated with increased CBC risk. The estimates for alcohol use (ever vs. never; RR = 1.15; 95% CI 1.02-1.31) and age at primiparity (≥ 25 vs. < 25 years; RR = 1.06; 95% CI 1.02-1.10) also showed an association with increased CBC risk. For parity (≥ 4 vs. nulliparous; RR = 0.56; 95% CI 0.42-0.76) and age at menopause (< 45 vs ≥ 45 years; RR = 0.79; 95% CI 0.67-0.93), results from two studies suggested a decreased CBC risk. We observed no association between CBC and smoking, age at menarche, oral contraceptive use, gravidity, breastfeeding, or menopausal status. Overall, the number of studies per risk factor was limited (n = 2-5).
CONCLUSIONS: BMI is a modifiable risk factor for CBC. Data on the effect of other modifiable lifestyle and reproductive factors are limited. For better counseling of patients on lifestyle effects, more studies are urgently needed.