Health outcomes of age at menarche in European women: a two-sample Mendelian randomization study

Liu, Yang; Xu, Xia; Lei, Lei; Wang, Xiang; Wu, Xuan; Xie, Su‐Yuan; Li, J.

doi:10.1093/postmj/qgad023

Cited by 4 publications

(2 citation statements)

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“…Early menarche age is linked to earlier estrogen exposure. Endometrial tumors express estrogen receptors, and greater exposure to circulating estrogens is linked to somatic mutation of endometrial cells through enhanced DNA replication and mitotic activity, which results in the malignant transformation of cells [36]. A meta-analysis from Gong, Wang and Ma, 2015 revealed that age at menarche is associated with endometrial cancer, where each delay of menarche every two years is associated with a 4% reduced risk (Risk Ratio=0.96; 95%CI:0.94 -0.98).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors Analysis of Endometrial Cancer at DR Soetomo Hospital in Surabaya, Indonesia

Dwi Irnasih,

Sandhika,

Dwi Jayanti

2024

IJRP

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Endometrial cancer is a common gynecological cancer that occurs frequently in perimenopausal and postmenopausal women. Several factors influence the incidence of endometrial cancer, such as age, family history of cancer, Body Mass Index, parity, diabetes mellitus, age at menarche, menopausal status, and age at first birth. This study aims to determine the risk factors associated with endometrial cancer in Dr. Soetomo's hospital in Surabaya. This research uses an analytical observational design with a case-control approach. The subjects were chosen by convenience sampling, and 70 patients in the case group and 69 in the control group were obtained. Bivariate analysis using Mann-Whitney and Chi-square, then multivariate analysis using the logistic regression test with significance p<0.05. The results showed that age, family history of cancer, diabetes mellitus, menopausal status, and age at first birth were related to endometrial cancer. Body mass index, parity, and age at menarche are variables not associated with endometrial cancer. Diabetes mellitus is the most dominant factor in increasing endometrial cancer incidence with Odd Ratio (OR)= 7.085 (95% CI; 1. 299-38.637). This research provides information about what factors are related to and influence the incidence of endometrial cancer. The development of these findings needs to be carried out in a larger sample size and using a cohort study.

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Section: Discussionmentioning

confidence: 99%

Risk Factors Analysis of Endometrial Cancer at DR Soetomo Hospital in Surabaya, Indonesia

Dwi Irnasih,

Sandhika,

Dwi Jayanti

2024

IJRP

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“…This correlation may be due to a variety of factors, including hormonal imbalances, genetics, lifestyles such as diet and physical activity, and others (8). Additionally, the timing of puberty has important implications for long-term health outcomes, with early puberty associated with increased risk of certain health conditions such as breast cancer and cardiovascular disease (9)(10)(11). Therefore, understanding the relationship between body composition and puberty is important for promoting health and preventing disease across the lifespan.…”

Section: Introductionmentioning

confidence: 99%

Association between body fat distribution and age at menarche: a two sample Mendelian randomization study

Xue,

Wang,

Chen

et al. 2024

Front. Pediatr.

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BackgroundNumerous studies have examined the association between obesity and age at menarche (AAM), with most focusing on traditional obesity indicators such as body mass index. However, there are limited studies that explored the connection between body fat distribution and AAM, as well as a scarcity of Mendelian randomization (MR) studies.MethodsIn this study, we conducted a two-sample MR study to evaluate the causal effects of eight body fat distribution indicators on AAM. Inverse variance weighted (IVW) method was used for primary analysis, while supplementary approaches such as MR-Egger and weighted median were also utilized. Considering that the eight exposures were highly correlated, we performed an MR Bayesian model averaging (MR-BMA) analysis to prioritize the effect of major exposure on AAM. A series of sensitivity analyses were also performed.ResultsFrom a range of 82–105 single nucleotide polymorphisms (SNPs) were utilized as genetic instrumental variables for each of the exposure factors. After Bonferroni correction, we found that whole body fat mass (β: −0.17; 95% CI: −0.24, −0.11), left leg fat percentage (β: −0.14; 95% CI: −0.21, −0.07), left leg fat mass (β: −0.20; 95% CI: −0.27, −0.12), left arm fat percentage (β: −0.18; 95% CI: −0.26, −0.11) and left arm fat mass (β: −0.18; 95%CI: −0.26, −0.10) were associated with decreased AAM using random effects IVW method. And the beta coefficients for all MR evaluation methods exhibited consistent trends. MR-BMA method validated that left arm fat percentage plays a dominant role in AAM.ConclusionsOur MR study suggested that body fat has broad impacts on AAM. Obtaining more information on body measurements would greatly enhance our comprehension of pubertal development.

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Menarche—a journey into womanhood: age at menarche and health-related outcomes in East Asians

Chiou,

Lin,

Chang

et al. 2024

Human Reproduction

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STUDY QUESTION Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION Our findings were specific to Han Taiwanese individuals, with genetic correlation analyses conducted in East Asians. Further research in other ethnic groups is necessary. WIDER IMPLICATIONS OF THE FINDINGS Our study provides insights into the genetic architecture of AAM and its health-related outcomes in East Asians, highlighting causal links between BMI/T2D and earlier AAM, which may suggest potential prevention strategies for early puberty. STUDY FUNDING/COMPETING INTEREST(S) The work was supported by China Medical University, Taiwan (CMU110-S-17, CMU110-S-24, CMU110-MF-49, CMU111-SR-158, CMU111-MF-105, CMU111-MF-21, CMU111-S-35, CMU112-SR-30, and CMU112-MF-101), the China Medical University Hospital, Taiwan (DMR-111-062, DMR-111-153, DMR-112-042, DMR-113-038, and DMR-113-103), and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-039-063-MY3, MOST 111-2314-B-039-064-MY3, MOST 111-2410-H-039-002-MY3, and NSTC 112-2813-C-039-036-B). The funders had no influence on the data collection, analyses, or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER N/A.

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Health outcomes of age at menarche in European women: a two-sample Mendelian randomization study

Cited by 4 publications

References 40 publications

Risk Factors Analysis of Endometrial Cancer at DR Soetomo Hospital in Surabaya, Indonesia

Risk Factors Analysis of Endometrial Cancer at DR Soetomo Hospital in Surabaya, Indonesia

Association between body fat distribution and age at menarche: a two sample Mendelian randomization study

Menarche—a journey into womanhood: age at menarche and health-related outcomes in East Asians

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