{"title":"体育活动与常见妇科疾病的因果关系:一项双样本孟德尔随机化研究。","authors":"Mengyu Fu, Xiaoyue Zhu, Jie Chen, Jiewen Guan, Hongmei Ding, Qinqin Gao, Songbing Qin","doi":"10.62347/PGYY9493","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>While physical activity (PA) patterns are epidemiologically linked to gynecologic pathologies, establishing causality remains uncertain. This Mendelian randomization (MR) study evaluated causal relationships between PA phenotypes and gynecologic disorders.</p><p><strong>Methods: </strong>Using European-ancestry female genome-wide association study (GWAS) data, we analyzed eight gynecologic disorders and four PA instruments. Primary inverse-variance weighted (IVW) estimates were supplemented by sensitivity analyses (MR-Egger, weighted median, MR-PRESSO) to address pleiotropy and heterogeneity.</p><p><strong>Results: </strong>Our MR revealed subtype-specific effects: walking for pleasure [OR = 0.63, 95% CI: 0.41-0.96], strenuous sports [OR = 0.34, 95% CI: 0.16-0.74], and other exercises [OR = 0.70, 95% CI: 0.49-0.99]) reduced ER<sup>+</sup> breast cancer (BC) risk, while leisure screen time increased risk (OR = 1.08, 95% CI: 1.004-1.163). Only other exercises protected against ER<sup>-</sup> BC (OR = 0.60, 95% CI: 0.38-0.96). Exercise frequency inversely correlated with endometrial cancer (EC) (walking: OR = 0.20; strenuous sports: OR = 0.06; other exercises: OR = 0.41) and endometriosis (ES) (strenuous sports: OR = 0.17; other exercises: OR = 0.26), but was positively associated with sedentary behavior (EC: OR = 1.36). Ovarian cyst (OCS) risk decreased with walking (OR = 0.34) and other exercises (OR = 0.28), yet increased with screen time (OR = 1.23). Paradoxically, walking showed strong positive (OR = 31.48) and strenuous exercise inverse (OR = 0.004) associations with polycystic ovary syndrome (PCOS). No causal links emerged for cervical cancer (CC), ovarian cancer (OC), or uterine fibroids (UF).</p><p><strong>Conclusion: </strong>This first MR evidence demonstrates PA's differential causal effects on gynecologic disorders, particularly highlighting exercise modality-specific protection against ER<sup>+</sup> BC, EC, and ES. Paradoxical PCOS associations warrant mechanistic investigation. Findings underscore PA as a modifiable preventive factor and advocate for subtype-tailored exercise guidelines in women's health.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"17 5","pages":"3753-3765"},"PeriodicalIF":1.7000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170402/pdf/","citationCount":"0","resultStr":"{\"title\":\"Causal relationship between physical activity and common gynecologic conditions: a two-sample Mendelian randomization study.\",\"authors\":\"Mengyu Fu, Xiaoyue Zhu, Jie Chen, Jiewen Guan, Hongmei Ding, Qinqin Gao, Songbing Qin\",\"doi\":\"10.62347/PGYY9493\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>While physical activity (PA) patterns are epidemiologically linked to gynecologic pathologies, establishing causality remains uncertain. This Mendelian randomization (MR) study evaluated causal relationships between PA phenotypes and gynecologic disorders.</p><p><strong>Methods: </strong>Using European-ancestry female genome-wide association study (GWAS) data, we analyzed eight gynecologic disorders and four PA instruments. Primary inverse-variance weighted (IVW) estimates were supplemented by sensitivity analyses (MR-Egger, weighted median, MR-PRESSO) to address pleiotropy and heterogeneity.</p><p><strong>Results: </strong>Our MR revealed subtype-specific effects: walking for pleasure [OR = 0.63, 95% CI: 0.41-0.96], strenuous sports [OR = 0.34, 95% CI: 0.16-0.74], and other exercises [OR = 0.70, 95% CI: 0.49-0.99]) reduced ER<sup>+</sup> breast cancer (BC) risk, while leisure screen time increased risk (OR = 1.08, 95% CI: 1.004-1.163). Only other exercises protected against ER<sup>-</sup> BC (OR = 0.60, 95% CI: 0.38-0.96). Exercise frequency inversely correlated with endometrial cancer (EC) (walking: OR = 0.20; strenuous sports: OR = 0.06; other exercises: OR = 0.41) and endometriosis (ES) (strenuous sports: OR = 0.17; other exercises: OR = 0.26), but was positively associated with sedentary behavior (EC: OR = 1.36). Ovarian cyst (OCS) risk decreased with walking (OR = 0.34) and other exercises (OR = 0.28), yet increased with screen time (OR = 1.23). Paradoxically, walking showed strong positive (OR = 31.48) and strenuous exercise inverse (OR = 0.004) associations with polycystic ovary syndrome (PCOS). No causal links emerged for cervical cancer (CC), ovarian cancer (OC), or uterine fibroids (UF).</p><p><strong>Conclusion: </strong>This first MR evidence demonstrates PA's differential causal effects on gynecologic disorders, particularly highlighting exercise modality-specific protection against ER<sup>+</sup> BC, EC, and ES. Paradoxical PCOS associations warrant mechanistic investigation. Findings underscore PA as a modifiable preventive factor and advocate for subtype-tailored exercise guidelines in women's health.</p>\",\"PeriodicalId\":7731,\"journal\":{\"name\":\"American journal of translational research\",\"volume\":\"17 5\",\"pages\":\"3753-3765\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-05-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170402/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of translational research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.62347/PGYY9493\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of translational research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.62347/PGYY9493","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Causal relationship between physical activity and common gynecologic conditions: a two-sample Mendelian randomization study.
Objective: While physical activity (PA) patterns are epidemiologically linked to gynecologic pathologies, establishing causality remains uncertain. This Mendelian randomization (MR) study evaluated causal relationships between PA phenotypes and gynecologic disorders.
Methods: Using European-ancestry female genome-wide association study (GWAS) data, we analyzed eight gynecologic disorders and four PA instruments. Primary inverse-variance weighted (IVW) estimates were supplemented by sensitivity analyses (MR-Egger, weighted median, MR-PRESSO) to address pleiotropy and heterogeneity.
Results: Our MR revealed subtype-specific effects: walking for pleasure [OR = 0.63, 95% CI: 0.41-0.96], strenuous sports [OR = 0.34, 95% CI: 0.16-0.74], and other exercises [OR = 0.70, 95% CI: 0.49-0.99]) reduced ER+ breast cancer (BC) risk, while leisure screen time increased risk (OR = 1.08, 95% CI: 1.004-1.163). Only other exercises protected against ER- BC (OR = 0.60, 95% CI: 0.38-0.96). Exercise frequency inversely correlated with endometrial cancer (EC) (walking: OR = 0.20; strenuous sports: OR = 0.06; other exercises: OR = 0.41) and endometriosis (ES) (strenuous sports: OR = 0.17; other exercises: OR = 0.26), but was positively associated with sedentary behavior (EC: OR = 1.36). Ovarian cyst (OCS) risk decreased with walking (OR = 0.34) and other exercises (OR = 0.28), yet increased with screen time (OR = 1.23). Paradoxically, walking showed strong positive (OR = 31.48) and strenuous exercise inverse (OR = 0.004) associations with polycystic ovary syndrome (PCOS). No causal links emerged for cervical cancer (CC), ovarian cancer (OC), or uterine fibroids (UF).
Conclusion: This first MR evidence demonstrates PA's differential causal effects on gynecologic disorders, particularly highlighting exercise modality-specific protection against ER+ BC, EC, and ES. Paradoxical PCOS associations warrant mechanistic investigation. Findings underscore PA as a modifiable preventive factor and advocate for subtype-tailored exercise guidelines in women's health.