DataSheet_5_A causal examination of the correlation between hormonal and reproductive factors and low back pain.pdf

BackgroundThe relationship between hormonal fluctuations in the reproductive system and the occurrence of low back pain (LBP) has been widely observed. However, the causal impact of specific variables that may be indicative of hormonal and reproductive factors, such as age at menopause (ANM), age at menarche (AAM), length of menstrual cycle (LMC), age at first birth (AFB), age at last live birth (ALB) and age first had sexual intercourse (AFS) on low back pain remains unclear.
MethodsThis study employed Bidirectional Mendelian randomization (MR) using publicly available summary statistics from Genome Wide Association Studies (GWAS) and FinnGen Consortium to investigate the causal links between hormonal and reproductive factors on LBP. Various MR methodologies, including inverse-variance weighted (IVW), MR-Egger regression, and weighted median, were utilized. Sensitivity analysis was conducted to ensure the robustness and validity of the findings. Subsequently, Multivariate Mendelian randomization (MVMR) was employed to assess the direct causal impact of reproductive and hormone factors on the risk of LBP.
ResultsAfter implementing the Bonferroni correction and conducting rigorous quality control, the results from MR indicated a noteworthy association between a decreased risk of LBP and AAM (OR=0.784, 95% CI: 0.689-0.891; p=3.53E-04), AFB (OR=0.558, 95% CI: 0.436-0.715; p=8.97E-06), ALB (OR=0.396, 95% CI: 0.226-0.692; p=0.002), and AFS (OR=0.602, 95% CI: 0.518-0.700; p=3.47E-10). Moreover, in the reverse MR analysis, we observed no significant causal effects of LBP on ANM, AAM, LMC and AFS. MVMR analysis demonstrated the continued significance of the causal effect of AFB on LBP after adjusting for BMI.
ConclusionOur study explored the causal relationship between ANM, AAM, LMC, AFB, AFS, ALB and the prevalence of LBP. We found that early menarche, early age at first birth, early age at last live birth and early age first had sexual intercourse may decrease the risk of LBP. These insights enhance our understanding of LBP risk factors, offering valuable guidance for screening, prevention, and treatment strategies for at-risk women.

研究背景：生殖系统激素波动与下腰痛（low back pain, LBP）的发生之间的关联已被广泛观察到。然而，一些可反映激素与生殖相关因素的特定变量，如绝经年龄（age at menopause, ANM）、初潮年龄（age at menarche, AAM）、月经周期长度（length of menstrual cycle, LMC）、首次生育年龄（age at first birth, AFB）、末次活产年龄（age at last live birth, ALB）以及首次性交年龄（age first had sexual intercourse, AFS）对下腰痛的因果影响仍不明确。
研究方法：本研究采用双向孟德尔随机化（Bidirectional Mendelian randomization, MR）方法，借助公开的全基因组关联研究（Genome Wide Association Studies, GWAS）与芬兰基因联盟（FinnGen Consortium）汇总统计数据，探究激素与生殖相关因素与下腰痛之间的因果关联。本研究采用了多种孟德尔随机化分析策略，包括逆方差加权（inverse-variance weighted, IVW）、MR-Egger回归以及加权中位数法，并通过敏感性分析确保研究结果的稳健性与有效性。随后，本研究采用多变量孟德尔随机化（Multivariate Mendelian randomization, MVMR）方法，评估生殖与激素相关因素对下腰痛发病风险的直接因果影响。
研究结果：经邦费罗尼校正与严格质量控制后，孟德尔随机化分析结果显示，初潮年龄（AAM）、首次生育年龄（AFB）、末次活产年龄（ALB）以及首次性交年龄（AFS）与下腰痛发病风险降低存在显著关联：初潮年龄对应的比值比（odds ratio, OR）=0.784，95%置信区间（confidence interval, CI）为0.689~0.891，p=3.53×10^-4；首次生育年龄OR=0.558，95%CI=0.436~0.715，p=8.97×10^-6；末次活产年龄OR=0.396，95%CI=0.226~0.692，p=0.002；首次性交年龄OR=0.602，95%CI=0.518~0.700，p=3.47×10^-10。此外，反向孟德尔随机化分析结果显示，下腰痛对绝经年龄（ANM）、初潮年龄（AAM）、月经周期长度（LMC）以及首次性交年龄（AFS）并无显著因果影响。多变量孟德尔随机化分析进一步表明，在校正身体质量指数（Body Mass Index, BMI）后，首次生育年龄对下腰痛的因果效应仍具有统计学显著性。
研究结论：本研究探究了绝经年龄（ANM）、初潮年龄（AAM）、月经周期长度（LMC）、首次生育年龄（AFB）、首次性交年龄（AFS）、末次活产年龄（ALB）与下腰痛患病率之间的因果关联。研究发现，初潮年龄较早、首次生育年龄较早、末次活产年龄较早以及首次性交年龄较早，均可能降低下腰痛的发病风险。本研究结果加深了我们对下腰痛危险因素的认知，可为高危女性的筛查、预防及治疗策略提供有价值的指导依据。