Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
Front Endocrinol (Lausanne). 2024 May 10;15:1326761. doi: 10.3389/fendo.2024.1326761. eCollection 2024.
The 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.
This 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.
After 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.
Our 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.
生殖系统中的激素波动与腰痛(LBP)的发生之间的关系已被广泛观察到。然而,特定变量的因果影响,这些变量可能是激素和生殖因素的指标,例如绝经年龄(ANM)、初潮年龄(AAM)、月经周期长度(LMC)、初产年龄(AFB)、末次活产年龄(ALB)和初次性交年龄(AFS)与腰痛之间的因果关系仍不清楚。
本研究使用来自全基因组关联研究(GWAS)和芬兰遗传研究联盟的公开汇总统计数据,采用双向孟德尔随机化(MR)方法,探讨激素和生殖因素与 LBP 之间的因果关系。使用了各种 MR 方法,包括逆方差加权(IVW)、MR-Egger 回归和加权中位数。进行敏感性分析以确保结果的稳健性和有效性。随后,采用多变量孟德尔随机化(MVMR)来评估生殖和激素因素对 LBP 风险的直接因果影响。
在实施 Bonferroni 校正并进行严格的质量控制后,MR 的结果表明,LBP 的风险降低与 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)和 AFS(OR=0.602,95%CI:0.518-0.700;p=3.47E-10)呈显著负相关。此外,在反向 MR 分析中,我们没有发现 LBP 对 ANM、AAM、LMC 和 AFS 有显著的因果影响。MVMR 分析表明,在调整 BMI 后,AFB 对 LBP 的因果效应仍然显著。
本研究探讨了 ANM、AAM、LMC、AFB、AFS、ALB 与 LBP 发生率之间的因果关系。我们发现,初潮早、初产年龄早、末次活产年龄早和初次性交年龄早可能会降低 LBP 的发病风险。这些发现加深了我们对 LBP 危险因素的理解,为高危女性的筛查、预防和治疗策略提供了有价值的指导。