MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Nat Commun. 2024 Feb 6;15(1):1103. doi: 10.1038/s41467-023-44459-6.
We explore the relation between age at menarche, parity and age at natural menopause with 249 metabolic traits in over 65,000 UK Biobank women using multivariable regression, Mendelian randomization and negative control (parity only). Older age of menarche is related to a less atherogenic metabolic profile in multivariable regression and Mendelian randomization, which is largely attenuated when accounting for adult body mass index. In multivariable regression, higher parity relates to more particles and lipids in VLDL, which are not observed in male negative controls. In multivariable regression and Mendelian randomization, older age at natural menopause is related to lower concentrations of inflammation markers, but we observe inconsistent results for LDL-related traits due to chronological age-specific effects. For example, older age at menopause is related to lower LDL-cholesterol in younger women but slightly higher in older women. Our findings support a role of reproductive traits on later life metabolic profile and provide insights into identifying novel markers for the prevention of adverse cardiometabolic outcomes in women.
我们利用英国生物库超过 65000 名女性的 249 项代谢特征，通过多变量回归、孟德尔随机化和阴性对照（仅考虑生育次数）研究了初潮年龄、生育次数和自然绝经年龄与这些代谢特征之间的关系。多变量回归和孟德尔随机化分析表明，初潮年龄较大与动脉粥样硬化程度较低的代谢特征相关，但当考虑到成年人体重指数时，这种相关性就会减弱。在多变量回归分析中，较高的生育次数与 VLDL 中的更多颗粒和脂质有关，而在男性阴性对照中则没有观察到这种关系。在多变量回归和孟德尔随机化分析中，自然绝经年龄较大与炎症标志物的浓度较低有关，但由于与年龄相关的特定影响，我们观察到 LDL 相关特征的结果不一致。例如，绝经年龄较大与较年轻女性的 LDL 胆固醇水平较低有关，但对较年长女性而言，该水平则略有升高。我们的研究结果支持生殖特征对晚年代谢特征的作用，并为识别预防女性不良心血管代谢结局的新标志物提供了线索。
