Department of Public Health, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Am J Obstet Gynecol. 2022 Oct;227(4):603.e1-603.e29. doi: 10.1016/j.ajog.2022.06.009. Epub 2022 Jun 11.
Use of hormonal intrauterine devices has grown during the last decades. Although hormonal intrauterine devices act mostly via local effects on the uterus, measurable concentrations of levonorgestrel are absorbed into the systemic circulation. The possible metabolic changes and large-scale biomarker profiles associated with hormonal intrauterine devices have not yet been studied in detail.
To examine through the metabolomics approach the metabolic profile of patients using hormonal intrauterine devices and how this metabolic profile is affected by duration and discontinuation of use.
The study consisted of cross-sectional analyses of 5 population-based surveys (FINRISK and FinHealth studies), spanning from 1997 to 2017. All fertile-aged participants (18-49 years) in the surveys with available information on hormonal contraceptive use and metabolomics data (n=5649) were included in the study. Altogether, 211 metabolic measures of users of hormonal intrauterine devices (n=1006) were compared with those of nonusers of hormonal contraception (n=4643) via multivariable linear regression models. To allow comparison across multiple measures, association magnitudes were reported in standard deviation units of difference in biomarker concentration compared with the reference group.
After adjustment for covariates, levels of 141 metabolites differed in current users of hormonal intrauterine devices compared with nonusers of hormonal contraception (median difference in biomarker concentration, 0.09 standard deviation): lower levels of particle concentration of larger lipoprotein subclasses, triglycerides, cholesterol and derivatives, apolipoproteins A and B, fatty acids, glycoprotein acetyls, and aromatic amino acids. The metabolic pattern of hormonal intrauterine device use did not change according to duration of use. When comparing previous users and never-users of hormonal intrauterine devices, no significant metabolic differences were observed.
The use of hormonal intrauterine devices was associated with several moderate metabolic changes previously associated with reduced arterial cardiometabolic risk. The metabolic effects were independent of duration of use of the hormonal intrauterine devices. Moreover, the metabolic profiles were similar after discontinuation of hormonal intrauterine device use and in never-users.
在过去几十年中,荷尔蒙宫内节育器的使用有所增加。尽管荷尔蒙宫内节育器主要通过对子宫的局部作用发挥作用,但可测量浓度的左炔诺孕酮被吸收到全身循环中。与荷尔蒙宫内节育器相关的可能代谢变化和大规模生物标志物谱尚未详细研究。
通过代谢组学方法检查使用荷尔蒙宫内节育器的患者的代谢谱,以及这种代谢谱如何受使用时间和停用的影响。
这项研究包括对 1997 年至 2017 年期间进行的 5 项基于人群的调查(FINRISK 和 FinHealth 研究)进行的横断面分析。所有有生育能力的参与者(18-49 岁)在调查中都有荷尔蒙避孕使用信息和代谢组学数据(n=5649),均纳入研究。总共,通过多变量线性回归模型,将 211 项荷尔蒙宫内节育器使用者(n=1006)的代谢测量值与非荷尔蒙避孕使用者(n=4643)进行比较。为了能够在多个测量值之间进行比较,报告了与参考组相比,生物标志物浓度差异的标准差单位的关联幅度。
调整了协变量后,与非荷尔蒙避孕使用者相比,当前使用荷尔蒙宫内节育器的使用者的 141 种代谢物水平存在差异(生物标志物浓度的中位数差异,0.09 个标准差):较大脂蛋白亚类、甘油三酯、胆固醇及其衍生物、载脂蛋白 A 和 B、脂肪酸、糖蛋白乙酰基和芳香族氨基酸的颗粒浓度较低。荷尔蒙宫内节育器使用的代谢模式不随使用时间的长短而改变。比较之前使用和从未使用过荷尔蒙宫内节育器的使用者,未观察到明显的代谢差异。
使用荷尔蒙宫内节育器与之前与降低动脉心血管代谢风险相关的几种中等代谢变化有关。代谢效应独立于荷尔蒙宫内节育器的使用时间。此外,在停止使用荷尔蒙宫内节育器后和从未使用者中,代谢谱相似。