Toffol Elena, Haukka Jari, Jousilahti Pekka, Lehtoranta Lara, Joensuu Anni, Partonen Timo, Erlund Iris, Heikinheimo Oskari
Department of Public Health, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Department of Healthcare and Social Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
Acta Obstet Gynecol Scand. 2025 Sep;104(9):1640-1651. doi: 10.1111/aogs.15176. Epub 2025 Jun 12.
The use of combined oral contraceptives (COCs), but not of progestin-only pills (POPs) is associated with an increased risk of cardiovascular events. A detailed examination of how different oral contraceptives impact the metabolism in the short- and long-term has not been conducted. This study comparatively examines cross-sectional and longitudinal metabolomics-based profiles of different COCs and POPs, and explores how they perform relative to a metabolically safer contraceptive option.
Data were obtained from a population-based survey (Health 2000) and its 11-year follow-up (Health 2011). Altogether, 212 metabolic measures in OC users (n = 299; COC, n = 245; POP, n = 33) were compared to those in non-users of hormonal contraception (HC; n = 1422), and in users of a levonorgestrel intrauterine device (LNG-IUD; n = 341) via multivariable general estimating equations models adjusted for age, body mass index, duration of use, study cohort, diseases, medication use, alcohol use, smoking, and physical activity. Participants with complete longitudinal information (n = 327) were divided into continuers, stoppers, starters, switchers, and never-user groups, and the 11-year changes in the levels of each metabolite were compared.
Use of COCs, but not of POPs, was associated with altered levels of several metabolic measures compared to HC non-use or to use of LNG-IUD: higher concentrations and ratios of monounsaturated fatty acids but lower ratios of polyunsaturated fatty acids, and higher concentrations and ratios of triglycerides in lipoproteins. Additionally, in comparison to HC non-use or to use of LNG-IUD, users of third generation or other COCs had higher levels of inflammation markers and of cholesterol, but a lower percentage of cholesterol and a higher percentage of triglycerides in lipoproteins. Continuation or starting of LNG-IUD was not related to changes in metabolic profiles, while women who changed or stopped using COCs had greater levels of unsaturation and lower levels of total and lipoprotein triglycerides and other lipids.
The use of COCs, especially of third generation and other COCs, is related to various metabolic alterations suggestive of increased cardiovascular risk. Conversely, the use of POPs and LNG-IUD appeared metabolically safe. These associations were mostly reversible after interruption of use or switch to different preparations.
复方口服避孕药（COC）的使用与心血管事件风险增加相关，而仅含孕激素的避孕药（POP）则不然。尚未对不同口服避孕药如何在短期和长期影响代谢进行详细研究。本研究比较了不同COC和POP基于代谢组学的横断面和纵向概况，并探讨它们相对于代谢更安全的避孕选择的表现。
数据来自一项基于人群的调查（2000年健康调查）及其11年随访（2011年健康调查）。通过针对年龄、体重指数、使用时长、研究队列、疾病、药物使用、饮酒、吸烟和身体活动进行调整的多变量一般估计方程模型，将299名口服避孕药使用者（n = 299；COC使用者n = 245；POP使用者n = 33）的212项代谢指标与非激素避孕（HC）使用者（n = 1422）以及左炔诺孕酮宫内节育器（LNG-IUD）使用者（n = 341）的指标进行比较。具有完整纵向信息的参与者（n = 327）被分为持续使用者、停用者、开始使用者、转换使用者和从未使用者组，并比较了每种代谢物水平的11年变化。
与未使用HC或使用LNG-IUD相比，使用COC而非POP与几种代谢指标水平的改变相关：单不饱和脂肪酸的浓度和比例较高，但多不饱和脂肪酸的比例较低，脂蛋白中甘油三酯的浓度和比例较高。此外，与未使用HC或使用LNG-IUD相比，第三代或其他COC的使用者炎症标志物和胆固醇水平较高，但脂蛋白中胆固醇百分比较低，甘油三酯百分比较高。继续使用或开始使用LNG-IUD与代谢谱变化无关，而更换或停止使用COC的女性不饱和程度更高，总甘油三酯和脂蛋白甘油三酯及其他脂质水平更低。
使用COC，尤其是第三代和其他COC，与各种提示心血管风险增加的代谢改变有关。相反，使用POP和LNG-IUD在代谢方面似乎是安全的。这些关联在停药或改用不同制剂后大多是可逆的。
