The association between hypercoagulability and use of drospirenone (DRSP) and ethinylestradiol (EE) containing combined oral contraceptives (COCs) is an important clinical concern. We have previously reported that the two formulations of DRSP combined with EE (namely, DRSP/20EE and DRSP/30EE) bring about a prothrombotic state in hemostatic traits of female users. We report here the serum metabolomic changes in the same study cohort in relation to the attendant prothrombotic state induced by COC use, thus offering new insights on the underlying biochemical mechanisms contributing to the altered coagulatory profile with COC use. A total of 78 healthy women participated in this study and were grouped as follows: control group not using oral contraceptives (n = 25), DRSP/20EE group (n = 27), and DRSP/30EE group (n = 26). Untargeted metabolomics revealed changes in amino acid concentrations, particularly a decrease in glycine and an increase in both cysteine and lanthionine in the serum, accompanied by variations in oxidative stress markers in the COC users compared with the controls. Of importance, this study is the first to link specific amino acid variations, serum metabolites, and the oxidative metabolic profile with DRSP/EE use. These molecular changes could be linked to specific biophysical coagulatory alterations observed in the same individuals. These new findings lend evidence on the metabolomic substrates of the prothrombotic state associated with COC use in women and informs future personalized/precision medicine research. Moreover, we underscore the importance of an interdisciplinary approach to evaluate venous thrombotic risk associated with COC use.

中文翻译：

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口服避孕药与屈螺酮和乙炔雌二醇合用引起的血栓形成相关的血清代谢组学变化。

高凝性与使用含有联合口服避孕药（COC）的屈螺酮（DRSP）和炔雌醇（EE）之间的关联是一个重要的临床问题。我们以前曾报道过，DRSP与EE结合的两种配方（即DRSP / 20EE和DRSP / 30EE）在女性使用者的止血性状中引起血栓形成前状态。我们在这里报告了同一研究队列中与COC使用引起的伴随血栓形成状态相关的血清代谢组学变化，从而提供了对潜在的生化机制的新见解，这些潜在的生化机制有助于COC使用改变了凝血特性。共有78名健康女性参加了这项研究，分为以下 几组：未使用口服避孕药的对照组（n = 25），DRSP / 20EE组（n = 27）和DRSP / 30EE组（n = 26）。未靶向的代谢组学揭示了氨基酸浓度的变化，特别是血清中甘氨酸的减少以及半胱氨酸和羊毛硫氨酸的增加，与对照组相比，COC使用者的氧化应激标志物发生了变化。重要的是，这项研究是第一个将特定氨基酸变异，血清代谢物和氧化代谢谱与DRSP / EE使用联系起来的研究。这些分子变化可能与在同一个体中观察到的特定生物物理凝血改变有关。这些新发现为与妇女使用COC相关的血栓形成前状态的代谢组学底物提供了证据，并为未来的个性化/精准医学研究提供了依据。此外，