Hoirisch-Clapauch Silvia
Hematology Department, Vascular Medicine, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil.
Semin Thromb Hemost. 2025 Jun;51(4):401-411. doi: 10.1055/s-0044-1788324. Epub 2024 Jul 19.
Fibrinolytic enzymes modify various substrates required for tissue remodeling, playing a crucial role in mechanisms underlying resilience, reward processing, ovulation, embryo implantation, and placentation. Individuals with low resilience and reduced reward responsiveness, when exposed to chronic stress, are at increased risk of experiencing a range of negative emotions. Chronic anxiety and melancholia are examples of negative emotions associated with hypercortisolism, while fear and atypical depression are characterized by systemic inflammation. Both cortisol and inflammatory cytokines stimulate the production of plasminogen activator inhibitor-1 (PAI-1), a potent fibrinolysis inhibitor. Chronic anxiety, fear, and depression are among the many hypofibrinolytic conditions increasing the risk of oligo-anovulation, miscarriage, fetal growth restriction, and preeclampsia. Although significant, the impact of negative emotions on implantation is not as obvious as on ovulation or placentation. Other hypofibrinolytic conditions that may affect female reproduction through mechanisms dependent or independent of PAI-1 include metabolic disturbances (e.g., due to consumption of highly palatable foods, often used to alleviate negative affect), inflammation, hyperhomocysteinemia, hypothyroidism, hypercortisolism, antiphospholipid antibodies, and the 4G allele of the PAI-1 gene. Benzodiazepines and antidepressants should be used with caution in the first trimester as this combination may cause malformations. Also, selective serotonin reuptake inhibitors have fibrinolytic properties that increase the risk of bleeding after surgical procedures. Psychological interventions, especially group therapy, are effective in the prevention of reproductive disorders. Controlled trials are needed to test the hypothesis that female reproductive health depends on psychological well-being, a balanced diet and physical activity, suppression of inflammation and autoantibodies, and homocysteine and hormonal homeostasis.
纤维蛋白溶解酶可修饰组织重塑所需的各种底物，在恢复力、奖赏处理、排卵、胚胎着床和胎盘形成等机制中发挥关键作用。恢复力低且奖赏反应性降低的个体，在暴露于慢性应激时，出现一系列负面情绪的风险会增加。慢性焦虑和忧郁症是与皮质醇增多症相关的负面情绪的例子，而恐惧和非典型抑郁症的特征是全身炎症。皮质醇和炎性细胞因子均刺激纤溶酶原激活物抑制剂-1（PAI-1）的产生，PAI-1是一种强效的纤维蛋白溶解抑制剂。慢性焦虑、恐惧和抑郁是众多低纤维蛋白溶解状态中的几种，这些状态会增加少排卵、流产、胎儿生长受限和先兆子痫的风险。尽管负面情绪对着床的影响很大，但其影响不如对排卵或胎盘形成那么明显。其他可能通过依赖或不依赖PAI-1的机制影响女性生殖的低纤维蛋白溶解状态包括代谢紊乱（例如，由于食用常被用来缓解负面影响的美味食物所致）、炎症、高同型半胱氨酸血症、甲状腺功能减退、皮质醇增多症、抗磷脂抗体以及PAI-1基因的4G等位基因。在孕早期应谨慎使用苯二氮䓬类药物和抗抑郁药，因为这种联合用药可能会导致畸形。此外，选择性5-羟色胺再摄取抑制剂具有纤维蛋白溶解特性，会增加手术后出血的风险。心理干预，尤其是团体治疗，对预防生殖障碍有效。需要进行对照试验来检验以下假设：女性生殖健康取决于心理健康、均衡饮食和体育活动、炎症和自身抗体的抑制以及同型半胱氨酸和激素的稳态。
