The impact of micronized progesterone on cardiovascular events – a systematic review

Biologically identical menopausal hormone therapy (MHT) including micronized progesterone (MP) has gained much attention. We aimed to assess the impact of MP in combined MHT on venous and arterial thromboembolism (VTE/ATE) (e.g. deep venous thrombosis/pulmonary embolism, myocardial infarction [MI] and ischemic stroke). Articles were eligible if they provided endpoints regarding cardiovascular events and use of exogenous MP. Literature searches were designed and executed for the databases Medline, Embase, CINAHL, the Cochrane Library, ClinicalTrials.gov and interdisciplinary database Web of Science. Twelve studies consisting of randomized controlled trials (RCTs), case–control studies and prospective or retrospective cohort studies were included, and risk of bias was assessed. Only a minority assessed thromboembolic events as a primary endpoint, showing that in contrast to norpregnane derivatives, primary and recurrent VTE risk was not altered by combining estrogens with MP, which was also true for ischemic stroke risk. Similarly, in placebo-controlled RCTs assessing VTE/ATE as adverse events there were no significant intergroup differences. Studies on MI as a primary endpoint are missing. In conclusion, while available data suggest that MP as a component in combined MHT may have a neutral effect on the vascular system, more RCTs investigating the impact of MP alone or in combined MHT on vascular primary endpoints are needed.

生物等效绝经激素治疗（menopausal hormone therapy, MHT）包含微粒化黄体酮（micronized progesterone, MP），近年来受到学界广泛关注。本研究旨在评估联合MHT中应用MP对静脉和动脉血栓栓塞症（venous and arterial thromboembolism, VTE/ATE，即深静脉血栓形成/肺栓塞、心肌梗死[myocardial infarction, MI]及缺血性脑卒中）的影响。纳入研究需提供与心血管事件终点及外源性MP使用相关的数据。本研究针对Medline、Embase、CINAHL、Cochrane Library、ClinicalTrials.gov以及跨学科数据库Web of Science开展了系统性文献检索。最终纳入12项研究，涵盖随机对照试验（randomized controlled trials, RCTs）、病例对照研究以及前瞻性或回顾性队列研究，并对各项研究的偏倚风险进行了评估。仅有少数研究将血栓栓塞事件作为主要终点，结果显示，与去甲孕酮衍生物（norpregnane derivatives）不同，雌激素联合MP并未改变原发性及复发性VTE风险，缺血性脑卒中风险亦无显著变化。同样，在以VTE/ATE为不良事件的安慰剂对照RCTs中，各组间未观察到显著差异。针对作为主要终点的心肌梗死的相关研究仍存在空白。综上，现有数据表明，作为联合MHT组成成分的MP可能对血管系统呈中性影响，但仍需开展更多RCTs，以单独或联合MHT的形式评估MP对血管系统主要终点的影响。