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

Abstract

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.

摘要

包括微粒化黄体酮（MP）在内的生物学上相同的绝经激素替代治疗(MHT)受到了广泛的关注。我们的目的是评估MP在连续联合MHT中对静脉和动脉血栓栓塞（VTE/ATE）（如深静脉血栓/肺栓塞、心肌梗死[MI]和缺血性卒中）的影响。如果文章中提供关于心血管事件和外源性事件作为MP应用的终点, 则符合纳入条件。通过Medline、Embase、CINAHL、Cochrane、ClinicalTrials.gov和跨学科数据库Web of Science进行文献检索。纳入12项研究, 包括随机对照试验(RCT)、病例对照研究和前瞻性或回顾性队列研究, 并评估偏倚风险。只有少数人将血栓栓塞事件作为主要终点, 这表明与非孕酮衍生物相比, 雌激素与MP联合应用不会改变原发性和复发性VTE风险及缺血性卒中风险。同样, 在评估VTE/ATE为不良事件的随机对照研究中, 组间无显著差异。目前还没有将MI作为主要终点的研究。总之, 虽然现有数据表明MP作为连续联合MHT中的一个组分可能对血管系统具有中性作用, 但还需要更多的随机对照研究来证明MP单独或连续联合MHT对心血管事件为主要终点的影响。

Keywords:

• Micronized progesterone
• combined estrogen–progestogen therapy
• menopausal hormone therapy
• stroke
• myocardial infarction
• venous thromboembolism
• pulmonary embolism
• systematic review

Acknowledgements

The authors are grateful for the support of Ms Daniela Hostettler for ordering the full-text papers.

Potential conflict of interest

L.M.K., A.S., H.J. and M.v.W. have no conflict of interest. P.S. has been part of a German-speaking expert board funded by DR. KADE/BESINS Pharma GmbH. The authors alone are responsible for the content and writing of the article.

Source of funding

Nil.