Haemostatic and metabolic impact of estradiol pills and drospirenone-containing ethinylestradiol pills vs. levonorgestrel-containing ethinylestradiol pills: A literature review

Abstract

Objective Since its introduction 50 years ago, the contraceptive pill has continuously evolved to decrease the risk of venous thromboembolism (VTE) associated with its use. An increased risk of VTE still remains, however. Other concerns, such as effects on lipid and carbohydrate metabolism, have also been reported. In this study we compared two reference combined oral contraceptives (COCs) containing ethinylestradiol (EE)/levonorgestrel (LNG) and EE/drospirenone (DRSP) with COCs containing estradiol (E₂) (estradiol valerate [E₂V]/dienogest [DNG] and E₂/nomegestrol acetate [NOMAC]). They were evaluated according to their influence on recognised haemostatic and metabolic markers.

Methods A literature search of the MEDLINE/PubMed database was conducted for head-to-head studies. EE/LNG was chosen as the comparator pill.

Results The haemostatic impact of E₂ pills and EE/LNG has been extensively compared, in contrast to that of EE/DRSP and EE/LNG. Changes in haemostatic and metabolic marker levels between EE/LNG and E₂V/DNG were generally not statistically significant. E₂/NOMAC showed statistically significantly favourable results on haemostatic markers and had a neutral effect on carbohydrate and lipid metabolism when compared with EE/LNG.

Conclusion E₂/NOMAC exhibits less haemostatic and metabolic impact than EE/LNG and other COCs, suggesting that it may be a promising candidate to reduce residual VTE risk associated with COC use. Confirmation from a well-powered prospective clinical trial is, however, needed.

Chinese Abstract

摘要

目的 自50年前推出以来,口服避孕药不断降低与其使用相关的静脉血栓栓塞(VTE)的风险。但是，增加的静脉血栓栓塞风险仍然存在。其他担忧，如对脂质和碳水化合物代谢的影响也有报道。这项研究中，我们将含炔雌醇（EE）/左炔诺孕酮（LNG）和含炔雌醇/屈螺酮（DRSP）的2个参照复方口服避孕药(COCs)与含雌二醇（E2）（戊酸雌二醇[E2V] /地诺孕素[DNG]和雌二醇/醋酸诺美孕酮[NOMAC]）的复方口服避孕药进行比较。根据它们对已确定的止血和代谢指标的影响来评估。

方法使用MEDLINE/PubMed数据库文献检索进行头对头研究。选择炔雌醇/左炔诺孕酮作为对照组。

结果相比于炔雌醇/屈螺酮和炔雌醇/左炔诺孕酮的止血影响，雌二醇片和炔雌醇/左炔诺孕酮的止血影响被广泛比较。炔雌醇/左炔诺孕酮与戊酸雌二醇/地诺孕素之间的止血和代谢指标的变化则不具统计学意义。与炔雌醇/左炔诺孕酮相比，雌二醇/醋酸诺美孕酮对止血指标具有明显有利的结果，对碳水化合物和脂质代谢则是中性效应。

结论相比于含炔雌醇/左炔诺孕酮口服避孕药及其他口服避孕药，含雌二醇/醋酸诺美孕酮口服避孕药具有更少的止血和代谢影响，这表明它可能是降低与口服避孕药相关的静脉血栓栓塞风险的一种有希望的候选药品。然而，这仍需要良好的前瞻性临床试验来验证。

关键词

复合口服避孕药，雌二醇，炔雌醇，止血指标，脂质和碳水化合物代谢指标，孕激素，静脉血栓栓塞

KEYWORDS:

• Combined oral contraceptive
• Estradiol
• Ethinylestradiol
• Haemostatic markers
• Markers of lipid and carbohydrate metabolism
• Progestin
• Venous thromboembolism

ACKNOWLEDGEMENTS

The manuscript was prepared with writing and editorial assistance from Jean-Louis Carsol and Daniel Loniewski, both employed by Publicis Life Brands International.

Declaration of interest: IL has a financial relationship (lecturer, member of advisory boards and/or consultant) with Bayer, MSD and Teva. NC-B shares expertise as a lecturer, member of advisory boards and/or consultant with HRA Pharma, Gedeon Richter and Teva/Theramex, without personal gain; she currently supervises a PhD student in receipt of a grant by HRA Pharma (October 2012–October 2015). CJ is a consultant with HRA Pharma, MSD and Teva/Theramex. SL is the recipient of grants and honoraria from MSD, Teva and Pfizer Inc. PL has received lecture fees, is a member of advisory boards and/or consultant with Bayer, Effick, HRA Pharma, MSD and Teva/Theramex. REN has had financial relationships (lecturer, member of advisory boards and/or consultant) with Bayer Pharma, Eli Lilly, Gedeon Richter, HRA Pharma, MSD, Novo Nordisk, Pfizer Inc., Shionogi and Teva. AP shares expertise as a lecturer, member of advisory boards and/or consultant with Bayer, Abbott, Amgen and Teva/Theramex, without personal gain.