Non-oral delivery of ethinyl estradiol (EE) does not reduce its biochemical impact compared to oral treatment. This is in contrast to non-EE oestrogens for which differential effects of route of... Show moreNon-oral delivery of ethinyl estradiol (EE) does not reduce its biochemical impact compared to oral treatment. This is in contrast to non-EE oestrogens for which differential effects of route of delivery have been described in the literature. Furthermore, non-oral non-EE oestrogens seem to have less unfavourable impact on haemostasis parameters and SHBG than non-oral EE, as do oral non-EE oestrogens compared to oral EE. Although these conclusions follow from an indirect comparison of results, they are in line with findings on oral and non-oral hormone replacement therapy and that the risk of venous thrombo-embolism is not reduced by non-oral routes of administration of EE-containing combined hormonal contraceptives. So far, no gold standard exists for estimating the risk of cardiovascular disease during the course of development of hormonal contraceptives. This is mainly due to the lack of data on the exact mechanism of steroid-induced disease. This has resulted in a lack of consensus on which biomarkers or biomarker fractions to study. The solution would be to investigate biomarkers and the relevant clinical outcome prospectively in one study. Such a study will entail a great deal of expense, but will provide with reliable information and prove more efficient in the long term. Show less