Can changes in sex hormone binding globulin predict the risk of venous thromboembolism with combined oral contraceptive pills?. A discussion based on recent recommendations from the European agency for evaluation of medicinal products regarding third generation oral contraceptive pills

Background. Recent studies have indicated that the risk of thromboembolic disease (VTE) in users of combined oral contraceptive pills (COCs) varies not only with estrogen dose, but also with the progestogen in pills with the same estrogen dose. The aim of this article is to discuss sex hormone binding globulin (SHBG) as a marker of estrogenicity and as a surrogate indicator for the potential risk of VTE in users of COC. Material and methods. Using data from the literature, we investigated the relationship between the risk of VTE with various COCs and their effects on SHBG. We also collected data on the effects on SHBG by some combined preparations, where there are no VTE data. Results. There appears to be a relationship between the risk of VTE and the effect on SHBG. Monophasic preparations containing levonorgestrel, having the lowest risk of VTE, cause an average SHBG increase of around 50%. COCs containing desogestrel or gestodene cause an average SHBG increase of 200-300%. A preparation with cyproterone acetate, carrying a higher risk of VTE than desogestrel and gestodene, cause a 300-400% SHBG increase. With the recently developed combined preparations, there is a 150% SHBG increase with norgestimate and a 250-300% increase with drosperinone and dienogest. Conclusions. We propose that the change in SHBG with a COC could be interpreted as a measure of total estrogenicity and used as a predictor of the risk of VTE. Preparations containing drosperinone, dienogest, cyproterone acetate and norgestimate are equally or more estrogenic than the more thoroughly studied COCs, containing desogestrel or gestodene and should not be considered a safer substitute.