Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives

摘要

Objectives Estetrol (E-4) is a natural estrogen produced by the human fetal liver. In combination with drospirenone (DRSP) or levonorgestrel (LNG), E-4 blocks ovulation and has less effect on haemostatic biomarkers in comparison with ethinylestradiol (EE) combined with DRSP. This study evaluates the impact of several doses of E-4/DRSP and E-4/LNG on safety parameters such as liver function, lipid metabolism, bone markers and growth endocrine parameters.Methods This was a dose-finding, single-centre, controlled study performed in healthy women aged 18 to 35 years with a documented pretreatment ovulatory cycle. Participants received 5 mg or 10 mg E-4/3 mg DRSP; 5 mg, 10 mg or 20 mg E-4/150 g LNG; or 20 g EE/3 mg DRSP as a comparator for three consecutive cycles in a 24/4-day regimen. Changes from baseline to end of treatment in liver parameters, lipid metabolism, bone markers and growth endocrinology were evaluated.Results A total of 109 women were included in the study. Carrier proteins were minimally affected in the E-4/DRSP and E-4/LNG groups, in comparison with the EE/DRSP group, where a significant increase in sex hormone-binding globulin was observed. Similarly, minor effects on lipoproteins were observed in the E-4 groups, and the effects on triglycerides elicited by the E-4 groups were significantly lower than those in the EE/DRSP group. No imbalances in bone markers were observed in any groups. No alterations in insulin-like growth factor were observed in the E-4 groups.Conclusions E-4-containing combinations have a limited effect on liver function, lipid metabolism, and bone and growth endocrine parameters.