Pharmacodynamics and pharmacokinetics after repeated subcutaneous administration of three gonadotrophin preparations

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Follicular development after 7-days subcutaneous administration of Normegon, Follegon and Metrodin-HP

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

Objectives Estetrol (E4) is a natural estrogen produced by the human fetal liver. In combination with drospirenone (DRSP) or levonorgestrel (LNG), E4 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 E4/DRSP and E4/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 E4/3 mg DRSP; 5 mg, 10 mg or 20 mg E4/150 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 E4/DRSP and E4/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 E4 groups, and the effects on triglycerides elicited by the E4 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 E4 groups.Conclusions E4-containing combinations have a limited effect on liver function, lipid metabolism, and bone and growth endocrine parameters. © 2015 The European Society of Contraception and Reproductive Health

Single and multiple dose pharmacokinetics and pharmacodynamics of the gonadotrophin-releasing hormone antagonist Cetrorelix in healthy female volunteers

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Reduced hemostatic effects with drospirenone-based oral contraceptives containing estetrol vs. ethinyl estradiol

Objective The effects of estetrol (E4), a natural fetal estrogen, combined with drospirenone (DRSP) were evaluated on plasma levels of sex hormone-binding globulin (SHBG), angiotensinogen and 12 hemostasis markers. Study design Combinations of 3 mg DRSP with 5 or 10 mg E4 were compared with YAZ® (20 mcg ethinyl estradiol and 3 mg DRSP; EE/DRSP) in parallel groups of 15–18 healthy young women. Main outcome was the relative change from pretreatment to the end (day 24±1) of the third treatment cycle. Results All E4 combinations showed low estrogen impact compared to EE/DRSP. Effects on SHBG and angiotensinogen of 10 mg E4 combined with DRSP were 15%–20% that of EE/DRSP. Both E4/DRSP combinations reduced D-dimer level and the 5 mg E4/DRSP combination also decreased fragment 1+2. Conclusions The reduction in coagulation markers suggests an anticoagulant effect from DRSP. The indications of a low thrombosis risk for E4 preparations should be validated in larger studies. Implication statement • The oral estrogens, 17-β-estradiol and ethinyl estradiol, are known for significant effects on estrogenic and hemostatic variables.• Effects of oral estetrol (E4) combined with drospirenone (DRSP) are significantly less for these variables.• This suggests a low procoagulant effect of E4/DRSP that should be clinically verified for low antithrombotic consequences. © 2016 Elsevier Inc