title: Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives.
abstract: OBJECTIVE
  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 μg LNG; or 20 μg 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.
authors.affiliation: a * Estetra SPRL , Liège , Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Mawet
authors.affiliation: a * Estetra SPRL , Liège , Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Maillard
authors.affiliation: b Dinox BV, Groningen , the Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: Klipping
authors.affiliation: c Pantarhei Bioscience BV , Zeist , the Netherlands.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Zimmerman
authors.affiliation: a * Estetra SPRL , Liège , Belgium.|d University of Liège , Liège , Belgium.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.affiliation: c Pantarhei Bioscience BV , Zeist , the Netherlands.
authors.forename: Herjan J T
authors.initials: HJ
authors.lastname: Coelingh Bennink
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000736:Androstenes / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D024042:Collagen Type I / Q000097:blood / Q000187:drug effects; D003277:Contraceptives, Oral, Combined / Q000493:pharmacokinetics / Q000494:pharmacology*; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology; D004953:Estetrol / Q000493:pharmacokinetics / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000187:drug effects / Q000378:metabolism; D016912:Levonorgestrel / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000502:physiology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D015675:Osteocalcin / Q000097:blood / Q000187:drug effects; D010455:Peptides / Q000097:blood / Q000187:drug effects; D012738:Sex Hormone-Binding Globulin / Q000187:drug effects / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000736:Androstenes; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D024042:Collagen Type I; D003277:Contraceptives, Oral, Combined; D003280:Contraceptives, Oral, Synthetic; D004967:Estrogens; D000451:Mineralocorticoid Receptor Antagonists; D010455:Peptides; D012738:Sex Hormone-Binding Globulin; D014280:Triglycerides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D004953:Estetrol; C035144:drospirenone
keywords: Bone markers; Drospirenone; Endocrinology; Estetrol; Levonorgestrel; Lipid metabolism; Liver function