title: Impact on hepatic estrogen-sensitive proteins by a 1-year contraceptive vaginal ring delivering Nestorone® and ethinyl estradiol.
abstract: OBJECTIVE
  Estrogen-sensitive hepatic proteins were assessed in women using a contraceptive vaginal ring (CVR) delivering 150mcg Nestorone® (NES) and 15mcg ethinyl estradiol (EE).
  
  
  METHODS
  A substudy of the Contraceptive Clinical Trials Network of the National Institute of Child Health and Human Development enrolled 129 participants, with assessments of factor VIII, fibrinogen, protein S (PS) and sex hormone binding globulin (SHBG). Thirty-six participants had used combined hormonal contraceptives (CHCs) in the cycle preceding first CVR use (recent users) and 70 had no history of recent use (nonusers).
  
  
  RESULTS
  Mean values at baseline were within the normal range for all four proteins but were higher for factor VIII, fibrinogen and SHBG and significantly lower for PS in recent compared to nonusers. During NES/EE CVR use, factor VIII, fibrinogen and PS were within the normal range; however, SHBG levels were increased by nearly 100% at Cycle 13. The change from baseline to final evaluation was statistically significant for all proteins in nonusers. The change in recent users was significant for factor VIII at Cycle 6 and for SHBG at Cycles 6 and 13, but not for PS or fibrinogen.
  
  
  CONCLUSIONS
  NES/EE CVR for up to 13cycles was associated with changes from baseline in plasma levels of factor VIII, fibrinogen and PS that were within the normal range, with SHBG levels above the normal range by Cycle 6. Nonusers of CHC before CVR showed wider changes in values versus recent users whose baseline values were increased by previous EE exposure.
  
  
  CONCLUSIONS
  Recent use of CHCs demonstrated significant changes in all four measured hepatic proteins at baseline compared to nonusers. Use of the NES/EE CVR further changed these hepatic protein markers, but values remained within the normal range. Prebaseline exposure to estrogen can obscure interpretation of hepatic proteins changes associated with a second CHC.
authors.affiliation: Clinical Research Center, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: archerdf@evms.edu.
authors.forename: D F
authors.initials: DF
authors.lastname: Archer
authors.affiliation: Center for Reproductive Health, Cincinnati, OH 45219, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Thomas
authors.affiliation: Department of Biological Hematology, Hotel-Dieu-Cochin Hospital, Paris 75014, France.
authors.forename: J
authors.initials: J
authors.lastname: Conard
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10017, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Merkatz
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10017, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Creasy
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10017, USA.
authors.forename: K
authors.initials: K
authors.lastname: Roberts
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10017, USA.
authors.forename: M
authors.initials: M
authors.lastname: Plagianos
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892-2425, USA.
authors.forename: D
authors.initials: D
authors.lastname: Blithe
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10017, USA.
authors.forename: R
authors.initials: R
authors.lastname: Sitruk-Ware
mesh_terms: D000328:Adult; D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D003274:Contraceptive Devices, Female; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology; D004967:Estrogens / Q000008:administration & dosage*; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005169:Factor VIII / Q000187:drug effects; D005260:Female; D005340:Fibrinogen / Q000187:drug effects; D006801:Humans; D009653:Norprogesterones / Q000008:administration & dosage*; D017293:Protein S / Q000187:drug effects; D012738:Sex Hormone-Binding Globulin / Q000187:drug effects
chemical_list: D003271:Contraceptive Agents, Female; D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D004967:Estrogens; D009653:Norprogesterones; D017293:Protein S; D012738:Sex Hormone-Binding Globulin; D004997:Ethinyl Estradiol; C029167:ST 1435; D005169:Factor VIII; D005340:Fibrinogen
keywords: Coagulation proteins; Contraception; Ethinyl estradiol; Nestorone; SHBG; Vaginal ring