title: Endogenous estradiol metabolism during treatment with oral contraceptives.
abstract: OBJECTIVE
  Recent clinical studies indicate that an increase in D-ring estradiol metabolites over A-ring metabolites may be a risk factor for breast cancer. The present work was aimed to investigate the effect of oral contraceptives (OC) on the endogenous estradiol metabolism in premenopausal women.
  
  
  METHODS
  Two studies were conducted, firstly comparing 2 different progestins, i.e. norethisterone and dienogest, each in combination with a constant ethinyl estradiol dosage (study A) and secondly comparing a single progestin, i.e. levonorgestrel in 2 ethinyl estradiol/progestin dosage combinations (study B). The main A- and D-ring metabolites, i.e. 2-OHE1 and 16-OHE1, were measured by enzyme immunoassay in 8-h night-urine collected before and after 3 cycles of OC administration.
  
  
  RESULTS
  In study A, i.e. ethinyl estradiol plus dienogest or norethisterone acetate, the ratios of 16-OHE1 to 2-OHE1 before administration were 0.62 and 0.68, and after 3 months 0.31 and 0.54, respectively. The ratio after ethinyl estradiol and dienogest was significantly lower after treatment. In study B, i.e. ethinyl estradiol plus levonorgestrel (0.03 mg/0.15 mg and 0.02 mg/0.1 mg), the ratios before treatment were 0.71 and 0.75 for the higher and the lower dosages, respectively, which changed not significantly to 0.73 and 0.71 after 3 cycles.
  
  
  CONCLUSIONS
  OCs containing norethisterone acetate, dienogest or levonorgestrel did not have a negative effect on estradiol metabolism, i.e. they did not elicit a higher D-ring metabolism, which is considered to increase breast cancer risk.
authors.affiliation: Section of Endocrinology and Menopause, University Women's Hospital, Tübingen, Germany. endo.meno@med.uni-tuebingen.de
authors.forename: A O
authors.initials: AO
authors.lastname: Mueck
authors.forename: H
authors.initials: H
authors.lastname: Seeger
authors.forename: D
authors.initials: D
authors.lastname: Wallwiener
mesh_terms: D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000627:therapeutic use*; D004958:Estradiol / Q000378:metabolism*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000652:urine; D016912:Levonorgestrel / Q000627:therapeutic use; D009277:Nandrolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009640:Norethindrone / Q000008:administration & dosage / Q000627:therapeutic use; D017697:Premenopause; D016032:Randomized Controlled Trials as Topic
chemical_list: D003277:Contraceptives, Oral, Combined; D006894:Hydroxyestrones; C026702:16-hydroxyestrone; D004997:Ethinyl Estradiol; C023635:dienogest; D004958:Estradiol; D016912:Levonorgestrel; D009277:Nandrolone; D009640:Norethindrone; C024980:2-hydroxyestrone