title: Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial.
abstract: OBJECTIVE
  Breakthrough bleeding or even unwanted pregnancies have been reported in women during concomitant therapy with oral contraceptives and St John's wort extract. The aim of the present study was to investigate the effects of St John's wort extract on oral contraceptive therapy with respect to ovarian activity, breakthrough bleeding episodes and the pharmacokinetics of ethinyloestradiol and 3-ketodesogestrel.
  
  
  METHODS
  Eighteen healthy females were treated with a low-dose oral contraceptive (0.02 mg ethinyloestradiol, 0.150 mg desogestrel) alone (control cycle) or combined with 300 mg St John's wort extract given twice daily (cycle A) or three times daily (cycle B). Ovarian activity was assessed by measuring follicle maturation and serum oestradiol and progesterone concentrations. The number of breakthrough bleeding episodes and the pharmacokinetics of ethinyloestradiol and 3-ketodesogestrel were assessed under steady-state conditions.
  
  
  RESULTS
  During concomitant administration of low-dose oral contraceptive and St John's wort, there was no significant change in follicle maturation, serum oestradiol or progesterone concentrations when compared with oral contraceptive treatment alone. However, significantly more subjects reported intracyclic bleeding during cycles A (13/17 (77%), P < 0.015) and cycle B (15/17 (88%), P < 0.001) than with oral contraceptives alone (6/17 (35%)). The AUC(0,24 h) and Cmax of ethinyloestradiol remained unchanged during all study cycles, whereas the AUC(0,24 h) and Cmax of 3-ketodesogestrel decreased significantly from 31.2 ng ml-1 h to 17.7 ng x ml-1 h (43.9%; 95% confidence interval (CI) -49.3, -38.5, P = 0.001) and from 3.6 ng x ml -1 to 3.0 ng x ml -1(17.8%; CI -29.9, -5.7, P = 0.005), respectively, during cycle A and by 41.7% (CI -47.9, -35.6; P = 0.001) and by 22.8% (CI -31.2, -13.3; P < 0.001) during cycle B respectively, compared with the control cycle.
  
  
  CONCLUSIONS
  There was no evidence of ovulation during low-dose oral contraceptive and St John's wort extract combination therapy, but intracyclic bleeding episodes increased. Bleeding irregularities may adversely effect compliance to oral contraceptives and together with St John's wort-induced decreases in serum 3-ketodesogestrel concentrations, enhance the risk of unintended pregnancies.
authors: Department of Clinical Pharmacology and Toxicology, Women's Hospital, University Clinic Basel/Kantonsspital, Basel, Switzerland.
authors: Arabelle
authors: A
authors: Pfrunder
authors: Monika
authors: M
authors: Schiesser
authors: Simone
authors: S
authors: Gerber
authors: Manuel
authors: M
authors: Haschke
authors: Johannes
authors: J
authors: Bitzer
authors: Juergen
authors: J
authors: Drewe
mesh_terms: D000328:Adult; D003276:Contraceptives, Oral / Q000493:pharmacokinetics; D003280:Contraceptives, Oral, Synthetic / Q000493:pharmacokinetics; D017135:Desogestrel / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004967:Estrogens / Q000493:pharmacokinetics*; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D020902:Hypericum / Q000009:adverse effects*; D010053:Ovary / Q000187:drug effects; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000494:pharmacology; D014592:Uterine Hemorrhage / Q000209:etiology
chemical_list: D003276:Contraceptives, Oral; D003280:Contraceptives, Oral, Synthetic; D004967:Estrogens; D010936:Plant Extracts; D004997:Ethinyl Estradiol; D017135:Desogestrel