Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding

Contraception. 2005 Jun;71(6):402-8. doi: 10.1016/j.contraception.2004.11.004.


Objectives: This study evaluated the effect of the herbal remedy St. John's Wort on oral contraceptive (OC) therapy with respect to the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding.

Methods: Sixteen healthy women were treated with a low-dose OC (Loestrin 1/20) and a placebo for two consecutive 28-day cycles in a single-blind sequential trial. Treatment with St John's Wort 300 mg three times daily was then added for two additional 28-day cycles. Outcomes compared between control and treatment cycles included the pharmacokinetics of norethindrone and ethinyl estradiol, daily bleeding diaries, follicle growth, changes in cervical mucus and progesterone levels drawn at 7- to 10-day intervals.

Results: Treatment with St. John's Wort was associated with a significant 13-15% reduction in the dose exposure from the contraceptive. Breakthrough bleeding increased in the treatment cycles, as did evidence of follicle growth and probable ovulation.

Conclusion: St. John's Wort is associated with increased metabolism of norethindrone and ethinyl estradiol, breakthrough bleeding, follicle growth and ovulation. Women using OCs should be cautioned that St. John's Wort might interfere with contraceptive effectiveness.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Contraceptives, Oral, Synthetic / pharmacokinetics*
  • Contraceptives, Oral, Synthetic / pharmacology
  • Drug Interactions
  • Estrogens / pharmacokinetics
  • Estrogens / pharmacology
  • Ethinyl Estradiol / pharmacokinetics*
  • Ethinyl Estradiol / pharmacology
  • Female
  • Herb-Drug Interactions*
  • Humans
  • Hypericum / metabolism*
  • Metrorrhagia
  • Norethindrone / pharmacokinetics*
  • Norethindrone / pharmacology
  • Ovulation / drug effects*


  • Contraceptives, Oral, Synthetic
  • Estrogens
  • Ethinyl Estradiol
  • Norethindrone