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


CONCLUSIONS
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.
Murphy
Patricia A
PA
College of Nursing, University of Utah, Salt Lake City, UT 841112-5880, USA. patricia.murphy@nurs.utah.edu
Kern
Steven E
SE
Stanczyk
Frank Z
FZ
Westhoff
Carolyn L
CL
D000328:Adult; D003280:Contraceptives, Oral, Synthetic / Q000493:pharmacokinetics* / Q000494:pharmacology; D004347:Drug Interactions; D004967:Estrogens / Q000493:pharmacokinetics / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D041743:Herb-Drug Interactions; D006801:Humans; D020902:Hypericum / Q000378:metabolism*; D008796:Metrorrhagia; D009640:Norethindrone / Q000493:pharmacokinetics* / Q000494:pharmacology; D010060:Ovulation / Q000187:drug effects*
D003280:Contraceptives, Oral, Synthetic; D004967:Estrogens; D004997:Ethinyl Estradiol; D009640:Norethindrone