Co-administration of St. John's wort and hormonal contraceptives: a systematic review

Contraception. 2016 Dec;94(6):668-677. doi: 10.1016/j.contraception.2016.07.010. Epub 2016 Jul 18.


Objectives: St. John's wort (SJW) is a known strong inducer of the cytochrome P450 (CYP) 3 A4 enzyme, and both the ethinyl estradiol and progestin components of hormonal contraceptives are substrates of CYP3A4. This systematic review examined whether the co-administration of SJW and hormonal contraceptives leads to significant safety or efficacy concerns.

Study design: Systematic review.

Methods: PubMed and Cochrane Library databases were searched for articles of any comparative study design (clinical or pharmacokinetic) that examined potential interactions between SJW and hormonal contraceptives in women of reproductive age.

Results: Of the 48 identified articles, four studies met inclusion criteria and compared use of combined oral contraceptives (COCs) alone to the use of COCs co-administered with SJW. Two studies demonstrated no change in markers of ovulation, but one study demonstrated increased follicular growth and probable ovulation when COCs were co-administered with SJW. Three studies demonstrated an increased risk of breakthrough bleeding with COCs and SJW. Three studies showed changes in at least one pharmacokinetic parameter that suggested a significantly decreased exposure to hormone concentrations when COCs were co-administered with SJW. The only study that did not demonstrate any significant pharmacokinetic differences examined a SJW product containing a low amount of hypericin.

Conclusion: Limited evidence showing increased risk of ovulation and breakthrough bleeding raises concern for decreased contraceptive efficacy when COCs are co-administered with SJW. The pharmacokinetic evidence is mixed but suggests that SJW administration may be associated with weak to moderate induction of the metabolism of COCs.

Keywords: Depression; Drug interactions; Hormonal contraception; Hypericum perforatum; St. John's wort.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Contraceptives, Oral, Combined / adverse effects*
  • Contraceptives, Oral, Hormonal / adverse effects*
  • Depression / drug therapy
  • Female
  • Herb-Drug Interactions*
  • Humans
  • Hypericum / adverse effects
  • Hypericum / chemistry*
  • Metrorrhagia / chemically induced
  • Ovulation / drug effects
  • Plant Extracts / adverse effects*
  • Randomized Controlled Trials as Topic
  • Risk Assessment


  • Contraceptives, Oral, Combined
  • Contraceptives, Oral, Hormonal
  • Plant Extracts