Abstract
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
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Article info
Publication history
Published online: July 18, 2016
Accepted:
July 13,
2016
Received:
February 26,
2016
Footnotes
☆Financial support: none.
☆☆Conflicts of interest: none.
★Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention nor the Food and Drug Administration.
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.
