Although evidence is limited, a new systematic review in Contraception indicates a greater risk of ovulation and breakthrough as well as reduced contraceptive efficacy when combined oral contraceptives (COCs) are co-administered with St. John’s wort. 

Ethinyl estradiol and progestin found in hormonal contraceptives are CYP3A4 substrates. St. John’s wort is a strong inducer of the CYP3A4 enzyme. Scientists from the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) conducted a review to examine whether St. John’s wort and hormonal contraceptives administered together would lead to significant safety or efficacy issues. 

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Four studies met the inclusion criteria and evaluated the use of COCs alone vs. COCs with St. John’s wort. The authors found that two studies showed no change in markers of ovulation and one demonstrated higher follicular growth and probable ovulation when COCs were given with St. John’s wort. An increased risk of breakthrough bleeding with co-administration was observed in three studies. 

Three studies also demonstrated changes in at least one pharmacokinetic parameter that suggested a significantly decreased exposure to hormone concentrations when COCs were co-administered with St. John’s wort. The one study that did not show any significant pharmacokinetic differences had evaluated a St. John’s wort product with low hypericin levels.

Overall, the administration of St. John’s wort may be associated with weak to moderate induction of the metabolism of COCs based on mixed pharmacokinetic evidence, the authors concluded.

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