Estradiol and St John's Wort: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
St John's Wort
No brand names on recordEstradiol
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Reduced hormonal contraceptive exposure and increased risk of contraceptive failure
Interaction Deep Dive
Avoid concomitant use of St. John's wort (CYP3A4 inducer) and hormonal contraceptives1 as it may reduce the contraceptive exposure and diminish effectiveness 2. Pregnancy and breakthrough bleeding have been reported when St. John's wort was taken concurrently with hormonal contraceptives 91011. In a study, concomitant use of a CYP3A4 inducer disproportionally increased the rate of unplanned pregnancy with oral and implanted contraceptives; therefore, consider intrauterine or intravaginal routes if coadministration is required 3. Use an alternative method of contraception during coadministration and for at least 28 days after discontinuation of St. John's wort 2.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of hormonal contraceptives; induction of intestinal P-glycoprotein drug transporter by St. John's wort
Literature reports
9 reports — tap to read
a) Concomitant use of a CYP3A4 inducer with oral or implantable contraceptive products containing levonorgestrel (684 events) or etonogestrel/desogestrel (864 events) was associated with a disproportionately higher rate of unintended pregnancy compared to all other event types reported to the FDA Adverse Event Reporting System (FAERS) between 1971 and 2020 [levonorgestrel (14,504 total events); etonogestrel/desogestrel (9348 total events)]. When compared between CYP3A4 inducer exposure vs no exposure, cases of unintended pregnancy made up a significantly higher proportion of total events when levonorgestrel was administered orally (32.8% vs 10.5%) or as an implant (51.9% vs 11.9%), and a similar association was identified with implanted etonogestrel products (42.5% vs 13.1%). However, when contraceptives were administered as an intrauterine device (levonorgestrel, 10.3% vs 11.5%) or intravaginal ring (etonogestrel, 10.9% vs 8.7%), no significant associations were identified. Oral desogestrel (pro-drug of etonogestrel) in combination with ethynyl estradiol also was not significantly affected (11.8% vs 17.4%). Intrauterine and vaginal ring products may be preferred in lieu of oral and implantable contraceptive products in women concomitantly receiving CYP3A4 inducers 3.
b) In a systematic review of studies of pharmacokinetic interactions involving St John's Wort, concomitant use with ethinyl estradiol in 4 studies resulted in no change in ethinyl estradiol AUC with products containing hyperforin dosages of 0.4 mg/day, and a decrease in ethinyl estradiol AUC of 10% to 34% with hyperforin dosages of 2.4 to 33 mg/day 4.
c) In a systematic review of studies of pharmacokinetic interactions involving St John's Wort, concomitant use with norethindrone in 2 studies resulted in a 11% to 12% decrease in norethindrone AUC with products containing hyperforin dosages of 27 to 33 mg/day 4.
d) In a systematic review of studies of pharmacokinetic interactions involving St John's Wort, concomitant use with desogestrel in 2 studies resulted in a 42% decrease in the AUC of ketodesogestrel, the active desogestrel metabolite with products containing hyperforin dosages of 4.8 to 7.5 mg/day and no change in AUC with 0.4 mg/day 4.
e) There have been 8 reports of breakthrough bleeding and 1 case of changed menstrual bleeding by women 23 to 31 years of age who were taking St. John's wort and oral contraceptives. Most of the women had been taking oral contraceptives for a long time. The time between coadministration of St. John's wort and onset of problems was approximately 1 week for most patients. Induction of CYP3A4, which metabolizes steroids, is suggested to be the cause 5.
f) Three case reports detail women taking ethinyl estradiol and desogestrel combination contraceptives who experienced breakthrough bleeding while taking hypericum. The author cites the possible mechanism of this interaction as a CYP3A4 induction by St. John's wort, causing increased metabolism and consequent lowering of ethinyl estradiol concentrations 6.
g) St. John's wort caused breakthrough bleeding in 7 of 12 women taking oral contraceptives. Twelve healthy female subjects received a combination oral contraceptive (ethinyl estradiol/norethindrone) for three months. During months 2 and 3, St. John's wort 300 mg was administered 3 times daily. Follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone, ethinyl estradiol, and norethindrone concentrations as well as CYP3A enzyme activity were assessed in months 1 and 3. FSH, LH and progesterone concentrations on days 11 through 16 were not altered by St. John's wort. St. John's wort significantly increased the oral clearance of norethindrone from 8.2 to 9.5 L/hr . Seven of 12 subjects experienced breakthrough bleeding during month 3, compared with 2 of twelve in month 1. The authors conclude that long-term St. John's wort administration alters the efficacy and disposition of combination oral contraceptives due to the ability of St. John's wort to induce intestinal wall CYP3A 7.
h) Two women experienced unintended pregnancy within 5 months of starting St. John's wort. Both had used oral contraceptives for more than 8 years 8.
i) A 36-year-old female experienced an unplanned pregnancy associated with the concomitant use of St. John's wort and an oral hormonal contraceptive (ethinyl estradiol/dienogest (Valette(R). She had self-medicated with St. John's wort extract (Helarium(R) 425, Bionorica) up to 1700 mg daily for approximately 3 months before conception. She was on no other medications 9.
Common questions
Can I take Estradiol and St John's Wort together?
Reduced hormonal contraceptive exposure and increased risk of contraceptive failure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Estradiol and St John's Wort interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Estradiol or St John's Wort need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (11)
- Product Information: FEMLYV orally disintegrating tablets, norethindrone acetate, ethinyl estradiol orally disintegrating tablets. Millicent U.S. Inc (per FDA), East Hanover, NJ, 2024. DailyMed
- Product Information: JADELLE(R) subdermal implants, levonorgestrel subdermal implants. Bayer Corp (per FDA), Pittsburgh, PA, 2016.
- Sunaga T, Cicali B, Schmidt S, et al: Comparison of contraceptive failures associated with CYP3A4-inducing drug-drug interactions by route of hormonal contraceptive in an adverse event reporting system. Contraception 2021; 103(4):222-224. PubMed
- Chrubasik-Hausmann S, Vlachojannis J, & McLachlan AJ: Understanding drug interactions with St John's wort (Hypericum perforatum L.): impact of hyperforin content. J Pharm Pharmacol 2019; 71(1):129-138.
- Yue QY, Bergquist C, & Gerden B: Safety of St. John's Wort (Hypericum perforatum) (letter). Lancet 2000; 355(9203):576-577. PubMed
- Ernst E: Second thoughts about safety of St. John's Wort. Lancet 1999; 354(9195):2014-2016. PubMed
- Gorski J, Hamman M, Wang Z, et al: The effect of St. John's Wort on the efficacy of oral contraception (abstract MPI-80). Clin Pharmacol Ther 2002; 71(2):P25.
- Anon: St. John's Wort may influence other medication. Medical Products Agency. Sweden. 2002.
- Schwarz UI, Buschel B, & Kirch W: Unwanted pregnancy on self-medication with St. John's wort despite hormonal contraception (letter). Br J Clin Pharmacol 2003; 55(1):112-113. PubMed
- Anon: St. John's Wort may influence other medication. Medical Products Agency. Sweden. 2002.
- Ernst E: Second thoughts about safety of St John's Wort. Lancet 1999; 354(9195):2014-2016. PubMed
Keep reading about St John's Wort
Keep reading about Estradiol
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