The short answer
St. John's wort may reduce estradiol exposure or benefit and change uterine bleeding patterns. Product warnings cover estradiol patches and gel, but the size of the effect is uncertain and no universal dose adjustment or spacing interval is established.
What this answer covers
Route matters: transdermal estradiol may be less affected than oral estradiol, but the difference is not quantified.
- Supplement or preparation
- St. John's wort
- Medication ingredient
- estradiol
Evidence and practical considerations
Absorption & effectiveness
Two exact estradiol product sources independently warn that St. John's wort can reduce estrogen exposure or effect. Direct human effect-size evidence is non-equivalent ethinyl-estradiol combination therapy, so the conclusion is conditional and route-aware rather than a quantified class-wide claim.
- Exact scope
- St. John's wort with estradiol
- Medication form and route
- oral estradiol; transdermal estradiol patch; topical estradiol gel
- Timing or duration
- Enzyme induction generally requires repeated St. John's wort exposure; onset and offset depend on the Hypericum preparation, dose, duration, and estradiol route.
What remains uncertain
- Direct human trials returned by the search studied ethinyl estradiol plus progestins, not estradiol.
- Transdermal estradiol may be less affected than oral estradiol, but the remaining magnitude and clinical relevance are not quantified.
- St. John's wort products differ substantially in hyperforin content and induction potential.
- No universal dose adjustment or dose-separation interval is supported.
Factors that may matter: oral versus transdermal or topical route; Hypericum preparation and hyperforin content; dose and duration; indication; baseline symptom control; uterine bleeding changes.
Read the supporting source summaries
Source 1: current national regulatory product data sheet
medsafe.govt.nz · Source check Jul 24, 2026
Population: People using an estradiol transdermal patch for hormone replacement therapy.
The data sheet states that St. John's wort may induce estrogen metabolism, causing decreased effects and changes in uterine bleeding; transdermal estrogen may be less affected than oral hormones because it avoids first-pass metabolism.
Does not quantify estradiol concentration change or clinical failure rate and does not define the Hypericum preparation or duration.
Source 2: current U.S. regulatory product labeling
dailymed.awsprod.nlm.nih.gov · Source check Jul 24, 2026
Population: Postmenopausal women using topical estradiol gel.
Labeling states that St. John's wort preparations may reduce estrogen plasma concentrations, therapeutic effects, or change the uterine bleeding profile.
Class-mechanism wording within an exact estradiol-gel label; no product-specific clinical trial or quantified effect.
Source 3: peer-reviewed human pharmacokinetic study used only as non-equivalent context
pubmed.ncbi.nlm.nih.gov · Source check Jul 24, 2026
Population: Healthy women using a combination oral contraceptive containing ethinyl estradiol and norethindrone.
St. John's wort shortened ethinyl-estradiol half-life and increased norethindrone clearance, supporting enzyme induction.
Wrong estrogen identity and combination product; no estradiol RxCUI 4083 route or formulation. Effect sizes and contraceptive outcomes cannot be transferred.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Research summary published |
Article revision: 73f2ce996a53c850
This guide brings together the evidence records used by our interaction checker. Each finding retains its own preparation limits, research date, and source summaries.
Full citations require verification. Reading this answer and the source summaries does not.
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