The short answer
St. John's wort may reduce the contraceptive effectiveness of norethindrone 0.35 mg pills and cause breakthrough bleeding. Discuss it with the prescriber before starting; the sources call for individual review and do not establish a universal prohibition, backup duration or washout interval.
What this answer covers
Applies to oral norethindrone 0.35 mg progestin-only contraceptive tablets; combination pills, norethindrone acetate and other indications are distinct.
- Supplement or preparation
- St. John's wort
- Medication ingredient
- norethindrone
Evidence and practical considerations
Absorption & effectiveness
Exact norethindrone 0.35 mg labeling directly warns that St. John's wort can induce metabolism and transport and may reduce contraceptive-steroid effectiveness. A small human study also directly measured increased clearance of the norethindrone component, but only in an ethinyl-estradiol/norethindrone combination. Systematic-review and CDC guidance support the concern while explicitly documenting the absence of progestin-only studies and direct pregnancy outcomes. The claim is therefore publishable as supported with conditions for oral contraceptive use, without transferring quantitative effects from combined or acetate products.
- Exact scope
- St. John's wort with norethindrone
- Medication form and route
- oral norethindrone 0.35 mg progestin-only contraceptive tablet
- Timing or duration
- Applies during concurrent use. Human pharmacokinetic studies evaluated St. John's wort 300 mg three times daily for approximately 21 to 28 days; onset, offset, and effect magnitude for the exact 0.35 mg progestin-only tablet are not established.
What remains uncertain
- The exact 0.35 mg norethindrone label provides a qualitative warning but no product-specific pharmacokinetic or pregnancy-risk estimate.
- The strongest exact-active-ingredient pharmacokinetic study measured norethindrone 1 mg within an ethinyl-estradiol combination; the magnitude and clinical consequences cannot be transferred to a norethindrone-only 0.35 mg pill.
- The Murphy study used norethindrone acetate plus ethinyl estradiol and is not an exact-identity study despite measuring circulating norethindrone.
- The systematic review found mixed pharmacokinetic evidence, limited pharmacodynamic concern, and no direct pregnancy outcomes or progestin-only studies.
- CDC classifies St. John's wort with progestin-only pills as category 2 rather than an absolute contraindication.
Factors that may matter: St. John's wort preparation and hyperforin or hypericin content; dose and duration of St. John's wort use; norethindrone product and dose; late or missed norethindrone doses; absence of a reliable nonhormonal backup method; use specifically for pregnancy prevention.
Read the supporting source summaries
Source 1: current United States regulatory prescribing information for exact norethindrone product
dailymed.nlm.nih.gov · Source check Jul 24, 2026
Population: Patients using exact oral norethindrone 0.35 mg progestin-only tablets for contraception.
The exact product label states that herbal products containing St. John's wort may induce hepatic cytochrome P450 enzymes and P-glycoprotein and may reduce contraceptive-steroid effectiveness, with possible breakthrough bleeding.
The warning is qualitative; it provides no exact 0.35 mg norethindrone pharmacokinetic estimate, pregnancy-risk estimate, St. John's wort dose threshold, or product-specific backup duration.
Source 2: peer-reviewed prospective human pharmacokinetic study
pubmed.ncbi.nlm.nih.gov · Source check Jul 24, 2026
Population: Twelve healthy premenopausal women using oral contraception for at least three months.
St. John's wort increased norethindrone oral clearance from 8.2 ± 2.7 to 9.5 ± 3.4 L/h (P=.042) and reduced norethindrone Cmax; breakthrough bleeding was reported by 7/12 with coadministration versus 2/12 during the contraceptive-only cycle, while measured gonadotropin and progesterone outcomes were not significantly changed.
Small fixed-sequence study; norethindrone was 1 mg inside an ethinyl-estradiol combination, not a norethindrone-only 0.35 mg pill; it was not powered for pregnancy or contraceptive-failure outcomes; the confidence intervals did not firmly establish bioinequivalence.
Source 3: peer-reviewed prospective human pharmacokinetic and pharmacodynamic study retained as non-transferable contextual evidence
pubmed.ncbi.nlm.nih.gov · Source check Jul 24, 2026
Population: Sixteen healthy women aged 18 to 35 years using a low-dose combined oral contraceptive.
The study reported a 12.6% reduction in measured norethindrone AUC and a 31.2% increase in apparent clearance, along with more breakthrough bleeding, larger follicles, and evidence of probable ovulation.
The tested Loestrin 1/20 product contained norethindrone acetate plus ethinyl estradiol, not exact norethindrone 0.35 mg alone. The measured circulating norethindrone endpoint does not authorize identity, dose, product, or efficacy transfer to RxCUI 7514. The study was small, sequential, and had no pregnancy endpoint.
Source 4: peer-reviewed systematic review
pmc.ncbi.nlm.nih.gov · Source check Jul 24, 2026
Population: Women of reproductive age in four comparative studies of St. John's wort with combined oral contraceptives.
Three studies showed at least one pharmacokinetic change suggesting lower hormone exposure; several showed more breakthrough bleeding, and one showed increased follicular growth or probable ovulation. The review concluded that limited evidence raises concern for reduced contraceptive efficacy.
All included comparative evidence involved combined oral contraceptives; no study specifically examined progestin-only contraceptives, and direct pregnancy outcomes were absent. Pharmacokinetic results were mixed and varied by St. John's wort preparation.
Source 5: current United States contraceptive clinical guideline
cdc.gov · Source check Jul 24, 2026
Population: People considering or using progestin-only contraceptives, including progestin-only pills.
CDC assigns category 2 to St. John's wort with progestin-only pills and states that, although no evidence specifically examined progestin-only contraceptives, pharmacokinetic and pharmacodynamic studies raise concern for reduced hormonal-contraceptive effectiveness through increased estrogen and progestin metabolism.
The recommendation is based on indirect evidence; the effect may depend on St. John's wort dose and variable active-ingredient concentration, and it does not quantify risk for norethindrone 0.35 mg.
Research assessment: · Open full citations ↗
Timing & monitoring
The exact norethindrone patient monograph directly requires patients to disclose St. John's wort and not start it without healthcare-provider discussion, and exact 0.35 mg labeling supplies the clinical reason. Current CDC guidance recognizes an effectiveness concern but does not classify the combination as an absolute contraindication. The publishable requirement is therefore disclosure and clinician review; avoidance may be selected clinically for pregnancy prevention, but is not encoded as a universal mandate.
- Exact scope
- St. John's wort with norethindrone
- Medication form and route
- oral norethindrone 0.35 mg progestin-only contraceptive tablet
- Timing or duration
- Disclosure and clinician review apply before starting St. John's wort and throughout concurrent use. The exact sources do not define a universal washout or backup-contraception interval.
What remains uncertain
- Exact patient information requires disclosure and discussion before starting St. John's wort, but does not say that every concurrent use is absolutely contraindicated.
- The exact label warns of reduced effectiveness but gives no universal backup-method or washout instruction.
- CDC category 2 for progestin-only pills supports individualized clinical review rather than an unqualified prohibition.
- Combined-pill pharmacokinetic data explain the concern but do not determine management for every norethindrone product, dose, or indication.
Factors that may matter: use of norethindrone for pregnancy prevention; St. John's wort preparation and active-constituent content; dose and duration of St. John's wort use; late or missed norethindrone doses; availability of reliable alternative or backup contraception.
Read the supporting source summaries
Source 1: current United States patient medication information for exact norethindrone product class
medlineplus.gov · Source check Jul 24, 2026
Population: Patients taking progestin-only oral norethindrone contraceptives.
The exact norethindrone patient information identifies St. John's wort as an interacting herbal product, directs patients to tell their doctor and pharmacist, and says not to start it during norethindrone use without discussing it with the healthcare provider.
The monograph does not state that all concurrent use is absolutely contraindicated and does not specify a backup method or washout interval.
Source 2: current United States regulatory prescribing information for exact norethindrone product
dailymed.nlm.nih.gov · Source check Jul 24, 2026
Population: Patients using exact oral norethindrone 0.35 mg progestin-only tablets for contraception.
The label specifically names St. John's wort and warns that hepatic-enzyme and P-glycoprotein induction may reduce contraceptive-steroid effectiveness and cause breakthrough bleeding.
The label does not explicitly mandate avoidance, specify backup contraception, or quantify product-specific risk.
Source 3: current United States contraceptive clinical guideline
cdc.gov · Source check Jul 24, 2026
Population: People considering or using progestin-only contraceptives, including progestin-only pills.
CDC assigns category 2 to St. John's wort with progestin-only pills: use is not absolutely contraindicated, but limited indirect evidence raises concern for decreased effectiveness, breakthrough bleeding, ovulation, and increased progestin metabolism.
No evidence specifically examined progestin-only contraceptives with St. John's wort; preparation-dependent effects are possible.
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: 47c4e93eef14877f
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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