Drug & supplement interaction

Indole-3-carbinol + Ethinyl Estradiol, Norethindrone

Ethinyl Estradiol, Norethindrone brand names: Femhrt, Loestrin 21, Ovcon 35 21, Ovcon 50 28, Necon 0.5 35 21, and others.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Ethinyl Estradiol, Norethindrone falls into 2 drug categories that Indole-3-carbinol can interact with; the most serious is rated moderate. Theoretically, indole-3-carbinol might increase the metabolism of CYP1A2 substrates and lower serum concentrations.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Indole-3-carbinol and Ethinyl Estradiol, Norethindrone

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Indole-3-carbinol interacts with whole categories of medication. Ethinyl Estradiol, Norethindrone falls into 2 of those categories, so it can interact with Indole-3-carbinol in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 2

Why this applies to Ethinyl Estradiol, Norethindrone

Ethinyl Estradiol, Norethindrone falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Indole-3-carbinol interacts with.

Theoretically, indole-3-carbinol might increase the metabolism of CYP1A2 substrates and lower serum concentrations.
Animal research shows that indole-3-carbinol induces CYP1A2 enzymes.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the basic idea with your birth control pill (the ethinyl estradiol and norethindrone combo). Indole-3-carbinol, the compound found in broccoli and cabbage and sold in concentrated supplements, may speed up a liver enzyme called CYP1A2. Since your liver partly uses this pathway to clear the estrogen part of your pill, revving it up could, in theory, lower the hormone levels in your blood and make the pill less reliable.

I want to be honest about how shaky this is. The concern comes only from animal and lab studies, not from real people, so it's far from proven. Eating broccoli at dinner is not a worry. If you're considering a concentrated I3C supplement while relying on this pill for birth control, please run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. He YH, Friesen MD, Ruch RJ, Schut HA. Indole-3-carbinol as a chemopreventive agent in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) carcinogenesis: inhibition of PhIP-DNA adduct formation, acceleration of PhIP metabolism, and induction of cytoch
Moderate

ESTROGENS

2 of 2

Ethinyl Estradiol, Norethindrone also falls under ESTROGENS.

Indole-3-carbinol might interfere with the effects of estrogen therapy.
Preliminary clinical and in vitro evidence shows that indole-3-carbinol has antiestrogenic activity.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for your birth control pill. The estrogen part of this combo, ethinyl estradiol, works by acting on estrogen receptors in your body. Indole-3-carbinol (I3C) is thought to push estrogen activity in the opposite direction, meaning it may blunt some of estrogen's effects. It can also nudge the liver to clear estrogen a bit faster. In theory, that could slightly weaken what the estrogen in your pill is doing.

Honestly, this is mostly lab and animal data, not proven in real people on the pill. Eating broccoli or cabbage at dinner is no concern at all. Concentrated I3C supplements are the question mark. If you're relying on this pill for contraception or hormone symptoms, just run the supplement by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol 2000;78:123-9. PubMed
  2. Kim, Y. S. and Milner, J. A. Targets for indole-3-carbinol in cancer prevention. J.Nutr.Biochem. 2005;16(2):65-73. PubMed
  3. Anon. Indole-3-carbinol. Monograph. Alternative Medicine Review 2005;10(4):337-42.
  4. McAlindon TE, Gulin J, Chen T, et al. Indole-3-carbinol in women with SLE: effect on estrogen metabolism and disease activity. Lupus 2001;10:779-83. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Indole-3-carbinol Also Interacts With Other Medications

Indole-3-carbinol has 293 moderate known drug interactions in our database — the Ethinyl Estradiol, Norethindrone one above is among them. If you take anything else, check it against the full list below.

Moderate 293 No known interaction 2,537 (incl. Ethinyl Estradiol, Norethindrone)
Taking anything else?

Check Another of Your Medications Against Indole-3-carbinol

Covers the 2,830 medications we’ve checked against Indole-3-carbinol. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Ethinyl Estradiol, Norethindrone

This page covers Indole-3-carbinol only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl Estradiol, Norethindrone page lists 240 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 196 moderate · 38 minor.

From our pharmacist’s overview on the Ethinyl Estradiol, Norethindrone page

“If you take a birth control pill or hormone therapy containing ethinyl estradiol and norethindrone (Loestrin, Femhrt, and others), a few supplements can genuinely undermine it, so read this page with care. Six of the 240 ingredients on file are rated major, and those six come first.”

Reviewed by 2 · Jul 18, 2026

Open the Ethinyl Estradiol, Norethindrone interaction page

One more smart check

Taking Indole-3-carbinol as Part of a Dietary Supplement Product? Check It for Interactions

We hold 287 real supplement products containing Indole-3-carbinol, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Indole-3-carbinol. Your product may carry other ingredients that interact with Ethinyl Estradiol, Norethindrone too, on top of Indole-3-carbinol — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Indole-3-carbinol and Ethinyl Estradiol, Norethindrone Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Indole-3-carbinol
Top 25%

#349 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Ethinyl Estradiol, Norethindrone
Top 10%

#240 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Indole-3-carbinol

What is Indole-3-carbinol?

  • Estrogen and hormone balance support
  • Breast and cervical health
  • Prostate health
  • Antioxidant and 'detox' support
  • General cancer-prevention interest

Indole-3-carbinol (I3C) is a compound formed when you eat cruciferous vegetables like broccoli and cabbage, and it is sold as a supplement mainly for hormone-related and cell-protective effects. Most human evidence is preliminary or comes from lab and animal studies, so it should not be relied on to prevent or treat any disease. Talk to your pharmacist or doctor before using it, and avoid it in pregnancy and breastfeeding.

Read the full Indole-3-carbinol monograph & all interactions
Keep checking

Other Drugs & Indole-3-carbinol

Browse every other medication we’ve checked against Indole-3-carbinol — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
293Moderate
0Minor
2,536No known interaction
293 Moderate 2,536 No interaction
Moderate

293 interactions

Showing 60 of 293 moderate interactions — see all 293 on the Indole-3-carbinol page.

No interaction 2,536 drugs checked — show the list

We also checked Indole-3-carbinol against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,536 medications checked with no known interaction — see the full Indole-3-carbinol list.

See the full Indole-3-carbinol interactions page
See every supplement checked against Ethinyl Estradiol, Norethindrone, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Indole-3-carbinol monograph › Uses, safety, and every drug interaction in one place Ethinyl Estradiol, Norethindrone supplement interactions › Every supplement checked against Ethinyl Estradiol, Norethindrone, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Indole-3-carbinol and Ethinyl Estradiol, Norethindrone Together: Common Questions

Can you take Indole-3-carbinol with Ethinyl Estradiol, Norethindrone?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Indole-3-carbinol and Ethinyl Estradiol, Norethindrone?
Ethinyl Estradiol, Norethindrone belongs to more than one drug category, and Indole-3-carbinol interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Indole-3-carbinol and Ethinyl Estradiol, Norethindrone interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Ethinyl Estradiol, Norethindrone and Indole-3-carbinol?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.