Drug & supplement interaction

Indole-3-carbinol + Drospirenone, Estetrol

Drospirenone, Estetrol brand name: Nextstellis.

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

Drospirenone, Estetrol 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 Drospirenone, Estetrol

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. Drospirenone, Estetrol 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 Drospirenone, Estetrol

Drospirenone, Estetrol 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

Nextstellis is a birth control pill that combines drospirenone with estetrol, a newer estrogen. Here's the concern with indole-3-carbinol: in animal and lab work, it appears to speed up a liver enzyme (CYP1A2) that helps process certain hormones. If that holds true in people, your body could clear the hormones a bit faster, which in theory might lower the levels in your blood.

What would that mean practically? A weaker contraceptive effect (less reliable pregnancy protection) and possibly more breakthrough bleeding or spotting. I want to be honest though, this is theoretical and based on animal studies, not proven in humans. Broccoli on your dinner plate is not the worry here, concentrated supplements are. Before adding I3C, please check with your pharmacist or doctor.

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

Drospirenone, Estetrol 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

Nextstellis pairs the estrogen estetrol with drospirenone, and it is most often used as a birth control pill. Here is the concern: indole-3-carbinol (I3C) has antiestrogen activity and can nudge your liver to break down estrogen faster. In theory, that could weaken the estrogen part of your pill. Estetrol is the active estrogen here (not a prodrug), so less of it working could mean more spotting or breakthrough bleeding, and we never want to risk reduced contraceptive reliability.

Keep in mind this warning rests mostly on lab and animal data, so it is far from certain in real people. A normal plate of broccoli is unlikely to matter, but concentrated I3C supplements are a different story. Please check with your pharmacist or doctor before combining them.

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 Drospirenone, Estetrol 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. Drospirenone, Estetrol)
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 Drospirenone, Estetrol

This page covers Indole-3-carbinol only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Drospirenone, Estetrol page lists 245 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 · 200 moderate · 39 minor.

From our pharmacist’s overview on the Drospirenone, Estetrol page

“The stakes with Nextstellis (drospirenone and estetrol) are the ones that come with any birth control pill, because an interaction that lowers its hormone levels can mean an unplanned pregnancy, and I would treat this list with genuine seriousness. Most of what is here changes how the body handles the hormones.”

Reviewed by 2 · Jul 18, 2026

Open the Drospirenone, Estetrol 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 Drospirenone, Estetrol 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 Drospirenone, Estetrol 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%

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

29 days ago today
Medication Drospirenone, Estetrol
Top half

#895 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 Drospirenone, Estetrol, 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 Drospirenone, Estetrol supplement interactions › Every supplement checked against Drospirenone, Estetrol, 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 Drospirenone, Estetrol Together: Common Questions

Can you take Indole-3-carbinol with Drospirenone, Estetrol?
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 Drospirenone, Estetrol?
Drospirenone, Estetrol 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 Drospirenone, Estetrol 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

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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.