Drug & supplement interaction

Diindolylmethane + 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
The bottom line Moderate

Ethinyl Estradiol, Norethindrone falls into 2 drug categories that Diindolylmethane can interact with; the most serious is rated moderate. Theoretically, diindolylmethane might increase or decrease the effects of estrogens.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Interaction report

Diindolylmethane and Ethinyl Estradiol, Norethindrone

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

Why Are There 2 Interactions?

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

Moderate

ESTROGENS

1 of 2

Why this applies to Ethinyl Estradiol, Norethindrone

Ethinyl Estradiol, Norethindrone falls under ESTROGENS — the group Diindolylmethane interacts with.

Theoretically, diindolylmethane might increase or decrease the effects of estrogens.
Diindolylmethane might have mild estrogenic or antiestrogenic effects. Theoretically, large amounts of diindolylmethane might interfere with hormone replacement therapy.
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

Your Loestrin (or similar pill) combines two hormones, ethinyl estradiol and norethindrone, to either prevent pregnancy or manage menopause symptoms. DIM is interesting here because it changes how your body processes estrogen, and it may act a little like estrogen in some situations or block it in others. Because of that, taking concentrated DIM supplements alongside your hormone pill could, in theory, nudge its effect slightly up or down.

I want to be honest: this concern is theoretical, based on how DIM works in the lab, not on real cases in people. The everyday DIM you get from eating broccoli or cabbage is very unlikely to matter. Still, before starting a DIM supplement, check with your pharmacist or doctor so we keep your hormones steady.

References
  1. Riby JE, Chang GHF, Firestone GL, Bjeldanes LF. Ligand-independent activation of estrogen receptor function by 3,3'-diindolylmethane in human breast cancer cells. Biochem Pharmacol 2000;60:167-77. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 2

Ethinyl Estradiol, Norethindrone also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, diindolylmethane might lower serum levels of CYP1A2 substrates.
In vitro evidence suggests that diindolylmethane can induce CYP1A2. Theoretically, it might increase metabolism of CYP1A2 substrates and lower serum concentrations. This interaction has not been reported in humans.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

Here's the gist: your birth control combines ethinyl estradiol and norethindrone, and your liver partly clears the estrogen part using an enzyme called CYP1A2. In lab dishes, DIM seems to speed that enzyme up. In theory, a faster enzyme could break down the hormones a little quicker and nudge their blood levels down, which could mean slightly weaker effect, like spotting or breakthrough bleeding, or in the worst case less reliable protection.

I want to be honest about how shaky this is. This is only test-tube data, it has never actually been seen in people, and it's rated minor and unlikely. So I wouldn't lose sleep over it, but since this pill works best when it's steady, run it by your pharmacist or doctor before adding DIM.

References
  1. Lake BG, Tredger JM, Renwick AB, et al. 3'3-diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. Xenobiotica 1998;28:803-11. PubMed
  2. Jellinck, P. H., Forkert, P. G., Riddick, D. S., Okey, A. B., Michnovicz, J. J., and Bradlow, H. L. Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation. Biochem.Pharmacol. 3-9-1993;45(5):1129-1136. 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

Diindolylmethane Also Interacts With Other Medications

Diindolylmethane has 115 moderate, 153 minor 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.

Taking anything else?

Check Another of Your Medications Against Diindolylmethane

Covers the 2,830 medications we’ve checked against Diindolylmethane. Pick one to open its full report.

From our Q&A

Questions About Diindolylmethane or Ethinyl Estradiol, Norethindrone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Diindolylmethane or Ethinyl Estradiol, Norethindrone, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Ethinyl Estradiol, Norethindrone

This page covers Diindolylmethane 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 Diindolylmethane as Part of a Dietary Supplement Product? Check It for Interactions

We hold 933 real supplement products containing Diindolylmethane, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Diindolylmethane. Your product may carry other ingredients that interact with Ethinyl Estradiol, Norethindrone too, on top of Diindolylmethane — 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 Diindolylmethane 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 Diindolylmethane
Top 25%

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

29 days ago today
Medication Ethinyl Estradiol, Norethindrone
Top 25%

#450 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 Diindolylmethane

What is Diindolylmethane?

Diindolylmethane
  • Estrogen/hormone balance
  • Acne and hormonal skin issues
  • Prostate health support
  • Cancer-risk reduction (unproven)
  • PMS and menopause symptoms
  • General 'detox' support

Diindolylmethane (DIM) is a compound made when your body digests cruciferous vegetables, and it is sold as a supplement mainly for hormone balance and cancer prevention. Although early lab studies look interesting, strong human evidence is lacking for most of these uses. Talk with your pharmacist or doctor before taking DIM, especially if you have a hormone-sensitive condition.

Read the full Diindolylmethane monograph & all interactions
Keep checking

Other Drugs & Diindolylmethane

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

0Major
115Moderate
153Minor
2,561No known interaction
Moderate

115 interactions

Showing 60 of 115 moderate interactions — see all 115 on the Diindolylmethane page.

Minor

153 interactions

Showing 60 of 153 minor interactions — see all 153 on the Diindolylmethane page.

No interaction 2,561 drugs checked — show the list
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
Pharmacist Counseling Corner

Taking Diindolylmethane and Ethinyl Estradiol, Norethindrone Together: Common Questions

Can you take Diindolylmethane 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 Diindolylmethane and Ethinyl Estradiol, Norethindrone?
Ethinyl Estradiol, Norethindrone belongs to more than one drug category, and Diindolylmethane 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 Diindolylmethane 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 Diindolylmethane?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.