Drug & supplement interaction

Diindolylmethane + Estradiol, Norgestimate

Estradiol, Norgestimate brand name: Ortho-Prefest.

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

Estradiol, Norgestimate 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?
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Interaction report

Diindolylmethane and Estradiol, Norgestimate

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. Estradiol, Norgestimate 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 Estradiol, Norgestimate

Estradiol, Norgestimate 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

Ortho-Prefest combines estradiol (an estrogen) with norgestimate (a progestin), and it works by keeping your hormone levels steady. Here's the catch with DIM: it can nudge how your body handles estrogen, and it may act a little estrogen-like or a little anti-estrogen-like depending on the situation. Because of that, large supplement-sized doses of DIM could theoretically push your hormone therapy in either direction, making it slightly stronger or slightly weaker.

I want to be honest that this is theoretical, based on pharmacology rather than solid human studies. The amount you'd get from eating broccoli or cabbage is very unlikely to matter; concentrated capsules are the bigger question. If you notice changes like breakthrough bleeding, breast tenderness, or returning hot flashes, check in with your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
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

Estradiol, Norgestimate 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 with Ortho-Prefest (estradiol plus norgestimate) and DIM. In test-tube studies, DIM appears to speed up an enzyme called CYP1A2, which is one of the pathways your body uses to break down estrogen. If DIM revved that up, your hormone levels could in theory dip a bit lower, which might mean a weaker effect, things like breakthrough spotting or a return of menopausal symptoms such as hot flashes.

That said, I want to be honest about how thin this is. This is only a theoretical concern from lab data, and it has never actually been reported in people. The real risk is likely very small. Still, since hormone therapy matters, it's worth a quick chat with your pharmacist or doctor before adding DIM.

Contact Dr. Brian directly if you have additional questions on this interaction
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 Estradiol, Norgestimate one above is among them. If you take anything else, check it against the full list below.

Moderate 115 Minor 153 No known interaction 2,562 (incl. Estradiol, Norgestimate)
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 Estradiol, Norgestimate

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 Estradiol, Norgestimate, 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 Estradiol, Norgestimate

This page covers Diindolylmethane only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Estradiol, Norgestimate page lists 159 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Adrafinil (moderate) and African Wild Potato (moderate).

By severity: 3 major · 126 moderate · 30 minor.

From our pharmacist’s overview on the Estradiol, Norgestimate page

“Ortho-Prefest pairs estradiol with norgestimate, a hormone therapy most often prescribed for menopause symptoms, and its interaction list warrants genuine care rather than a quick skim. Of the 159 supplements and herbs on file, three carry a major rating, and all involve common products.”

Reviewed by 2 · Jul 18, 2026

Open the Estradiol, Norgestimate 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 Estradiol, Norgestimate 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 Estradiol, Norgestimate 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%

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

29 days ago today
Medication Estradiol, Norgestimate
Top half

#755 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
115 Moderate 153 Minor 2,561 No 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

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

Showing the 60 most looked-up of 2,561 medications checked with no known interaction — see the full Diindolylmethane list.

See the full Diindolylmethane interactions page
See every supplement checked against Estradiol, Norgestimate, 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
Diindolylmethane monograph › Uses, safety, and every drug interaction in one place Estradiol, Norgestimate supplement interactions › Every supplement checked against Estradiol, Norgestimate, 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 Diindolylmethane and Estradiol, Norgestimate Together: Common Questions

Can you take Diindolylmethane with Estradiol, Norgestimate?
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 Estradiol, Norgestimate?
Estradiol, Norgestimate 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 Estradiol, Norgestimate 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.