Drug & supplement interaction

Diindolylmethane + Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate brand name: Activella.

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

Estradiol, Norethindrone Acetate 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, Norethindrone Acetate

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, Norethindrone Acetate 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, Norethindrone Acetate

Estradiol, Norethindrone Acetate 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

Activella combines estradiol with a progestin (norethindrone), and people usually take it to ease menopause symptoms like hot flashes and night sweats. Here's the thing about DIM: it can nudge how your body handles estrogen, and in lab studies it has shown both mild estrogen-like and mild anti-estrogen effects. Because it can pull in either direction, the worry is that larger supplement doses might slightly throw off the balance your hormone therapy is meant to provide.

I want to be honest that this is theoretical, based on pharmacology rather than real patient reports. The veggie-sized amounts you get from broccoli are unlikely to matter; concentrated DIM capsules are the bigger question. If hot flashes return or change, or you notice unexpected spotting, loop in your pharmacist or doctor before adjusting 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, Norethindrone Acetate 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 DIM and your Activella (estradiol plus norethindrone). In lab dishes, DIM seems to rev up a liver enzyme called CYP1A2, which is one of the helpers that breaks down estrogen. If that sped-up clearance happened in your body, the worry would be slightly lower estrogen levels, which could mean your hormone therapy works a little less well (think return of hot flashes, night sweats, or breakthrough spotting).

The reassuring part: this is only a theory from test-tube studies and has never actually been reported in people. It's rated minor and unlikely, so I wouldn't panic. Still, since this is a hormone product and DIM affects estrogen too, it's worth a quick chat with your pharmacist or doctor before adding it.

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, Norethindrone Acetate 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, Norethindrone Acetate)
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, Norethindrone Acetate

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, Norethindrone Acetate, 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, Norethindrone Acetate

This page covers Diindolylmethane only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Estradiol, Norethindrone Acetate page lists 212 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), Acacia Rigidula (moderate) and Adrafinil (moderate).

By severity: 3 major · 171 moderate · 38 minor.

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

“Activella pairs estradiol with norethindrone as hormone therapy, and because the treatment depends on steady hormone levels in the blood, supplements that raise or lower those levels warrant real scrutiny. Three of the 212 interacting ingredients rate major, and all three hit that weak point: St.”

Reviewed by 2 · Jul 18, 2026

Open the Estradiol, Norethindrone Acetate 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, Norethindrone Acetate 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, Norethindrone Acetate 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%

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

29 days ago today
Medication Estradiol, Norethindrone Acetate
Steady interest

#2,389 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, Norethindrone Acetate, 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, Norethindrone Acetate supplement interactions › Every supplement checked against Estradiol, Norethindrone Acetate, 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, Norethindrone Acetate Together: Common Questions

Can you take Diindolylmethane with Estradiol, Norethindrone Acetate?
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, Norethindrone Acetate?
Estradiol, Norethindrone Acetate 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, Norethindrone Acetate 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 Estradiol, Norethindrone Acetate and Diindolylmethane?

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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.