Drug & supplement interaction

Dhea + Letrozole

Letrozole brand name: Femara.

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

Letrozole falls into 2 drug categories that Dhea can interact with; the most serious is rated moderate. Theoretically, DHEA might increase the levels of drugs metabolized by CYP3A4.

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

Dhea and Letrozole

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

Why Are There 2 Interactions?

Dhea interacts with whole categories of medication. Letrozole falls into 2 of those categories, so it can interact with Dhea 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 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Letrozole

Letrozole falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Dhea interacts with.

Theoretically, DHEA might increase the levels of drugs metabolized by CYP3A4.
Some preliminary evidence shows that DHEA may inhibit CYP3A4; however, the clinical significance of this potential interaction is not known.
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 thing to keep in mind with letrozole (Femara) and DHEA. Letrozole is processed by a liver enzyme called CYP3A4, and there's some early, fairly weak evidence that DHEA might slow that enzyme down. If it does, letrozole could clear out of your body a little more slowly and build up. In theory that might mean more of the usual letrozole side effects, like hot flashes, joint and muscle aches, tiredness, or headache.

But honestly, this is mostly theoretical and based on thin evidence, so I wouldn't lose sleep over it. The bigger concern is that DHEA raises estrogen, and letrozole works by lowering estrogen to treat breast cancer, so the two may work against each other. Please check with your oncologist or pharmacist before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Frye RF, Kroboth PD, Folan MM, et al. Effect of DHEA on CYP3A-mediated metabolism of triazolam. Clin Pharmacol Ther 2000;67:109 (abstract PI-82).
Moderate

AROMATASE INHIBITORS

2 of 2

Letrozole also falls under AROMATASE INHIBITORS.

Theoretically, DHEA might interfere with the clinical effects of aromatase inhibitors.
DHEA is a potent estrogen agonist, which may antagonize the anti-estrogen activity of aromatase inhibitors.
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 concern with pairing DHEA and letrozole. Letrozole works by lowering the amount of estrogen your body makes, which helps starve hormone-sensitive breast cancer. The catch is that your body can turn DHEA into estrogen (and testosterone). So adding DHEA could quietly push estrogen levels back up, which is the opposite of what letrozole is trying to do. In theory, that could blunt the benefit you're counting on.

I'll be honest: this warning comes from lab and animal data, not strong human studies, so we don't know exactly how big the effect is. But because letrozole is fighting an estrogen-driven cancer, this isn't one I'd gamble on. Please don't start DHEA without first checking with your oncologist or pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Morris KT, Toth-Fejel S, Schmidt J, et al. High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: a renewed role for adrenalectomy. Surgery 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

Dhea Also Interacts With Other Medications

Dhea has 767 moderate, 8 minor known drug interactions in our database — the Letrozole one above is among them. If you take anything else, check it against the full list below.

Moderate 767 Minor 8 No known interaction 2,055 (incl. Letrozole)
Taking anything else?

Check Another of Your Medications Against Dhea

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

From our Q&A

Questions About Dhea or Letrozole

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Dhea or Letrozole, 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 Letrozole

This page covers Dhea only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Letrozole page lists 142 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), 7-methoxyflavone (moderate) and Acacia Rigidula (moderate).

By severity: 3 major · 99 moderate · 40 minor.

From our pharmacist’s overview on the Letrozole page

“Letrozole (Femara) is prescribed to keep hormone-driven breast cancer from returning, so a supplement that shifts its blood level can quietly undercut treatment. Give this list of 142 ingredients genuine respect, and learn the three major entries first.”

Reviewed by 2 · Jul 18, 2026

Open the Letrozole interaction page

One more smart check

Taking Dhea as Part of a Dietary Supplement Product? Check It for Interactions

We hold 945 real supplement products containing Dhea, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Dhea. Your product may carry other ingredients that interact with Letrozole too, on top of Dhea — 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 Dhea and Letrozole 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 Dhea
Top 25%

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

29 days ago today
Medication Letrozole
Top 5%

#50 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 Dhea

What is Dhea?

Dhea
  • Anti-aging and low DHEA levels
  • Mood and depression
  • Vaginal dryness and sexual health
  • Fertility support
  • Muscle mass and athletic performance
  • Adrenal insufficiency

DHEA is a natural hormone that the body makes and that declines with age, and it is sold as a supplement claiming many benefits. The evidence is mixed and limited for most uses, and because it acts as a hormone it can cause real side effects. Talk to a pharmacist or doctor before using it, especially if you have a hormone-sensitive condition.

Read the full Dhea monograph & all interactions
Medication

About Letrozole

What Is Letrozole Used For?

Brand name: Femara

Letrozole (brand name Femara, or available as generic letrozole tablets) is used to treat breast cancer in postmenopausal women whose tumors are hormone receptor positive — meaning the cancer feeds on estrogen. It is used in several situations: as an adjuvant treatment (therapy given after primary treatment to reduce the risk of the cancer returning) for early breast cancer, and as extended adjuvant treatment for women who have already completed five years of tamoxifen therapy.

Femara and letrozole tablets are also used as first-line or second-line treatment for locally advanced or metastatic (spread to other areas) breast cancer in postmenopausal women, including cases where the cancer has progressed after other anti-estrogen therapy.

See full Letrozole drug information
Keep checking

Other Drugs & Dhea

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

0Major
767Moderate
8Minor
2,054No known interaction
767 Moderate 8 Minor 2,054 No interaction
Moderate

767 interactions

Showing 60 of 767 moderate interactions — see all 767 on the Dhea page.

Minor

8 interactions

No interaction 2,054 drugs checked — show the list

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

Showing the 60 most looked-up of 2,054 medications checked with no known interaction — see the full Dhea list.

See the full Dhea interactions page
See every supplement checked against Letrozole, 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
Dhea monograph › Uses, safety, and every drug interaction in one place Letrozole supplement interactions › Every supplement checked against Letrozole, ranked by severity Letrozole drug information › The full plain-English guide to this medication 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 Dhea and Letrozole Together: Common Questions

Can you take Dhea with Letrozole?
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 Dhea and Letrozole?
Letrozole belongs to more than one drug category, and Dhea 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 Dhea and Letrozole 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 Letrozole and Dhea?

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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.