Drug & supplement interaction

Dhea + Estradiol

Estradiol brand names: Estrace, Gynodiol, Vagifem, Estring, Vivelle, and others.

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

Estradiol 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 Estradiol

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. Estradiol 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 Estradiol

Estradiol 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 estradiol and DHEA. Your liver uses an enzyme called CYP3A4 to help break estradiol down and clear it out. Some early lab evidence hints that DHEA may slow that enzyme a bit. If that happened, estradiol could build up slightly and you might notice more estrogen-type effects, like breast tenderness, bloating, nausea, headaches, or spotting.

I want to be honest though: this is mostly theoretical and based on weak, anecdotal evidence, so we really don't know how much it matters in real life. There's an added wrinkle too: DHEA is itself a hormone the body can turn into estrogen, so it may nudge hormone levels even without touching the enzyme. Since estradiol is hormone therapy, it's worth running this combo past your pharmacist or doctor before starting DHEA.

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).
Minor

ESTROGENS

2 of 2

Estradiol also falls under ESTROGENS.

Theoretically, DHEA might increase the effects and adverse effects of estrogen therapy.
DHEA is a precursor to estrogen and androgen and is metabolized into those substances. In clinical research, DHEA supplements increase the levels of these hormones. Also, in clinical research, estrogen-progestin oral contraceptives and conjugated estrogens reduce blood levels of DHEA and DHEA-S. The clinical significance of these findings is unclear.
Severity Minor 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 simple version: DHEA is a hormone building block your body can turn into estrogen. So if you're already using estradiol (whether it's a vaginal cream, ring, insert, or a patch), adding DHEA could nudge your estrogen activity a little higher. In theory, that might mean slightly stronger estrogen effects, like breast tenderness, bloating, spotting, or headaches.

Now the honest part: this concern comes mostly from lab and early research, not strong human studies, so it's rated as a minor, possible interaction. For low-dose vaginal estradiol especially, very little reaches the rest of your body, so the real-world overlap is probably small. Still, if you have a hormone-sensitive condition, it's worth a quick chat with your pharmacist or doctor before combining them. Please don't start or stop anything on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Callies F, Arlt W, Siekmann L, et al. Influence of oral dehydroepiandrosterone (DHEA) on urinary steroid metabolites in males and females. Steroids 2000;65:98-102. PubMed
  2. Hunt PJ, Gurnell EM, Huppert FA, et al. Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trial. J Clin Endocrinol Metab 2000;85:4650-6.. PubMed
  3. Johannsson G, Burman P, Wiren L, et al. Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab 2002;87:2046-52. PubMed
  4. Stomati M, Monteleone P, Casarosa E, et al. Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause. Gynecol Endocrinol 2000;14:342-63.. PubMed
  5. Villareal DT, Holloszy JO, Kohrt WM. Effects of DHEA replacement on bone mineral density and body composition in elderly women and men. Clin Endocrinol (Oxf) 2000;53:561-8. PubMed
  6. Pino JA, Marbot R. Volatile flavor constituents of acerola (Malpighia emarginata DC.) fruit. J Agric Food Chem 2001;49:5880-2.
  7. Nair KS, Rizza RA, O'Brien P, et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 2006;355:1647-59. PubMed
  8. Aisaka, K., Mori, H., Ogawa, T., Kigawa, T. Effects of dehydroepiandrosterone-sulphate (DHEA-S) administration on puerperal lactation and maternal prolactin and estradiol levels. Nippon Sanka Fujinka Gakkai Zasshi 1984;36(10):1935-42.
  9. Lauritzen, C. [Therapeutic attempts with dehydroepiandrosterone sulfate in threatened pregnancies]. Arch Gynakol 1971;211(1):247-9.
  10. Mortola, J. F. Yen, S. S. The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women. J Clin Endocrinol Metab 1990;71(3):696-704. PubMed
  11. Rabijewski, M., Zgliczynski, W. [Positive effects of DHEA therapy on insulin resistance and lipids in men with angiographically verified coronary heart disease--preliminary study]. Endokrynol Pol 2005;56(6):904-10.
  12. Weiss, E. P., Shah, K., Fontana, L., Lambert, C. P., Holloszy, J. O., Villareal, D. T. Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone. Am J Clin Nutr 2009;89(5):1459-67. PubMed
  13. Jankowski, C. M., Gozansky, W. S., Kittelson, J. M., Van Pelt, R. E., Schwartz, R. S., Kohrt, W. M. Increases in bone mineral density in response to oral dehydroepiandrosterone replacement in older adults appear to be mediated by serum estrogens. J Clin E PubMed
  14. Poretsky, L., Song, L., Brillon, D. J., Ferrando, S., Chiu, J., McElhiney, M., Ferenczi, A., Sison, C., Haller, I., Rabkin, J. Metabolic and hormonal effects of oral DHEA in premenopausal women with HIV infection: a randomized, prospective, placebo-contro
  15. Libe, R., Barbetta, L., Dall'Asta, C., Salvaggio, F., Gala, C., Beck-Peccoz, P., Ambrosi, B. Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalism. J Endocrinol Invest 2004;27 PubMed
  16. Genazzani, A. R., Inglese, S., Lombardi, I., Pieri, M., Bernardi, F., Genazzani, A. D., Rovati, L., Luisi, M. Long-term low-dose dehydroepiandrosterone replacement therapy in aging males with partial androgen deficiency. Aging Male 2004;7(2):133-43. PubMed
  17. Gebre-Medhin, G., Husebye, E. S., Mallmin, H., Helstrom, L., Berne, C., Karlsson, F. A., Kampe, O. Oral dehydroepiandrosterone (DHEA) replacement therapy in women with Addison's disease. Clin Endocrinol (Oxf) 2000;52(6):775-80. PubMed
  18. Yeung, T. W., Li, R. H., Lee, V. C., Ho, P. C., Ng, E. H. A randomized double-blinded placebo-controlled trial on the effect of dehydroepiandrosterone for 16 weeks on ovarian response markers in women with primary ovarian insufficiency. J Clin Endocrinol PubMed
  19. Klove, K. L., Roy, S., Lobo, R. A. The effect of different contraceptive treatments on the serum concentration of dehydroepiandrosterone sulfate. Contraception 1984;29(4):319-24. PubMed
  20. Cibula, D., Fanta, M., Vrbikova, J., Stanicka, S., Dvorakova, K., Hill, M., Skrha, J., Zivny, J., Skrenkova, J. The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogena
  21. White, T., Jain, J. K., Stanczyk, F. Z. Effect of oral versus transdermal steroidal contraceptives on androgenic markers. Am J Obstet Gynecol 2005;192(6):2055-9. PubMed
  22. Christiansen, J. J., Bruun, J. M., Christiansen, J. S., Jorgensen, J. O., Gravholt, C. H. Long-term DHEA substitution in female adrenocortical failure, body composition, muscle function, and bone metabolism: a randomized trial. Eur J Endocrinol 2011;165(2 PubMed
  23. Bloch, M., Ish-Shalom, S., Greenman, Y., Klein, E., Latzer, Y. Dehydroepiandrosterone treatment effects on weight, bone density, bone metabolism and mood in women suffering from anorexia nervosa-a pilot study. Psychiatry Res 2012;200(2-3):544-9. PubMed
  24. Merritt, P., Stangl, B., Hirshman, E., Verbalis, J. Administration of dehydroepiandrosterone (DHEA) increases serum levels of androgens and estrogens but does not enhance short-term memory in post-menopausal women. Brain Res 11-5-2012;1483:54-62. PubMed
  25. Stangl, B., Hirshman, E., and Verbalis, J. Administration of dehydroepiandrosterone (DHEA) enhances visual-spatial performance in postmenopausal women. Behav Neurosci 2011;125(5):742-52. PubMed
  26. Genazzani, A. R., Stomati, M., Valentino, V., Pluchino, N., Pot, E., Casarosa, E., Merlini, S., Giannini, A., Luisi, M. Effect of 1-year, low-dose DHEA therapy on climacteric symptoms and female sexuality. Climacteric 2011;14(6):661-8. PubMed
  27. Dayal, M., Sammel, M. D., Zhao, J., Hummel, A. C., Vandenbourne, K., Barnhart, K. T. Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids. J Womens Health (Larchmt) 2005;14(5):391-400. PubMed
  28. Vogiatzi, M. G., Boeck, M. A., Vlachopapadopoulou, E., el-Rashid, R., New, M. I. Dehydroepiandrosterone in morbidly obese adolescents: effects on weight, body composition, lipids, and insulin resistance. Metabolism 1996;45(8):1011-5. PubMed
  29. Bernardi, F., Pieri, M., Stomati, M., Luisi, S., Palumbo, M., Pluchino, N., Ceccarelli, C., Genazzani, A. R. Effect of different hormonal replacement therapies on circulating allopregnanolone and dehydroepiandrosterone levels in postmenopausal women. Gyne DOI
  30. Schlegel, W., Petersdorf, L. I., Junker, R., Schulte, H., Ebert, C., Von Eckardstein, A. The effects of six months of treatment with a low-dose of conjugated oestrogens in menopausal women. Clin Endocrinol (Oxf) 1999;51(5):643-51. PubMed
  31. Buster, J. E., Casson, P. R., Straughn, A. B., Dale, D., Umstot, E. S., Chiamori, N., and Abraham, G. E. Postmenopausal steroid replacement with micronized dehydroepiandrosterone: preliminary oral bioavailability and dose proportionality studies. Am J Ob
  32. Stanczyk, F. Z., Slater, C. C., Ramos, D. E., Azen, C., Cherala, G., Hakala, C., Abraham, G., and Roy, S. Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term oral dehydroepiandrosterone treatment in postmenopausal women. Menopa PubMed
  33. Liao YH, Liao KF, Kao CL, et al. Effect of dehydroepiandrosterone administration on recovery from mix-type exercise training-induced muscle damage. Eur J Appl Physiol 2013;113(1):99-107. PubMed
  34. Yeung TW, Chai J, Li RH, et al. A randomized, controlled, pilot trial on the effect of dehydroepiandrosterone on ovarian response markers, ovarian response, and in vitro fertilization outcomes in poor responders. Fertil Steril 2014;102(1):108-115.e1. 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 Estradiol 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. Estradiol)
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.

Everything else you take

See Every Supplement That Interacts With Estradiol

This page covers Dhea only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Estradiol page lists 213 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 · 172 moderate · 38 minor.

From our pharmacist’s overview on the Estradiol page

“Estradiol (Estrace, Vivelle, Vagifem, and other brands) is estrogen therapy, and its interaction list deserves careful reading, especially the three entries rated major. Grapefruit can push estradiol levels higher, St.”

Reviewed by 2 · Jul 18, 2026

Open the Estradiol 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 Estradiol 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 Estradiol 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%

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

29 days ago today
Medication Estradiol
Top 25%

#398 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
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 Estradiol, 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 Estradiol supplement interactions › Every supplement checked against Estradiol, 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 Dhea and Estradiol Together: Common Questions

Can you take Dhea with Estradiol?
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 Estradiol?
Estradiol 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 Estradiol 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 and Dhea?

Our pharmacists answer your medication & supplement questions — free.

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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.