Drug & supplement interaction

Horny Goat Weed + Estradiol, Medroxyprogesterone

Estradiol, Medroxyprogesterone brand name: Divitren.

Moderate Interaction
The bottom line Moderate

Estradiol, Medroxyprogesterone falls into 3 drug categories that Horny Goat Weed can interact with; the most serious is rated moderate. Theoretically, horny goat weed might increase the effects and side effects of CYP1A2 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Horny Goat Weed and Estradiol, Medroxyprogesterone

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Horny Goat Weed interacts with whole categories of medication. Estradiol, Medroxyprogesterone falls into 3 of those categories, so it can interact with Horny Goat Weed in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Estradiol, Medroxyprogesterone

Estradiol, Medroxyprogesterone falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Horny Goat Weed interacts with.

Theoretically, horny goat weed might increase the effects and side effects of CYP1A2 substrates.
In vitro, horny goat weed leaf extract inhibits CYP1A2. This effect has not been reported in humans.
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 gist for your Divitren (estradiol plus medroxyprogesterone). Part of how your body clears estrogen runs through a liver enzyme called CYP1A2. In test-tube studies, horny goat weed appears to slow that enzyme down. If that happened in real life, your estrogen could clear a bit more slowly and build up, which might mean stronger hormone effects, things like breast tenderness, bloating, nausea, headaches, or breakthrough bleeding.

The important part: this has only been seen in lab dishes, not in actual people, so it's theoretical and likely modest at most. I wouldn't lose sleep over it, but since hormone therapy carries its own clotting risks, it's worth a quick chat with your pharmacist or doctor before adding this supplement.

References
  1. Zhong Q, Shi Z, Zhang L, et al. The potential of Epimedium koreanum Nakai for herb-drug interaction. J Pharm Pharmacol 2017;69(10):1398-408. doi: 10.1111/jphp.12773.
Moderate

ESTROGENS

2 of 3

Estradiol, Medroxyprogesterone also falls under ESTROGENS.

Theoretically, concomitant use of horny goat weed with estrogens might increase their therapeutic and adverse effects.
In vitro evidence suggests that horny goat weed has estrogenic activity. In clinical research, horny goat weed has been shown to increase blood levels of estrogen in some females.
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 Divitren contains estradiol (an estrogen) paired with medroxyprogesterone. Here's the concern with horny goat weed: in lab studies and some early human research, this herb seems to act a bit like estrogen itself and may even nudge your own estrogen levels upward. Stacking that on top of the estradiol you're already taking could, in theory, add to the estrogen effect.

What might that look like in real life? Things like breast tenderness, bloating, nausea, headaches, or spotting could become more noticeable. I want to be honest though, this is a theoretical interaction based on how the herb behaves in the lab, not something proven in people on your exact regimen. Since estrogen therapy carries its own risks, I'd skip the horny goat weed until you check with your pharmacist or doctor first.

References
  1. De Naeyer A, Pocock V, Milligan S, De Keukeleire D. Estrogenic activity of a polyphenolic extract of the leaves of Epimedium brevicornum. Fitoterapia 2005;76:35-40. PubMed
  2. Zhang CZ, Wang SX, Zhang Y, et al. In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms. J Ethnopharmacol 2005;98:295-300. PubMed
  3. Yap SP, Shen P, Li J, et al. Molecular and pharmacodynamic properties of estrogenic extracts from the traditional Chinese medicinal herb, Epimedium. J Ethnopharmacol 2007;113:218-24. PubMed
  4. Yan, F. F., Liu, Y., Liu, Y. F., and Zhao, Y. X. Herba Epimedii water extract elevates estrogen level and improves lipid metabolism in postmenopausal women. Phytother.Res. 2008;22(9):1224-1228. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Estradiol, Medroxyprogesterone also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, horny goat weed might increase the effects and side effects of CYP3A4 substrates.
In vitro, horny goat weed extract inhibits CYP3A4 and suppresses CYP3A4 mRNA expression. This effect has not been reported in humans.
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 basic idea with your hormone combo (estradiol plus medroxyprogesterone). Both hormones are cleared by a liver enzyme called CYP3A4. In test-tube studies, horny goat weed seems to slow that enzyme down. If that also happened in people, your body might clear these hormones a little more slowly, letting their levels creep up. That could mean more of the usual estrogen-progestin side effects, things like breast tenderness, nausea, bloating, headaches, mood changes, or spotting.

I want to be honest with you though: this is only laboratory data, and it has not been shown in actual humans. So it's a theoretical concern, not a proven problem. Still, since hormone therapy carries its own risks, it's worth a quick chat with your pharmacist or doctor before adding this herb.

References
  1. Li K, Yu XH, Maskey AR, et al. Cytochrome P450 3A4 suppression by epimedium and active compound kaempferol leads to synergistic anti-inflammatory effect with corticosteroid. Front Pharmacol 2023;13:1042756. 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

Horny Goat Weed Also Interacts With Other Medications

Horny Goat Weed has 964 moderate known drug interactions in our database — the Estradiol, Medroxyprogesterone 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 Horny Goat Weed

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

From our Q&A

Questions About Horny Goat Weed or Estradiol, Medroxyprogesterone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Horny Goat Weed or Estradiol, Medroxyprogesterone, 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, Medroxyprogesterone

This page covers Horny Goat Weed only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Estradiol, Medroxyprogesterone page lists 206 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 · 165 moderate · 38 minor.

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

“A woman taking Divitren (estradiol plus medroxyprogesterone) for menopause symptoms deserves a clear warning here, because all three major-rated entries on this list of 206 supplements are things people take casually. Grapefruit can push hormone levels higher than intended, St.”

Reviewed by 2 · Jul 18, 2026

Open the Estradiol, Medroxyprogesterone interaction page

One more smart check

Taking Horny Goat Weed as Part of a Dietary Supplement Product? Check It for Interactions

We hold 183 real supplement products containing Horny Goat Weed, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Horny Goat Weed. Your product may carry other ingredients that interact with Estradiol, Medroxyprogesterone too, on top of Horny Goat Weed — 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 Horny Goat Weed and Estradiol, Medroxyprogesterone 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 Horny Goat Weed
Top 25%

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

29 days ago today
Medication Estradiol, Medroxyprogesterone
Steady interest

#1,855 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 Horny Goat Weed

What is Horny Goat Weed?

Horny Goat Weed
  • Erectile dysfunction
  • Low libido
  • Fatigue and low energy
  • Bone health
  • Joint and menopausal symptoms
  • General 'vitality' or performance

Horny goat weed (Epimedium) is a traditional Chinese herb most often marketed for low libido and erectile problems, but solid human evidence for these uses is lacking. While short-term use seems generally tolerated by some people, quality and safety are not well studied, so talk to your pharmacist or doctor before trying it—especially if you have heart problems or take other medicines.

Read the full Horny Goat Weed monograph & all interactions
Keep checking

Other Drugs & Horny Goat Weed

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

0Major
964Moderate
0Minor
1,865No known interaction
Moderate

964 interactions

Showing 60 of 964 moderate interactions — see all 964 on the Horny Goat Weed page.

No interaction 1,865 drugs checked — show the list

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

Showing the 60 most looked-up of 1,865 medications checked with no known interaction — see the full Horny Goat Weed 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

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Pharmacist Counseling Corner

Taking Horny Goat Weed and Estradiol, Medroxyprogesterone Together: Common Questions

Can you take Horny Goat Weed with Estradiol, Medroxyprogesterone?
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 3 interactions listed for Horny Goat Weed and Estradiol, Medroxyprogesterone?
Estradiol, Medroxyprogesterone belongs to more than one drug category, and Horny Goat Weed 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 Horny Goat Weed and Estradiol, Medroxyprogesterone 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.