Drug & supplement interaction

Horny Goat Weed + Ethinyl Estradiol, Norethindrone

Ethinyl Estradiol, Norethindrone brand names: Femhrt, Loestrin 21, Ovcon 35 21, Ovcon 50 28, Necon 0.5 35 21, and others.

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

Ethinyl Estradiol, Norethindrone 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 Ethinyl Estradiol, Norethindrone

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. Ethinyl Estradiol, Norethindrone 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 Ethinyl Estradiol, Norethindrone

Ethinyl Estradiol, Norethindrone 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 short version on combining horny goat weed with your birth control pill (the ethinyl estradiol and norethindrone combo). One enzyme that helps your body break down ethinyl estradiol is called CYP1A2. In lab dish studies, horny goat weed leaf extract slowed that enzyme down a bit. If that happened in real life, the estrogen in your pill could hang around a little longer, which might nudge up familiar side effects like nausea, breast tenderness, bloating, or headaches.

I want to be honest, though: this has only been seen in test tubes, never in actual people, so it's mostly theoretical. Your pill isn't a prodrug, so it stays effective. Still, since safety data on this herb is thin, please run it by your pharmacist or doctor before starting it.

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

Ethinyl Estradiol, Norethindrone 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

Here's the gist with your birth control pill (the ethinyl estradiol part is the estrogen). Horny goat weed seems to have some estrogen-like activity of its own, and a few studies have shown it can nudge estrogen levels up in some women. Stacked on top of the estrogen already in your pill, that could in theory add to estrogen-related effects, things like breast tenderness, bloating, nausea, headaches, or mood changes.

I want to be honest about how shaky this is, though. It's mostly theoretical, based on lab work and a little human data, not strong proof that it causes problems. Still, since estrogen also carries a small clot risk, it's worth running this by your pharmacist or doctor before combining them rather than guessing on your own.

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

Ethinyl Estradiol, Norethindrone 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

Your birth control pill combines ethinyl estradiol and norethindrone, and both hormones are broken down by a liver enzyme called CYP3A4. In test-tube studies, horny goat weed appears to slow this enzyme down. If that happened in the body, the hormones could clear more slowly and build up a bit, which in theory might mean more estrogen-type side effects like nausea, breast tenderness, bloating, headaches, or mood changes.

Here's the honest part: this finding comes only from lab studies, not from people, so we really don't know if it matters in real life. I wouldn't lose sleep over it, but since this is a medicine you rely on, it's worth a quick chat with your pharmacist or doctor before adding the supplement.

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

Moderate 964 No known interaction 1,866 (incl. Ethinyl Estradiol, Norethindrone)
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 Ethinyl Estradiol, Norethindrone

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 Ethinyl Estradiol, Norethindrone, 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 Ethinyl Estradiol, Norethindrone

This page covers Horny Goat Weed only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl Estradiol, Norethindrone page lists 240 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 196 moderate · 38 minor.

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

“If you take a birth control pill or hormone therapy containing ethinyl estradiol and norethindrone (Loestrin, Femhrt, and others), a few supplements can genuinely undermine it, so read this page with care. Six of the 240 ingredients on file are rated major, and those six come first.”

Reviewed by 2 · Jul 18, 2026

Open the Ethinyl Estradiol, Norethindrone 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 Ethinyl Estradiol, Norethindrone 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 Ethinyl Estradiol, Norethindrone 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%

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

29 days ago today
Medication Ethinyl Estradiol, Norethindrone
Top half

#1,101 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
964 Moderate 1,865 No 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.

See the full Horny Goat Weed interactions page
See every supplement checked against Ethinyl Estradiol, Norethindrone, 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
Horny Goat Weed monograph › Uses, safety, and every drug interaction in one place Ethinyl Estradiol, Norethindrone supplement interactions › Every supplement checked against Ethinyl Estradiol, Norethindrone, 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 Horny Goat Weed and Ethinyl Estradiol, Norethindrone Together: Common Questions

Can you take Horny Goat Weed with Ethinyl Estradiol, Norethindrone?
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 Ethinyl Estradiol, Norethindrone?
Ethinyl Estradiol, Norethindrone 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 Ethinyl Estradiol, Norethindrone 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 Ethinyl Estradiol, Norethindrone and Horny Goat Weed?

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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.