Drug & supplement interaction

Black Cohosh + Ethinyl estradiol, Levonogestrel

Ethinyl estradiol, Levonogestrel brand name: Lybrel.

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

Ethinyl estradiol, Levonogestrel falls into 2 drug categories that Black Cohosh can interact with; the most serious is rated moderate. Theoretically, taking black cohosh with hepatotoxic drugs may increase the risk of liver damage.

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

Black Cohosh and Ethinyl estradiol, Levonogestrel

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

Why Are There 2 Interactions?

Black Cohosh interacts with whole categories of medication. Ethinyl estradiol, Levonogestrel falls into 2 of those categories, so it can interact with Black Cohosh in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

HEPATOTOXIC DRUGS

1 of 2

Why this applies to Ethinyl estradiol, Levonogestrel

Ethinyl estradiol, Levonogestrel falls under HEPATOTOXIC DRUGS — the group Black Cohosh interacts with.

Theoretically, taking black cohosh with hepatotoxic drugs may increase the risk of liver damage.
There is concern that black cohosh might be linked to cases of liver failure and autoimmune hepatitis.
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 simple version: your birth control pill, Lybrel (ethinyl estradiol with levonorgestrel), is processed by your liver, and so is black cohosh. The worry on file is that both can occasionally stress the liver, so taking them together might, in theory, add up to a higher chance of liver trouble. This is not about your pill working better or worse, it's purely a liver-safety question.

I want to be honest about the evidence here. It's weak, based mostly on rare case reports, not strong studies, so for most healthy people this is a low-level concern. Still, watch for signs like yellowing of the skin or eyes, dark urine, belly pain, or unusual tiredness, and check with your pharmacist or doctor before combining them, especially if you have any liver issues.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Whiting PW, Clouston A, Kerlin P. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2002;177:440-3. PubMed
  2. Lontos S, Jones RM, Angus PW, Gow PJ. Acute liver failure associated with the use of herbal preparations containing black cohosh. Med J Aust 2003;179:390-1.. DOI
  3. Cohen SM, O'Connor AM, Hart J, et al. Autoimmune hepatitis associated with the use of black cohosh: a case study. Menopause 2004;11:575-7. PubMed
  4. Vitetta L, Thomsen M, Sali A. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2003;178:411-2.. PubMed
  5. Cohen B, Schardt D. Center for Science in the Public Interest. Letter to Food and Drug Administration. Commissioner Mark McClellan, MD, PhD. March 4, 2004.
  6. Levitsky J, Alli TA, Wisecarver J, Sorrell MF. Fulminant liver failure associated with the use of black cohosh. Dig Dis Sci 2005;50:538-9. PubMed
  7. MHRA. Black cohosh (Cimicifuga racemosa) - risk of liver problems. Herbal Safety News July 2006. Available at: http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary= true&ssDocName=CON2024131&ssTargetNodeId=663.
  8. Lynch CR, Folkers ME, Hutson WR. Fulminant hepatic failure associated with the use of black cohosh: a case report. Liver Transpl 2006;12:989-92. PubMed
  9. Brar HS, Marathi R. Case of cholestatic drug-induced liver injury (DILI) associated with black cohosh. BMJ Case Rep 2021;14(5):e240408. PubMed
Moderate

ESTROGENS

2 of 2

Ethinyl estradiol, Levonogestrel also falls under ESTROGENS.

Theoretically, black cohosh may alter the effects of estrogen therapy.
Some research suggests that black cohosh has estrogenic effects. This may enhance or inhibit the effects of estrogen 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

Lybrel combines two hormones, ethinyl estradiol (an estrogen) and levonorgestrel, to prevent pregnancy. The concern here is mostly theoretical. Older lab ideas suggested black cohosh might act a little like estrogen, so on paper it could either add to or work against your estrogen. Honestly, most newer research does not support strong estrogen-like activity, and this caution rests only on test-tube and animal data, so the real-world risk looks low.

I would not expect black cohosh to make your birth control fail or to clearly worsen estrogen side effects like breast tenderness, nausea, or spotting. Still, since liver concerns exist with black cohosh, it is worth a quick chat with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kruse SO, Lohning A, Pauli GF, et al. Fukiic and piscidic acid esters from the rhizome of Cimicifuga racemosa and the in vitro estrogenic activity of fukinolic acid. Planta Med 1999;65:763-4.
  2. Seidlova-Wuttke D, Hesse O, Jarry H, et al. Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta. Eur J Endocrinol 2003;149:351-62. PubMed
  3. Dugoua JJ, Seely D, Perri D, et al. Safety and efficacy of black cohosh (cimicifuga racemosa) during pregnancy and lactation. Can J Clin Pharmacol 2006;13:e257-61.
  4. Nuntanakorn, P., Jiang, B., Einbond, L. S., Yang, H., Kronenberg, F., Weinstein, I. B., and Kennelly, E. J. Polyphenolic constituents of Actaea racemosa. J Nat Prod 2006;69(3):314-318.

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

Black Cohosh Also Interacts With Other Medications

Black Cohosh has 635 moderate, 16 minor known drug interactions in our database — the Ethinyl estradiol, Levonogestrel one above is among them. If you take anything else, check it against the full list below.

Moderate 635 Minor 16 No known interaction 2,179 (incl. Ethinyl estradiol, Levonogestrel)
Taking anything else?

Check Another of Your Medications Against Black Cohosh

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

Everything else you take

See Every Supplement That Interacts With Ethinyl estradiol, Levonogestrel

This page covers Black Cohosh only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl estradiol, Levonogestrel page lists 239 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 · 195 moderate · 38 minor.

From our pharmacist’s overview on the Ethinyl estradiol, Levonogestrel page

“A daily birth control pill like Lybrel (ethinyl estradiol with levonorgestrel) only works when enough hormone stays in the bloodstream, and that is exactly what several supplements on this page can undermine. This list deserves genuine care, starting with the six major-rated entries.”

Reviewed by 2 · Jul 18, 2026

Open the Ethinyl estradiol, Levonogestrel interaction page

One more smart check

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

We hold 1,472 real supplement products containing Black Cohosh, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Black Cohosh. Your product may carry other ingredients that interact with Ethinyl estradiol, Levonogestrel too, on top of Black Cohosh — 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 Black Cohosh and Ethinyl estradiol, Levonogestrel 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 Black Cohosh
Top 25%

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

29 days ago today
Medication Ethinyl estradiol, Levonogestrel
Top 25%

#447 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 Black Cohosh

What is Black Cohosh?

Black Cohosh
  • Hot flashes and night sweats
  • Other menopause symptoms
  • Mood changes during menopause
  • Premenstrual syndrome (PMS)
  • Menstrual cramps

Black cohosh is a North American plant most often used to ease menopause symptoms like hot flashes, but the research is mixed and far from settled. It is generally well tolerated for short-term use, though rare reports of liver problems mean you should talk with your pharmacist or doctor before trying it, especially if you have liver disease.

Read the full Black Cohosh monograph & all interactions
Keep checking

Other Drugs & Black Cohosh

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

0Major
635Moderate
16Minor
2,178No known interaction
635 Moderate 16 Minor 2,178 No interaction
Moderate

635 interactions

Showing 60 of 635 moderate interactions — see all 635 on the Black Cohosh page.

Minor

16 interactions

No interaction 2,178 drugs checked — show the list

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

Showing the 60 most looked-up of 2,178 medications checked with no known interaction — see the full Black Cohosh list.

See the full Black Cohosh interactions page
See every supplement checked against Ethinyl estradiol, Levonogestrel, 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
Black Cohosh monograph › Uses, safety, and every drug interaction in one place Ethinyl estradiol, Levonogestrel supplement interactions › Every supplement checked against Ethinyl estradiol, Levonogestrel, 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 Black Cohosh and Ethinyl estradiol, Levonogestrel Together: Common Questions

Can you take Black Cohosh with Ethinyl estradiol, Levonogestrel?
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 Black Cohosh and Ethinyl estradiol, Levonogestrel?
Ethinyl estradiol, Levonogestrel belongs to more than one drug category, and Black Cohosh 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 Black Cohosh and Ethinyl estradiol, Levonogestrel 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.