Drug & supplement interaction

Milk Thistle + Conjugated Estrogens, Medroxyprogesterone Acetate

Conjugated Estrogens, Medroxyprogesterone Acetate brand names: Prempro, Premplus.

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

Conjugated Estrogens, Medroxyprogesterone Acetate falls into 4 drug categories that Milk Thistle can interact with; the most serious is rated moderate. Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Milk Thistle and Conjugated Estrogens, Medroxyprogesterone Acetate

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Milk Thistle interacts with whole categories of medication. Conjugated Estrogens, Medroxyprogesterone Acetate falls into 4 of those categories, so it can interact with Milk Thistle in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

GLUCURONIDATED DRUGS

1 of 4

Why this applies to Conjugated Estrogens, Medroxyprogesterone Acetate

Conjugated Estrogens, Medroxyprogesterone Acetate falls under GLUCURONIDATED DRUGS — the group Milk Thistle interacts with.

Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.
Laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Other laboratory research suggests that a milk thistle extract of silymarin might inhibit beta-glucuronidase, although the significance of this effect is unclear.
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 is the gist for Prempro (the estrogen plus medroxyprogesterone combo). Your body clears these hormones partly through a process called glucuronidation, and lab studies suggest milk thistle's silymarin can slow that pathway a bit. In theory, that could let estrogen and progestin levels drift a little higher, which might bump up side effects like breast tenderness, bloating, headaches, nausea, or breakthrough spotting.

The key word is theory. This concern comes only from test-tube and animal research, not from real patients, so the actual risk looks small. I would not lose sleep over it, but it is worth a quick mention to your pharmacist or doctor before adding milk thistle, especially since hormones already get a close eye.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 2000;28:1270-3. DOI
  2. Kim DH, Jin YH, Park JB, Kobashi K. Silymarin and its components are inhibitors of beta-glucuronidase. Biol Pharm Bull 1994;17:443-5. PubMed
  3. Sridar C, Goosen TC, Kent UM, et al. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 2004;32:587-94. PubMed
Minor

ESTROGENS

2 of 4

Conjugated Estrogens, Medroxyprogesterone Acetate also falls under ESTROGENS.

Theoretically, milk thistle might interfere with estrogen therapy through competition for estrogen receptors.
Animal research suggests that a milk thistle extract of silymarin binds to estrogen receptor beta.
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 gist with Prempro (your conjugated estrogens plus medroxyprogesterone) and milk thistle. The concern is purely theoretical and comes from lab and animal work, not from people. In those studies, silymarin (the active part of milk thistle) was able to attach to one type of estrogen receptor, the beta receptor. The worry is that it might gently compete with your estrogen at those sites and slightly blunt how well your therapy works.

In real life, this is rated minor, and the evidence is weak. If anything happened at all, you might notice a small return of symptoms like hot flashes or night sweats, but that's far from certain. I wouldn't lose sleep over it. Still, since this is hormone therapy, it's worth mentioning to your pharmacist or doctor so they can keep an eye on how you feel.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. El-Shitany NA, Hegazy S, El-Desoky K. Evidences for antiosteoporotic and selective estrogen receptor modulator activity of silymarin compared with ethinylestradiol in ovariectomized rats. Phytomedicine. 2010;17(2):116-25. PubMed
  2. Seidlová-Wuttke D, Becker T, Christoffel V, Jarry H, Wuttke W. Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx
Minor

P-GLYCOPROTEIN SUBSTRATES

3 of 4

Conjugated Estrogens, Medroxyprogesterone Acetate also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates. However, this effect does not seem to be clinically significant.
In vitro research shows that milk thistle can inhibit P-glycoprotein activity and 1 case report from the World Health Organization (WHO) adverse drug reaction database describes increased abdominal pain in a patient taking milk thistle and the cancer medication vincristine, a P-glycoprotein substrate, though this patient was also taking methotrexate. However, a small pharmacokinetic study in healthy volunteers shows that taking milk thistle (Enzymatic Therapy Inc.) 900 mg, standardized to 80% silymarin, in 3 divided doses daily for 14 days does not affect absorption of digoxin, a P-glycoprotein substrate.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the simple version for your Prempro (the conjugated estrogens plus medroxyprogesterone combo). Milk thistle can, at least in a test tube, gently block a cellular pump called P-glycoprotein that helps move certain medicines across the gut wall. In theory, slowing that pump could let a touch more of a medication get absorbed. Your hormone therapy is one of those P-glycoprotein passengers.

The good news: this is a theoretical, minor concern, and the real-world evidence suggests it doesn't add up to much. If it nudged your levels at all, you might notice common estrogen-related effects like breast tenderness, bloating, or nausea. That's unlikely. Still, it's worth a quick mention to your pharmacist or doctor before adding milk thistle, just so everyone's on the same page.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Gurley, B. J., Barone, G. W., Williams, D. K., Carrier, J., Breen, P., Yates, C. R., Song, P. F., Hubbard, M. A., Tong, Y., and Cheboyina, S. Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin phar
  2. Derosa G, Romano D, D'Angelo A, Maffioli P. Berberis aristata/Silybum marianum fixed combination (Berberol(®)) effects on lipid profile in dyslipidemic patients intolerant to statins at high dosages: a randomized, placebo-controlled, clinical trial. Phyto PubMed
  3. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

4 of 4

Conjugated Estrogens, Medroxyprogesterone Acetate also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
While laboratory research shows conflicting results, pharmacokinetic research shows that taking milk thistle extract 420-1350 mg daily does not significantly affect the metabolism of the CYP3A4 substrates irinotecan, midazolam, or indinavir. However, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP3A4 substrates, including gefitinib, sorafenib, doxorubicin, and vincristine.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for Prempro (conjugated estrogens with medroxyprogesterone). Both hormones are partly processed by a liver enzyme called CYP3A4, and milk thistle has been looked at as a possible blocker of that enzyme. In theory, if milk thistle slowed that pathway, your hormone levels could drift up a bit, which might mean more of the usual estrogen-type effects like breast tenderness, bloating, nausea, or spotting.

The good news is that this concern is mostly theoretical. Careful human studies showed milk thistle did not meaningfully change how the body clears similar CYP3A4 medicines, and the rating here is minor and unlikely. I wouldn't lose sleep over it, but it's still worth a quick mention to your pharmacist or doctor before adding the supplement.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 2000;28:1270-3. DOI
  2. Piscitelli SC, Formentini E, Burstein AH, et al. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 2002;22:551-6. PubMed
  3. Sridar C, Goosen TC, Kent UM, et al. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 2004;32:587-94. PubMed
  4. van Erp NP, Baker SD, Zhao M, et al. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 2005;11:7800-6.
  5. Budzinski JW, Trudeau VL, Drouin CE, et al. Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products. Can J Physiol Pharmacol 2007;85:966-78.
  6. Doehmer J, Weiss G, McGregor GP, Appel K. Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities. Toxicol In Vitro 2011;25:21-7. PubMed
  7. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  8. Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos. 2014;42(10):1611-6. PubMed
  9. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. 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

Milk Thistle Also Interacts With Other Medications

Milk Thistle has 253 moderate, 700 minor known drug interactions in our database — the Conjugated Estrogens, Medroxyprogesterone Acetate one above is among them. If you take anything else, check it against the full list below.

Moderate 253 Minor 700 No known interaction 1,877 (incl. Conjugated Estrogens, Medroxyprogesterone Acetate)
Taking anything else?

Check Another of Your Medications Against Milk Thistle

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

From our Q&A

Questions About Milk Thistle or Conjugated Estrogens, Medroxyprogesterone Acetate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Milk Thistle or Conjugated Estrogens, Medroxyprogesterone Acetate, 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 Conjugated Estrogens, Medroxyprogesterone Acetate

This page covers Milk Thistle only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Conjugated Estrogens, Medroxyprogesterone Acetate page lists 187 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 · 152 moderate · 32 minor.

From our pharmacist’s overview on the Conjugated Estrogens, Medroxyprogesterone Acetate page

“St. John's wort tops my list of concerns for anyone on Prempro (conjugated estrogens plus medroxyprogesterone), the combination hormone therapy for menopause symptoms.”

Reviewed by 2 · Jul 18, 2026

Open the Conjugated Estrogens, Medroxyprogesterone Acetate interaction page

One more smart check

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

We hold 4,560 real supplement products containing Milk Thistle, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Milk Thistle. Your product may carry other ingredients that interact with Conjugated Estrogens, Medroxyprogesterone Acetate too, on top of Milk Thistle — 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 Milk Thistle and Conjugated Estrogens, Medroxyprogesterone Acetate 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 Milk Thistle
Top 5%

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

29 days ago today
Medication Conjugated Estrogens, Medroxyprogesterone Acetate
Top half

#957 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 Milk Thistle

What is Milk Thistle?

Milk Thistle
  • Liver health and protection
  • Hepatitis
  • Cirrhosis
  • Gallbladder problems
  • High cholesterol
  • Type 2 diabetes support

Milk thistle is a popular herbal supplement most often used for liver health, and its main active component is a group of compounds called silymarin. While it is generally well tolerated, the scientific evidence that it meaningfully improves liver disease or other conditions is mixed and far from conclusive. Talk with your pharmacist or doctor before using it, especially if you have a liver condition or take other medicines.

Read the full Milk Thistle monograph & all interactions
Keep checking

Other Drugs & Milk Thistle

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

0Major
253Moderate
700Minor
1,876No known interaction
253 Moderate 700 Minor 1,876 No interaction
Moderate

253 interactions

Showing 60 of 253 moderate interactions — see all 253 on the Milk Thistle page.

Minor

700 interactions

Showing 60 of 700 minor interactions — see all 700 on the Milk Thistle page.

No interaction 1,876 drugs checked — show the list

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

Showing the 60 most looked-up of 1,876 medications checked with no known interaction — see the full Milk Thistle list.

See the full Milk Thistle interactions page
See every supplement checked against Conjugated Estrogens, Medroxyprogesterone Acetate, 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
Milk Thistle monograph › Uses, safety, and every drug interaction in one place Conjugated Estrogens, Medroxyprogesterone Acetate supplement interactions › Every supplement checked against Conjugated Estrogens, Medroxyprogesterone Acetate, 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 Milk Thistle and Conjugated Estrogens, Medroxyprogesterone Acetate Together: Common Questions

Can you take Milk Thistle with Conjugated Estrogens, Medroxyprogesterone Acetate?
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 4 interactions listed for Milk Thistle and Conjugated Estrogens, Medroxyprogesterone Acetate?
Conjugated Estrogens, Medroxyprogesterone Acetate belongs to more than one drug category, and Milk Thistle 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 Milk Thistle and Conjugated Estrogens, Medroxyprogesterone Acetate 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.