Drug & supplement interaction

Sage + Estradiol, Medroxyprogesterone

Estradiol, Medroxyprogesterone brand name: Divitren.

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

Estradiol, Medroxyprogesterone falls into 3 drug categories that Sage can interact with; the most serious is rated moderate. Theoretically, sage might increase levels of drugs transported by P-glycoprotein.

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

Sage and Estradiol, Medroxyprogesterone

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

Why Are There 3 Interactions?

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

Moderate

P-GLYCOPROTEIN SUBSTRATES

1 of 3

Why this applies to Estradiol, Medroxyprogesterone

Estradiol, Medroxyprogesterone falls under P-GLYCOPROTEIN SUBSTRATES — the group Sage interacts with.

Theoretically, sage might increase levels of drugs transported by P-glycoprotein.
In vitro research suggests that common sage (Salvia officinalis) can inhibit the multi-drug transporter protein, P-glycoprotein. 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 situation with sage and your Divitren (estradiol plus medroxyprogesterone). Sage has shown, in lab dish experiments only, that it can block a transporter called P-glycoprotein that helps move certain drugs through and out of your body. If that blocking effect happened in people, a bit more of your hormone medicine could stay in your system, which in theory might mean more of the usual estrogen-progestin effects like breast tenderness, bloating, nausea, headaches, or spotting.

The reassuring part: this has only been seen in test tubes, never confirmed in humans, so it's mostly theoretical. Cooking with sage in normal food amounts is very unlikely to matter. Concentrated extracts or sage essential oil are the bigger question marks. If you're thinking about a sage supplement, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Hellum, B. H. and Nilsen, O. G. In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol. 2008;102(5):466-475.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

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

Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP3A4. So far, this interaction 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 hormone therapy, which combines estradiol and medroxyprogesterone, is partly cleared by a liver enzyme called CYP3A4. In laboratory dishes, water-based sage extracts have slowed this enzyme down. If that were to happen in your body, your hormone levels could drift a little higher, which in theory might mean more of the usual estrogen-related effects like breast tenderness, bloating, nausea, headaches, or spotting.

Here's the honest part: this is only a theoretical concern. It comes from test-tube studies and has never been reported in real people, and the small amount of sage you'd use to season food is very unlikely to matter. Concentrated sage extracts or capsules are a different story. If you plan to take those regularly, just check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
  2. Hellum, B. H. and Nilsen, O. G. In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol. 2008;102(5):466-475.
Moderate

ESTROGENS

3 of 3

Estradiol, Medroxyprogesterone also falls under ESTROGENS.

Theoretically, sage might interfere with hormone therapy.
In vitro evidence suggests that geraniol, a constituent of Spanish sage (Salvia lavandulaefolia), exerts estrogenic activity. The clinical 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

Your Divitren is a hormone product that combines estradiol (an estrogen) with medroxyprogesterone (a progestin). The concern here is pretty mild. In lab studies, a compound found in Spanish sage called geraniol showed weak estrogen-like activity. In theory, layering that on top of your hormone therapy could nudge your overall estrogen effect slightly upward.

But I want to be clear: this is only test-tube evidence, and no human studies have shown it actually matters. Cooking with sage almost certainly won't do anything. If you're considering concentrated sage extracts or sage oil capsules, that's worth a quick chat with your pharmacist or doctor, especially since high-dose sage carries its own cautions.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Perry, N. S., Houghton, P. J., Sampson, J., Theobald, A. E., Hart, S., Lis-Balchin, M., Hoult, J. R., Evans, P., Jenner, P., Milligan, S., and Perry, E. K. In-vitro activity of S. lavandulaefolia (Spanish sage) relevant to treatment of Alzheimer's diseas

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

Sage Also Interacts With Other Medications

Sage has 1,295 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.

Moderate 1,295 No known interaction 1,535 (incl. Estradiol, Medroxyprogesterone)
Taking anything else?

Check Another of Your Medications Against Sage

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

Everything else you take

See Every Supplement That Interacts With Estradiol, Medroxyprogesterone

This page covers Sage 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 Sage as Part of a Dietary Supplement Product? Check It for Interactions

We hold 718 real supplement products containing Sage, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sage. Your product may carry other ingredients that interact with Estradiol, Medroxyprogesterone too, on top of Sage — 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 Sage 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 Sage
Top 25%

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

29 days ago today
Medication Estradiol, Medroxyprogesterone
Steady interest

#1,854 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 Sage

What is Sage?

Sage
  • Sore throat and mouth irritation
  • Digestive upset
  • Excessive sweating
  • Memory and thinking
  • Menopause symptoms (hot flashes)
  • General antioxidant support

Sage is a common kitchen herb that is generally safe in food amounts and is traditionally used for sore throats, digestion, sweating, and memory. Some early research is encouraging for sore throat and menopausal hot flashes, but most uses are not well proven. Concentrated extracts and the essential oil should be used carefully because high doses contain a compound called thujone, which can be harmful.

Read the full Sage monograph & all interactions
Keep checking

Other Drugs & Sage

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

0Major
1,295Moderate
0Minor
1,534No known interaction
1,295 Moderate 1,534 No interaction
Moderate

1,295 interactions

Showing 60 of 1,295 moderate interactions — see all 1,295 on the Sage page.

No interaction 1,534 drugs checked — show the list

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

Showing the 60 most looked-up of 1,534 medications checked with no known interaction — see the full Sage list.

See the full Sage interactions page
See every supplement checked against Estradiol, Medroxyprogesterone, 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
Sage monograph › Uses, safety, and every drug interaction in one place Estradiol, Medroxyprogesterone supplement interactions › Every supplement checked against Estradiol, Medroxyprogesterone, 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 Sage and Estradiol, Medroxyprogesterone Together: Common Questions

Can you take Sage 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 Sage and Estradiol, Medroxyprogesterone?
Estradiol, Medroxyprogesterone belongs to more than one drug category, and Sage 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 Sage 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.