Sage + Estradiol, Norethindrone Acetate
Estradiol, Norethindrone Acetate brand name: Activella.
Estradiol, Norethindrone Acetate 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 reportSage and Estradiol, Norethindrone Acetate
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, Norethindrone Acetate 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).
P-GLYCOPROTEIN SUBSTRATES
1 of 3Why this applies to Estradiol, Norethindrone Acetate
Estradiol, Norethindrone Acetate falls under P-GLYCOPROTEIN SUBSTRATES — the group Sage interacts with.
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.
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.
Activella combines two hormones, estradiol and norethindrone, used to ease menopause symptoms. One way your body moves these hormones around involves a transporter called P-glycoprotein. In lab dishes, concentrated sage seems to slow that transporter down. If the same thing happened in people, a bit more hormone could stay in your system, which in theory might mean more estrogen-type side effects like breast tenderness, bloating, nausea, headaches, or spotting.
Here's the honest part: this comes only from test-tube research, never confirmed in real people, so I wouldn't lose sleep over it. The sage you sprinkle on food is very unlikely to matter. Concentrated sage extracts or oil are a different story. If you're using those regularly, just give your pharmacist or doctor a heads-up.
- 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.
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
2 of 3Estradiol, Norethindrone Acetate also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP3A4. So far, this interaction has not been reported in humans.
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.
Your Activella combines two hormones, estradiol and norethindrone, and your liver relies on an enzyme called CYP3A4 to help clear the estrogen part. In lab dishes, water-based sage extracts have slowed that enzyme down a bit. If that happened in your body, the hormones could linger a little longer than usual, which in theory could nudge up side effects like breast tenderness, bloating, nausea, headaches, or spotting.
Here's the reassuring part: this is only a test-tube finding, and it has never actually been reported in people. Cooking with sage in your food is not a worry at all. If you want to take concentrated sage capsules or the essential oil regularly, just run it by your pharmacist or doctor first so they can keep an eye on things.
- 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
- 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.
ESTROGENS
3 of 3Estradiol, Norethindrone Acetate also falls under ESTROGENS.
In vitro evidence suggests that geraniol, a constituent of Spanish sage (Salvia lavandulaefolia), exerts estrogenic activity. The clinical significance of this effect is unclear.
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.
Activella combines two hormones, estradiol (an estrogen) and norethindrone (a progestin), to manage menopause symptoms like hot flashes and night sweats. The concern here is purely theoretical. In lab dish studies, a compound found in Spanish sage appeared to act a little like estrogen itself. Nobody has shown this actually matters in real people, so I don't want you to worry.
If anything, the worry would be that extra estrogen-like activity could add to your hormone therapy. In real life, the small amount of sage you'd use to season food is very unlikely to do anything. If you're taking concentrated sage extracts or the essential oil regularly, just mention it to your pharmacist or doctor so they can keep an eye on things.
- 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.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Sage Also Interacts With Other Medications
Sage has 1,295 moderate known drug interactions in our database — the Estradiol, Norethindrone Acetate one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Sage
We haven’t checked that one against Sage yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Sage. Pick one to open its full report.
See Every Supplement That Interacts With Estradiol, Norethindrone Acetate
This page covers Sage only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Estradiol, Norethindrone Acetate page lists 212 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 · 171 moderate · 38 minor.
From our pharmacist’s overview on the Estradiol, Norethindrone Acetate page
“Activella pairs estradiol with norethindrone as hormone therapy, and because the treatment depends on steady hormone levels in the blood, supplements that raise or lower those levels warrant real scrutiny. Three of the 212 interacting ingredients rate major, and all three hit that weak point: St.”
Reviewed by 2 · Jul 18, 2026
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, Norethindrone Acetate 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:
Where Sage and Estradiol, Norethindrone 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.
#252 of 1,452 supplements looked up here in the last 7 days
#2,331 of 2,830 medications looked up here in the last 7 days
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.
About Sage
What is 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.
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.
No drugs match “”.
1,295 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Nifedipine ›
- Ibuprofen ›
- Diphenhydramine ›
- Hydrocortisone ›
- Insulin (rdna) ›
- Naproxen ›
- Doxycycline ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Propranolol ›
- Tetracycline ›
- Lidocaine ›
- Ranitidine ›
- Hydrochlorothiazide ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Glyburide ›
- Glycopyrrolate ›
- Insulin (pork) ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Flurbiprofen ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Triamcinolone ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Diclofenac Potassium ›
- Doxorubicin ›
- Fluticasone ›
- Formoterol ›
- Hydralazine ›
- Indomethacin ›
- Insulin (human) ›
- Ipratropium ›
- Miconazole ›
- Morphine Sulfate ›
- Nitrazepam ›
- Procainamide ›
- Trimipramine ›
- Acetaminophen ›
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.
- Levothyroxine ›
- Methylphenidate ›
- Aspirin ›
- Rosuvastatin ›
- Escitalopram ›
- Docusate ›
- Hydroxyurea ›
- Valacyclovir ›
- Sumatriptan ›
- Amoxicillin ›
- Bupropion ›
- Bendamustine ›
- Acyclovir ›
- Methotrexate ›
- Azithromycin ›
- Isotretinoin ›
- Methylene Blue ›
- Ciprofloxacin ›
- Levothyroxine, Liothyronine ›
- Cephalexin ›
- Cyclopentolate ›
- Roxithromycin ›
- Pegunigalsidase Alfa-iwxj ›
- Ezetimibe ›
- Levothyroxine Sodium ›
- Daptomycin ›
- Amoxicillin, Clavulanate Potassium ›
- Dexmethylphenidate ›
- Mitomycin ›
- Hexobarbitone ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Factor 7a ›
- Levodopa ›
- Cefaclor ›
- Hethylphenidate Hcl ›
- Lenvatinib ›
- Azelaic Acid ›
- Phenylephrine ›
- Hydroxychloroquine ›
- Tenecteplase ›
- Vancomycin ›
- Dirithromycin ›
- Triptorelin ›
- Pizotifen ›
- Acetylsalicylic Acid ›
- Bentoquatam ›
- Ribavirin Aerosol ›
- Dextrothyroxine ›
- Tocainide ›
- Ropinirole ›
- Rocuronium ›
- Mitomycin C ›
- Lomustine ›
- Salbutamol Sulfate ›
- Digitoxin ›
- Chenodiol ›
- Gestodene ›
- Halothane ›
- Caspofungin ›
Showing the 60 most looked-up of 1,534 medications checked with no known interaction — see the full Sage list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Estradiol, Norethindrone Acetate Is Linked to Lower Levels of 5 Nutrients
Natural Medicines records Estradiol, Norethindrone Acetate as a medicine that can lower these. This is not an interaction with Sage — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Estradiol, Norethindrone Acetate nutrient depletion report ›
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Sage and Estradiol, Norethindrone Acetate Together: Common Questions
Can you take Sage with Estradiol, Norethindrone Acetate?
Why are there 3 interactions listed for Sage and Estradiol, Norethindrone Acetate?
How serious is the Sage and Estradiol, Norethindrone Acetate interaction?
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.