Drug & supplement interaction

Bacopa + Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate brand name: Activella.

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

Estradiol, Norethindrone Acetate falls into 2 drug categories that Bacopa can interact with; the most serious is rated moderate. Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.

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

Bacopa and Estradiol, Norethindrone Acetate

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

Why Are There 2 Interactions?

Bacopa interacts with whole categories of medication. Estradiol, Norethindrone Acetate falls into 2 of those categories, so it can interact with Bacopa in 2 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 2

Why this applies to Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Bacopa interacts with.

Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.
Research on the effects of bacopa extracts on CYP1A2 enzymes is conflicting. Some in vitro evidence shows that bacopa extract can moderately and non-competitively inhibit CYP1A2, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.
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 Activella (estradiol plus norethindrone). One of the liver enzymes that helps clear estrogen is called CYP1A2. In lab tests, bacopa has shown a mild ability to slow that enzyme down. If that slowdown happened in your body, your estrogen levels could drift up a little, which in theory might mean more of the usual estrogen-type side effects like breast tenderness, bloating, nausea, headaches, or spotting.

The honest part: this is theoretical. It comes from test-tube studies only, and even those disagree on whether the effect matters in real people. I wouldn't lose sleep over it, but if you plan to take bacopa regularly, mention it 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. Kar A, Pandit S, Mukherjee K, Bahadur S, Mukherjee PK. Safety assessment of selected medicinal food plants used in Ayurveda through CYP450 enzyme inhibition study. J Sci Food Agric 2017;97(1):333-40. doi: 10.1002/jsfa.7739. PubMed
  2. Ramasamy S, Kiew LV, Chung LY. Inhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized extract and constituents. Molecules 2014;19(2):2588-601. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

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

Theoretically, bacopa might increase the levels and adverse effects of CYP3A4 substrates.
Research on the effects of bacopa extracts on CYP3A4 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and competitively inhibit CYP3A4, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.
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 Activella combines two active hormones, estradiol and norethindrone, and your liver clears both of them partly through an enzyme called CYP3A4. The theory here is that bacopa might slow that enzyme down a little. If it does, your body could hold onto slightly more hormone than usual, which can nudge up the typical estrogen-and-progestin side effects: breast tenderness, bloating, nausea, headaches, mood shifts, or spotting.

I want to keep this in perspective, though. This concern comes only from lab and test-tube studies, and even those results disagree with each other. There's no real-world evidence of a problem in people, so I wouldn't lose sleep over it. Still, it's worth mentioning to your pharmacist or doctor before you start a daily bacopa supplement, just so someone who knows your full history can weigh in.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Kar A, Pandit S, Mukherjee K, Bahadur S, Mukherjee PK. Safety assessment of selected medicinal food plants used in Ayurveda through CYP450 enzyme inhibition study. J Sci Food Agric 2017;97(1):333-40. doi: 10.1002/jsfa.7739. PubMed
  2. Ramasamy S, Kiew LV, Chung LY. Inhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized extract and constituents. Molecules 2014;19(2):2588-601. 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

Bacopa Also Interacts With Other Medications

Bacopa has 916 moderate, 13 minor 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.

Moderate 916 Minor 13 No known interaction 1,901 (incl. Estradiol, Norethindrone Acetate)
Taking anything else?

Check Another of Your Medications Against Bacopa

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

Everything else you take

See Every Supplement That Interacts With Estradiol, Norethindrone Acetate

This page covers Bacopa 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

Open the Estradiol, Norethindrone Acetate interaction page

One more smart check

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

We hold 1,420 real supplement products containing Bacopa, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bacopa. Your product may carry other ingredients that interact with Estradiol, Norethindrone Acetate too, on top of Bacopa — 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 Bacopa 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.

Supplement Bacopa
Top 10%

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

29 days ago today
Medication Estradiol, Norethindrone Acetate
Steady interest

#2,342 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 Bacopa

What is Bacopa?

Bacopa
  • Memory and cognitive support
  • Anxiety and stress
  • ADHD symptoms
  • Age-related memory decline
  • General brain health

Bacopa is an Ayurvedic herb most often used for memory and thinking. Some small studies suggest it may modestly help memory when taken regularly for several weeks, but the evidence is limited and quality varies. It is generally well tolerated but can cause stomach upset, and it should be avoided in pregnancy and breastfeeding due to a lack of safety data.

Read the full Bacopa monograph & all interactions
Keep checking

Other Drugs & Bacopa

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

0Major
916Moderate
13Minor
1,900No known interaction
916 Moderate 13 Minor 1,900 No interaction
Moderate

916 interactions

Showing 60 of 916 moderate interactions — see all 916 on the Bacopa page.

Minor

13 interactions

No interaction 1,900 drugs checked — show the list

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

Showing the 60 most looked-up of 1,900 medications checked with no known interaction — see the full Bacopa list.

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

Can you take Bacopa with Estradiol, Norethindrone 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 2 interactions listed for Bacopa and Estradiol, Norethindrone Acetate?
Estradiol, Norethindrone Acetate belongs to more than one drug category, and Bacopa 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 Bacopa and Estradiol, Norethindrone 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.