Drug & supplement interaction

Yohimbe + 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 3 drug categories that Yohimbe can interact with; the most serious is rated moderate. Theoretically, CYP3A4 inhibitors might increase the levels and adverse effects of yohimbine, a constituent of yohimbe bark.

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

Yohimbe and Estradiol, Norethindrone Acetate

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

Why Are There 3 Interactions?

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

1 of 3

Why this applies to Estradiol, Norethindrone Acetate

Estradiol, Norethindrone Acetate falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS — the group Yohimbe interacts with.

Theoretically, CYP3A4 inhibitors might increase the levels and adverse effects of yohimbine, a constituent of yohimbe bark.
In vitro and clinical research shows that the yohimbe bark constituent, yohimbine, is metabolized by CYP3A4 enzymes. Theoretically, drugs that inhibit CYP3A4 might increase the levels and adverse effects of yohimbine.
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 thing to keep in mind with this pairing. Your Activella (estradiol with norethindrone) can act as a mild blocker of an enzyme called CYP3A4, which is the same enzyme that breaks down yohimbine from yohimbe bark. So in theory, taking yohimbe while on this hormone therapy could slow down how fast your body clears the yohimbine, letting it build up a bit.

If that happens, you might feel yohimbe's effects more strongly, things like a racing heart, jitteriness, anxiety, or a spike in blood pressure. I'll be honest, this is a theoretical concern based on how the two are processed, not something proven in studies. Still, since over-the-counter yohimbe is risky on its own, please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Le Corre P, Parmer RJ, Kailasam MT, et al. Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism. Clin Pharmacol Ther. 2004;76(2):139-53.
  2. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 3

Estradiol, Norethindrone Acetate also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, yohimbe might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that yohimbe extract induces CYP1A2 enzymes.
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

Your Activella combines two active hormones, estradiol and norethindrone, that your liver clears in part through an enzyme called CYP1A2. The concern here is that yohimbe might speed up that enzyme, which in theory could lower your hormone levels a little and make the medicine work less reliably. In practice, that might show up as breakthrough bleeding, spotting, or a return of menopausal symptoms like hot flashes.

Honestly, this is a very weak, theoretical concern. It comes only from lab studies, not from real people, and it is rated minor. I would worry more about yohimbe's own effects, like raising your blood pressure and heart rate. If you are considering yohimbe, please run it past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

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

Theoretically, yohimbe might decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that yohimbe extract induces CYP3A4 enzymes.
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 for your Activella (estradiol with norethindrone). Both of these hormones are partly broken down by a liver enzyme called CYP3A4. In a test-tube study, yohimbe seemed to speed that enzyme up. If that held true in people, it could clear your hormones a little faster and slightly lower their levels, which might mean a bit less benefit, such as a return of hot flashes or other menopause symptoms.

That said, this is theoretical and comes only from lab research, not from real patients, so I wouldn't lose sleep over it. The bigger concern with yohimbe itself is its tendency to raise blood pressure and heart rate. Before adding it, please run it by your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. 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

Yohimbe Also Interacts With Other Medications

Yohimbe has 9 major, 679 moderate, 436 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.

Major 9 Moderate 679 Minor 436 No known interaction 1,706 (incl. Estradiol, Norethindrone Acetate)
Taking anything else?

Check Another of Your Medications Against Yohimbe

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

Everything else you take

See Every Supplement That Interacts With Estradiol, Norethindrone Acetate

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

We hold 1,054 real supplement products containing Yohimbe, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Yohimbe. Your product may carry other ingredients that interact with Estradiol, Norethindrone Acetate too, on top of Yohimbe — 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 Yohimbe 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 Yohimbe
Top 25%

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

29 days ago today
Medication Estradiol, Norethindrone Acetate
Steady interest

#2,389 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 Yohimbe

What is Yohimbe?

Yohimbe
  • Erectile dysfunction
  • Low sex drive
  • Sexual performance
  • Weight loss
  • Athletic performance

Yohimbe is a West African tree bark that contains yohimbine, a compound mainly promoted for erectile dysfunction and as an aphrodisiac. A prescription form of yohimbine has some evidence for erectile dysfunction, but over-the-counter yohimbe supplements vary widely in content and can cause serious side effects like high blood pressure and fast heart rate. Because of these safety concerns, talk to your pharmacist or doctor before using it.

Read the full Yohimbe monograph & all interactions
Keep checking

Other Drugs & Yohimbe

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

9Major
679Moderate
436Minor
1,705No known interaction
9 Major 679 Moderate 436 Minor 1,705 No interaction
Major

9 interactions

Moderate

679 interactions

Showing 60 of 679 moderate interactions — see all 679 on the Yohimbe page.

Minor

436 interactions

Showing 60 of 436 minor interactions — see all 436 on the Yohimbe page.

No interaction 1,705 drugs checked — show the list

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

Showing the 60 most looked-up of 1,705 medications checked with no known interaction — see the full Yohimbe list.

See the full Yohimbe 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
Yohimbe 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 Yohimbe and Estradiol, Norethindrone Acetate Together: Common Questions

Can you take Yohimbe 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 3 interactions listed for Yohimbe and Estradiol, Norethindrone Acetate?
Estradiol, Norethindrone Acetate belongs to more than one drug category, and Yohimbe 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 Yohimbe 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

Still Have a Question About Estradiol, Norethindrone Acetate and Yohimbe?

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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.