Drug & supplement interaction

Bulbine Natalensis + Estradiol, Progesterone

Estradiol, Progesterone brand name: Bijuvanda.

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

Estradiol, Progesterone falls into 3 drug categories that Bulbine Natalensis can interact with; the most serious is rated moderate. Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP1A2 substrates.

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

Bulbine Natalensis and Estradiol, Progesterone

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

Why Are There 3 Interactions?

Bulbine Natalensis interacts with whole categories of medication. Estradiol, Progesterone falls into 3 of those categories, so it can interact with Bulbine Natalensis 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 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Estradiol, Progesterone

Estradiol, Progesterone falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Bulbine Natalensis interacts with.

Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that Bulbine natalensis stem extract slightly induces CYP1A2 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP1A2 substrates; however, this has not been studied 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 basic idea with Bijuva (estradiol plus progesterone). Your body uses several liver enzymes to break down estrogen, and one of them is called CYP1A2. In lab dish studies only, Bulbine natalensis appeared to slightly speed up that enzyme. If that were to happen in people, it could clear your estradiol a little faster and gently lower its levels. In real life that might mean your hormone therapy works a bit less well, so you could notice hot flashes, night sweats, or other menopause symptoms creeping back.

I want to be honest though: this is theoretical and comes only from test-tube work, never human studies, so the real-world effect is unknown. Given the liver concerns with this supplement too, please run it by your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Husain I, Manda V, Alhusban M, et al. Modulation of CYP3A4 and CYP2C9 activity by Bulbine natalensis and its constituents: An assessment of HDI risk of B. natalensis containing supplements. Phytomedicine 2021;81:153416. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

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

Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that Bulbine natalensis stem extract induces CYP3A4 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP3A4 substrates, but this has not been studied 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 gist with Bijuva (estradiol plus progesterone) and this supplement. Both hormones in Bijuva are processed by a liver enzyme called CYP3A4. In lab dishes, Bulbine natalensis seems to rev up that enzyme, which could mean your body clears these hormones a little faster than usual. If that happens, you might get less benefit from the therapy, with menopausal symptoms like hot flashes, night sweats, or vaginal dryness creeping back.

I want to be honest though: this is only test-tube evidence, not anything proven in people, so the real-world effect may be small or none. Given that this supplement also raises liver and kidney safety questions, I'd run it by your pharmacist or doctor before combining the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Husain I, Dale OR, Manda V, et al. Bulbine natalensis (currently Bulbine latifolia) and select bulbine knipholones modulate the activity of AhR, CYP1A2, CYP2B6, and P-gp. Planta Med 2022;88(12):975-984. PubMed
Moderate

P-GLYCOPROTEIN SUBSTRATES

3 of 3

Estradiol, Progesterone also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, Bulbine natalensis stem might increase the levels and clinical effects of p-glycoprotein substrates.
In vitro research shows that Bulbine natalensis stem extract induces p-glycoprotein mRNA expression; however, effects on transporter expression were not evaluated.
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 honest picture: this concern is purely theoretical. In a lab dish, Bulbine natalensis seemed to nudge a transporter called P-glycoprotein, which helps move hormones like the estradiol and progesterone in Bijuva through your body. The database flags Bijuva because it can ride along this same transporter pump.

If the supplement actually changed that pump in people (and we don't know that it does), it could slightly shift how much hormone stays in your system. That might mean a little more or less effect, such as breast tenderness, bloating, mood changes, or breakthrough spotting. I want to stress this is based on a test-tube study only, not real patients. Bigger picture, the bulbine itself raises liver and kidney safety questions, so please check with your doctor or pharmacist before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Husain I, Manda V, Alhusban M, et al. Modulation of CYP3A4 and CYP2C9 activity by Bulbine natalensis and its constituents: An assessment of HDI risk of B. natalensis containing supplements. Phytomedicine 2021;81:153416. 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

Bulbine Natalensis Also Interacts With Other Medications

Bulbine Natalensis has 918 moderate known drug interactions in our database — the Estradiol, Progesterone one above is among them. If you take anything else, check it against the full list below.

Moderate 918 No known interaction 1,912 (incl. Estradiol, Progesterone)
Taking anything else?

Check Another of Your Medications Against Bulbine Natalensis

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

Everything else you take

See Every Supplement That Interacts With Estradiol, Progesterone

This page covers Bulbine Natalensis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Estradiol, Progesterone 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, Progesterone page

“Bijuvanda combines estradiol and progesterone, a hormone therapy usually prescribed for menopause symptoms, and its interaction list warrants real care. Three of the 206 supplement ingredients on file carry a major rating, and those deserve your attention first.”

Reviewed by 2 · Jul 18, 2026

Open the Estradiol, Progesterone interaction page

One more smart check

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

We hold 51 real supplement products containing Bulbine Natalensis, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bulbine Natalensis. Your product may carry other ingredients that interact with Estradiol, Progesterone too, on top of Bulbine Natalensis — 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 Bulbine Natalensis and Estradiol, Progesterone 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 Bulbine Natalensis
Steady interest

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

29 days ago today
Medication Estradiol, Progesterone
Top half

#953 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 Bulbine Natalensis

What is Bulbine Natalensis?

  • Boosting testosterone
  • Improving libido
  • Muscle building and athletic performance
  • General male vitality

Bulbine natalensis is a South African plant marketed mainly as a testosterone-boosting and libido supplement, but the human evidence is essentially absent and most claims come from animal studies. Animal research has also raised concerns about possible liver and kidney harm at higher doses, so caution is warranted. Talk to your pharmacist or doctor before trying it.

Read the full Bulbine Natalensis monograph & all interactions
Keep checking

Other Drugs & Bulbine Natalensis

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

0Major
918Moderate
0Minor
1,911No known interaction
918 Moderate 1,911 No interaction
Moderate

918 interactions

Showing 60 of 918 moderate interactions — see all 918 on the Bulbine Natalensis page.

No interaction 1,911 drugs checked — show the list

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

Showing the 60 most looked-up of 1,911 medications checked with no known interaction — see the full Bulbine Natalensis list.

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

Can you take Bulbine Natalensis with Estradiol, Progesterone?
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 Bulbine Natalensis and Estradiol, Progesterone?
Estradiol, Progesterone belongs to more than one drug category, and Bulbine Natalensis 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 Bulbine Natalensis and Estradiol, Progesterone 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, Progesterone and Bulbine Natalensis?

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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.