Drug & supplement interaction

Bulbine Natalensis + Conjugated Estrogens, Methyltestosterone

Conjugated Estrogens, Methyltestosterone brand name: Premarin with Methyltestosterone.

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

Conjugated Estrogens, Methyltestosterone 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 CYP3A4 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 Conjugated Estrogens, Methyltestosterone

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. Conjugated Estrogens, Methyltestosterone 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 3A4 (CYP3A4) SUBSTRATES

1 of 3

Why this applies to Conjugated Estrogens, Methyltestosterone

Conjugated Estrogens, Methyltestosterone falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Bulbine Natalensis interacts with.

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 for your Premarin with Methyltestosterone. Both the estrogen and the testosterone parts of this pill are processed by a liver enzyme called CYP3A4. In lab and animal testing, Bulbine natalensis seems to rev up that enzyme, which could mean your body clears these hormones a little faster. That might make the medicine work less well, so you could notice things like return of hot flashes, night sweats, or other symptoms the combo was meant to control.

I want to be honest though: this is only a theory based on test-tube and animal data, with nothing proven in people. On top of that, Bulbine has raised liver concerns of its own. I'd skip guessing and run it by your doctor or pharmacist first.

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

2 of 3

Conjugated Estrogens, Methyltestosterone 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 short version on pairing Bulbine natalensis with your Premarin with Methyltestosterone. This combo hormone pill is partly handled by a cellular pump called P-glycoprotein, which helps move drugs in and out of cells. Some lab (test tube) research hints that Bulbine may rev up that pump, which could push a bit more of your hormone medication out and slightly lower how much stays in your body.

I want to be honest with you: this is theoretical and comes only from cell studies, not people, so it may not amount to much in real life. The bigger concern for me is that Bulbine itself has animal data suggesting possible liver and kidney strain. Since both estrogen and methyltestosterone can also stress the liver, please check with 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

TESTOSTERONE

3 of 3

Conjugated Estrogens, Methyltestosterone also falls under TESTOSTERONE.

Theoretically, using Bulbine natalensis stem with testosterone replacement therapy might increase the risk of adverse effects.
Animal research shows that Bulbine natalensis stem can increase testosterone levels.
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 medication already contains methyltestosterone, a form of testosterone. Bulbine natalensis is sold as a natural testosterone booster, and in animal studies it appeared to raise testosterone levels. So the worry here is simple stacking: piling a testosterone-like supplement on top of a medicine that already adds testosterone could push your hormone effects too high.

In real terms, that might mean more acne, oily skin, mood swings, fluid retention, or unwanted hair growth, and over time possible strain on the liver. Keep in mind this is only a theoretical concern based on animal data, not proven in people, and Bulbine itself has raised liver and kidney safety questions. 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. Yakubu MT, Afolayan AJ. Reproductive toxicologic evaluations of Bulbine natalensis Baker stem extract in albino rats. Theriogenology. 2009;72(3):322-32. PubMed
  2. Yakubu MT, Afolayan AJ. Effect of aqueous extract of Bulbine natalensis (Baker) stem on the sexual behaviour of male rats. Int J Androl. 2009;32(6):629-36.
  3. Yakubu MT, Afolayan AJ. Anabolic and androgenic activities of Bulbine natalensis stem in male Wistar rats. Pharm Biol. 2010;48(5):568-76.

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 Conjugated Estrogens, Methyltestosterone 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. Conjugated Estrogens, Methyltestosterone)
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 Conjugated Estrogens, Methyltestosterone

This page covers Bulbine Natalensis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Conjugated Estrogens, Methyltestosterone page lists 226 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 184 moderate · 36 minor.

From our pharmacist’s overview on the Conjugated Estrogens, Methyltestosterone page

“If you take conjugated estrogens with methyltestosterone (Premarin with Methyltestosterone), a hormone combination used for menopausal symptoms, read the six major-rated entries here before adding any supplement. Most of the 226 ingredients on file change how your body handles the hormones themselves.”

Reviewed by 2 · Jul 18, 2026

Open the Conjugated Estrogens, Methyltestosterone 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 Conjugated Estrogens, Methyltestosterone 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 Conjugated Estrogens, Methyltestosterone 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
Top half

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

29 days ago today
Medication Conjugated Estrogens, Methyltestosterone
Top half

#737 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 Conjugated Estrogens, Methyltestosterone, 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 Conjugated Estrogens, Methyltestosterone supplement interactions › Every supplement checked against Conjugated Estrogens, Methyltestosterone, 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 Conjugated Estrogens, Methyltestosterone Together: Common Questions

Can you take Bulbine Natalensis with Conjugated Estrogens, Methyltestosterone?
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 Conjugated Estrogens, Methyltestosterone?
Conjugated Estrogens, Methyltestosterone 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 Conjugated Estrogens, Methyltestosterone 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.