Drug & supplement interaction

Pregnenolone + Estradiol, Progesterone

Estradiol, Progesterone brand name: Bijuvanda.

Moderate Interaction
The bottom line Moderate

Estradiol, Progesterone falls into 3 drug categories that Pregnenolone can interact with; the most serious is rated moderate. Theoretically, taking pregnenolone might enhance the effects of estrogens.

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

Pregnenolone and Estradiol, Progesterone

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

Why Are There 3 Interactions?

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

Moderate

ESTROGENS

1 of 3

Why this applies to Estradiol, Progesterone

Estradiol, Progesterone falls under ESTROGENS — the group Pregnenolone interacts with.

Theoretically, taking pregnenolone might enhance the effects of estrogens.
Pregnenolone is a precursor for several steroid hormones, including estrogens.
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 thinking behind this one. Your body uses pregnenolone as an early raw material to make other hormones, and estrogen is one of the things it can be turned into. So on paper, adding pregnenolone on top of your Bijuva (estradiol and progesterone) might nudge your estrogen activity a little higher than the medication alone.

If that happened, you could notice more of the usual estrogen-related effects, like breast tenderness, bloating, nausea, headaches, or spotting. I want to be honest though: this is a theoretical concern based on how these hormones work, not something proven in studies. Since Bijuva is already a carefully dosed hormone product, please check with your pharmacist or doctor before adding pregnenolone rather than changing anything on your own.

References
  1. Devlin TM, ed. Textbook of Biochemistry With Clinical Correlations. third ed. New York: Wiley-Liss Inc., 1992.
Moderate

PROGESTIN

2 of 3

Estradiol, Progesterone also falls under PROGESTIN.

Theoretically, taking pregnenolone might enhance the effects of progestin.
Pregnenolone is a precursor for several steroid hormones, including progestin.
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 simple version. Your Bijuva pill gives you two hormones, estradiol and progesterone, usually to ease menopause symptoms. Pregnenolone is a hormone your body uses as a starting material to build other hormones, including progesterone-like ones. So the worry is that adding pregnenolone could nudge your hormone levels a little higher and add to what your medication is already doing.

I want to be honest, though: this is a theoretical concern based on how these hormones work, not on strong human studies. If it did matter, you might notice more progesterone-type effects like breast tenderness, bloating, mood changes, or drowsiness. Because we're talking about hormones, please loop in your doctor or pharmacist before combining them rather than guessing.

References
  1. Devlin TM, ed. Textbook of Biochemistry With Clinical Correlations. third ed. New York: Wiley-Liss Inc., 1992.
Moderate

PROGESTERONE

3 of 3

Estradiol, Progesterone also falls under PROGESTERONE.

Theoretically, taking pregnenolone might enhance the effects of progesterone.
In humans, some research shows that oral administration of pregnenolone can increase levels of progesterone. However, other research shows no effect on progesterone levels. It is possible the impact of pregnenolone on progesterone levels may be dose dependent.
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 simple picture: Bijuva already gives you progesterone (along with estradiol). Pregnenolone sits near the top of your body's hormone-making chain, and it can be converted into progesterone. So in theory, adding pregnenolone on top of your Bijuva could nudge your overall progesterone a bit higher than the dose alone.

If that happens, you might notice more of progesterone's usual effects, things like drowsiness, bloating, breast tenderness, or mood changes. But honestly, the evidence here is weak and theoretical. Some studies showed a small rise in progesterone, others showed none, and it may depend on dose. I wouldn't lose sleep over it, but since both are hormones, please run pregnenolone past your pharmacist or doctor before combining them.

References
  1. Ritsner MS, Gibel A, Shleifer T, et al. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry 20 PubMed
  2. Marx CE, Keefe RS, Buchanan RW, et al. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Neuropsychopharmacology 2009;34(8):1885-903. 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

Pregnenolone Also Interacts With Other Medications

Pregnenolone has 81 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.

Taking anything else?

Check Another of Your Medications Against Pregnenolone

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

Everything else you take

See Every Supplement That Interacts With Estradiol, Progesterone

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

We hold 303 real supplement products containing Pregnenolone, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Pregnenolone. Your product may carry other ingredients that interact with Estradiol, Progesterone too, on top of Pregnenolone — 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 Pregnenolone 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 Pregnenolone
Top 25%

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

29 days ago today
Medication Estradiol, Progesterone
Top half

#1,309 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 Pregnenolone

What is Pregnenolone?

Pregnenolone
  • Memory and cognitive support
  • Anxiety and stress
  • Anti-aging
  • Fatigue and low energy
  • Mood support

Pregnenolone is a hormone your body makes naturally and a building block for other hormones like cortisol, DHEA, estrogen, and testosterone. It is sold as a supplement for memory, mood, and anti-aging, but solid human evidence for these uses is very limited. Because it is a hormone, talk with your pharmacist or doctor before using it.

Read the full Pregnenolone monograph & all interactions
Keep checking

Other Drugs & Pregnenolone

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

0Major
81Moderate
0Minor
2,748No known interaction
Moderate

81 interactions

Showing 60 of 81 moderate interactions — see all 81 on the Pregnenolone page.

No interaction 2,748 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Pregnenolone and Estradiol, Progesterone Together: Common Questions

Can you take Pregnenolone 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 Pregnenolone and Estradiol, Progesterone?
Estradiol, Progesterone belongs to more than one drug category, and Pregnenolone 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 Pregnenolone 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

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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.