Drug & supplement interaction

Pregnenolone + Progesterone

Progesterone brand name: Milprosa.

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

Pregnenolone has a moderate interaction with Progesterone. Theoretically, taking pregnenolone might enhance the effects of progesterone.

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

Pregnenolone and Progesterone

Here is the interaction we found between these two, with the evidence behind it.

Moderate

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 version: your body uses pregnenolone as a raw material to build other hormones, and progesterone is one of the hormones it can be converted into. So in theory, adding a pregnenolone supplement on top of your prescribed progesterone could nudge your overall progesterone activity a bit higher.

If that happened, you might notice more of progesterone's usual effects, things like drowsiness, dizziness, breast tenderness, bloating, or mood changes. I want to be honest though: this is a theoretical concern based on how these hormones work, and the human studies are mixed (some showed a rise in progesterone, others showed nothing), possibly depending on the dose. Since both are hormones, please loop in your pharmacist or doctor before combining them rather than guessing.

Contact Dr. Brian directly if you have additional questions on this interaction
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 Progesterone one above is one of them. If you take anything else, check it against the full list below.

Moderate 81 No known interaction 2,749 (incl. Progesterone)
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.

From our Q&A

Questions About Pregnenolone or Progesterone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Pregnenolone or Progesterone, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Progesterone

This page covers Pregnenolone only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Progesterone page lists 126 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate), Adrafinil (moderate) and African Wild Potato (moderate).

By severity: 2 major · 91 moderate · 33 minor.

From our pharmacist’s overview on the Progesterone page

“Many people take progesterone (Milprosa) to support a pregnancy during fertility treatment or as part of hormone therapy, which is exactly when St. John's wort for mood or a morning glass of grapefruit juice can feel harmless.”

Reviewed by 2 · Jul 18, 2026

Open the 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 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 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%

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

29 days ago today
Medication Progesterone
Top 10%

#221 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
Medication

About Progesterone

What Is Progesterone Used For?

Brand name: Milprosa

Progesterone capsules (including Prometrium) are used to prevent endometrial hyperplasia (abnormal thickening of the uterine lining) in postmenopausal women with a uterus who are taking estrogen, and to treat secondary amenorrhea (missed periods not caused by pregnancy).

Progesterone injection is indicated for amenorrhea and abnormal uterine bleeding caused by a hormonal imbalance. Crinone vaginal gel is used as part of Assisted Reproductive Technology (ART) for progesterone supplementation or replacement, and Crinone 4% is also indicated for secondary amenorrhea. Vaginal inserts — including Endometrin and other progesterone vaginal insert products — are used to support embryo implantation and early pregnancy as part of an ART treatment program for infertile women.

See full Progesterone drug information
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
81 Moderate 2,748 No 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

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

Showing the 60 most looked-up of 2,748 medications checked with no known interaction — see the full Pregnenolone list.

See the full Pregnenolone interactions page
See every supplement checked against 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
Pregnenolone monograph › Uses, safety, and every drug interaction in one place Progesterone supplement interactions › Every supplement checked against Progesterone, ranked by severity Progesterone drug information › The full plain-English guide to this medication 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 Pregnenolone and Progesterone Together: Common Questions

Can you take Pregnenolone with 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.
How serious is the Pregnenolone and 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 Progesterone and Pregnenolone?

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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.