Drug & supplement interaction

Progesterone + Brexanolone

Brexanolone brand name: Zulresso.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 20, 2026
The bottom line No known interaction

We found no known interaction between Progesterone and Brexanolone in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first.

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Interaction report

Progesterone and Brexanolone

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Brexanolone and Progesterone in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Progesterone safety at a glance

Progesterone overall Use caution Progesterone is a hormone and should be used under medical supervision, not as a casual supplement.
Pregnancy Likely Unsafe When used orally, intramuscularly, intravaginally, or transdermally for purposes other than medically supervised adjunctive treatment for infertility. There... Read the full pregnancy detail
Breastfeeding Use caution Discuss with your doctor; appropriateness depends on the form and reason for use.

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center) — the full detail is in the Special populations card below. Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Brexanolone and Progesterone? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Brexanolone

Interactions in our licensed database are recorded against drug classes, not just single drug names. Brexanolone is filed under 2 classifications — antidepressant drugs, cns depressants. Progesterone has documented interactions with 2 drug classes — the most serious being estrogens (moderate) and paclitaxel (abraxane, onxol) (minor) — and none of Brexanolone’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Progesterone Does Interact With Other Medications

Progesterone has 41 moderate, 1 minor known drug interactions in our database — Brexanolone isn’t one of them. If you take anything else, check it against the full list below.

Moderate 41 Minor 1 No known interaction 2,788 (incl. Brexanolone)
Taking anything else?

Check Another of Your Medications Against Progesterone

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

What to actually watch for

What Progesterone Itself Has Been Linked To

This is not an interaction — nothing below involves Brexanolone. It is the side-effect record for Progesterone on its own, from the licensed Natural Medicines monograph. If something new turns up after you add Progesterone, this list is the first place to look. 6 entries are worth acting on rather than waiting out — marked below.

  • Blood clots Worth acting on Additional detail

    “Orally, progesterone can cause fatigue, drowsiness or insomnia, and headache. Topically, progesterone can cause headache. In one case report, a 37-year-old male crushed oral contraceptive pills containing progesterone and estrogen, mixed with water, and applied the mixture to the scalp twice daily for 3 months in an effort to stimulate hair growth. The patient developed a cerebral venous sinus thrombosis.”

    Progesterone · Natural Medicines adverse-effect record, reported in cluster headache.

    6 sources cited
    1. 506. Burnham TH, ed. Drug Facts and Comparisons, Updated Monthly. Facts and Comparisons, St. Louis, MO.
    2. 1224. Freeman EW, Weinstock L, Rickels K, et al. A placebo-controlled study of effects of oral progesterone on performance and mood. Br J Clin Pharmacol 1992;33:293-8. PubMed
    3. 2032. Pouly JL, Bassil S, Frydman R, et al. Luteal support after in-vitro fertilization: Crinone 8%, a sustained release vaginal progesterone gel, versus Utrogestan, an oral micronized progesterone. Hum Reprod 1996;11:2085-9.
    4. 69848. Soderpalm, A. H., Lindsey, S., Purdy, R. H., Hauger, R., and Wit, de H. Administration of progesterone produces mild sedative-like effects in men and women. Psychoneuroendocrinology 2004;29(3):339-354. PubMed
    5. 69986. Magill, P. J. Investigation of the efficacy of progesterone pessaries in the relief of symptoms of premenstrual syndrome. progesterone Study Group. Br.J.Gen.Pract. 1995;45(400):589-593.
    6. 108147. Hermann AC, Nafziger AN, Victory J, Kulawy R, Rocci ML Jr, Bertino JS Jr. Over-the-counter progesterone cream produces significant drug exposure compared to a food and drug administration-approved oral progesterone product. J Clin Pharmacol. 2005;45(6):61 PubMed
  • Yellowing of the skin or eyes Worth acting on Additional detail

    “Orally, progesterone can cause allergic skin rashes and hives. In one case, a female patient treated with progesterone for menorrhagia presented after only 1 week with refractory jaundice due to cholestatic hepatitis and cutaneous inflammation in the form of erythematous, slightly blanchable plaques on the legs, upper arms, and abdomen.”

    Progesterone · Natural Medicines adverse-effect record, reported in dermatitis.

    3 sources cited
    1. 506. Burnham TH, ed. Drug Facts and Comparisons, Updated Monthly. Facts and Comparisons, St. Louis, MO.
    2. 1224. Freeman EW, Weinstock L, Rickels K, et al. A placebo-controlled study of effects of oral progesterone on performance and mood. Br J Clin Pharmacol 1992;33:293-8. PubMed
    3. 105866. Afra TP, Razmi T M, Thoyyib M, et al. Autoimmune progesterone dermatitis as a clue to refractory jaundice in a young woman. Clin Exp Dermatol 2021;46(1):163-164. PubMed
  • Low mood Worth acting on Additional detail

    “Orally, progesterone can cause depression or make depression worse.”

    Progesterone · Natural Medicines adverse-effect record, reported in depression.

    3 sources cited
    1. 506. Burnham TH, ed. Drug Facts and Comparisons, Updated Monthly. Facts and Comparisons, St. Louis, MO.
    2. 1224. Freeman EW, Weinstock L, Rickels K, et al. A placebo-controlled study of effects of oral progesterone on performance and mood. Br J Clin Pharmacol 1992;33:293-8. PubMed
    3. 69944. Crammer, J. L. Premenstrual depression, cortisol and oestradiol treatment. Psychol.Med. 1986;16(2):451-455. PubMed
  • Hives Worth acting on Additional detail

    “Orally, progesterone can cause fluid retention and edema, acne, allergic skin rashes, and hives. When given intravenously, phlebitis has occurred at the injection site.”

    Progesterone · Natural Medicines adverse-effect record, reported in acne.

    4 sources cited
    1. 506. Burnham TH, ed. Drug Facts and Comparisons, Updated Monthly. Facts and Comparisons, St. Louis, MO.
    2. 1224. Freeman EW, Weinstock L, Rickels K, et al. A placebo-controlled study of effects of oral progesterone on performance and mood. Br J Clin Pharmacol 1992;33:293-8. PubMed
    3. 93742. Ma J, Huang S, Qin S, You C, Zeng Y. Progesterone for acute traumatic brain injury. Cochrane Database Syst Rev 2016;12:CD008409. PubMed
    4. 93748. Ma J, Huang S, Qin S, You C. Progesterone for acute traumatic brain injury. Cochrane Database Syst Rev 2012;10:CD008409. PubMed
  • Liver problems Worth acting on Additional detail

    “Progesterone can cause hepatotoxicity with elevated liver function tests. There is also some concern that autoimmune progesterone dermatitis (APD) can cause adverse hepatic effects, possibly due to the presence of progesterone receptors on cholangiocytes and hepatocytes.”

    Progesterone · Natural Medicines adverse-effect record, reported in dermatitis.

    2 sources cited
    1. 275. Young DS. Effects of Drugs on Clinical Laboratory Tests 4th ed. Washington: AACC Press, 1995.
    2. 105866. Afra TP, Razmi T M, Thoyyib M, et al. Autoimmune progesterone dermatitis as a clue to refractory jaundice in a young woman. Clin Exp Dermatol 2021;46(1):163-164. PubMed
  • Bleeding or bruising Worth acting on Additional detail

    “Orally, progesterone can cause altered menstrual cycles and irregular bleeding. Topically, progesterone can cause vaginal spotting.”

    Progesterone · Natural Medicines adverse-effect record, reported in bleeding.

    4 sources cited
    1. 506. Burnham TH, ed. Drug Facts and Comparisons, Updated Monthly. Facts and Comparisons, St. Louis, MO.
    2. 1224. Freeman EW, Weinstock L, Rickels K, et al. A placebo-controlled study of effects of oral progesterone on performance and mood. Br J Clin Pharmacol 1992;33:293-8. PubMed
    3. 69986. Magill, P. J. Investigation of the efficacy of progesterone pessaries in the relief of symptoms of premenstrual syndrome. progesterone Study Group. Br.J.Gen.Pract. 1995;45(400):589-593.
    4. 224. Leonetti HB, Longo S, Anasti JN. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol 1999;94:225-8. DOI
  • Changes to your period Additional detail

    Recorded for Progesterone in the same Natural Medicines adverse-effect record shown under Yellowing of the skin or eyes above.

  • Breast tenderness / Weight gain Additional detail

    Recorded for Progesterone in the same Natural Medicines adverse-effect record shown under Low mood above.

  • Acne Additional detail

    Recorded for Progesterone in the same Natural Medicines adverse-effect record shown under Low mood above.

Showing the 10 most notable of 18 recorded effects — ranked by how unusual each one is across medicines generally, with serious effects weighted up.

Everything above comes from the Natural Medicines adverse-effect record for Progesterone — expand a row for the licensed statement it rests on. We haven’t matched Brexanolone to its FDA label in our system yet, so we can’t compare its own side-effect list here — the leaflet that comes with your prescription is the authoritative list for Brexanolone.

Special populations

Progesterone in Pregnancy & Breastfeeding

Pregnancy Likely Unsafe

When used orally, intramuscularly, intravaginally, or transdermally for purposes other than medically supervised adjunctive treatment for infertility. There is insufficient reliable information available about the safety of any form of supplemental or non-prescription bioidentical progesterone products. Some research has shown that there are large variations in progesterone concentrations in non-prescription progesterone products.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.© 2026 Therapeutic Research Center

Overlapping uses

What Brexanolone Is Prescribed For, and What Progesterone Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Brexanolone is a prescription medicine with approved uses on its FDA label. Progesterone is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Progesterone has been studied for:

  • Postpartum depression studied, not established Progesterone has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

    Progesterone for postpartum depression

    Although there is interest in using oral and/or topical progesterone supplements or non-prescription bioidentical progesterone products for postpartum depression, there is insufficient reliable information about the clinical effects of these products for this condition.

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Brexanolone on your own; if you are taking Progesterone for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Progesterone or Brexanolone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Progesterone or Brexanolone, 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 Brexanolone

This page covers Progesterone only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Brexanolone page lists 79 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major), Kava (major) and L-tryptophan (major).

By severity: 6 major · 67 moderate · 6 minor.

From our pharmacist’s overview on the Brexanolone page

“Brexanolone (Zulresso) is an IV infusion for postpartum depression, and it already carries a boxed warning for excessive sedation and sudden loss of consciousness during treatment. That built-in risk is exactly what most of these 79 supplements press on, so treat this list with genuine care.”

Reviewed by 2 · Jul 18, 2026

Open the Brexanolone interaction page

One more smart check

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

We hold 3 real supplement products containing Progesterone, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Progesterone. Even though Progesterone itself has no known interaction with Brexanolone, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Progesterone and Brexanolone 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 Progesterone
Top half

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

29 days ago today
Medication Brexanolone
Top half

#1,221 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.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Progesterone reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Progesterone and Brexanolone records this page draws on were last updated July 11, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Progesterone

What is Progesterone?

  • Hormone replacement therapy
  • Supporting fertility and early pregnancy (under medical care)
  • Irregular or absent menstrual periods
  • Menopause-related symptoms (with estrogen)
  • Symptoms some attribute to low progesterone

Progesterone is a natural hormone, and prescription forms are used for fertility support, menstrual problems, and hormone therapy. Over-the-counter "natural" progesterone creams are not well standardized and their benefits are unproven, so any use of progesterone should be guided by a doctor or pharmacist.

Hormone (made in the body; supplement versions are synthesized, often from plant sterols) · Oral capsules, vaginal gels/inserts/suppositories, topical creams, intramuscular injections

An interaction check asks whether these two react with each other — it does not ask whether Progesterone is a good idea for someone in your situation. Here is what our Progesterone record says about it on its own.

Progesterone: dosing

There is no single standard dose for progesterone, and the right amount depends heavily on the form, the medical reason, and the person. Prescription dosing is set by a doctor based on the specific condition being treated.For over-the-counter creams, products vary widely in how much hormone they contain, and a reliable, proven dose has not been established.

From our Progesterone monograph — the full record covers uses, side effects and every documented interaction.

Read the full Progesterone monograph & all interactions
Medication

About Brexanolone Injection

What Is Brexanolone Injection Used For?

Brand name: Zulresso

  • Brexanolone injection is used for the treatment of postpartum depression (PPD) in adults. Brexanolone injection is in a class of medications called neurosteroid antidepressants. It works by changing the activity of certain natural substances in the brain.

See full Brexanolone Injection drug information
Keep checking

Other Drugs & Progesterone

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

0Major
41Moderate
1Minor
2,787No known interaction
41 Moderate 1 Minor 2,787 No interaction
Moderate

41 interactions

Minor

1 interaction

No interaction 2,787 drugs checked — show the list

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

Showing the 60 most looked-up of 2,787 medications checked with no known interaction — see the full Progesterone list.

See the full Progesterone interactions page
See every supplement checked against Brexanolone, ranked by severity
Evidence & sources

Progesterone References

The 21 references that drive our Progesterone monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Leonetti HB, Longo S, Anasti JN. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol 1999;94:225-8. DOI
  3. Greendale GA, Reboussin BA, Hogan P, et al. Symptom relief and side effects of postmenopausal hormones: results from the Postmenopausal Interventions Trial. Obstet Gynecol 1998;92:982-8.
  4. Young DS. Effects of Drugs on Clinical Laboratory Tests 4th ed. Washington: AACC Press, 1995.
  5. Burnham TH, ed. Drug Facts and Comparisons, Updated Monthly. Facts and Comparisons, St. Louis, MO.
  6. Chen FP, Lee N, Soong YK. Changes in the lipoprotein profile in postmenopausal women receiving hormone replacement therapy. Effects of natural and synthetic progesterone. J Reprod Med 1998;43:568-74.
  7. Espeland MA, Marcovina SM, Miller V, et al. Effect of postmenopausal hormone therapy on lipoprotein(a) concentration. Postmenopausal Estrogen/Progestin Interventions (PEPI) Investigators. Circulation 1998;97:979-86. DOI
  8. Freeman EW, Weinstock L, Rickels K, et al. A placebo-controlled study of effects of oral progesterone on performance and mood. Br J Clin Pharmacol 1992;33:293-8. PubMed
  9. Pouly JL, Bassil S, Frydman R, et al. Luteal support after in-vitro fertilization: Crinone 8%, a sustained release vaginal progesterone gel, versus Utrogestan, an oral micronized progesterone. Hum Reprod 1996;11:2085-9.
  10. Aebi S, Schnider T W, Los G, et al. A phase II/pharmacokinetic trial of high-dose progesterone in combination with paclitaxel. Cancer Chemother. Pharmacol. 1999;44(3):259-265. PubMed
  11. de, Wit H., Schmitt, L., Purdy, R., and Hauger, R. Effects of acute progesterone administration in healthy postmenopausal women and normally-cycling women. Psychoneuroendocrinology 2001;26(7):697-710. PubMed
  12. Soderpalm, A. H., Lindsey, S., Purdy, R. H., Hauger, R., and Wit, de H. Administration of progesterone produces mild sedative-like effects in men and women. Psychoneuroendocrinology 2004;29(3):339-354. PubMed
  13. Crammer, J. L. Premenstrual depression, cortisol and oestradiol treatment. Psychol.Med. 1986;16(2):451-455. PubMed
  14. Magill, P. J. Investigation of the efficacy of progesterone pessaries in the relief of symptoms of premenstrual syndrome. progesterone Study Group. Br.J.Gen.Pract. 1995;45(400):589-593.
  15. Ma J, Huang S, Qin S, You C, Zeng Y. Progesterone for acute traumatic brain injury. Cochrane Database Syst Rev 2016;12:CD008409. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Progesterone and Brexanolone Together: Common Questions

Is it safe to take Progesterone with Brexanolone?
We do not list a known interaction between Progesterone and Brexanolone. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Are Progesterone and Brexanolone used for the same thing?
They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for Progesterone in each. That is a conversation for your prescriber, especially if Brexanolone is being adjusted to a target.
How was the Progesterone and Brexanolone combination checked?
Interactions in our licensed database are recorded against drug classes. Brexanolone is filed under 2 classifications, and Progesterone has documented interactions with 2 drug classes — none of Brexanolone's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Progesterone interact with any other medications?
Yes. Progesterone has 42 documented drug interactions in our database — Brexanolone is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Brexanolone interact with any supplements?
Yes. Brexanolone has documented interactions with 79 supplements in our database — Progesterone is not one of them. The Brexanolone interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

Progesterone monograph Uses, safety profile, and every drug interaction in one place Brexanolone Injection drug information The full plain-English guide to this medication Brexanolone supplement interactions Every supplement checked against Brexanolone, 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 References The 21 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Brexanolone and Progesterone?

Our pharmacists answer your medication & supplement questions — free.

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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.