Herb & supplement monograph

Progesterone Drug Interactions, Uses, Effectiveness, Safety & More

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS ·Updated July 2026

What is this page for?

First and foremost: how Progesterone interacts with medications. The heart of this page is the interaction list — every drug Progesterone is known to interact with, and how serious each one is.

But these pages have grown well beyond that into a full monograph — what Progesterone is, what people use it for and how strong the evidence is, its safety and side effects, and answers to the questions we’re asked most — written and reviewed by the clinical staff at HelloPharmacist. It’s educational information from our licensed clinical databases, not medical advice, and we don’t sell or endorse products. Our editorial policy

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Progesterone Drug Interactions: The Bottom Line

From the HelloPharmacist Editorial Team · Updated July 2026

Based on the available evidence, the overall risk of a clinically significant Progesterone drug interaction appears low for most people. None of the listed interactions are rated major, and even the moderate ones rest on theoretical or limited human evidence rather than well-documented harm.

Interactions deserving the most attention

The combination that deserves the most thought is estrogens. Taking progesterone supplements alongside estrogen may change how the estrogen works, and in some postmenopausal women it appears to blunt part of estrogen's benefit; prescription combinations can also cause breast tenderness. The chemotherapy drug paclitaxel is worth mentioning too, since high-dose intravenous progesterone raised paclitaxel levels in one human study, though key blood cell counts were not affected and the meaning of this for supplements is unclear.

What the rest of the list means

Although progesterone carries a fairly long list of interacting medications, that number does not mean every combination is harmful. Most of these ratings are cautious, theoretical calls based on how progesterone might behave in the body, and in the cases studied, the predicted effects have not clearly produced meaningful problems in people.

Check your medications against Progesterone

Based on HelloPharmacist’s Progesterone interaction data and reviewed under our editorial standards.

Interaction report

Drugs that interact with Progesterone

42 medications have a known interaction with Progesterone, graded by severity. Select any drug for the full evidence-based detail.

Don’t want to scroll the list? Just ask.

Tell us the medications you take and we’ll check each one against Progesterone using our pharmacist-reviewed interaction data.

AI summaries are generated from our Progesterone interaction data for education only — always confirm with your pharmacist. How we use AI

2,830 drugs

Read The List Like a Pharmacist

What Severity, Likelihood & Evidence Mean

Severity — How Serious It Can Be

Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
No known interaction. Checked against our sources with nothing documented — not the same as proven safety.

Likelihood — How Well It’s Documented

Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
Probable. Interaction 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.
Possible. 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
Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

Where This Data Comes From

Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
Each drug listed above links to the full report for that exact Progesterone combination — clinical detail, likelihood, evidence level, and citations.
Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

The big picture

The kinds of drugs Progesterone affects

Every type of medication (drug category) Progesterone is known to interact with. Open any category for the detail — or search your exact drug in the checker above.

All 2 drug categories Progesterone interacts with

EstrogensPaclitaxel (abraxane, Onxol)

Estrogens

Theoretically, using estrogen along with progesterone supplements or non-prescription bioidentical progesterone products might alter the effects of estrogen.
Concomitant use of estrogen with prescription progesterone products can cause breast tenderness. Also, use of conjugated equine estrogens with oral micronized progesterone in postmenopausal patients seems to blunt the beneficial effects of estrogen on the lipoprotein profile, although it might not affect estrogen-induced reduction in plasma lipoprotein (a). It is unclear if this interaction would be clinically significant with the doses found in oral or topical progesterone supplements or non-prescription bioidentical products.

Likelihood Possible Evidence A

Paclitaxel (Abraxane, Onxol)

Theoretically, using paclitaxel along with progesterone supplements or non-prescription bioidentical progesterone products might increase paclitaxel levels and adverse effects.
Human research suggests that administering high-dose progesterone intravenously along with paclitaxel can increase plasma levels of paclitaxel without affecting neutrophil and platelet nadir counts. It is unclear if this interaction would be clinically significant with the doses found in oral or topical progesterone supplements or non-prescription bioidentical products.

Likelihood Possible Evidence B

Monograph

Progesterone: Uses, Safety & Side Effects

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS · Reviewed July 2026 ·

The bottom line

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.

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

People commonly use it for

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

Popular and traditional uses — not proof it works. See “Uses & effectiveness” below for the evidence.

Safety at a glance

OverallUse caution

Progesterone is a hormone and should be used under medical supervision, not as a casual supplement.

PregnancyLikely Unsafe

When used orally, intramuscularly, intravaginally, or transdermally for purposes other than medically supervised adjunctive treatment for infertility....

Read the full pregnancy detail

BreastfeedingInsufficient reliable information

Insufficient reliable information available; avoid using.

Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center). Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

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Overview

Progesterone is a hormone that your body makes naturally. In women it is produced mainly by the ovaries after ovulation and by the placenta during pregnancy. It plays a key role in the menstrual cycle, in preparing the uterus for pregnancy, and in maintaining a pregnancy.

Progesterone is not really an herb. Supplement and medication versions are made in a lab, often starting from plant sterols found in soy or wild yam, which are chemically changed into progesterone that matches the body's own hormone (sometimes called "micronized" or "bioidentical" progesterone).

You may see progesterone as prescription products (capsules, vaginal gels, suppositories, and injections) used for fertility and hormone therapy, as well as over-the-counter "natural progesterone" creams sold as supplements. The over-the-counter products are much less regulated and standardized.

How it works

Progesterone works by attaching to progesterone receptors found in tissues like the uterus, breasts, and brain. After ovulation, it prepares the lining of the uterus so a fertilized egg can implant, and it helps keep that lining stable during pregnancy.

It also balances the effects of estrogen. This is why it is paired with estrogen in hormone therapy — the progesterone helps keep the uterine lining from overgrowing.

In the brain, progesterone breaks down into compounds that may affect calming chemical signals, which is one proposed reason some people report effects on mood or sleep. Much of this remains an area of ongoing research, and effects from low-dose creams are uncertain.

Effectiveness

Does Progesterone work?

Here’s what the research actually shows for each use — graded by Natural Medicines and reviewed by Dr. Brian Staiger, PharmD.

Evidence overview · 18 uses evaluated

18 Insufficient evidence

How to read these evidence grades

Natural Medicines’ 7-point scale. We show each rating’s label word-for-word.

1EffectiveStrong, consistent evidence it works.

2Likely EffectiveGood evidence, though not yet conclusive.

3Possibly EffectiveSome evidence suggests a benefit.

4Possibly IneffectiveSome evidence it may not help.

5Likely IneffectiveFairly strong evidence it doesn’t help.

6IneffectiveStrong evidence it doesn’t work.

7Insufficient Reliable Evidence to RateToo little research to say either way.

For Progesterone, current evidence isn’t strong enough to rate any specific use. The conditions it has been studied for are listed below.

Also studied for 18 conditions — evidence insufficient to rate

Insufficient Reliable Evidence To Rate Amenorrhea