Drug & supplement interaction

Progesterone + Amitriptyline

Amitriptyline brand name: Elavil.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Progesterone and Amitriptyline 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. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Progesterone and Amitriptyline

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 Amitriptyline 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 Amitriptyline and Progesterone? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Amitriptyline

Interactions in our licensed database are recorded against drug classes, not just single drug names. Amitriptyline is filed under 15 classifications — including tricyclic antidepressants (tcas), antidepressant drugs, cytochrome p450 2c19 (cyp2c19) substrates. Progesterone has documented interactions with 2 drug classes — the most serious being estrogens (moderate) and paclitaxel (abraxane, onxol) (minor) — and none of Amitriptyline’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 — Amitriptyline 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. Amitriptyline)
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

No Interaction Found — But Data Suggests Progesterone and Amitriptyline May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. 4 of them are worth acting on rather than waiting out — marked below.

  • Yellowing of the skin or eyes Worth acting on Additional detail

    Progesterone

    “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

    Amitriptyline

    Listed in the ADVERSE REACTIONS section of the FDA label for Amitriptyline. Read the label on DailyMed ›

  • Hives Worth acting on Additional detail

    Progesterone

    “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

    Amitriptyline

    Listed in the ADVERSE REACTIONS section of the FDA label for Amitriptyline. Read the label on DailyMed ›

  • Liver problems Worth acting on Additional detail

    Progesterone

    “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

    Amitriptyline

    Listed in the ADVERSE REACTIONS section of the FDA label for Amitriptyline. Read the label on DailyMed ›

  • Bleeding or bruising Worth acting on Additional detail

    Progesterone

    “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

    Amitriptyline

    Listed in the ADVERSE REACTIONS section of the FDA label for Amitriptyline. Read the label on DailyMed ›

  • Breast tenderness / Weight gain Additional detail

    Progesterone

    Recorded for Progesterone in the same Natural Medicines adverse-effect record shown under Bleeding or bruising above.

    Amitriptyline

    Listed in the ADVERSE REACTIONS section of the FDA label for Amitriptyline. Read the label on DailyMed ›

  • Drowsiness Additional detail

    Progesterone

    “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

    Amitriptyline

    Listed in the ADVERSE REACTIONS section of the FDA label for Amitriptyline. Read the label on DailyMed ›

  • Trouble sleeping / Tiredness reported in 8.3% of FDA reports for Amitriptyline Additional detail

    Progesterone

    Recorded for Progesterone in the same Natural Medicines adverse-effect record shown under Bleeding or bruising above.

    Amitriptyline

    Listed in the ADVERSE REACTIONS section of the FDA label for Amitriptyline, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • Fever Additional detail

    Progesterone

    “Orally, progesterone can cause fever, breast discomfort or enlargement, and PMS-like symptoms. Additionally, use of progesterone with estrogen is associated with greater risk of mammary gland hyperplasia.”

    Progesterone · Natural Medicines adverse-effect record, reported in premenstrual syndrome (pms).

    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. 112975. Yan Z, Yun-Yun L, Zhou T, Li-Rong C, Xiao-Li Y, Yong L. The relationship between using estrogen and/or progesterone and the risk of mammary gland hyperplasia in women: a meta-analysis. Gynecol Endocrinol 2022;38(7):543-547. PubMed

    Amitriptyline

    Listed in the ADVERSE REACTIONS section of the FDA label for Amitriptyline. Read the label on DailyMed ›

Showing the 10 most notable of 13 shared effects — ranked by how unusual each one is, not just whether both lists mention it.

Reported for Progesterone but not commonly for Amitriptyline: blood clots, stomach upset, changes to your period and low mood.

Effects for Amitriptyline come from the ADVERSE REACTIONS section of its FDA label; effects for Progesterone come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 17,459 voluntary FDA FAERS reports for Amitriptyline that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

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

From our Q&A

Questions About Progesterone or Amitriptyline

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 Amitriptyline, 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 Amitriptyline

This page covers Progesterone only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline page lists 296 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 17 major · 228 moderate · 51 minor.

From our pharmacist’s overview on the Amitriptyline page

“Amitriptyline (Elavil), an older antidepressant now often prescribed for nerve pain, migraines, and sleep, is one of the drugs I genuinely want patients to be careful with, and 17 of the 296 supplement and herbal ingredients on this list carry a major rating. Most of the serious ones deepen the drowsiness amitriptyline already causes,…”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline 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 Amitriptyline, 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 Amitriptyline 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

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

29 days ago today
Medication Amitriptyline
Top 5%

#52 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 13, 2026. The Progesterone and Amitriptyline 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 Amitriptyline

What Is Amitriptyline Used For?

Brand name: Elavil

Amitriptyline HCL and Amitriptyline Hydrochloride tablets are used to relieve symptoms of depression. Depression that originates from within the body (called endogenous depression) tends to respond better than other types of depression.

Most-Reported Side Effects for Amitriptyline

From FAERS, the FDA’s public side-effect reporting system (17,459 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Nausea 1,535 reports
Headache 1,476 reports
Fatigue 1,448 reports
Dyspnea 1,442 reports
Dizziness 1,227 reports
See full Amitriptyline 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 Amitriptyline, 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 Amitriptyline Together: Common Questions

Is it safe to take Progesterone with Amitriptyline?
We do not list a known interaction between Progesterone and Amitriptyline. 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.
Do Progesterone and Amitriptyline have any of the same side effects?
Yes — our sources link each of them separately to 10 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
How was the Progesterone and Amitriptyline combination checked?
Interactions in our licensed database are recorded against drug classes. Amitriptyline is filed under 15 classifications, and Progesterone has documented interactions with 2 drug classes — none of Amitriptyline'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 — Amitriptyline 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 Amitriptyline interact with any supplements?
Yes. Amitriptyline has documented interactions with 296 supplements in our database — Progesterone is not one of them. The Amitriptyline 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 Amitriptyline drug information The full plain-English guide to this medication Amitriptyline supplement interactions Every supplement checked against Amitriptyline, 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 Amitriptyline 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.