Red Clover - Prometrium (Progesterone (prescription drug)) Interaction
Herbal: Red Clover
Also Known As: Trifolium pratense, Beebread, Clovone, Cow Clover, Daidzein, Genistein, Isoflavone, Meadow Clover, Miel des Prés, Phytoestrogen, Purple Clover, Trebol Rojo, Trèfle Commun, Trèfle des Prés, Trèfle Pourpre, Trèfle Rouge, Trèfle Rougeâtre, Trèfle Violet, Trefoil, Trifolium
Drug: Progesterone (prescription drug)
Brand names:
Prometrium, Endometrin, Utrogestan
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
May 25, 2025
Interaction Details
Progesterone (prescription drug) is classified as belonging to the following category: Cytochrome P450 2C19 (Cyp2C19) Substrates
Theoretically, red clover might increase the levels and clinical effects of drugs metabolized by CYP2C19.
In vitro evidence suggests that red clover weakly inhibits CYP2C19. This interaction has not been reported in humans.
Interaction Rating
Likelihood of Occurrence
UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
References
- Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1
Interaction Details
Progesterone (prescription drug) is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Substrates
Theoretically, red clover might increase levels of drugs metabolized by CYP3A4; however, a small clinical study found no effect.
In vitro evidence shows that red clover might inhibit CYP3A4 isoenzymes. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of alprazolam, a CYP3A4 probe substrate.
Interaction Rating
Likelihood of Occurrence
UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
References
- Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82.
- Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1
- Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939.
Red Clover Overview
Red clover (Trifolium pratense) is a perennial plant that is native to Europe and Asia, but is also found in many parts of the world, including North America.
Red clover has a long history of use in traditional medicine and is believed to have a number of potential health benefits. It is a rich source of isoflavones, which are thought to have estrogen-like effects and is therefore often marketed for women's health. It has been used to treat hot flashes and other menopause symptoms as well as cardiovascular disease, high cholesterol, and osteoporosis.
Progesterone (prescription drug) Overview
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Progesterone is used as a part of hormone replacement therapy in women who have passed menopause (the change of life) and have not had a hysterectomy (surgery to remove the uterus). Hormone replacement therapy usually includes estrogen, which is used to treat symptoms of menopause and reduce the risk of developing certain diseases. However, estrogen can also cause abnormal thickening of the lining of the uterus and increase the risk of developing uterine cancer. Progesterone helps to prevent this thickening and decreases the risk of developing uterine cancer. Progesterone is also used to bring on menstruation (period) in women of childbearing age who have had normal periods and then stopped menstruating. Progesterone is in a class of medications called progestins (female hormones). It works as part of hormone replacement therapy by decreasing the amount of estrogen in the uterus. It works to bring on menstruation by replacing the natural progesterone that some women are missing.
Red Clover - More Interactions
Red Clover interacts with 844 drugs
Interaction Rating Key
These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.
| Major | The combined use of these agents is strongly discouraged as serious side effects or other negative outcomes could occur. |
| Moderate | Use cautiously under the care of a healthcare professional or avoid this combination. A significant interaction or negative outcome could occur. |
| Minor | Be aware that there is a chance of an interaction. Watch for warning signs of a potential interaction. |
| Unknown | No interactions have been reported or no interaction data is currently available. |
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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
Drug descriptions are provided by MedlinePlus.
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In addition to being a clinical pharmacist specializing in pharmacotherapy, Dr. Brian Staiger is a registered herbalist through the American Herbalist Guild. He has combined his passion for pharmacy practice with the study of medical ethnobotany to improve patient care. Feel free to reach out about any of your herbal or medication questions!
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