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 DOI: 10.1258/1362180042721067

2004 10: 162Menopause IntAlyson Huntley

Drug-herb interactions with herbal medicines for menopause  

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JOURNAL OF THE BRITISH MENOPAUSE SOCIETY, December 2004

Review

Drug-herb interactions with herbalmedicines for menopauseAlyson Huntley Research Fellow Peninsula Medical School, Universities of Exeter and Plymouth

Address for correspondenceDr Alyson HuntleyResearch FellowComplementary MedicinePeninsula Medical SchoolUniversities of Exeter and Plymouth25 Victoria Park RoadExeter EX2 4NT, UK

SummaryHerbal medicine is one of most popular choices of complementarytherapies for women, particularly as an alternative treatment formenopausal symptoms. The most commonly used herbal medicinesfor the menopause is probably black cohosh (Actaea/Cimcifugaracemosa); other preparations used include red clover (Trifoliumpratense), dong quai (Angelica sinesis) and evening primrose(Oenothera biennis). Some of these herbal medicines have a verygood safety profile with little or no suggestion of interaction withconventional drugs. For others, there are many and significantdrug-herb interactions. This article outlines the major known andtheoretical drug-herb interactions of herbal medicines thought to beof benefit for menopausal symptoms, as well as discussing theimplications for the medical profession.

Key wordsDrug-herb interactions, herbal medicine, menopause, oestrogen,phytoestrogen

IntroductionHerbal medicine has become increasingly popular and isused more widely by women than men, particularly womenin their middle and advancing age.1 Women report usingherbal medicine for relief of their menopausal symptoms aswell as for increased energy, less joint pain, better sleep andimproved memory.2 However, despite this increased use ofherbal medicine, there is a lack of clinical evidence tosupport their safety and efficacy.3

There is also evidence that patients are less likely to reportadverse events from herbal medicines to their doctor thanthose from conventional medicine.4 Similarly, health profes-sionals do not always ask. This communication is critical foridentifying and avoiding the potential hazard of drug-herbinteractions. Such an interaction is more likely to occur ifpatients are choosing herbal medicines with the samereputed mechanism as their conventional medication if theyare taking three or more prescription/over the counter (OTC)drugs or high-risk drugs. Thus, it is essential for health

professionals to be aware of potential drug-herb interactionsof the most commonly used herbal medicines and thosewithin their area of expertise.

The most popular herbal medicine for relief of menopausalsymptoms, specifically hot flushes is black cohosh(Actaea/Cimicifuga racemosa). Red clover, a source ofisoflavones, is probably the second most used herbalmedicine.2 Other popular herbal medicines include St John’swort (Hypericum perforatum) for mood and mild tomoderate depression.5 Despite a lack of scientific investi-gation, herbal medicines such as dong quai (Angelicasinesis) and evening primrose (Oenothera biennis) as well asherbal combinations are also used for menopausalsymptoms.3 This article describes the drug-herb interactionsknown or theoretically associated with the most commonlyused herbal medicines by symptomatic menopausal women.

Black cohoshThe main constituents of black cohosh are triterpeneglycosides, phenolic acids, flavonoids, volatile oils andtannins.6 Black cohosh extracts do not contain significantamounts of phytoestrogenic compounds; recent researchsuggests that it is not oestrogenic in vitro and does notpromote breast cancer growth.7 There is no consensus onhow it might work to relieve hot flushes, although centralactivity is suggested.8 There are no known drug-herbinteraction issues with black cohosh extract. It is suggestedthat there is the potential for interaction with antihyper-tensive agents (increasing their action).9 However, to datethere is no clinical evidence to support this theory.

Dong quaiIn the Chinese Materia Medica dong quai is indicated fordisorders of menstruation including menopausalsymptoms.10 The herb is extracted from the root of Angelicasinensis and is used in traditional Chinese medicine tostrengthen the energy that emanates from the blood. Thesymptoms of “deficient blood energy” listed in Chinesetexts are similar to those that Western medicine associateswith menopause: menstrual flow abnormalities, nervousness,dizziness, insomnia and forgetfulness. Dong quai has beenused in traditional Chinese medicine for over 2000 years. Itmay enhance endogenous oestrogen production, containoestrogen substances or alleviate symptoms of oestrogendeficiency without altering oestrogen levels. Whether dongquai contains phytoestrogens is unclear.11

Dong quai contains osthole and ferulic acid that may inhibitplatelet aggregation, thus is contraindicated with anticoag-

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ulants and drugs that increase the risk of bleeding.9 Therehas been a case report of adverse events followingconcurrent use of dong quai with warfarin.12 Effect onexogenous hormone treatments is not known.9

Evening primroseEvening primrose is not actually a primrose but belongs tothe fuchsia (Onagraceae) family. Traditionally, the wholeplant has been used for its medicinal properties to treat awide range of conditions. Today, it is mainly the oil that isused for therapeutic purposes.13 Although neither themedical profession nor the pharmaceutical industry has everpromoted evening primrose oil (EPO) for the purpose, thereis a view among the public that it is effective in the controlof menopausal vasomotor symptoms, with only anecdotalcase reports to support this theory.14 Although EPOcontains about 9% cis-gamma linolenic acid, a precursor ofprostaglandin E1, there is no good scientific rationale yet forthe use of EPO for hot flushes.13,14

In terms of drug-herb interactions, there is the theoreticalrisk of interactions with anti-inflammatory drugs, corticos-teroids, beta-blockers, antipsychotics and anticoagulants.9Concomitant use with epileptogenic agents such as pheno-thiazines may increase the risk of seizures.9

Ginkgo (Ginkgo biloba)Although not specifically considered to be of benefit formenopausal symptoms such as hot flushes, ginkgo is thoughtto be of value for dementia and memory impairment.15

One randomised controlled trial on ginkgo with menopausalwomen suggested modest cognitive effects.16 Mainconstituents are ginkgolides, bilobalide and flavonoids.Ginkgo is thought to potentiate the action of anti-coagulants.9

Ginseng (Asian or Panax ginseng)Panax ginseng, a perennial herb native to Korea and China,has been used as a herbal medicine in eastern Asia forthousands of years. Modern therapeutic claims refer tovitality, immune function, cancer, cardiovascular disease andimprovement of cognitive, physical and sexual function.13

Beneficial effect of ginseng for the menopausal women hasfocused on health-related quality of life symptoms.17

Ginseng contains ginsenosides (triterpene saponins) that arethought to have oestrogenic properties. Drug-herbinteractions have been observed with warfarin, phenelzineand alcohol amongst other drugs.9

Kava (Piper methysticum)Kava is prepared from the rhizome of Piper methysticum. Inthe south Pacific, kava extracts have been traditionally usedfor recreational and medicinal purposes. It is known for itsanxiolytic properties, which is why it is thought beneficialfor women experiencing these types of symptoms during themenopause.18 Its active ingredients are kavapyrones, actingthrough the α-aminobutyric acid-A receptors in nerveendings. It was removed from the UK market in 2002, dueto a series of serious hepatic adverse events.19 Interactionshave been reported with alprazolam leading to excessivesedation, anticoagulants, where kavain, a component ofkava, inhibits platelet aggregation, and antipsychotics, where

the herb may decrease extrapyramidal side effects of drugs.9

Red clover (Trifolium pratense)Red clover has traditionally been used for chronic skinconditions. However, this herbal medicine is a source ofisoflavones and supplements containing extracts of the planthave become popular for menopausal symptoms.3 It hasbeen shown in vitro to have weak oestrogenic activity butwhether this has any effect when combined with oestrogenreplacement or oral contraceptives is unknown. In vitroresearch has shown that red clover may alter metabolism orthe effectiveness of drugs that are substrates of P450CYP3A4 isozymes.9

St John’s wortThe efficacy of St John’s wort in treating mild to moderatedepressive disorders has been demonstrated in a number ofrandomised double-blind, placebo-controlled trials andconfirmed by meta-analysis.5 Therefore, this herbaltreatment is an ideal choice for menopausal women experi-encing symptoms. However, the profile of drug-herbinteractions is extensive and includes lowering bloodconcentrations of cyclosporine, amitriptyline, digoxin,indinavir, warfarin, phenprocoumon and theophylline;furthermore, it causes breakthrough bleeding, delirium ormild serotonin syndrome when used concomitantly with oralcontraceptives (ethinyl-oestradiol/desogestrel), loperamideor selective serotonin-reuptake inhibitors (setaline,paroxetine, nefazodone), respectively.20

Wild yam (Dioscorea spp.)Another popular treatment is wild yam extract, often appliedin the form of a cream. Wild yam contains steroidalsaponins, including diosgenin, a sapogenin claimed toinfluence steroid hormone synthesis.21 Diosgenin combinedwith clofibrate caused a greater decrease in LDL than eithersubstance alone in rats.22 Diosgenin has also been shown toprevent indomethacin-induced ulcers and lowered serumlevel of the drug in rats.23 In vitro research using wild yamshowed an anti-oestrogenic effect. Any effect on exogenoushormone treatment is unknown.9

Lesser well known herbals reputed to be of benefitfor menopausal symptomsThe following herbals are also likely to be found in herbalcombinations for menopausal symptoms:Burdock (Arctium lappa) is reputed to have oestrogenicactivities and theoretically to interact with antidiabeticmedications.13

Chaste tree/berry (Vitex agnus castus) is a herbal remedygenerally used for women’s health care, most commonlypremenstrual syndrome but also menopausal symptoms andfemale infertility. The main constituents are flavonoids,iridoids and linoleic acid. Theoretically, interactions arepossible with oral contraceptives, hormone replacementtherapy and dopamine agonists and antagonists.24

Flax seed (Linum usitatissimum) is reputed to haveoestrogenic, anti-oestrogenic and steroid-like activity. Thereare no known side effects. The absorption of other drugsmay be negatively affected.25

Geranium (Pelargonium graveolens) is reputed to have

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hormonal effects.25 No information is available as to drug-herb interactions.Liquorice (Glycyrrhiza glabra) contains isoflavones andglycyrrhetinic acid. One component, beta-sitosterol, isreputed to influence oestrogen activity. Adverse effects areconsistent with adrenocorticotrophic actions and it is thoughtto interact with antihypertensives, anticoagulants, antidi-abetic medications and oral contraceptives.13

Motherwort (Leonorus cardiaca) contains alkaloidleonurine, which is thought to stimulate uterine activity. It isalso thought to have the potential to interact with cardiacglycosides and antihypertensives.13

Sage (Salvia officinalis) is traditionally thought to haveantihydrotic properties and has the potential to interact withanti-hypertensives and antidiabetics.13

Hops (Humulus lupulus) Hops have a long history of use asa sedative; thus, they have been traditionally used forinsomnia and nervous tension. Theoretical interactions existfor central nervous system depressants, antipsychotics,hormonal agents and any drugs metabolised by thecytochrome-P450 system such as warfarin, anticonvulsants,digoxin, theophylline and HIV protease inhibitors.13

DiscussionThe increasing use of herbal medicines by the generalpublic, especially in combination with prescriptionmedicines, suggests that adverse drug-herb interactions maybe of significant public health consequence. There is a widerange of herbals available as OTC medications for women’smenopausal symptoms. These include both mono-preparations and herbal combinations. Some of thesepopular herbal medicines have a very good safety profilewith little or no suggestion of interaction with conventionaldrugs such as black cohosh. Despite this, it is important toremember in such cases that herbal medicines are intendedto be taken over an extended period of time, which providesthe opportunity for enzyme induction and other mechanismsof interaction to take effect.26

For other preparations, such as St John’s wort and ginseng,there is a long list of known and theoretical drug-herbinteractions. If women are taking combination products, it isquite likely they are not aware of all the herbal componentsof that preparation. Reports of drug-herb interactions arenow becoming more common, although rare compared withdrug-drug interactions.26 In the absence of hard data,potential or theoretical interactions are being highlighted.

One area of concern discussed recently is the potential foradverse interactions with analgesic drugs and herbalmedicines. Non-steroidal anti-inflammatory drugs, partic-ularly aspirin, have the potential to interact with herbalmedicines known to possess antiplatelet activity, such asgingko, dong quai, ginseng and those containing coumarin(such as motherwort, red clover), thereby enhancing the riskof bleeding.27 Acetaminophen may also interact with ginkgoamongst other herbal medicines.27

All these issues are of concern to the medical profession.Communication is essential and any medical consultationshould involve discussion of OTC products the patient maybe taking and the potential for interactions, regardless oftheir severity. Thus, it is imperative that the medicalprofession should be well informed as to recommended

dosages and known or theoretical safety and interaction data.Current evidence suggests that the medical profession haslittle training in herbal toxicities and drug interactions.28,29

One of the most important sources of such information -besides searching medical databases such as Medline - is theMedicines and Healthcare products Regulatory Agency(MHRA) web site.19

Thus, drug-herb interactions exist and may pose a serioushealth risk in some patients, including women taking herbalmedicines for their menopausal symptoms. Some evidenceexists for these interactions; however, in the absence of datait is also important to be aware of theoretical interactions.The medical profession needs to be aware of suchinteractions between herbal medicine and drugs, giveappropriate precautionary advice and in the UK use theyellow card system if they suspect such an occurrence.However, as most of the interaction information available isfrom individual case reports, animal studies and in vitrodata, further research is needed to confirm and assess theclinical significance of these potential interactions in orderto maximise patient safety.

Conflict of interest: None declared

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