Herbs and adolescent girls: Avoiding the hazards of self-treatment

March 1, 2000

Herbs and supplements are heavily marketed to teens, who think they are well educated about their use. What many dont realize is that natural is not synonymous with safe. Staying one step ahead with informed questions and answers is your best defense against overlooking an important diagnosis.

 

Herbs and adolescent girls:
Avoiding the hazards of self-treatment

By Paula Gardiner, Lisa A. Conboy, and Kathi J. Kemper, MD, MPH

Herbs and supplements are heavily marketed to teens, whothink they are well educated about their use. What many don't realize isthat "natural" is not synonymous with "safe." Stayingone step ahead with informed questions and answers is your best defenseagainst overlooking an important diagnosis.

An adolescent girl has been referred to your office by a family physicianfor evaluation of a possible eating disorder. As you ask the patient abouther history of menstrual periods, she tells you they have been irregularand asks if you know of any herbal remedies that can help make her moreregular. Wisely, you ask if she's already tried any herbal remedies forher periods or for any other health problem. "Oh yes!" she exclaims,"I've taken Ma huang to give me extra energy, and I took some eveningprimrose oil and dandelion to help with my PMS. There's this site on theWeb that tells you about this stuff. You can even order it over the Internet."

Today's teens are self-treating such conditions as premenstrual syndrome(PMS), urinary tract infections (UTIs), obesity, and even pregnancy withalternatives to traditional medical treatments. They believe such herbsand dietary supplements to be safe because they are natural, but the truthis that few have undergone the scrutiny of double-blind controlled studiesto assess their efficacy or safety. Keeping informed about the state ofherb use in teens and the potential risks and benefits is essential formeaningful discussion with adolescent patients.

Adolescents use herbs and other dietary supplements more often than anyother form of complementary and alternative medicine (CAM). CAM appealsto adolescents because it offers autonomy and a seemingly safe, naturalalternative to mainstream medicine. Most use CAM in combination with traditionalmedicine and would like to talk with their doctors about CAM strategies.Thus, pediatricians need to initiate discussion with educated questionsand be ready with current, accurate information.

The frequency of CAM use, and herb use in particular, varies among adolescentgroups. It is substantial among well-insured, healthy populations.1Among adolescent athletes, 29% of boys and 12% of girls report taking supplements.2Among patients with chronic or recurrent illnesses such as cancer, cysticfibrosis, and rheumatoid arthritis, 40% to 80% report using CAM.3Among homeless teens, 70% report using CAM with 74% of those using herbs.4Herbal remedies are also commonly used by many cultural groups, includingAsians, Hispanics, and Native Americans.

In general, girls are more likely than boys to seek health care includingCAM therapy. Some of the most common ailments for which girls employ CAMare PMS, UTIs, obesity, menstrual irregularities, and unwanted pregnancy(see Table 1).

 

 

Premenstrual syndrome

Between 80% and 90% of teenage girls report symptoms prior to menstruationincluding breast tenderness, food cravings, abdominal discomfort, headache,water retention, fatigue, mood swings, depression, and impulsivity.5Pediatricians are increasingly finding that their teen patients are usingherbs to supplement or replace traditional hormonal remedies (oral contraceptives,progesterone, danazol, transdermal estradiol) and symptomatic therapies(antidepressants, anxiolytics, diuretics, anti-inflammatory analgesics).Some herbs, like chasteberry, are used as natural hormones. Others, likeevening primrose oil (EPO), are used as natural anti-inflammatories. Stillothers, such as dong quai, have been adapted from other healing systems.

Chasteberry (Vitex agnus-castus) derives its namefrom the belief that the plant promotes chastity. In ancient Greece andRome, it was used to diminish sexual desire. In fact, use by monks in theMiddle Ages led to the common name for vitex—Monk's pepper. Today,herbalists recommend the berry for treating PMS, cyclic breast discomfort,menopausal symptoms, amenorrhea, and other menstrual irregularities. Othertraditional uses include as a digestive aid, as a treatment for fibroidcysts and infertility, and as an agent to induce lactation (lactagogue).

Chasteberry's chemical constituents include progesterone, hydroxyprogesterone,testosterone, epitestosterone, androstenedione, iridoid, glycosides, agnosidem,aucubin, flavonoids, and volatile oils. Animal and human studies have shownvitex to affect the regulation of hormones at the pituitary level throughdopaminergic receptors and prolactin release.

In Europe, open studies and clinical trials using vitex to treat PMSshow some effectiveness. For example, a randomized, controlled study of175 women with PMS compared Agnolyt (1 capsule of 3.5 to 4.5 mg dried chastetree extract) to 200 mg of vitamin B6 for three months. Thosetreated with vitex had "considerably more marked alleviation"of the PMS symptoms of breast tenderness, edema, tension, headache, constipation,and depression.6 Similarly, a double-blind, placebo-controlledstudy of 100 subjects found that 1.8 mL of vitex extract daily for threemonths reduced menstrual-associated breast pain.7 In a 1993 double-blind,randomized, controlled study of over 200 women with PMS symptoms, however,vitex (600 mg three times a day for three months) demonstrated a statisticaldifference in alleviating only the symptoms of jitters and restlessness.8No randomized controlled trials have evaluated the long-term treatment ofPMS symptoms with vitex in teens, compared vitex to the standard treatmentof oral contraceptives, or evaluated its interactions with standard treatment.

Side effects associated with vitex are rare but include stomach upset,itching, mild rash, and headache. No detailed clinical toxicology studieson vitex exist. There is one reported case of mild ovarian hyperstimulationin an adult using vitex.9 Vitex is not recommended for pregnantwomen because it can affect prolactin levels. The recommend dose of vitexis 30 to 40 mg daily. Several months of use are generally required beforebenefits are noted. Clearly, more research is needed to assess the long-termefficacy and safety of vitex in young women.

Evening primrose oil (Oenothera biennis L) is abiennial herb native to North America. Its seed oil is used medicinallyand is considered one of the best natural sources of the essential fattyacid (EFA) gamma linoleic acid (GLA). Commercial varieties of EPO containapproximately 72% linoleic acid (LA) and 9% GLA. GLA is also found in borageoil (20% to 26% GLA) and black currant oil (14% to 19% GLA). EPO is commonlyused to treat PMS, eczema, diabetic neuropathy, fibrocystic breasts, cyclicmastalgia, and rheumatoid arthritis. British physicians routinely recommendEPO supplements for women suffering from cyclic mastalgia. EPO is widelyavailable over the counter and is relatively inexpensive.

The rationale for the many different uses of EPO is based on the metabolismof GLA into various prostaglandins. LA is converted into GLA, which is metabolizedto dihomo-gamma linoleic acid (DGLA) through the arachidonic acid pathwayinto prostaglandin E1 (PGE1) and subscript 3-series leukotrienes. PGE1 hasanti-inflammatory properties. EPO is thought to help in PMS by modulatingendogenous inflammatory symptoms. Levels of GLA tend to be lower in womensuffering from PMS, particularly mastalgia, than in women without PMS.10

Data on the effectiveness of exogenous administration of GLA to treatPMS are conflicting. A 1996 meta-analysis of five randomized, placebo-controlledtrials concluded that most studies were of insufficient quality to drawa clear conclusion, but that EPO appeared to be of little value in managingmost PMS symptoms.11 Two randomized, controlled trials, however,were not included in the meta-analysis; both concluded that EPO was helpfulin treating PMS­associated breast pain. One found that EPO was as effectivefor severe breast pain as bromocriptine, but less effective than danazol.12In the other study, three grams of EPO significantly reduced breast pain,both clinically and statistically, over three months of treatment.13

Evening primrose oil is well tolerated. Infrequent side effects includemild gastrointestinal distress, nausea, loose stools, and headache. Whilea maximum safe dosage has not been determined for children or for pregnantor lactating women, most studies suggest that EPO is beneficial in dosagesof 3 g per day, divided into two to three doses, and taken for a minimumof four to six weeks. In 1999, this dosage regimen cost approximately $20a month.

Dong quai. In traditional Chinese medicine, dong quai (Angelicasinensis) is used primarily to "balance" the female systemand thus ease menstrual irregularities and menopausal complaints. Modernherbalists also recommend it for anemia, fatigue, constipation, anxiety,and PMS. Traditionally, it is used in combination with other herbs and notin isolation.

There is a remarkable lack of scientific evidence for dong quai's effectivenessin treating PMS. Its chemical constituents include furocoumarins, b-sitosterol,flavonoids, and others, but its mechanism of action remains unknown. Inmice and rabbits, dong quai aqueous extracts stimulated uterine contractions,while the essential oil inhibited contractions.14 Animal studiesalso report anticoagulant, analgesic, antiarrhythmic, and hypotensive effects.

Numerous Chinese case studies suggest that herbal formulas containingdong quai may be helpful with menstrual irregularities,15 butthere are no controlled studies backing this claim in either adults or adolescents.Dong quai is not traditionally recommended for pregnant or lactating womenbecause of its purported action as a uterine stimulant. It also may causephotosensitivity and enhance the effect of anticoagulants. Other potentialside effects include gastrointestinal upset and rash.

Urinary tract infections

Approximately 12.5% of girls between 14 and 17 years of age develop aUTI.16 And as sexual activity increases, so does the rate ofUTIs. The mainstay treatment for UTIs is antimicrobials. Two herbal counterpartsare cranberry, which inhibits bacterial adhesion to the bladder wall, anduva ursi, whose metabolites have direct antimicrobial effects.

Cranberry. Initially, cranberry (Vaccinium macrocarpon)was believed to help prevent UTIs because its benzoic acid is metabolizedto and excreted as hippuric acid, which has a mild bacteriostatic effect.Later, researchers noted that drinking large amounts of cranberry juiceleads to urinary acidification. More recently, cranberry's benefits havebeen attributed to its proanthocyanidin content. Proanthocyanidin impedesthe adhesion of gram-negative bacterial uropathogens to the bladder epithelium.17

In vitro and animal data, as well as epidemiologic and controlled trialsin humans, have supported this physiologic rationale. In a case controlstudy of sexually active college students, regular ingestion of cranberryjuice was associated with a 50% reduction in the odds of first time UTI.18In a controlled clinical trial of elderly women prone to recurrent UTIs,those assigned to receive 300 mL daily of artificially sweetened commercialcranberry juice cocktail had significantly reduced odds of UTI (42%) comparedto women who received similar tasting placebo juice.19 In a controlled,crossover trial involving younger women with a history of recurrent UTIs,significantly fewer UTIs occurred during daily treatment with 400 mg ofcranberry concentrate than during the control period.20

Other than allergic reaction, there are no known side effects or risksof cranberry to children or pregnant or lactating women. Persons prone todiabetes, obesity, or dental cavities should exercise caution when drinkinglarge amounts of sweetened fruit juices. Cranberry has not been evaluatedas a preventative therapy for those at high risk of UTIs, such as individualswith indwelling catheters, nor is it recommended as sole therapy for cystitisor pyelonephritis.

Uva ursi (bearberry). This evergreen native of Europe andthe northern United States has long been used by Native American and Europeanherbalists to treat UTIs and renal stones. Today, bearberry (Arctostaphylosuva-ursi) is recommended by the European Scientific Cooperative on Phytotherapyfor "uncomplicated UTIs not requiring antibiotics."21

Uva ursi's chemical constituents include the antimicrobial aglycone hydroquinones(arbutins), tannins, and flavonoids. In vitro, uva ursi exhibits antimicrobialactivity against Escherichia coli, Ureaplasma urealyticum, Proteus vulgaris,Enterococcus, and Candida albicans. The urine of patients givenuva ursi shows a high level of antimicrobial activity against pathogenssuch as Escherichia, Enterobacter, and Staphylococcus.It is most effective in an alkaline environment.

German case studies of adults support uva ursi's use in treating painfuland frequent urination. In a randomized controlled trial of 57 women sufferingfrom recurrent UTIs, those assigned to the uva ursi group had significantlyfewer recurrent infections than the control group.22 No randomizedcontrolled trials have evaluated the effectiveness of uva ursi in preventingor treating cystitis or pyelonephritis in young women, nor compared it tostandard antimicrobial therapy. Adolescents should be educated to seek medicalevaluation for UTI symptoms and not to rely on herbal self-treatment.

Herbalists recommend that uva ursi not be taken for more than one weekat a time or more than five times a year because of the potential risksassociated with tannins and hydroquinones. Tannins can cause significantgastrointestinal toxicity. Taking uva ursi with meals may minimize thiseffect. In animals, hydroquinones are mutagenic and carcinogenic, but animalsappear to metabolize hydroquinones differently than humans. Thus, theserisks appear to be minimal in humans. Still, uva ursi is not recommendedfor pregnant or lactating women or for children younger than 12 years ofage. Uva ursi should not be taken with urine acidifiers such as cranberryjuice or vitamin C because this may minimize its antimicrobial effects.

Weight loss

Obesity has reached epidemic proportions in the US adolescent population.Even teens who are not overweight often worry that they are. Social, biological,and psychological pressures can push girls toward developing an eating disorder.All of these factors lead many adolescents to the weight loss sections oftheir local pharmacies and CAM Web sites.

Weight loss drugs typically contain diuretics, cathartics, and stimulants,all of which carry substantial risk. Herbal alternatives often contain chemicalswith similar effects and risks. Despite public perceptions to the contrary,herbal weight loss remedies are not necessarily safer simply because theyare natural products.

Diuretic herbs. The dandelion (Taraxacum officinale)grows throughout most of North America. The leaves and roots have been usedtraditionally as a diuretic, laxative, cholagogue (bile stimulant), andliver tonic. Their constituent chemicals include sesquiterpene lactones(bitters), triterpenes and sterols, flavonoids, mucilage, and inulin. Inmice and rats, a 4% strength dandelion leaf extract produced a diureticeffect similar to furosemide.23 Despite widespread traditionaluse, there are no case studies or randomized controlled trials in humansthat evaluate dandelion's diuretic effects. Further, the potential interactionof dandelion with other diuretics is unknown.

Dandelion may cause an allergic reaction in individuals sensitive tomembers of the aster family. No data are available on safety or toxicityduring pregnancy, lactation, or childhood.

Cathartic herbs. Senna (Cassia senna) is a shrub,the leaves and pods of which have been used traditionally as a stimulantlaxative. Senna's anthraquinone glycosides are converted by colonic bacteriato rhein-anthrone, which stimulates colonic motility and increases fluidsecretion. Senna's use as a laxative is well supported by controlled studiesin humans.24,25 In fact, it can be found in many over-the-counterlaxatives (such as Ex Lax) and herbal laxative teas (such as Smooth Move).

Acute side effects can include cramps and diarrhea. Chronic senna usecan lead to dependency and low potassium levels, potentiating the toxicityof cardiac glycosides. Senna should not to be used by patients with undiagnosedabdominal pain or intestinal obstruction. It should not be used for morethan 10 days because of the risk of dependency and potential side effects.A few studies have shown senna to be safe for use during pregnancy and lactation.26

Stimulant herbs. Of the many species of ephedra, Ephedrasinica is among those most often used medicinally. The dried stems havebeen used traditionally in China as a bronchial dilator, diuretic, allergyremedy, and treatment for the common cold. Ephedra was a popular bronchialdilator and decongestant in the US through the early 1970s until it wasremoved from the market because of its cardiovascular side effects. Ephedraalso is well known today for its stimulant effect and is used in many weightloss products and recreational drugs.

Ephedra's active ingredients are the alkaloids ephedrine and pseudoephedrine.Ephedrine stimulates the central nervous system, elevates blood pressure,increases heart rate, dilates the bronchioles, and suppresses appetite.Pseudoephedrine has similar effects. Ephedra's chemical cousin, phenylpropanolamine,is included in several well-known nonprescription diet drugs.

Human trials show mixed results with regard to ephedra's effectivenessas a weight loss aid. One randomized, placebo-controlled, double-blind studyof 180 obese patients found that restricted diet and a 20 mg ephedrine/200mg caffeine combination resulted in significantly greater weight loss, clinicallyand statistically, than diet and placebo.27 A randomized, double-blind,cross-over trial of 10 obese women showed significantly more weight loss,clinically and statistically, during periods of restricted diet plus 150mg of ephedra per day than during treatment with diet alone.28Another double-blind study of 46 obese patients comparing diet and ephedrinevs. diet alone, however, found no significant difference in weight lossbetween the two groups and significantly more side effects in the ephedragroup.29

Ephedra can have serious side effects similar to those of amphetamines,including insomnia, restlessness, anxiety, irritability, tachycardia, cardiacarrhythmias, hypertension, dependence, and death resulting from heart failure.Taking ephedra in combination with potassium-losing agents such as sennaand dandelion may potentiate its arrhythmogenic effects. Patients takingMAO inhibitors and those with diabetes, glaucoma, or thyroid disease shouldavoid ephedra. There are no human data examining its safety during pregnancy,lactation, or childhood. Adolescents should be strongly cautioned abouttaking it.

Use of ephedra as a recreational drug and reports of side effects, includingwell-publicized fatal overdoses, have led some states to ban or strictlylimit its sale. Still, it can be bought online via the Internet at one ofthe many virtual drug and supplement stores.

Herbs and pregnancy

Currently, 95.9 pregnancies occur per 1,000 girls between the ages of15 and 19 years, and more than 90% of those teens describe their pregnanciesas unintended.30 Today, teenagers have access to informationabout pregnancy termination and regulation of menses in books, magazines,and on the Internet. This includes information and misinformation aboutherbs traditionally used as abortifacients. Several case reports documentserious health effects, including death, among women using herbs to inducemenses or terminate pregnancies.31

Pregnant teenagers also choose herbal treatments for a variety of pregnancy-relatedconditions, such as miscarriage prevention, lactation, and morning sickness.Since many prescribed drugs are contraindicated in pregnancy, an unknowingteenager may substitute an herbal remedy, but "natural" is notalways safer. An herb used to treat a common ailment in a nonpregnant personmay be harmful to a fetus or pregnant woman. Pennyroyal, for example, isan herb used to treat common colds, but it also has abortifacient properties.Table 2 lists other herbs contraindicated during pregnancy.

 

 

Pennyroyal. Since Roman times, pennyroyal (Mentha pulegium),a member of the mint family, has been used as an abortifacient, as an emmenagogue(an agent that induces menses), and to induce labor. Pennyroyal oil is thoughtto stimulate uterine contractions and to possess carminative, antispasmodic,antiseptic, and diaphoretic properties. It has also been used systemicallyto treat respiratory ailments like pneumonia, common colds, mouth sores,weakness, flatulence, and colic, and applied topically for gout and skineruptions.

The active chemical component in pennyroyal is pulegone, which is toxicin large doses. Pulegone is oxidized by the hepatic cytochrome P-450 systeminto menthofuran; it has been shown to deplete glutathione.32Menthofuran causes direct hepatic and pulmonary cellular damage in a mannersimilar to acetaminophen. There have been a few reports of hepatic necrosiscaused by pennyroyal oil.33 While the exact mechanism of pennyroyaloil toxicity in humans is not clearly defined, several deaths have beendocumented since 1897.31

Symptoms of a toxic dose of pennyroyal oil are severe and can be rapidlyfatal. They include gastrointestinal upset, confusion, syncope, anxiety,seizure, tachycardia, and diaphoresis. In large doses, pennyroyal oil causesabortion, renal damage, and hepatotoxicity. The toxic dose is only 10 mL(approximately 2 tsp) of the essential oil.31 Adolescents shouldbe warned that there are no herbs or nonprescription remedies that willsuccessfully and safely terminate a pregnancy.

The need for informed discussion

As they face new health problems, today's teenagers are seeking alternativesto traditional medical treatments. Herbal products are now heavily marketedand readily available. As more and more adolescents try these products,we must be armed with current and accurate information about their use.Table 3 lists some evidence-based resources that may be helpful with thisrapidly evolving field and that may help facilitate informed discussionabout herb use and other alternative medical treatments with our adolescentpatients.

 

 

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6. Lauritzen C, Reuter H, Repges R: Treatment of premenstrual tensionsyndrome with Vitex agnus castus: Controlled double-blind study vs. pyridoxine.Phytomedicine 1997;4:183

7. Halaska M, Raus K, Beles P, et al: Treatment of cyclical mastodyniausing an extract of Vitex agnus-castus: Results of a double-blind comparisonwith a placebo. Ceska Gynekol 1998;63:388

8. Turner S, Mills S: A double-blind clinical trial on an herbal remedyfor premenstrual syndrome: A case study. Complementary Therapies in Medicine1993;1:73

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11. Budeiri D, Li Wan Po A, Dornan JC: Is evening primrose oil of valuein the treatment of premenstrual syndrome? Control Clin Trials 1996;17:60

12. Pye JK, Mansel RE, Hughes LE: Clinical experience of drug treatmentsfor mastalgia. Lancet 1985;2:373

13. Pashby N: A clinical trial of evening primrose oil in mastalgia.Brit J Surg 1981;68:801

14. Yoshihiro K: The physiological actions of tang-quai and cnidium.Bull Oriental Health Arts Inst 1985;10:269

15. Zhiping H, Dazeng W, Lingyi S, et al: Treating amenorrhea in vitalenergy-deficient patients with angelica sinensis-astragalus membranaceusmenstruation-regulating decoction. J Tradit Chin Med 1986;6:187

16. Zielske J, Lohr K, Brook R, et al: Conceptualization and measurementof physiologic health for adults: Urinary tract infection. Rand Corporation,1981

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24. Kinnunen O, Winblad I, Koistinen P, et al: Safety and efficacy ofa bulk laxative containing senna versus lactulose in the treatment of chronicconstipation in geriatric patients. Pharmacology 1993;47(Suppl 1):253

25. Passmore AP, Davies KW, Flanagan PG, et al: A comparison of Agiolaxand lactulose in elderly patients with chronic constipation. Pharmacology1993;47(Suppl 1):249

26. Mengs U: Reproductive toxicological investigations with sennosides.Arzneimittel-Forschung 1986;36:1355

27. Toubro S, Astrup A, Breum L, et al: Safety and efficacy of long-termtreatment with ephedrine, caffeine, and ephedrine/caffeine mixture. IntJ Obes 1993;17:69

28. Pasquali R, Cesari MP, Melchionda N, et al: Does ephedrine promoteweight loss in low-energy-adapted obese women? Int J Obes 1987;11:163

29. Pasquali R, Baraldi G, Cesari MP, et al: A controlled trial usingephedrine in the treatment of obesity. Int J Obes 1985;9:93

30. Spitz AM, Velebil P, Koonin LM, et al: Pregnancy, abortion, and birthrates among US adolescents—1980, 1985, and 1990. JAMA 1996;275:989

31. Anderson IB, Mullen WH, Meeker JE, et al: Pennyroyal toxicity: Measurementof toxic metabolite levels in two cases and review of the literature. AnnIntern Med 1996;124:726

32. Gordon WP, Forte AJ, McMurtry RJ, et al: Hepatotoxicity and pulmonarytoxicity of pennyroyal oil and its constituent terpenes in the mouse. ToxicolAppl Pharmacol 1982;65:413

33. Bakerink JA, Gospe SM, Diamond RJ, et al: Multiple organ failureafter ingestion of pennyroyal oil from herbal tea in two infants. Pediatrics1996;98:944

MS. GARDINER is a Research Associate at the Center for Holistic PediatricEducation and Research and a fourth-year medical student at Tufts UniversitySchool of Medicine, Boston, MA.
MS. CONBOY is a PhD candidate at the Harvard School of Public Health,Cambridge, MA.
DR. KEMPER is Director, Center for Holistic Pediatric Education andResearch, Children's Hospital, Boston.



Kathi Kemper, Paula Gardiner, Lisa Conboy. Herbs and adolescent girls: Avoiding the hazards of self-treatment.

Contemporary Pediatrics

2000;3:133.