This Practice Bulletin was developed by the ACOG Committee on Practice Bulletins — Gynecology with the assistance of Maida Taylor, MD. The information is designed to aid practitioners in making decisions about appropriate obstetric and gynecologic care. These guidelines should not be construed as dictating an exclusive course of treatment or procedure. Variations in practice may be warranted based on the needs of the individual patient, resources, and limitations unique to the institution or type of practice.

Use of Botanicals for Management of Menopausal Symptoms

Lack of confidence in the espoused benefits of hormone replacement therapy (HRT) coupled with a significant array of side effects of HRT, results in fewer than 1 in 3 women choosing to take HRT. The use of alternatives to conventional HRT has become more accessible and acceptable to many women. As more women choose these alternatives, physicians are confronted with the challenges of how to advise patients about alternative medicine and how to determine which therapies may be safe and effective. This document will examine available scientific information on alternative therapies for treatment of menopausal symptoms and provide recommendations on efficacy and potential adverse consequences.

Background

Discontent with Current Pharmaceutical Regimens

Hormone replacement therapy is associated with various side effects and complications; 30–40% of patients experience some degree of abnormal bleeding in the first year of hormone use, which often results in discontinuation of use (1). Initiating HRT also is viewed by some women as treating menopause as a medical disorder, which is seen by a large segment of the population as a natural, normal part of the aging process. In addition, many women believe that estrogen therapy may increase the risk of breast cancer, and the fear of breast cancer is most often cited as the reason for lack of initiation (2).

Complementary and Alternative Medicine

Complementary medicine can be defined as those systems, practices, interventions, modalities, professions, therapies, applications, theories, or claims that are currently not an integral part of the conventional medical system (3). Alternatively, conventional medicine refers to medicine as it is generally practiced and widely taught by medical doctors, doctors of osteopathy, and their allied health professionals (4). Alternative medicine encompasses a number of systematic medical practices based on physical assessments that differ from physiology as it is taught in Western medical institutions. The most recognizable and widely employed alternatives are biologic-based therapies such as botanical medicines, dietary supplements, vitamins, minerals, and orthomolecular medicine. In a 1998 survey, alternative medicine visits exceeded visits to conventional primary care providers, and 70% of such encounters were never discussed with the patient's regular personal physician (5). In addition, a national survey reported the highest rates of use in the groups aged 35–49 years (42%) and 50–64 years (44%) (6). Three theories were proposed by the investigator as tentative predictors of use of alternatives therapies: 1) dissatisfaction with conventional medicine; 2) viewing alternatives as more empowering because of their over-the-counter status; and 3) perceiving alternatives as more compatible with personal values or ethical or religious belief systems. Predictors of alternative care use were reported to include higher educational level, poorer health status, holistic orientation to health, having had a transformational experience changing one's world view, and several chronic health conditions such as anxiety, back problems, chronic pain, and urinary tract problems. Only 4.4% of respondents relied primarily on alternative therapies.

In 1997, out-of-pocket expenditures for alternative therapies were estimated at $27 billion, which was more than the out-of-pocket expenditures for all physician services that year (7). Recently, third-party carriers have started providing coverage for alternative therapies, sometimes assessing an extra premium for such expanded benefits.

Complementary and Alternative Medicines Used in Menopause

The symptoms associated with perimenopause and menopause stimulate a healthy concern about wellness and motivate women to undertake appropriate interventions to lower health risks associated with menopause. Interest in alternative medicine can be viewed simply as a natural extension of interest in nutrition, exercise, and other behavioral, nonpharmacologic interventions directed at maintaining well-being. Unfortunately, many of the alternatives promoted and touted as substitutes for HRT do not offer any substantiated health benefits.

According to the North American Menopause Society, nonhormonal interventions commonly used for menopause include a healthy diet, exercise, vitamins, and calcium supplements. The North American Menopause Society also indicates that more than 30% of women use acupuncture, natural estrogen, herbal supplements, or so-called plant estrogens (8). Alternative therapies to conventional HRT include botanical products, vitamins and minerals, unconventional hormones and steroids sold over-the-counter as nutritional supplements or as cosmetics, and nonproprietary single and combination estrogen and progestin preparations custom blended by compounding pharmacies.

Most studies of menopausal interventions, including phase-III clinical trials of estrogenic drugs, show a 20–30% response rate in placebo groups. Unconventional interventions need to be studied in well-controlled trials before their use can be supported. Documentation of efficacy is essential because these products should yield effective results of a magnitude large enough to warrant their costs, which are substantial.

Botanical Medicine

Up to one half of drugs commonly used today are either plant products or phytochemicals that were initially isolated from botanical material but are now synthesized by chemical processing techniques. Outside of pharmaceutical preparations, plants are used therapeutically in the form of herbs, oils, pills, teas, or tinctures (see box). In addition, currently used products include highly concentrated extracts of phytochemicals, synthetic derivatives, and even steroids like dehydroepiandrosterone (DHEA) and androstenedione, which are classified as food supplements because they are produced from plant precursor sterols.

Dietary Plant Estrogen/Phytoestrogens

Plants do not make estrogens in the classic sense of the term. Plants make sterol molecules, many of which exert weak estrogenic activity in animals although their effects increase when large quantities are ingested. These compounds, phytoestrogens, often possess structural similarities to more active human and animal estrogens. Plant sterols are used as the precursors for the biosynthetic production of mass-manufactured therapeutic pharmaceutical-grade steroids. A number of plants used to treat symptoms of menopause have been identified in botanical medicine texts as having estrogenic activity, but research has contradicted these traditional assumptions (9).

Phytoestrogens are classified into three groups (10):

1. Isoflavones, particularly, genistein and daidzein, are plant sterol molecules found in soy and garbanzo beans and other legumes, which are most often consumed in products like tempeh, soy, miso, and tofu. Generally, 1 g of soy protein yields 1.2–1.7 mg of isoflavones, depending on the type of soybean used as the source of the protein.

2. Lignins are a constituent of the cell wall of plants and are bioavailable as a result of the effect of intestinal bacteria on grains. The highest amounts are found in the husk of seeds used to produce oils, especially flaxseed. The whole seed added to salad or cereal, or flaxseed meal or flour can be used as a food additive.

3. Coumestans have steroidlike activity but are not a significant source of phytoestrogens for most individuals. High concentrations are found in red clover, sunflower seeds, and bean sprouts and are known to have estrogenic effects when ingested by animals.

Asian diets are typically high in soy foods and contain an average of 40–80 mg of active forms of isoflavones per day, while American diets average less than 3 mg per day. American and European diets tend to elevate plasma levels of sex hormones and decrease sex-hormone-binding-globulin concentrations, thus increasing the exposure of peripheral tissues to the effects of circulating estrogens. High-soy diets act through several mechanisms to lower effective circulating and tissue levels of steroids. High isoflavone intake may depress luteinizing hormone (LH) levels and secondarily depresses estrogen production (11, 12).

The plant lignan and isoflavonoid glycosides become hormonelike compounds with weak estrogenic and antioxidative activity through the action of intestinal flora. Red clover is a rich source of isoflavones, as well as coumestans, and is used commercially to make isoflavone supplements. These compounds exert detectable effects on circulating gonadotropins and sex steroids, suggesting that they have biological activity (12).

They also can act on intracellular enzymes, protein synthesis, growth factors, cellular proliferation, differentiation, and angiogenesis. Limited observational studies on isolated populations in cross-cultural comparison suggest that the incidence of cancer and atherosclerotic disease decreases with increasing intake of bioflavonoids and that diphenolic isoflavonoids and lignans are cancer-protective compounds (13).

These protective effects have accrued in populations over a lifetime. It is unclear that changing one's intake of isoflavones or soy protein at age 50 years will significantly lower the lifetime risk of these diseases. A directive advising lifelong adherence to a diet rich in a variety of fruits and vegetables while limiting the intake of animal protein and fat should apply to men and women of all ages, not just those experiencing their menopausal transition. Moreover, no single synthetic or chemical derived from soy is thought to match the benefits derived from ingesting soy foods. The effects—either beneficial or detrimental—of prolonged intake of supra-dietary levels of soy or isoflavone are unknown.

Bean products are rich sources of diphenols, which are thought to lower cancer risk by modifying hormone metabolism and production and limiting cancer cell growth. Bean foods also provide large amounts of fiber, and fiber modifies the level of sex hormones by increasing gastrointestinal motility. Fiber alters bile acid metabolism and partially interrupts the enterohepatic circulation causing increased estrogen excretion by decreasing the rate of estrogen reuptake in the enterohepatic system (14).

Manufacturing and Regulating Botanicals

The federal Dietary Supplement Health and Education Act of 1994 (DSHEA) defined dietary supplements and limited the claims that can be made on supplement labels and in supporting literature. Manufacturers are responsible for ensuring the safety of their supplement products. Supplements are neither foods nor drugs, so manufacturers do not have to provide any evidence to support purported benefits before marketing their products. The Food and Drug Administration (FDA) oversees the industry, but the Federal Trade Commission is responsible for identifying inappropriate or unsubstantiated claims and enforcing DSHEA regulations.

In 1997, the FDA proposed a new dietary supplement rule allowing supplements to make structural or functional claims, but not disease claims. Such language as "supports well-being" or "helps promote heart health" would be allowed, while statements like "lowers cholesterol" would not be permitted. Supplements that "...expressly or implicitly claim to diagnose, treat, prevent, or cure a disease...[would be] ...regarded as drugs and have to meet the safety and effectiveness standards for drugs..." (15). The American Botanical Council objects to the FDA attempting to redefine the DSHEA, while the American Medical Association supports the refined definitions.

Botanicals are subject to a high degree of variation in production. Plants grown in the field may have different amounts of active constituents due to growing conditions. Products coming out of production facilities may vary greatly in the amount of active ingredients.

The botanical industry has set up voluntary guidelines, and some manufacturers have signed agreements in kind affirming that they will produce products set to an industry-defined standard. However, without mandatory oversight, problems of adulteration, contamination, and dose standardization will continue. Consequently, buyers and their physicians need to beware.

Uses for Botanicals in Menopausal Women

A brief description of several commonly used botanicals follows. Also included are their suggested and advertised uses.

Vasomotor Symptoms

Soy Products.

The effects of soy protein found in whole foods, soy protein isolates, and those of isoflavone isolates made into powders or pills may not all be the same. Even soy foods are not necessarily reliable sources of biologically active isoflavones. The alcohol processing often used in the manufacture of tofu and soy milk removes the biologically active forms, the aglyconic isoflavones. Producers of soy foods recognize that the public is interested in isoflavone supplements, and many indicate in their product labeling the amounts and forms of isoflavones found in the foodstuff. Although the mechanisms of action of soy and dietary isoflavones are not fully understood, they appear to involve binding to the estrogen receptor. For this reason, one should not assume these dietary supplements are safe for women with estrogen-dependent cancers, most importantly breast cancer.

Black Cohosh.

Black cohosh was the principle ingredient in Lydia Pinkham's Vegetable Compound, an ethanolic extract sold over-the-counter in the United States and in Europe. A black cohosh extract is one of the leading botanicals sold in Germany and is the country's top selling menopausal herbal remedy. The German Commission E Monographs state that black cohosh has estrogenlike action, suppresses LH, binds to estrogen receptors, has no contraindications to its use, and that the only side effect is occasional gastric discomfort (16).

Black cohosh has been found to reduce LH levels in rats that had ovariectomies and to reduce LH levels in postmenopausal women after 8 weeks of use (17). Despite these LH effects, other studies in humans and animals indicate that black cohosh has no estrogenic effects on sex-steroid-dependent tissues. In one unpublished double-blind, randomized study, black cohosh did not affect follicle-stimulating hormone, LH, estradiol, estrone, prolactin, sex-hormone-binding globulin, endometrial thickness, or vaginal maturation index (18). No claims are made regarding cardiac or bone effects, and black cohosh is suggested only for treatment of menopausal symptoms such as hot flashes, sleep disorders, anxiety, and depression and for nonmenopausal conditions like dysmenorrhea and premenstrual syndrome.

Evening Primrose.

The evening primrose plant (also called evening star) produces seeds rich in gamma linolenic acid (GLA) and also contains several anticoagulant substances. Commercial preparations made from fixed oil sources are generally 72% linolenic acid (LA) and 14% GLA. Thus, each 500-mg capsule will contain 45 mg of GLA and 365 mg of LA plus lesser amounts of oleic, palmitic, and stearic acid. Because GLA is elaborated by the placenta, and because high concentrations are found in breast milk, it is suggested that GLA is the nutritionally perfect fatty acid for humans. With respect to the gynecologic uses of GLA, evening primrose is commonly recommended for mastalgia and mastodynia, premenstrual syndrome, menopausal symptoms, and bladder symptoms.

Dong Quai.

Dong Quai (also seen as Dang Gui and Tang Kuei), a type of angelica, is the most commonly prescribed Chinese herbal medicine for "female problems" (19). Dong Quai supposedly regulates and balances the menstrual cycle and is said to strengthen the uterus. Dong Quai is used in traditional Chinese medicine to nourish and "tonify" blood. It also is said to exert estrogenic activity. Most herbal practitioners seem to agree it is contraindicated during pregnancy and lactation.

Mood Disturbances

St. John's Wort.

Extracts of the flower hypericum perforatum, known as St. John's wort, have been used for centuries to treat mild to moderate depression. The constituents include hypericin, pseudohypericin, and flavonoids. Several unconfirmed mechanisms of action for the psychotropic effects of St. John's wort have been proposed, including monamine oxidase inhibition, suppression of corticotropin-releasing hormone, and serotonin receptor blockade. Hypericin does not appear to be a monamine oxidase inhibitor (20).

Commercial preparations often contain generally recommended doses; one capsule three times a day provides a cumulative dose equivalent to the upper limit of doses found in the literature to date. Side effects are similar to, but far less than, those of standard antidepressant medications, including dry mouth, dizziness, and constipation.

Valerian Root.

Valerian root, the common valerian or garden heliotrope, has been used traditionally as a tranquilizer and soporific. The active constituent has never been identified but is thought to be a gamma aminobutyric acid (GABA) derivative. Note that a similar GABA-like compound has been found in chamomile, which is also proffered as an herbal sleep aid. Before the advent of benzodiazepines and barbiturates, many psychiatric disorders were treated with valerian. Although it has no demonstrable toxicity and degrades rapidly, there have been reports of dystonic reactions and visual disturbances, perhaps mediated by other drugs used concomitantly. Little is known about the actions, effects, or potential interactions of valerian with other drugs. After L-tryptophan was taken off the market, valerian use became popular again. Most botanical texts advise against its use during pregnancy and lactation.

Loss of Libido/Vaginal Dryness/Dyspareunia

Chasteberry.

Chasteberry or vitex also is known as Chaste tree, Monk's pepper, agnus castus, Indian spice, sage tree hemp, and tree wild pepper. It has been recommended by some for vaginal dryness at menopause and also for depression. Vitex contains hormonelike substances, which competitively bind receptors and produce antiandrogenic effects; it is often recommended to reduce libido in males because of its proposed value as an antiaphrodisiac. Antithetically, vitex also is recommended by some to enhance libido in menopausal women.

In vitro and animal studies have suggested that vitex inhibits prolactin, and perhaps explains the purported benefit of recommending vitex for mastalgia and premenstrual syndrome. A placebo-controlled, double-blind clinical trial of 20 male subjects used 120-, 240-, and 480-mg extracts of vitex, which did not demonstrate any effect on prolactin (21). Another single-armed study in 56 women with mastodynia showed a reduction in prolactin in the treatment group compared with controls (22). Studies, the quality of which cannot be assessed, claim that vitex corrects inadequate luteal phase, and that it restores LH activity.

Ginseng.

There are many types of ginseng (Panax ginseng)—Siberian, Korean, American, White, and Red. All are promoted as "adaptogens," which help one cope with stress and supposedly boost immunity. Ginseng also is reputed to be an aphrodisiac, a claim that is unsubstantiated by medical evidence. It also is promoted as a means of improving athletic performance and inducing weight loss without the need for diet or exercise. There is evidence that ginseng does not improve athletic performance, despite claims made (23). Reports of antioxidant effects and reduced rates of disease, particularly cancer rates, are suspect because the products in general use have been found to contain little or no active ingredients (24).

Menstrual Disorders/Menorrhagia

Wild Yam.

Yam extracts, tablets, and creams claim to be progesterone substitutes and also are touted as a natural source of DHEA. Sterol structures from the plant are used as precursors in the biosynthesis of progesterone, DHEA, and other steroids, but do not have inherent biological activity. Claims are made that the plant sterol dioscorea is converted into progesterone in the body and alleviates "estrogen dominance." There is no human biochemical pathway for bioconversion of dioscorea to progesterone or DHEA in vivo. Mexican yam extract more accurately is estrogenic, containing considerable diosgenin, an estrogenlike substance found in plants. Some estrogenic effects might be expected from eating these species of yams, but only if large quantities of raw yams are consumed (25). Yams from the grocery store generally are not the varieties known to contain significant amounts of dioscorea or diosgenin. Yam extracts also are purported to be effective for uterine cramps.

Clinical Considerations and Recommendations

A limited body of scientific information about botanicals is available in English. A few publications from Europe and Asia are available in full text. Most of the literature includes in vitro effects, animal models, and open, often single-armed or nonrandomized studies. The amount and sophistication of studies of most alternative therapies do not meet the current standards for evidence-based recommendations.

• Are there useful nonpharmaceutical supplements or botanicals for treatment of vasomotor symptoms, including hot flashes, flushes, and night sweats?

Soy/Isoflavone Isolates.

In one study, women given a soy protein supplement with 40 mg of protein and 76 mg of isoflavones had a 45% reduction in vasomotor symptoms compared with a 30% reduction in controls who received a placebo (26). Other research demonstrated a 40% reduction in vasomotor symptoms when diet was supplemented with soy flour, but the vaginal maturation index did not improve (27). Based on these limited studies, the use of soy may have benefits.

Black Cohosh.

Although a dozen studies of women taking black cohosh extracts show an apparent reduction in symptomatology, the studies are largely unblinded, use unvalidated tools to measure outcomes, and contain small numbers of patients. Based on this limited evidence, there appears to be a positive effect on sleep disorders, mood disturbance, and hot flashes (28). There have been no reports of black cohosh toxicity. No clinical studies have reported efficacy or safety of black cohosh beyond 6 months of use. Black cohosh should not be confused with blue cohosh, Caulophyllum thalictroides, which has weak nicotine activity and toxic potential.

Evening Primrose.

A meta-analysis of clinical trials of evening primrose oil used to treat premenstrual syndrome concluded that of the seven controlled trials, only five were properly randomized (29). In the only one of the five trials that was blinded, evening primrose was ineffective in treating premenstrual syndrome. To date, there is only one randomized, double-blind, placebo-controlled study of the use of GLA in the treatment of vasomotor symptoms during menopause (30). Although the women taking GLA had "significant improvement... in the maximum number of night time flushes," GLA provided no benefits beyond those seen with placebo.

Dong Quai.

Kaiser Permanente conducted a double-blind controlled clinical trial using a daily dose of 4.5 g of dong quai (9). Dong quai and placebo both reported a 25% reduction in hot flashes. Critics of the study have noted that the dose of dong quai was lower than that often used in traditional Chinese medicine, and that dong quai is never employed as an isolated intervention. The argument is made that the botanicals must be taken together in a balanced formula and that the therapeutic outcome requires that proper synergy take place between the components. However, its benefit cannot be substantiated based on available evidence.

Dong quai is potentially toxic. It contains numerous coumarinlike derivatives and may cause excessive bleeding or interactions with other anticoagulants (31). Dong quai also contains psoralens and is potentially photosensitizing, which has led to concern about an increased risk of sun-exposure-related skin cancers (32).

Ginseng.

Ginsana, the largest manufacturer of ginseng, funded a study of 384 women to investigate the effects of ginseng in menopausal women. No differences were found between treatment subjects and placebo controls in vasomotor symptoms, but significant improvements were reported in quality of life measures, particularly depression, general health, and well-being scores (33).

• Are there alternative, nonpharmaceutical supplements or botanicals that have demonstrated usefulness in the treatment of sleep, mood and affective, cognitive, and other behavioral disorders associated with menopause syndrome?

St. John's Wort.

A meta-analysis of 15 controlled trials encompassing 1,757 cases found that St. John's wort hypericin in doses less than 1.2 mg per day produced a 61% improvement in mild to moderate depression, while doses up to 2.7 mg per day produced a 75% improvement (34). Its efficacy in the treatment of severe depression is not documented. Some have suggested that St. John's wort is helpful in treating seasonal affective disorder. No clinical studies have reported results or safety parameters beyond 2 years of use.

St. John's wort is also potentially photosensitizing (24), and concern has been raised about an increased rate of cataracts. The issue of possible interactions between St. John's wort and selective serotonin reuptake inhibitors or monamine oxidase inhibitors has been raised. Some consultants advise against using St. John's wort for weeks to months after stopping these drugs. Interaction with anesthetic agents has also been reported (35).

Valerian Root.

In 1998, the U.S. Pharmacopeia (USP) stated in its monograph on valerian: "Studies supporting this use are not good enough to prove that it is effective. Therefore, USP advisory panels do not support its use" (36). There is a case report of high-output congestive heart failure, tachycardia, and delirium attributed to acute withdrawal from valerian (37). Based on available data, valerian appears not to be useful, and may be harmful.

• Are there alternative, nonpharmaceutical supplements or botanicals that have been shown to be useful for treatment of decreased libido, vaginal dryness, or dyspareunia?

Soy/Isoflavones.

Findings regarding the effects of soy supplements on vaginal maturation index are inconsistent with some showing improvements (11) and others showing no change (12). Different isoflavones may have a differential impact on estrogen-sensitive tissues, so that various types of dietary soy may affect the lower genital tract with a significant degree of variability (12, 27). Therefore, some soy products may be useful in the treatment of vaginal dryness and dyspareunia, although sources of isoflavones and beneficial amounts have yet to be clarified.

Chasteberry or Vitex.

Although vitex's supposed antihormonal activity serves as the basis for advising its use in treating mastalgia, all claims of efficacy in women are poorly documented. Although studies of vitex use in menopause are limited, a recent randomized trial assessed the effects of vitex in women with premenstrual syndrome, which may apply to women with similar complaints in menopause. After three cycles of vitex, significant improvements in mood alteration, anger, headache, and breast fullness were reported on a self assessment screening tool. However, other menstrual symptoms, like bloating, remained unchanged. Physician ratings of patients' conditions also indicated better effects than with placebo (38).

Ginseng.

No published studies have documented that ginseng has an effect on libido in menopausal women. Moreover, 54 ginseng products examined by the American Botanical Council proved to have little ginseng (60%) or no ginseng (25%), and many were heavily adulterated with caffeine (24). Other analyses have found significant variation in the active ingredient, ginsenosides, as well as high levels of pesticides or lead. Ginseng may hold some promise in the treatment of fatigue, depression, immunosuppression, and other health problems, but it cannot be recommended as a treatment for menopause. For its other indications, caution is advised given the poor production standards and lack of quality evidence for the claims made.

• Are there alternative, nonpharmaceutical supplements or botanicals that are useful for the treatment of menstrual disorders during perimenopause and menopause?

Wild and Mexican Yam.

Based on the lack of bioavailability, the hormones in wild and Mexican yam would not be expected to have any efficacy. Wild yam extracts are neither estrogenic nor progestational, and although many yam extract products contain no yam, some are laced with progesterone. Perhaps some may even contain medroxy-progesterone. Oral ingestion does not produce serum levels. There are no published reports demonstrating the efficacy of wild yam cream. A 1-month supply costs more than $25, while a month of commercially produced vaginal estrogen cream costs less than $20 (39).

• Are there useful alternative, nonpharmaceutical supplements or botanicals for the prevention of coronary heart disease and osteoporosis?

Soy/Isoflavone Isolates.

There is some evidence to indicate that high isoflavone intake may favorably affect lipid profile and is, by extension, thought to reduce cardiac disease risk. However, study results are conflicting. A study in Finland found an inverse relationship between isoflavone intake and coronary heart disease in both women and men (40), but similar benefits have not been demonstrated in the United States (41). A meta-analysis showed higher soy intake is associated with significant improvement in lipid profiles (42). Soy protein intake of approximately 47 g per day correlated with a statistically significant 9.3% reduction in serum cholesterol, a 12.9% reduction in serum low-density lipoprotein cholesterol, a 10.5% reduction in serum triglycerides, and an insignificant 2.4% increase in high- density lipoproteins. Isoflavone isolates containing 40 mg of isoflavone isolates have been shown to induce a 23% increase in arterial compliance after 1 year of use, an increase equal to that seen in women receiving conjugated equine estrogens (43).

Dietary soy or isolated isoflavone supplements may have a salutary effect on bone mass. Ipriflavone, a synthetic version of genistein, slows bone reabsorption and stimulates collagen synthesis in bone. Pharmaceutical quality ipriflavone is approved in Europe and Japan for treatment of osteoporosis using 600 mg per day. Ipriflavone with supplemental calcium has been found to decrease bone loss in natural menopause in some studies (44, 45), but not others (46), to decrease bone loss after surgically induced menopause (47), and in women with gonadotropin-agonist-induced bone loss (48).

No published studies have investigated the role of clinical monitoring in patients using alternative medicine therapies. However, alternative steroid products may pose a risk for consequences of excessive steroid ingestion. Androgens are associated with abnormal liver functions as well as potential hyperandrogenicity. Estrogens compounded by an alternative therapy pharmacy may produce varying serum estradiol levels in women or increased estrogen bioactivity without detectable changes in circulating estradiol. Risks of excessive levels include hepatic effects and increased risk of deep vein thrombosis.

Although most botanicals appear to be harmless, products may be adulterated or contaminated. In addition, all menopausal women taking any pharmaceutical or alternative preparation should have blood pressure readings, mammograms, and Pap tests at recommended intervals. Women using estrogen supplements who are relying on unconventional estrogenic or progestational therapies such as transdermal progesterone cosmetic creams should be monitored according to standard guidelines for women taking unopposed estrogen—that is, endometrial surveillance should be considered. In counseling patients, the risk of adverse effects from these therapies must be weighed against the costs associated with any routine testing. Further guidelines for counseling patients regarding the use of complementary and alternative medicine are shown in the box. Also, it is important for clinicians to be aware of issues surrounding referral to alternative care providers (3).

Summary of Recommendations

Given the general lack of standardization of products, the relatively short duration of therapy and follow-up in the available data, and the difficulty of interpreting the available clinical data, few recommendations can be made with confidence. The following conclusions can be drawn in reference to short-term (<=2 years) use of botanical and alternative medicine for the management of menopause.

The following recommendations are based primarily on consensus and expert opinion (Level C):

• Soy and isoflavones may be helpful in the short-term (<=2 years) treatment of vasomotor symptoms. Given the possibility that these compounds may interact with estrogen, these agents should not be considered free of potential harm in women with estrogen-dependent cancers.
• St. John's wort may be helpful in the short-term (<=2 years) treatment of mild to moderate depression in women.
• Black cohosh may be helpful in the short-term (<=6 months) treatment of women with vasomotor symptoms.
• Soy and isoflavone intake over prolonged periods may improve lipoprotein profiles and protect against osteoporosis. Soy in foodstuffs may differ in biological activity from soy and isoflavones in supplements.

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