Use of alternative and complementary medicine in menopause.

OBJECTIVES: To review the clinical evidence available for the treatment of menopausal symptoms with alternative and complementary medicine. METHODS: The MEDLINE, PREMEDLINE and COCHRANE electronic databases for the years 1980-2002 were searched for articles concerning soy products, black cohosh, dong quai, acupuncture, ginseng and evening primrose oil. Studies pertaining to menopausal vasomotor symptoms, lipid profiles and bone mineral densities of postmenopausal women were included. The data from clinical trials were reviewed. RESULTS: Soy isoflavones slightly decrease total cholesterol and LDL levels. The clinical significance of this small change is yet to be determined. The synthetic isoflavone derivative ipriflavone increases bone mineral density in healthy peri- and postmenopausal women with moderate bone mineral densities. Although earlier reports have claimed that soy is beneficial for the improvement of vasomotor symptoms, recent data do not support this claim. There are insufficient data on the other alternative therapies for treating menopausal symptoms at this time. CONCLUSION: Alternative and complementary medicine may play a role in the management of menopause, however, well-designed large studies are still needed.     

Drug-herb interactions with herbal medicines for menopause

Herbal medicine is one of most popular choices of complementary therapies for women, particularly as an alternative treatment for menopausal symptoms. The most commonly used herbal medicines for the menopause is probably black cohosh (Actaea/Cimcifuga racemosa); other preparations used include red clover (Trifolium pratense), dong quai (Angelica sinesis) and evening primrose (Oenothera biennis). Some of these herbal medicines have a very good safety profile with little or no suggestion of interaction with conventional drugs. For others, there are many and significant drug-herb interactions. This article outlines the major known and theoretical drug-herb interactions of herbal medicines thought to be of benefit for menopausal symptoms, as well as discussing the implications for the medical profession.     

Hot flashes revisited: pharmacological and herbal options for hot flashes management. What does the evidence tell us?

BACKGROUND: Hot flashes are the most frequent symptoms of menopause and the most common reason for climacteric women seeking medical advice. Estrogen therapy is by far the most effective therapy. However, fears of side-effect of estrogen therapy urged many patients to seek alternative modalities for symptomatic relief. METHODS: The MEDLINE database for the years 1975-2004 was searched for clinical placebo-controlled trials for the treatment of hot flashes with alternative therapy. Articles reporting the use of progesterone, alpha adrenergic agonists, anti-depressants, anti-convulsants, soy products, black cohosh (BC), red clover, dong quai, ginseng root, evening primrose oil, vitamin E, and wild yam were included. RESULTS AND CONCLUSIONS: A critical review of the literature shows that progesterone may have an independent effect on relieving hot flashes. New nonhormonal agents such as selective serotonin-uptake-inhibitor anti-depressants and a new anti-convulsant gabapentin yielded promising results on small well-conducted studies. Isoflavone's effect on hot flashes is variable and inconsistent, and only modest and delayed improvement of symptoms could be expected by BC and vitamin E. There are insufficient data on the other herbal alternative therapies at this time. Well-designed large studies are needed to further explore new modalities of treatment.     

Herbal remedies for menopausal symptoms: are we cautious enough?

OBJECTIVES: To evaluate adverse effects of herbal remedies consumed by menopausal women for control of the climacteric syndrome. METHODS: We examined the long term safety and herb-drug interactions of commonly used herbal therapy such as soy, black cohosh, dong quai, ginseng and vitamin E. RESULTS: Even carefully designed studies on herbal treatments for vasomotor menopausal symptoms never addressed specifically safety issues. Sporadic reports show dangerous adverse effects of these herbal preparations as well as hazardous interactions between botanic compounds and conventional medications. CONCLUSIONS: The unrestricted sale of plant products constitutes a new situation for physicians with little training in phytotherapy. The qualitative and quantitative diversity of the commercially available preparations, the absence of precise prescribing guidelines, and the risk of self-prescribed medication justify the introduction of 'phyto-vigilance'. Physicians should warn their patients about the lack of evidence regarding safety and possible interactions of herbal remedies with concurrent medications.     

Herbal remedies for menopausal symptoms: Are we cautious enough?

Objectives To evaluate adverse effects of herbal remedies consumed by menopausal women for control of the climacteric syndrome.

Methods We examined the long term safety and herb-drug interactions of commonly used herbal therapy such as soy, black cohosh, dong quai, ginseng and vitamin E.

Results Even carefully designed studies on herbal treatments for vasomotor menopausal symptoms never addressed specifically safety issues. Sporadic reports show dangerous adverse effects of these herbal preparations as well as hazardous interactions between botanic compounds and conventional medications.

Conclusions The unrestricted sale of plant products constitutes a new situation for physicians with little training in phytotherapy. The qualitative and quantitative diversity of the commercially available preparations, the absence of precise prescribing guidelines, and the risk of self-prescribed medication justify the introduction of ‘phyto-vigilance’. Physicians should warn their patients about the lack of evidence regarding safety and possible interactions of herbal remedies with concurrent medications.     

Red clover isoflavones and menopausal health

Menopausal symptoms such as hot flushes and night sweats can be very disrupting. While hormone replacement therapy is an effective therapy, concerns about side effects and breast cancer risk have stimulated interest into alternative therapies such as phytoestrogens. These are oestrogen-like compounds made by plants. Two major sources of phytoestrogens are soy and red clover. Data on randomised controlled trials of red clover for the control of menopausal symptoms are presented. The conflicting data are encouraging and suggest that phytoestrogens are a treatment modality that needs pursuing.     

Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial

Objective: To evaluate possible estrogenic effects of dong quai on vaginal cells and on endometrial thickness in postmenopausal women.

Design: Double-blind, randomized, placebo-controlled clinical trial.

Setting: Department of Obstetrics and Gynecology in a large health maintenance organization (HMO).

Patient(s): Seventy-one postmenopausal women (mean age [±SD], 52.4 ± 6 years) who had follicle-stimulating hormone levels (third-generation assay) of >30 mIU/mL with hot flashes.

Intervention(s): Subjects were randomized to treatment with either dong quai or placebo for 24 weeks.

Main Outcome Measure(s): Endometrial thickness was measured by transvaginal ultrasonography; vaginal cells were evaluated for cellular maturation; menopausal symptoms were evaluated by reviewing the Kupperman index and the diary of vasomotor flushes.

Result(s): We observed no statistically significant differences between groups in endometrial thickness, in vaginal maturation index, in number of vasomotor flushes, or in the Kupperman index.

Conclusion(s): Used alone, dong quai does not produce estrogen-like responses in endometrial thickness or in vaginal maturation and was no more helpful than placebo in relieving menopausal symptoms.     

Alternative Therapiemöglichkeiten zur Hormontherapie in der Postmenopause

Despite increasing interest in alternative therapies for menopausal hot flashes that avoid use of estrogens, the efficacy and safety of other options currently are not well supported. In women who need relief for mild vasomotor symptoms isoflavones or black cohosh are recommended. Non-hormonal treatments are not as effective as estrogens in relieving hot flashes. There is a suggestion, but no conclusive evidence, that isoflavones have a beneficial effect on bone health and that there is an association between lifelong soya bean intake und reduced risk of breast cancer. Recommended options for women with contraindications relating to estrogen-containing treatments include serotonin reuptake inhibitors and gabapentin.     

"Bust enhancing" herbal products

"Bust enhancing" herbal products are widely advertised. No clinical trials have been published. These products contain a variety of ingredients, including grains, hops, saw palmetto, dong quai, chaste-tree berry, wild yam, kava, fennel, black cohosh, and fenugreek. Several of these herbs are hormonally active; for example, hops contain 8-prenylnaringenin, a phytoestrogen that is more potent than other dietary phytoestrogens. Many bust-enhancing dietary supplements contain substrates for Fusarium, a fungus that produces zearalenone, a potent estrogen that has been associated with breast enlargement in humans and other species. The use of bust-enhancing products should be discouraged because of lack of evidence for efficacy and long-term safety concerns.     

Safety of alternative treatments for menopausal symptoms after breast cancer: a qualitative systematic review.

AIM: This qualitative review analyzes systematically the safety of drugs used to alleviate menopausal symptoms, other than hormone replacement therapy, in breast cancer patients. METHODS: We searched systematically studies using tibolone, serotonin reuptake inhibitors, clonidine, veralipride, gabapentin, black cohosh and phytoestrogens in breast cancer patients. We selected five studies for which we evaluated the methodology, characteristics of the studied populations, outcomes in terms of mortality and recurrence rates. RESULTS: Four trials were conducted using tibolone in breast cancer patients: one double-blind, randomized trial, one prospective controlled study, and two uncontrolled studies. They considerably lack power to detect any difference in breast cancer recurrence or mortality between the treated and control patients. Similar conclusions have to be drawn from the only controlled retrospective study analyzing the safety of antidepressants and antihistamines. We were unable to find studies reporting the safety of the other drugs in breast cancer patients. CONCLUSIONS: There are no valuable data indicating the absence of a harmful effect of drugs used to alleviate climacteric symptoms in breast cancer patients. There is a need for randomized trials to assess the safety of these drugs. In the meantime, patients should be informed about the absence of safety data.     

Dietary supplements and herbal remedies for premenstrual syndrome (PMS): a systematic research review of the evidence for their efficacy

Many women with PMS use alternative therapies, although there has been little research to demonstrate their efficacy. This systematic review provides a comprehensive discussion of dietary supplements and herbal remedies commonly used for premenstrual syndrome (PMS), including calcium, magnesium, vitamin B6, evening primrose oil, Vitex agnus castus, ginkgo biloba and St John's Wort. Randomized controlled trials of magnesium and evening primrose oil have produced conflicting results, in contrast to the substantial evidence for the efficacy of calcium and vitamin B6. There are insufficient data to advocate the use of ginkgo biloba, Vitex agnus castus and St John's Wort, although preliminary data seem supportive. Greater standardization of PMS diagnosis and assessment, with randomized, double‐blind, placebo‐controlled trials using larger, representative samples, strict, prospectively confirmed diagnostic criteria and assessment of treatment efficacy, would help to clarify the role of these alternative PMS treatments. Although much of the clinical research is preliminary and/or inadequately controlled, this review will be relevant to the practicing clinician looking for greater understanding of the alternative therapies available to their patients with PMS.     

Phytoestrogens for treatment of menopausal symptoms: a systematic review

OBJECTIVE: To assess the efficacy and tolerability of phytoestrogens for treatment of menopausal symptoms. DATA SOURCES: We searched the Cochrane Library and MEDLINE from 1966 to March 2004, using a detailed list of terms related to phytoestrogens and menopausal symptoms and also hand-searched abstracts from relevant meetings. METHODS OF STUDY SELECTION: Randomized trials were eligible if they involved symptomatic perimenopausal or postmenopausal women, compared phytoestrogen with placebo or control, reported hot flush frequency or menopausal symptom scores, and were at least 4 weeks in duration. TABULATION, INTEGRATION, AND RESULTS: Data were extracted onto standardized forms using a prospectively developed protocol. Twenty-five trials involving 2,348 participants met criteria. At baseline, the mean age was 53.1 years, mean duration of menopause was 4.3 years, and mean daily hot flush frequency was 7.1. Mean study duration was 17 weeks. Trials were grouped into categories according to type of phytoestrogen: soy foods, beverages, or powders (n = 11); soy extracts (n = 9); and red clover extracts (n = 5). Of the 8 soy food trials reporting hot flush frequency outcomes, 7 were negative. Five trials of soy foods provided information to calculate effect sizes; these were in the small-to-medium range, favoring placebo in 3 trials and soy in 2. Of the 5 soy extract trials reporting hot flush frequency, 3 (including the 2 largest trials) were negative. Effect sizes were calculated for 2 soy extract trials: one favored placebo with small effect size and the other favored soy with moderate effect size. Red clover trials showed no improvement in hot flush frequency (weighted mean difference -0.60, 95% confidence interval -1.71 to 0.51). Adverse effects were primarily gastrointestinal and taste intolerance in the soy food and beverage trials. CONCLUSION: The available evidence suggests that phytoestrogens available as soy foods, soy extracts, and red clover extracts do not improve hot flushes or other menopausal symptoms.     

Non-hormonal treatment of vasomotor symptoms in gynecological cancer patients

Gynaecological cancer patients generally suffer from an earlier and more severe menopausal syndrome than the general female population. Hormone replacement therapy is often contraindicated and there are non-hormonal treatments that are proven to be more effective than placebo in randomized controlled trials, e.g., some antidepressants, gabapentine and clonidine. The main limits to the use of these drugs in controlling hot flashes are the off-label use for this purpose, the very short follow-up and the fact that data come from studies performed on breast cancer, not on gynecological cancer patients. Patients believe that drugs derived from plants could be effective in relieving hot flashes and that they are harmless. Evidence is contrary to this belief and estrogen-sensitive cancer patients should be warned of the potential, though very weak, estrogenic effect of phytoestrogens and other "natural" drugs, and that their efficacy is close to that of a placebo.     

Menopausal symptoms and alternative medicine

With the large number of women entering the perimenopausal and menopausal age range in the next decade, use of alternatives to standard hormone replacement therapy will increase. Women’s views of conventional hormone replacement and trends toward “complementary and alternative medicines” have contributed to an increased use of alternative treatments for menopausal symptoms. Growing media coverage and lay literature available on “natural” therapies for the climacteric are making it virtually impossible for practitioners to remain unfamiliar with the various regimens. Information on phytoestrogens, natural progesterones, mineral and vitamin supplements, herbal treatments, exercise, relaxation, acupuncture and homeopathy is flooding the market. Although alternatives to conventional hormone therapy are becoming mainstream, scientific evidence on the safety and efficacy of “natural” therapies is limited. Lack of standardization of alternative supplements and lack of regulation also make it difficult for both consumers and practitioners to evaluate these therapies. Well-designed, controlled studies are needed to obtain further information about these regimens. This, however, is no excuse for practitioners to be unaware of what products are available and their possible benefits and adverse effects. The evidence for various alternative therapies for menopausal symptoms is reviewed in both the lay and medical literature.     

Phytoestrogens

The soy-isoflavones genistein and daidzein and the flaxseed-lignans secoisolariciresinol and matairesinol belong to the group of phytoestrogens. Epidemiological data suggest that phytoestrogens have a preventive effect against various estrogen-related diseases/symptoms such as breast cancer, menopausal symptoms, cardiovascular diseases, and osteoporosis. To prove these assumptions, available controlled clinical trials have been critically reviewed. Especially soy-isoflavones have been extensively studied. There is no scientific evidence for an effect of phytoestrogens on menopausal symptoms and risk factors of breast cancer. However, isoflavones-containing soy protein can lower total cholesterol, LDL cholesterol, and triglyceride serum levels. The strongest evidence exists for a preventive effect of soy isoflavones on postmenopausal bone loss of the lumbar spine. Distinct effects on estrogen-related diseases can be explained at least in part by the different affinity of isoflavones to estrogen receptors alpha and beta and the distinct tissue distribution of these receptors.     

Taking an integrated approach: managing women with phytoestrogens

An integrated approach can be employed when counselling women about menopausal management options, where lifestyle, complementary therapies and hormone replacement therapy (HRT) are discussed. Women might opt to use an alternative approach to HRT for a variety of reasons, e.g. fear of side-effects and risks or contraindications to HRT. There are many choices of dietary and herbal approaches for menopausal symptoms, which essentially divide into food supplements and herbal medicines. The choice can often be overwhelming and confusing for the woman. Of concern, the evidence for efficacy and safety of some of these complementary therapies can be extremely limited or non-existent. In order to enable women to make a fully informed choice, it is important that, when a recommendation is made regarding a specific complementary therapy, it should focus on preparations for which a significant dataset exists for efficacy and safety and in which there is ongoing research and development. One of the most extensively studied food supplements has been the phytoestrogenic preparation containing red clover isoflavones. There have been six randomized trials thus far studying the impact on vasomotor symptoms, three of which have shown a significant benefit compared to placebo. There are also data from small randomized and observational trials showing positive outcomes for surrogate markers of osteoporosis and cardiovascular disease. A recent study using validated depression scales has shown that women using red clover isoflavones may also derive psychological benefits. Safety data are reassuring for the endometrium and breast, although further studies would be welcome, particularly in women with significant medical risks.     

Behandlung von klimakterischen Beschwerden nach Brustkrebs

Background

Women with a history of breast cancer often suffer from climacteric symptoms. Hormonal therapies are known to reduce these symptoms but are not recommended in women with a history of breast cancer due to their potential adverse effects.

Objectives

The goal of this work is to give a literature overview on the efficacy of non-hormonal therapies as a therapy option for this patient group.

Materials and methods

In a PubMed search, relevant studies and meta-analyses from 1997–2014 that provided data on treatment of menopausal symptoms with hormonal replacement therapy versus nonhormonal therapies were identified.

Results

Hormone replacement therapy is not recommended in patients with history of breast cancer. Lifestyle modification is the basis in treating climacteric symptoms. Daily isoflavone intake of 50–60 mg can significantly reduce frequency and severity of hot flushes if not present more than 4 times/day. Cimicifuga racemosa allays hot flushes, depressive mood, and might be associated with prolonged disease-free survival. Its efficacy is comparable to transdermal estrogen. Off-label use of antidepressants like paroxetin and venlafaxin and anticonvulsants like gabapentin can be used as second line treatment with good efficacy.

Conclusion

Studies on nonhormonal therapies provide evidence for efficacy so that breast cancer patients do have an alternative treatment option for climacteric disorders. Nevertheless, hormone replacement is still more effective. More well-designed trials are needed to further investigate nonhormonal therapies.     

Black cohosh (Cimicifuga racemosa): a systematic review of adverse events

Black cohosh (Cimicifuga racemosa) is used most often to treat symptoms that can occur during menopause. However, in the last years, several concerns regarding its safety have been voiced. The aim of this systematic review was to evaluate the clinical evidence for or against the safety of black cohosh. Systematic literature searches were conducted in 5 computerized databases (Medline, Embase, Amed, Phytobase, and Cochrane Library). The references of all located articles were scanned for further relevant publications. Any type of clinical data that included case reports and observational studies was considered. No language restrictions were imposed. Thirteen clinical trials (all of which indicated relative safety), 3 postmarketing surveillance studies, 4 case series, and 8 single case reports were identified. Clinical studies suggest black cohosh to be safe. In most case reports, causal attribution is problematic. In conclusion, black cohosh has been associated with serious safety concerns that urgently require further investigation.