Phytoestrogens: a potential role in hormone replacement therapy

Phytoestrogens are plant substances that are recognized to have varying degrees of estrogenic activity. As the demographics of our society move toward an aging population, obstetrician/gynecologists should be prepared to care for the growing numbers of perimenopausal and menopausal women. While hormone replacement therapy (HRT) has been shown to have many benefits, its use is still somewhat controversial. Studies show that only 10% of women eligible for HRT actually use it, reflecting the controversy as well as the lack of education of both providers and patients. Given the imperfections of traditional HRT, other options are being explored. These include the development of new “designer estrogens,” as well as alternative therapies. Unfortunately, because a clinician’s training is in traditional medicine, patients frequently learn more about these alternatives from the lay press than from their physicians. Therefore it is our responsibility to educate ourselves with scientific data about these therapies, the better to inform and guide our patients. With this goal in mind, this article reviews the current literature on phytoestrogens, which may provide an alternative to standard HRT.     

ACOG Practice Bulletin no. 28: Clinical Management Guidelines for Obstetrician-Gynecologists. 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.     

Acupuncture in managing menopausal symptoms: hope or mirage?

There is an increased interest amongst women in seeking alternatives for hormone replacement therapy because of their fear of side-effects. It is claimed that acupuncture is effective for curing menopausal symptoms, and to be a safe treatment in the hands of well-trained and qualified practitioners. About one million acupuncture treatments are given in the National Health Service and two million privately each year in England for various indications. However, because its mechanism of action is not fully understood in physiological terms, acupuncture is considered by many clinicians to be of no value. This article reviews the currently available evidence as regards the effectiveness and safety of acupuncture in treating menopausal symptoms.     

A comprehensive approach to the menopause: so far, one size should fit all

Although extensive studies have indicated that the benefits of hormone replacement therapy outweigh the risks, many women and health care providers have concerns about safety and side effects. Many alternative therapies are popular with patients, and menopausal women in the United States spent more than $600 million in 1999 alone purchasing these therapies. Several of the more commonly used alternative therapies for the menopause are critically appraised in this article. For women who choose not to take estrogen, and for those who do, the additional benefits of calcium, vitamin D, exercise, stress reduction, and different dietary and lifestyle adaptations may enhance the quality of life as they age. Although they have the potential for being effective and safe options, there has been limited clinical research for the other alternative therapies. Gynecologists and other health care providers should be aware of the lack of evidence for the effectiveness of most of these therapies when they address patient's questions and concerns. Our information about alternative therapies will increase in the coming years. Ultimately, the growing number of available treatment choices will allow individualization of the treatment. Nevertheless, until prospective studies with prolonged follow-up are conducted to evaluate the risks and benefits of different alternative therapies, hormone replacement therapy, which is better studied, will remain the treatment of first choice, and "one size fits all" will continue to describe the management plan for most peri- and postmenopausal women at least in the near future. LEARNING OBJECTIVES: After completion of this article, the reader will be able to summarize the various alternatives to hormonal therapy for menopausal symptoms, describe the effects of phytoestrogens in the management of menopausal symptoms, and explain the origin and clinical use of the more common herbal therapies.     

Hormone replacement therapy update: who should we be prescribing this to now?

PURPOSE OF REVIEW: To summarize results from the Women's Health Initiative trial and other recent randomized placebo-controlled trials of hormone replacement therapy, which fundamentally changed our understanding of its risks and benefits. RECENT FINDINGS: The Women's Health Initiative study for the first time provided evidence of harmful effects of hormone replacement therapy on the cardiovascular system and also confirmed significantly increased risk of breast cancer which was previously documented in a metaanalysis. Most recent studies indicate a particularly harmful effect of combined estrogen/progestin regimens in terms of increased breast cancer risk. SUMMARY: The effects of hormone replacement therapy on coronary heart disease, stroke, venous thromboembolism, breast cancer, gallbladder, diabetes, cognitive function, health-related quality of life, colorectal cancer, osteoporosis and menopausal symptoms are discussed briefly. The emphasis is on providing concise clinical guidelines for hormone replacement therapy use in new circumstances. We also discuss some alternative therapeutic modalities for women who have menopausal symptoms, but contraindications for hormone replacement therapy.     

Perimenopausal and postmenopausal hormone replacement therapy Part 1. An update of the literature on benefits and risks

As life expectancy increases and members of the postwar generation settle into their fifth decade of life, hormone replacement therapy—estrogen or an estrogen-progestin combination—has become a major research interest. An extensive, but often confusing and even contradictory, literature exists on the uses of hormone replacement for the treatment and prevention of a multitude of difficulties that may be associated with the perimenopausal and postmenopausal periods. These include hot flushes, vaginal changes, urinary tract changes, changes in sexuality, affective or emotional symptoms, changes in the oral mucosa and skin, loss of memory and Alzheimer's disease, bone loss and osteoporosis, and cardiovascular disease. This article reviews the literature in each of these areas. It also reviews studies relating to possible side effects of hormone therapy, including endometrial cancer, gall bladder disease, and breast cancer. The article outlines principles for practitioners to follow in assisting women to make informed and individualized decisions about this therapy. Part II of this article, which will will cover specific therapeutic regimens and their management, as well as alternative therapies and preventive measures.     

Nahrungsergänzungsmittel im Klimakterium

Dietary supplements are becoming increasingly popular among women seeking alternatives to treatment with estrogens for managing menopausal symptoms. The objective of this paper was to assess the effectiveness of dietary supplements. Although individual trials suggest benefits from certain supplements, data are insufficient to support the effectiveness of dietary supplements for the management of menopausal symptoms.     

A comparative review of the risks and benefits of hormone replacement therapy regimens

The Women's Health Initiative (a large, randomized, placebo-controlled trial) investigated the effect of conjugated equine estrogens combined with medroxyprogesterone acetate on specific potential long-term benefits and risks. A review of the clinical studies that have investigated different types and regimens of estrogens combined with progestins was conducted to assess how applicable the results of the Women's Health Initiative are to hormone replacement therapy regimens in general. The studies that were reviewed were limited to randomized clinical trials and observational studies that have been published over the last 15 years (1987-2002) and to meta-analyses and reviews that may have included the literature before 1987. The increased risks for venous thromboembolism, stroke, coronary heart disease, and breast cancer that were identified in the Women's Health Initiative trial have also been reported with postmenopausal hormone therapies that contain a variety of estrogen and progestin products. The beneficial effects that were noted in the Women's Health Initiative, with respect to reductions in fractures and colorectal cancer, have not been evaluated in large, randomized controlled trials that use different estrogen/progestin combinations; however, observational trials that used a variety of estrogen or hormone replacement therapy products and randomized clinical studies that evaluated bone mineral density (an excellent predictor of fracture risk) with different estrogen/hormone replacement therapy regimens would suggest that results would be similar to those found in the Women's Health Initiative. Although the relief of menopausal symptoms, the primary reason women seek treatment, was not included in the overall benefit/risk analysis of the Women's Health Initiative, numerous trials suggest that all therapies are effective. Overall, these data indicate that the benefit/risk analysis that was reported in the Women's Health Initiative can be generalized to all postmenopausal hormone replacement therapy products.     

Perimenopausal and Postmenopausal Hormone Replacement Therapy; Part 1. An Update of the Literature on Benefits and Risks*

As life expectancy increases and members of the postwar generation settle into their fifth decade of life, hormone replacement therapy—estrogen or an estrogen-progestin combination—has become a major research interest. An extensive, but often confusing and even contradictory, literature exists on the uses of hormone replacement for the treatment and prevention of a multitude of difficulties that may be associated with the perimenopausal and postmenopausal periods. These include hot flushes, vaginal changes, urinary tract changes, changes in sexuality, affective or emotional symptoms, changes in the oral mucosa and skin, loss of memory and Alzheimer's disease, bone loss and osteoporosis, and cardiovascular disease. This article reviews the literature in each of these areas. It also reviews studies relating to possible side effects of hormone therapy, including endometrial cancer, gall bladder disease, and breast cancer. The article outlines principles for practitioners to follow in assisting women to make informed and individualized decisions about this therapy. Part II of this article, which will appear in the May/June 1996 issue of the Journal of Nurse-Midwifery, will cover specific therapeutic regimens and their management, as well as alternative therapies and preventive measures.     

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.     

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.     

Perimenopausal and postmenopausal hormone replacement therapy: Part 2. Hormonal Regimens and Complementary and Alternative Therapies

As midwives increasingly provide care to women throughout the lifecycle, they need to become familiar with a variety of treatments for perimenopausal and postmenopausal problems and preventive measures for the potentially disabling conditions that can accompany aging. This article reviews various regimens of hormone replacement therapy. It discusses types of estrogen and progestin, appropriate dosages, routes of administration, and duration of therapy. It offers guidelines for initiation, contraindications, and required follow-up. It addresses the management of side effects and problems. The article briefly reviews a variety of complementary and alternative therapies including various self-help measures, such as nutrition and exercise, and selected herbal treatments. Part 1 of this article, which appeared in the January/February 1996 issue of JNM, reviewed the literature on recommended therapeutic and preventive indications for hormone replacement therapy, providing guidelines for the provision of informed consent.     

PERIMENOPAUSAL AND POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY: Part 2. Hormonal Regimens and Complementary and Alternative Therapies*

As midwives increasingly provide care to women throughout the lifecycle, they need to become familiar with a variety of treatments for perimenopausal and postmenopausal problems and preventive measures for the potentially disabling conditions that can accompany aging. This article reviews various regimens of hormone replacement therapy. It discusses types of estrogen and progestin, appropriate dosages, routes of administration, and duration of therapy. It offers guidelines for initiation, contraindications, and required follow-up. It addresses the management of side effects and problems. The article briefly reviews a variety of complementary and alternative therapies including various self-help measures, such as nutrition and exercise, and selected herbal treatments. Part 1 of this article, which appeared in the January/February 1996 issue of JNM, reviewed the literature on recommended therapeutic and preventive indications for hormone replacement therapy, providing guidelines for the provision of informed consent.     

Use of alternative therapies in menopause

Hormone replacement therapy has traditionally been used to treat the accompanying symptoms of oestrogen deficiency in menopause. However, not all women can, or prefer to, receive this treatment and alternatives should be considered to reduce the increased risk of osteoporosis and heart disease in menopausal women. This chapter reviews the current literature on the efficacy of phyto-oestrogens in preventing cardiovascular disease, various cancers and osteoporosis, as well as treating the vasomotor and other menopause-related symptoms. Select herbal therapies, as well as selective oestrogen receptor modulators, are also considered.     

Phytoestrogens as hormone replacement therapy: an evidence-based approach

Postmenopausal women have sought nonestrogen alternatives to hormone replacement in order to avoid possible risks and side effects of the therapy. Selective estrogen receptor modulators have been developed to tailor therapy to a specific risk/benefit profile that will best fit the patient. More women have looked to phytoestrogens, such as the isoflavones found in the soy plant, to tailor their menopausal therapy in a “natural” way. This review examines the evidence regarding the risks and benefits of isoflavones as hormone replacement therapy. Controlled trials have shown a reduction in postmenopausal hot flashes when subjects’ diets were supplemented with soy. There is less evidence for a benefit in vaginal dryness symptoms. Furthermore, dietary supplementation also appears to lower total and low-density lipoprotein cholesterol in hypercholesterolemic subjects. A synthetic isoflavone, ipriflavone, has been shown in controlled trials to prevent postmenopausal bone loss, though there is much less evidence that soy isoflavones will accomplish this goal. Finally, although unopposed estrogen replacement may promote breast and endometrial cancer, there is no evidence that phytoestrogens will do the same. In contrast, great interest has been taken in the potential cancer-protective effects of phytoestrogens, though prospective evidence in postmenopausal women is not available. Although data regarding the use of isoflavone extracts are incomplete, dietary supplementation with soy foods appears to be a safe and possibly beneficial option for postmenopausal women.     

Feminorm good night to treat the menopause

Hot flashes are a common and distressing symptom of menopause, affecting approximately 62-83% of women undergoing the menopausal transition. Several pharmacologic treatments for hot flashes, including hormone replacement therapy (HRT) have been shown to reduce the frequency and intensity of hot flashes. However, some women prefer not to use HRT and seek alternative treatments, such as phytoestrogens. Feminorm, Feminorm Duo and Feminorm good night have a beneficial effect on vasomotor symptoms, depression, osteoporosis and cardio-vascular diseases.     

Decision analysis of hormone replacement therapy after the Women's Health Initiative

OBJECTIVES: The purpose of this study was to estimate the quality-adjusted life expectancy with and without hormone replacement therapy. STUDY DESIGN: We compared the quality-adjusted life expectancy with and without combination hormone replacement therapy in three cohorts of women with menopausal symptoms over a 20-year period using a Markov decision-analysis model. Women were either at high or low risk for breast cancer and coronary heart disease or at high risk for osteoporosis. RESULTS: Hormone replacement therapy decreases life expectancy slightly compared with no hormone replacement therapy if menopausal symptoms are not considered. However, if relief from menopausal symptoms is considered and the usefulness of life with symptoms is worth <0.996 compared with life without symptoms, then 5 years of hormone replacement therapy provides equivalent quality-adjusted life-years. CONCLUSION: Combination hormone replacement therapy decreases life expectancy if quality of life with menopausal symptoms is not considered. However, the benefit of hormone replacement therapy can exceed the risk for women with menopausal symptoms.     

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.