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.     

Hormone replacement therapy: curse or blessing?

There is a controversial discussion on the risks and benefits of hormonal replacement therapy (HRT), and many women and doctors have revised their opinions of HRT over the last few years. Complementary and alternative therapies can be considered an option to treat menopausal symptoms. The following issue summarizes the actual knowledge of treatment options of menopausal symptoms.     

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.     

Evidence-based practice in women's health: hormone therapy for women at menopause

Women's health providers, especially midwives, must take into account the known benefits and risks, as well as the "unknown," when recommending the use of hormone therapy for menopausal women, especially as it relates to heart disease, breast cancer, impaired cognition, and osteoporosis. The most recent evidence available from various studies about the benefits and risks of estrogen and hormone therapy at menopause suggests that, although hormone therapy may be protective in some women against heart disease and osteoporosis, evidence is less certain about the benefits of hormone protection against impaired cognition and the risks of breast cancer with use. The clinical approach used by midwives in which individualizing care based on each woman's health status history as well as preferences is highly appropriate for women in the perimenopausal and menopausal period.     

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.     

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.     

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.     

The randomized world is not without its imperfections: reflections on the Women's Health Initiative Study

In May 2002, the Women's Heath Initiative (WHI) clinical trial, designed to clarify the risks and benefits of combination hormone replacement therapy, came to a premature halt. An interim safety review after an average follow-up of 5.2 years found that a combination of estrogen and progestin often prescribed to postmenopausal women increased the risk of invasive breast cancer, heart disease, stroke, and pulmonary embolism. The combination hormone therapy reduced bone fractures and colorectal cancer, but not enough to outweigh the other risks. The WHI trial presents a challenge for patients, physicians, and epidemiologists, since many observational studies have shown cardiovascular benefits of long-term hormone replacement therapy (HRT). At the same time, a companion paper in the same journal reported an epidemiologic study with a 13.4-year mean follow-up suggesting that estrogen replacement therapy, when used alone for 10 years or more, increases the risk of ovarian cancer. The medical community is still recovering from these twin shocks and trying to digest the results of both of these studies. The WHI study calls into question the long-term use of HRT in healthy women. The benefit of the temporary use of estrogen in controlling disruptive symptoms of the menopause is not being contested. Absent from many news releases are the hedging and equivocation typical of other reported clinical trials. There are still some "hanging chads" out there, and this commentary is designed to examine the uncertainties that remain after the WHI report. It is also intended to suggest development of alternative strategies to control symptoms of the menopausal transition that will reduce risks of HRT. The evidence from the WHI study will need to be incorporated into medical decision making, but clinical decisions, like most human decisions, are complex and in the final analysis must be based on information from many sources.     

早发性卵巢功能不全激素补充治疗利弊评价

早发性卵巢功能不全（POI）指女性在40岁之前卵巢活动衰退的临床综合征,以月经紊乱伴高促性腺激素及低雌激素为特征。POI患者可出现潮热、出汗等绝经期症状,远期可发生骨质疏松、心血管疾病等问题。激素补充治疗（HRT）是POI患者的有效治疗方法。文章对POI患者应用HRT的获益及可能存在的风险进行综合分析与评价。     

A Nurse's Guide to Hormone Replacement Therapy

Menopause is a natural event most women experience as they enter their 5th decade. As human life expectancy has lengthened, health issues concerning women in mid-life have become a major focus in holistic, preventive health care, which is heavily influenced by nurses. Controversy continues about the risks and benefits of hormone replacement therapy for women during their years of perimenopause and postmenopause. Evidence is compiling, however, that indicates the benefits of exogenous hormones may outweigh these concerns. As nurses, we must have a current knowledge of hormone replacement therapy to counsel our patients effectively. This article presents information to assist the nurse in meeting this goal.     

早发性卵巢功能不全激素补充治疗利弊评价

早发性卵巢功能不全（POI）指女性在40岁之前卵巢活动衰退的临床综合征，以月经紊乱伴高促性腺激素及低雌激素为特征。POI患者可出现潮热、出汗等绝经期症状，远期可发生骨质疏松、心血管疾病等问题。激素补充治疗（HRT）是POI患者的有效治疗方法。文章对POI患者应用HRT的获益及可能存在的风险进行综合分析与评价。     

The Use of Complementary and Alternative Medicines Among a Sample of Canadian Menopausal‐Aged Women

Introduction : Despite questionable efficacy and safety, many women use a variety of complementary and alternative medicine (CAM) therapies to relieve menopause symptoms. Methods : We examined the determinants and use of CAM therapies among a sample of menopausal‐aged women in Canada by using a cross‐sectional Web‐based survey. Results : Four hundred twenty‐three women who were contacted through list serves, e‐mail lists, and Internet advertisements provided complete data on demographics, use of CAM, therapies, and menopausal status and symptoms. Ninety‐one percent of women reported trying CAM therapies for their symptoms. Women reported using an average of five kinds of CAM therapies. The most common treatments were vitamins (61.5%), relaxation techniques (57.0%), yoga/meditation (37.6%), soy products (37.4%), and prayer (35.7%). The most beneficial CAM therapies reported were prayer/spiritual healing, relaxation techniques, counseling/therapy, and therapeutic touch/Reiki. Demographic factors and menopausal symptoms contributed to 14% of the variance (P < .001) in the number of CAM therapies tried. Discussion : Results support previous research showing that menopausal women have high user rates of CAM therapy and show that specific demographic factors and somatic symptomatology relate to use of CAM therapies. Health care providers can benefit from understanding the determinants and use of CAM by women during the menopause transition if they are to help and provide quality care for this population.     

Hormone therapy in the WHI era

The announcement in July 2002 in the media of the results of the combined continuous hormone treatment arm of the Women's Health Initiative (WHI) had a profound effect on perceptions about hormone therapy among the lay public and the medical profession. Careful scrutiny of the announcement and the subsequent publications leads to the conclusion that the widespread fear of hormone therapy that was generated was not supported by the facts. WHI was not designed to be, nor can it be, interpreted as a randomised controlled trial of menopausal hormone therapy--rather, it was a trial of chronic disease prevention, particularly aimed at the possible cardiovascular benefits of a specific combination hormone therapy in postmenopausal women. The results, which were consistent with existing data, did not and do not warrant any major change in the previously established guidelines for the use of hormone therapy. Tibolone has emerged as an alternative treatment for menopausal symptoms, but its long-term benefits and risks have yet to be documented.     

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.     

Local and systemic options for hormone replacement therapy

Women now have an array of options for hormone replacement therapy (HRT). Yet, the medical practitioner faces many challenges in helping women explore these options. Which therapy is right for which woman? What are the risks and benefits of each therapy? Providing hormone replacement therapy entails assessing the individual woman's need for hormone replacement therapy given her cardiovascular health, bone health, vasomotor symptoms, bleeding patterns, and attitudes. A woman who chooses to use HRT has many options, including therapies that vary in preparation, dosing schedule, route of administration, and systemic or local effects. This paper reviews the variety of preparations. Healthcare practitioners now can individualize HRT. The challenge is to evaluate, counsel, and treat women in a way that will promote satisfaction, and thus long-term use of HRT.     

Hormone replacement therapy and risk of malignancy

PURPOSE OF REVIEW: The fact that today our concern is oriented towards the risks rather than the benefits of hormone replacement therapy could be the clearest message about our current position. The safety of hormone replacement therapy, an estrogen-progestin combination which has been sympathetic to and supportive of disturbing menopausal symptoms of women, is seriously challenged. RECENT FINDINGS: Four randomized trials have now reported on the results of hormone replacement therapy in major potentially fatal conditions, in more than 20,000 women studied for about 5 years. The main concern regarding the increased risk of malignancy in healthy postmenopausal women in western countries has been breast cancer. It is estimated to cause an extra case in about six per 1000 users aged 50-59 and 12 per 1000 aged 60-69. Over the same period the estimated risk of endometrial cancer rates are not increased, with a relative risk of 0.76 per 1000 users aged 50-59. Overall, however, the increased incidence of malignancies is greater than any reduction, one per 230 users aged 50-59 and one per 150 aged 60-69. Randomized trials examining other important but rarer malignancies, like ovarian, gall bladder and urinary bladder cancer, are either nonexistent or too small to reliably describe any effects of hormone replacement therapy. SUMMARY: Conclusively epidemiological evidence suggests that hormone replacement therapy is associated with a small but substantial increase in breast cancer risk and combined estrogen-progesterone regimens further increase this hazard. Additionally, the evidence from the recent double blind placebo controlled randomized trial on the slight increase in the incidence of adverse cardiovascular events, has turned our orientation away from hormone replacement therapy as a long term therapy in postmenopausal women. In this review, the effort is to approach comprehensively and globally the information on the risks of hormone replacement therapy on several cancer sites.     

The impact of hormone replacement therapy on quality of life and willingness to pay

Objective To measure the gain in quality of life due to hormone replacement therapy for women with mild and severe menopausal symptoms.
Design Prospective study where data on quality of life and willingness to pay were collected by interview.
Setting Department of Gynaecology at Sodertalje Hospital near Stockholm.
Participants One hundred and four women aged 45 to 65 years treated for menopausal symptoms for at least one month.
Methods Quality oflife was measured by the time tradeoff and rating scale methods. The willingness to pay for hormone replacement therapy was investigated using the contingent valuation method.
Main outcome measures The quality adjusted life year weight measured with the rating scale and time tradeoff methods, and willingness to pay.
Results The increase in the quality adjusted life year weight due to hormone replacement therapy for women with mild symptoms was 0.26 according to the rating scale method and 0.18 according to the time tradeoff method. For women with severe symptoms the quality adjusted life year weight increased by 0.50 according to the rating scale method and by 0.42 according to the time tradeoff method. The mean willingness to pay for hormone replacement therapy per month was 2300 Swedish krone for women with mild symptoms and 4800 Swedish krone for women with severe symptoms (£1 = 10.3 Swedish krone).
Conclusions Hormone replacement therapy leads to a major improvement in quality of life for women with menopausal symptoms. Both for women with mild and severe menopausal symptoms the willingness to pay for the treatment also greatly exceeds the costs, indicating that hormone replacement therapy is economically beneficial for women with menopausal symptoms.