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1 From the Division of Health, Behavior and Nutrition, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
2 Supported by the Einstein Cancer Center. 3 Presented at the conference "Women and Micronutrients: Addressing the Gap Throughout the Life Cycle," held in New York, NY, June 5, 2004. 4 Address reprint requests and correspondence to J Wylie-Rosett, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. E-mail: jwrosett{at}aecom.yu.edu.
ABSTRACT
Micronutrient and herbal/phytochemical supplements are of increasing interest as potential alternatives to using estrogen therapy in treating menopausal symptoms. This article provides an overview of the questionnaires that assess menopausal symptoms and research efforts to better standardize symptom assessment. The reported rate of symptoms varies by ethnicity, stage of menopause, hormonal therapy and the measurement method. The use of estrogen therapy has declined sharply after the Women's Health Initiative (WHI) Hormone Trial was stopped early because the potential risks outweighed potential benefits. There is a limited research base that addresses the efficacy of supplements in controlling menopausal symptoms. The generalizability of several studies is limited because the study participants experiences menopause as the results of treatment for breast cancer. The article concludes with a review of guidelines and of issues that need to be addressed in future research studies with emphasis on questions related to clinical practice.
Key Words: Menopausal symptoms • micronutrients • supplements • phytoestrogen • herbal supplements • estrogen • progestin • cancer • heart disease
INTRODUCTION
Micronutrient and herbal/phytochemical supplements are of increasing interest as potential alternatives to using estrogen therapy in treating menopausal symptoms. The objectives of this article are to address following 4 questions. (1) What is known about the symptoms of menopause? This will be addressed with an overview of various instruments that are used to assess menopausal symptoms and factors that are related to the prevalence of reported symptoms. (2) What is the current evidence regarding hormone (replacement) therapy? This will focus on the of the WHI Hormone Trial findings (1). How publication of the WHI findings are related to the decline in estrogen prescriptions will also be addressed. (3) What is known about micronutrients and phytochemical treatment in menopause? Studies of supplements will be reviewed, focusing on factors that may affect generalization of the findings. (4) What clinical and research questions need to be addressed now? The article will conclude with a review of factors affecting the design of studies, questions that need to be addressed, and guidelines for addressing menopausal symptoms. Clinicians can use such guidelines to develop an open dialogue and individual tailoring of advice for women during menopause based on risk profile and symptoms (2). The review of guidelines will also address limitations in the evidence base for recommending micronutrients and phytoestrogens/herbal supplements as possible alternatives to hormonal therapy for women who suffer from menopausal symptoms.
WHAT IS KNOWN ABOUT THE SYMPTOMS OF MENOPAUSE?
The term "menopause" comes from the Greek words meno (month) and pause (to end). Thus, the literal definition is the end of the cycle of monthly menstrual bleeding. Menopause develops as the result of decreased estrogen and a disruption of the hormonal cycle associated with ovulation. The absence of menstrual periods for 12 mo is usually used as the definition of "natural" menopause. The age at which menopause occurs varies widely ranging from late thirties to late fifties with the range for most women being between ages 48 and 55 y. Self-reported data from middle age women, who participated in the Behavioral Risk Factor Surveillance System (BRFSS) in Florida, Minnesota, and Tennessee, indicate that the most common symptom is hot flashes or flushes, which was reported by 60% of the women (3). Night sweats were reported by 48% of the women, and 41% reported trouble sleeping.
The perimenopausal transition lasts for about 4 y for most women experiencing natural menopause. Vasomotor menopausal symptoms commonly develop one to 2 y before the cessation of menstrual flow. A longitudinal study of menopausal women found that 46% of women report hot flushes and bouts of sweating in the year immediately preceding menopause. The proportion reporting vasomotor symptoms increased to 67% during the first year after menopause, and fell to 49% in the second postmenopausal year (4). An overview of how hormonal transition in menopause is related to occurrence of vasomotor symptoms is provided in Table 1. Hysterectomized women experience surgical menopause, which is often accompanied by an abrupt onset of vasomotor symptoms. Chemotherapy and radiation can also induce a fairly rapid onset of the vasomotor and other menopausal symptoms with 30% of women under 35 y of age experience ovarian failure premenopausal women after undergoing chemotherapy; the proportion increases to half for women age 35 to 40 y and to 75% to 90% for women over 40 y of age (5). In addition to age, the chemotherapy dosage is a major predictor of premature menopause. Treatment of menopausal symptoms in this group is particularly complex because of ongoing treatment and risk related to having cancer as well as the abrupt onset of symptoms.
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TABLE 1. Changes in hormones and the natural history of menopausal symptoms1
A population based study conducted in Sweden, the Women's Health in Lund Area study, found that after controlling for other variables, the frequency and severity of hot flushes was more almost 3-fold higher in women who had oophoerectomy, was over 50% higher in women drinking large amounts of alcohol, and was 30% higher in women who gained weight. This study also assessed vaginal dryness, which is the symptom commonly associated with atrophy of estrogen-sensitive tissue, although urinary difficulties such as stress incontinence can also occur (6). For the postmenopausal women in this Swedish cohort, vaginal dryness was almost 2 fold higher in the women age 58–64 y than in women 50–53 y of age. However, having menopause later (after age 53 y) was associated with a lower likelihood of vaginal dryness than having menopause at earlier age (6). It appears that women who have menopause early may suffer more symptoms over a longer period of time, which may be linked to lower endogenous estrogen production or an earlier shutoff of estrogen production. Obesity and larger waist circumferences were associated with less vaginal dryness presumably due to higher estrogen and androgen hormones (6).
There are several standardized menopausal quality of life questionnaires that address psychosocial domains, vasomotor symptoms, and/or some urogyncocological dimensions associated with menopause. Schneider (7) identified 5 standardized menopausal questionnaires that met the following 4 criteria: (1) factor analysis, (2) subscales measuring different aspects of symptoms, (3) sound psychometic properties, and (4) and standardized among populations of women. The characteristics of these questionnaires are listed in Table 2. All of the questionnaires include some aspect of emotional well-being. Three of the questionnaires (the Greene Climactic Scale, the Women's Health Questionnaire, and the Menopausal Symptom List) include vasomotor symptoms, and only the Menopausal Rating Scale includes urogenital subscale. A recent paper suggested adding items to menopausal symptoms scales to assess voice impairment focusing on discomfort when talking and changes in voice quality because of the frequency of encountering these as clinical problems (8).
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TABLE 2. Characteristics of menopausal specific scales1
The Study of Women's Health Across the Nation (SWAN) assessed menopausal symptoms in a multiethnic cohort of over 16 000 American women aged 40–55 y. The 5 ethnic/racial groups represented included African Americans, Chinese Americans, Hispanic American, Japanese Americans, and Euro American (described as white). The African American women had the highest frequency of hot flashes followed by Hispanic American and Euro American women, respectively. In the SWAN cohort, the Chinese and Japanese American women reported lower rates of hot flashes (9). The Hispanic American women were more likely to report heart pounding as a symptom. Ironically, quality of life ratings were not associated with frequency of symptoms. The Chinese and Japanese American women were less likely to view going into menopause as a positive experience and to expect to become irritable or depressed (10). Being less acculturated and speaking Cantonese or Japanese was associated with poorer scores for attitudes about menopause. However, the scores did not differ on the basis of acculturation or language preference among the Hispanic American women. Variables associated with increased reporting of hot flashes are summarized in Table 3.
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TABLE 3. Assessment of variables associated with increased reporting of hot flashes1
WHAT IS THE CURRENT EVIDENCE REGARDING HORMONE (REPLACEMENT) THERAPY?
The emerging data from the WHI has dramatically reduced prescriptions for estrogen for postmenopausal women (11). Ironically, estrogen prescriptions for postmenopause was referred to as estrogen, or hormone, replacement therapy (HRT) until the findings of the WHI hormone trial indicated the risks outweighed the benefits. Indeed, terminology changed from HRT to hormone therapy (HT) after the early stopping of the WHI estrogen plus progestin trial in 2002 and the conjugated equine estrogen in 2004 (12, 13) The dramatic shifts in use of hormone therapy for postmenopausal women are quite remarkable.
A 1995 national population-based telephone survey of 500 postmenopausal (50 to 74 y of age) women indicated that 37.6% of the women reported current estrogen therapy. The proportion was 3-fold higher for women who had undergone a hysterectomy compared with women who had not (60 versus 20%) (14). Women in the South and the West were > 2 and half times more likely to use HRT than women in the Northeast (14). Use was 4-fold higher in college graduates than those with lower education, and the frequency of use in women with diabetes mellitus was less than one-fifth that of women without diabetes (14). However, the frequency of hormone usage was not related to other cardiac risk factors and most psychological characteristics.
An examination of hormone trends in the United Stated from 1995 to 2003 by Hersh, Stefanick, and Stafford was derived from National Prescription Audit database and the National Disease and Therapeutic Index data (11). The total annual hormone prescriptions in the United States increased from 58 million in 1995 to 90 million with an annual increase of 15 million per year. The prescriptions remained stable until 2002 when the results of the WHI were released. The number of prescriptions dropped by 66% for Prempro (the estrogen plus progestin combination used in the WHI) and by 33% for Premarin (the conjugated equine estrogen used in the WHI) (11). The total number of women for whom postmenopausal estrogen was prescribed rose from 10 million in 1995 to a peak of 15 million in 2001, and fell back to 10 million in 2003.
The WHI findings were foreshadowed by the Heart and Estrogen/Progestin Replacement Study (HERS), which examined the effect of hormone replacement therapy on the rate of recurrent heart problems in women who already had heart disease and was published in 1998 (15). Generalizing from the HERS results was difficult due to the small sample size and eligibility criteria. The WHI included over 27 000 women, which was 10 times the number of women included in the HERS. In addition, HERS inclusion criteria included having had previous myocardial infarction and exclusion criteria included having had a hysterectomy. As the results of these stringent eligibility criteria, only 2% of the WHI Hormone Trial participants would have qualified for HERS.
The overall findings of the WHI are summarized in Table 4 (12,13,16–20). In the Estrogen-plus-Progestin study, women taking combined estrogen plus progestin had more heart attacks, strokes, blood clots, and breast cancers compared with women taking placebo. Women taking estrogen plus progestin also had fewer colorectal cancers and hip fractures, and there was no effect on the number of deaths. The increased risk of stroke and the decreased risk of fractures were also seen in women taking CEE (18) alone, which could raise questions about whether the effects were due to estrogen per se. However, the findings that CEE did not increase breast cancers or decrease colorectal cancers were different from the estrogen-plus-progestin results. Continued analyses are trying to determine the reasons for the differences. Women who have a hysterectomy may differ in other health characteristics compared with women who have not. Alternately, progestin may change disease risks and benefits when added to CEE.
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TABLE 4. Results of the Women's Health Initiative Hormone Trial1
On the benefit side, women taking CEE had fewer hip fractures. For other diseases of interest, the picture was not clear. Either there were no effects of CEE, or the data were not strong enough for scientists to be sure they were real. For example, the unexpected finding that fewer women taking CEE had breast cancer needs further study. The effect of CEE on blood clots was also uncertain. The CEE appeared to have a neutral effect on heart attacks, colorectal cancer, and death because the differences were very small.
The WHI results indicate that for every 10 000 women taking CEE, 12 more women per year would have strokes; the overall stroke incidence in the WHI was 44 women in the CEE group compared with 32 women in the placebo group. For deep vein thrombosis (DVT), the increase was 6 more per 10 000 per year. It not clear if more women taking CEE had increased risk of pulmonary emboli. The mixed results of the WHI with respect to risk and benefits on hormones has resulted in the need for a greater dialogue between clinicians and patients to evaluate the potential risks and benefits on an individual basis.
WHAT IS KNOWN ABOUT MICRONUTRIENTS AND PHYTOCHEMICALS IN MENOPAUSE?
Hot flashes, which are the primary symptom of menopause, appear to be caused by dysfunction of the central thermoregulatory system when estrogen availability is decreased. Norepinephrine and serotonin pathways are thought lower the low the set point for the thermoregulatory nucleus, which allows heat loss to be regulated by a subtle change in core temperature. Hot flashes are preceded by a rise in norepinephrine, and injecting norepinephrine can induce an elevation in the core temperature. The elevation in core temperature by these hormones is thought to be counterregulated by endophrin and catecholestrogen, which are metabolic byproducts of estrogen and other sex hormones. These complex interrelationships are illustrated in Figure 1 (21). Micronutrients or photochemicals should be examined with respect to how they may have impact on this proposed model of thermoregulation. Phytoestrogens need to be examined for their estrogenic function and their potential to bind receptors and thereby block the normal pathways by which estrogen regulates thermoregulation. Herbal supplements that may have serotonin receptor uptake inhibitory functions are also being examined for potential use in thermoregulation.
FIGURE 1.. Heavy lines denote key pathways involved in promoting or inhibiting the adjustment of core temperature via hot flash reaction triggered by the hypothalamus. Dashed lines indicate reactions that inhibit hot flash reactions. Adapted from reference 4.
There are over 40 manufacturers that market herbal products for menopause symptom control (22), but to date little is known about the efficacy. Behavioral Risk Factor Surveillance System (BRFSS) data indicate that 46% of women have used complementary or alternative therapy for menopausal symptoms (3). The alternative approaches, which included herbal and, to a lesser extent, micronutrient supplements, were often used in combination with conventional approaches prescribed or recommended by their health care provider (23). Women with more severe symptom ratings were more likely to use alternative/complementary approaches. About one-third of women reported not using either alternative/complementary or conventional approaches for menopausal symptoms. Another survey found that only a little over half of women who used herbal products for menopausal symptoms indicated that their physician was aware of their usage of herbal products (3, 23).
Baseline data from participants in the SWAN study indicate that 48.5% had used at least one complementary or alternative therapy during the preceding year (24). Complementary and alternative therapy users were more likely to be younger, have more education, be white, and reside in California than the nonusers. Herbal therapies were more likely to be selected by the Chinese American women than other groups, but emotional stress and anxiety were associated with herbal therapy among the Japanese American women as well (24).
A 1999 National Institutes of Health workshop identified knowledge that should be researched to provide an adequate evidence base to assess the growing public interest in phytoestrogens and other products for menopausal symptoms and other health issues for older adults (25). Several recent reviews, editorials, and commentaries have addressed the evidence base for alternative and complementary medicine focusing on the interest generated by increased caution in using estrogen therapy (26–33). Micronutrient and herbal supplements that are commonly used to treat menopausal symptoms include vitamin E, black cohosh, soy, and other phytoestrogens, which are used to treat the vasomotor symptoms. Other herbal treatments such as ginko biloba, ginseng, and St. Johns wort have been used for mood related symptoms, and valerin has been used for sleep disturbances associated with menopause, but these issues are beyond the scope of the present review. Interpretation of study findings is hampered by the small sample size, variability in the product tested (especially for the soy), and the clinical characteristics of the study population (menopause induced by treatment of breast cancer). With the decline in popularity of postmenopausal hormone therapy, the clinical and research interest to address the effects of alternative/complementary on menopausal symptoms is likely to increase dramatically. Research that focuses on micronutrient and related treatments is likely to increase to provide an evidence base to address questions posed by menopausal women and their care providers.
VITAMIN E
Although Vitamin E is widely used for treating hot flashes, the research database is extremely limited (26). A randomized crossover trial (4 wk per treatment condition) conducted in 120 women treated for breast cancer found that Vitamin E (800 IU) resulted in 1 fewer hot flash per day than the placebo (34). Despite the lower occurrence of hot flashes, an end of study survey indicated a low interest in using vitamin E for hot flashes (34). Whether the findings can be generalized to women undergoing naturally occurring or surgical menopause remains to be determined. Controlled studies are needed to assess the effects of vitamin E on symptoms using one of the standardized menopausal symptom questionnaires and on hormones affected by menopause. Research also needs to address how vitamin E affects the metabolic pathways involved in the hot flash reaction.
BLACK COHOSH (CIMICIFUGA RACEMOSA, BLACK SNAKEROOT)
Black cohosh, botanically a member of the buttercup family, has been widely used in Native American therapy for a variety of ailments including dysmenorrhea and labor pains as well as for the treatment of menopausal symptoms (35–40). Concentrated extracts of black cohosh is sold as a standardized product. Remifemin © is the product most widely used in reach studies, although a number of companies produce black cohosh extract. The formulation of Remifemin has changed over time, but currently, 1 tablet contains black cohosh extract corresponding to 20 mg of crude drug standardized to 1% 27-deoxyacetin (35). It has been difficult to discern the effects of black cohosh despite the availability of a standardized formulation and reported findings from 3 of 4 randomized trials indicating a reduction in menopausal symptoms (27, 35). The black cohosh treatment regimen was confounded by other treatments or open lavel treatment (27, 35).
Black cohosh contains a number of compounds with potential bioactivity including tritepene, glycosides, resin, salycilates, isoferulic acid, sterols, and alkaloids. Analysis of black cohosh from various woodlands in the Eastern United States and Remifemin yielded no formononectin, the phytoestrogen thought to account for the reported reduction in menopausal symptoms (27, 39). While black cohosh contained a standard quantity of 27-deoxactin, little is known about the variability in other potentially bioactive compounds that have been found in analyses of black cohosh samples. Many of these compounds may have potential benefits, but potential risks also need to be considered. Women with breast cancer are often advised to avoid black cohosh due to the lack of evidence to conclude that it is safe (36).
The mechanism of action by which black cohosh reduces hot flashes is not understood. Black cohosh does not appear to alter the hormonal pattern associated with menopause, low estrogen accompanied by elevated luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The effects of black cohosh on vaginal tissue are also not clear (37). It is possible that it affects the pathway down stream from the estrogen. The National Center of Complementary and Alternative Medicine at the NIH has funded a randomized, controlled clinical trial to determine whether black cohosh reduces the frequency and severity of hot flashes and other menopausal symptoms (37). Additional rigorously controlled studies are needed to ascertain the true effects of black cohosh on menopausal symptoms and to make an evidenced-based decision regarding who may benefit and for whom its use the risks are likely to outweigh any potential benefits (35).
PHYTOESTROGENS FROM SOY, RED CLOVER, AND FLAX
The phytoestrogens that have been isolated from a variety of plant food are phenolic (rather than steroidal) compounds; the major categories of phytoestrogens include isoflavones, lignans, and coumestans (33). Phytoestrogens can function as selective estrogen receptor modulators (SERMs) by binding to receptors for estrogen metabolites. SERMs may function as estrogen metabolites in some tissues but not in others. While laboratory-developed SERMs are widely used in treating women with estrogen receptor positive cancers, less is known about the SERM function of phytoestrogens. Soy, other beans, clover, and alfafa contain isoflavone precursors, which are converted to genistein, daidzein, and equol by intestinal bacteria. Flax seeds, other seeds, legumes, whole grains, and some fruits and vegetables contain lignan precursors that can be converted to enterolactone and enteridiol by intestinal bacteria. The phytoestrogens can have estrogenic activity as potential dietary derived modulators with endocrine function.
To date, studies have been small and lack statistical power, and these studies cannot be readily aggregated to increase the statistical power due to differences in their methodologies. In the systematic review by Kronenberg and Fugh-Berman, only 3 of the 12 randomized controlled trials found that soy phytoestrogen supplements or soy products reduced the frequency or severity of hot flashes. In one of the studies the decrease in hot flashes was accompanied by increases in 17ß-estradiol and decreases in total and LDL cholesterol (27). Flax seeds have been reported to have estrogenic, antiestrogenic, and steroid-like activity (22).
Although the phytoestrogen in soy is often used by women who are trying to control menopausal symptoms, a recent study found that 25 g of flax seed alters metabolism of estradiol in favor of 2-hydroxyestrone, which is less biologically active (41). Theoretically, the metabolic shift could be accompanied by a reduction in menopausal symptoms. However, there are no published studies that have focused on the potential of flax seed in controlling menopausal symptoms. A soy beverage did not reduce the hot flash score (frequency and severity) to any greater extent than the placebo in a study involving women with breast cancer (42).
Red clover contains the phytoestrogen formononectin, biochanin A, daidzein, and genistein. Isoflavone and other supplements derived from red clover are readily available. The overall finding of research to date is that red clover and its related supplements are not better than placebo in controlling hot flashes. Promensil (total isoflavone content 40 mg per tablet), which was not found to be beneficial in controlling menopausal symptoms in a study that tested the 40-mg dosage, was found to reduce moderate to severe symptoms at 80 mg per day (43). Promensil was also not found to affect breast tissue density, unlike estrogen, which increases density, and tamoxifen, which reduces density. How the phytoestrogens interact with SERMs needs to be evaluated (44). More research is also needed to address how commonly eaten foods that contain phytoestrogens (fennel, celery, parsley, nuts, whole grains, apples and alfalfa) affect menopausal symptoms as well as addressing the effects of supplements.
OTHER HERBAL SUPPLEMENTS
Dong quai is prepared as a tonic in traditional Chinese medicine, and is unclear if it contains compounds that have estrogenic properties (45). There are little data on the effects of dong quai because in traditional Chinese medicine it is usually in combination with other herbs. The only published randomized controlled trial found that dong quai was no better than the placebo in reducing menopausal symptoms (45).
There are no controlled studies on the other herbal supplements that are sometimes recommended for menopausal symptoms. Evening primrose oil, which is a rich source of gamma linolenic acid, an intermediate compound between cis-linolic acid and prostaglandin, is used to treat mood swing, irritability, and breast tenderness associated with premenstrual syndrome and menopause. Wild yam is also used to treat a variety of menstrual problems and menopausal symptoms. American ginseng is sometime used for menopausal symptoms because it is considered to have a cooling effect, while Asian ginseng is considered a heat-raising tonic (46). Other herbs that are used for their potential effects on mood and may alter the seratonin pathway, which are sometimes recommended to menopausal women, include kava kava, St Johns wort, and sage. Flavonoids are also of interest because they appear to have a weak estrogenic effect, but the data are limited to 1 study potentially promising study testing herperidin from citrus fruit in combination with vitamin C (26). An overview of the potential benefits and risks of micronutrients and phytochemicals used for menopausal symptoms is presented in Table 5.
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TABLE 5. Overview of potential benefits and risk: use of micronutrients and phytochemicals for menopausal symptoms
WHAT CLINICAL AND RESEARCH QUESTIONS NEED TO BE ADDRESSED NOW?
Clinicians face a considerable challenge in providing individually tailored assessments of the potential risks and benefits of estrogen therapy and the complementary and alternative options to estrogen. The concept of "shared decision making balance for evidenced-based patient choice" has emerged as health care providers are rethinking how to discuss estrogen therapy with women during and after menopause (47). Alternative options that women in one survey mentioned include: herbal preparations/vitamin supplements, healthy living (diet/exercise) and mind/body practice (prayer and mental healing). The range of options mentioned did not vary by race, ethnicity, or surgical status.
The 2003 position statement from North American Menopause Society addressed alternatives to estrogen therapy. The specific recommendations included, "First consider lifestyle changes, either alone or combined with a nonprescription remedy, such as dietary isoflavones, black cohosh, or vitamin E. For moderate to severe menopause-related hot flashes estrogen-containing treatments or progestogens, venlafaxine, paroxetine, fluoxetine, or gabapentin. Clinicians are advised to enlist women's participation in decision making when weighing the benefits, harms, and scientific uncertainties of therapeutic options" (2).
On the other hand, clinicians are urged to recommend medical alternatives to estrogen and to be more directive and less collaborative in advising patients. The 2003 review by Amato and Marcus focused on the inadequacy of the evidence base with regard to dietary supplements, stating "Phytoestrogens and black cohosh appear to be safe when used for short periods of time, much larger and longer studies are needed to detect infrequent but potentially serious adverse events....Women who do not wish to take hormone therapy to treat menopausal symptoms should be encouraged to consider using selective serotonin reuptake inhibitors and other conventional therapeutic options" (48)
Clearly a wide range of options can be used to treat menopausal symptoms. The dialogue should begin with eliciting the potential symptoms. For women who are encountering depression, which may or may not be directly related to menopause, the treatment needs are quite different from a woman whose mood is upbeat but she is experiencing hot flashes. An open dialogue can help achieve a solution that is acceptable to each woman who has symptoms. Questions of research interest that also need to be addressed in the clinical dialogue include:
How do risks for heart disease, breast cancer, and osteoporosis influence decision-making with regard to taking estrogen for each postmenopausal woman?
Which postmenopausal women currently on estrogen therapy should stop?
What should be anticipated as side effects associated with stopping estrogen therapy?
What long-term safety issues need to be considered if a women on each of the alternative therapies?
CONCLUSIONS
Menopausal symptoms are common, but vary by BMI, ethnicity, smoking status, and other lifestyle variables. The results of the WHI have altered the assumption that estrogen therapy could reduce cardiovascular risks that rise after menopause. With the decline in prescriptions for estrogen, the potential role of micronutrients and phytochemicals in controlling menopausal symptoms is of increased interest. Vitamin and phytoestrogens (eg, black cohosh, soy) may be beneficial, but studies have variable results. Collaborative decision making can help women with hot flashes reduce symptoms.
The declining usage of estrogen therapy is likely to increase research that addresses how micronutrients, phytoestrogens, and other food/herb derived compounds affect menopausal symptoms. The scientific rigor of studies needs to be improved so that the benefits and potential risks of the treatment options for menopausal symptoms are better delineated. Research questions that need to be addressed include:
What are the effects of a combined micronutrient and phytoestrogen dietary approach? How does the metabolism of micronutrients and phytochemicals relate to their potential benefit in preventing or treating hot flashes and other menopausal symptoms?
It is reasonable to test the potential maximal effect that can be achieved by combining the wide variety of foods containing phytoestrogens with supplements such as black cohash and vitamin E. The combined effect of these foods needs to be evaluated. The research design for such a study could be patterned after the study by Jenkins et al, which tested a portfolio diet that combined cholesterol lowering dietary approaches (49). Combining dietary approaches with other lifestyle approaches such as physical activity, and light weight clothing is also worthy of study. What are the potential safety issues/adverse effects of phytoestrogen supplements? What are the long-term effects? How do they affect cancer risk in women with a personal or family history of estrogen positive breast cancer? Human and animal model research needs to evaluate potential safety issues for women with estrogen receptor positive cancers.
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