Integrative therapies for menopause.

Abstract: Menopause is a transitional time for women. This gives practitioners an opportunity to focus on recommending healthy life-style changes. Hormone replacement therapy (HRT) has been the mainstay of therapy for menopausal symptoms. With recent research findings, women and their physicians are seeking alternatives that do not carry the risks associated with HRT. Exercise has been shown to help some women with symptoms of hot flashes, as have relaxation techniques and deep breathing. Dietary changes to incorporate whole foods and soy are thought by some to help with menopausal symptoms, and are recommended because of a positive impact on heart disease and obesity; soy isoflavones may also help with menopausal symptoms. Botanicals such as black cohosh and red clover have been shown in some studies to decrease severity and frequency of hot flashes. We recommend that HRT be prescribed when other measures have failed to adequately control symptoms. Bioidentical hormones are preferred in our practice.

Key Words: alternative therapy, bioidentical hormones, black cohosh, menopause

**********

Menopause, if not induced surgically, is part of normal female physiology and marks an important transition in women's lives. The perimenopausal period lasts an average of about 4 years. As a result of advancing life expectancy, women will spend about one third of their lives after menopause. (1) Because of controversy and uncertainty about using hormone replacement therapy (HRT), many women request a more holistic approach to this natural transition. (2) An integrative approach involves use of diet, exercise, mind-body skills, supplements, and herbs to control symptoms. An integrative approach to menopause would include use of hormones only if necessary to control symptoms after other therapies have failed.

A holistic approach to menopause may allow the patient to adopt a more healthful lifestyle and healthy attitude about aging. Many patients and physicians have recently changed their approach to managing menopause in light of evidence published as part of the Women's Health Initiative regarding increased risk of major health complications associated with HRT use. In a large study of women at midlife, about half of study respondents reported use of alternative therapies, and these women were more likely to be physically active and less likely to be current smokers. (3) Only 54 of 100 women using alternative therapies responding to a health survey reported such use to their physicians. (4) Seventy-six percent of women surveyed in one study used alternative therapies; 89 to 100% of these women found alternative therapies to be somewhat or very helpful. They concluded that the use of alternative therapies among women undergoing menopause is common. Women find them beneficial, and physicians should inquire about use of these therapies. (5)

Physiology

Changes in the ovary begin occurring several years before cessation of menses. Females are born with a finite number of follicles, and this number declines with age. Estradiol is produced by maturing follicles. Because the number of follicles is depleted in perimenopausal women, estradiol levels decline and eventually can no longer support endometrial development, and menses cease. (1)

After menopause, women produce androstenedione, which is converted to estrone in peripheral body fat. Obese women produce about 200 [micro]g of estrone per day and because of this have less risk of development of hot flashes and osteoporosis but are at greater risk of development of endometrial hyperplasia and adenocarcinoma. Thin women produce about 40 [micro]g of estrone daily, which makes it more likely that they will have osteoporosis and hot flashes. (1) Decreases in estrogen levels are thought to cause changes in the thermoregulation in the hypothalamus, which is the presumed mechanism for hot flashes. (1) Many women will experience this transition with few problems. One third of more than 2,500 patients surveyed required no therapy for the treatment of menopausal symptoms. (6)

Mind-body Therapies

Hunter (7) showed that multiple psychosocial factors predict the quality of life for women during the menopausal period. Among these factors are the woman's emotional and physical health, social situation, stressful life events, and beliefs about menopause. Hunter suggests a health promotion intervention that (1) provides information about menopause and treatment options, (2) gives opportunity for discussion of attitudes, (3) teaches healthy diet, exercise, and smoking avoidance, (4) provides stress management, and (5) provides time for group discussion about personal health and social issues that would be beneficial to menopausal women. (7) Hunter tested this by dividing 45-year-old premenopausal women into two groups. The "prepared" group participated in two workshops and the "control" group did not receive any intervention. Follow-up at 3 months, 15 months, and 5 years showed that the prepared group had increased knowledge and decreased negative beliefs about menopause. The prepared group tended to exercise more and use less HRT. The control group was more likely to attribute moods swings, decreased libido, increased weight, and physical discomfort to menopause than the prepared group. The prepared group reported less sexual difficulty (P < 0.06), whereas the control group had decreased interest in sex (P < 0.02). They concluded that a group visit model would be an excellent way to routinely offer short educational sessions for women entering the perimenopausal period. (8)

Hot flashes are one problem for menopausal women and are very similar to the stress response. Estrogen is lower, whereas cortisol, heart rate, and skin temperature are elevated. One exception is that during the stress response there is peripheral vasoconstriction, whereas during hot flashes there is peripheral vasodilation, which causes flushing of the face. (9) On the basis of these observations, several researchers have investigated whether relaxation techniques might decrease the stress response, outflow of catecholamines, and hot flashes. Swartzman et al (10) studied 21 women who had more than six hot flashes per day. During a stress intervention, which included a timed arithmetic test, a loud noise, and a stressful film, the women reported 47% more perceptions of hot flashes and physiologic monitoring recorded 43% more hot flashes than during a nonstress intervention. Another study compared a group trained in relaxation techniques with a placebo group and subjected both groups to heat to induce hot flashes. The relaxation group had a lower frequency of hot flashes as well as an increased time to the onset of hot flashes during the test. (11) These studies support the relation between the stress relaxation and hot flashes.

In a study of relaxation training including muscle relaxation, autosuggestion to create a cool temperature, and temperature biofeedback, the four participants had a 41 to 90% decrease in hot flashes. This was maintained at 1 month, 4 months, and 6 months after treatment. (12) A study of 33 amenorrheic women showed that trained paced respiration (slow deep breathing) was better than muscle relaxation or alpha-wave electroencephalographic biofeedback for decreasing the number of daily hot flashes. (13) Cognitive behavior intervention, which included (1) relaxation training, (2) information sharing about hot flashes and stress, and (3) discussion of menopause in general, actually improved mood, lowered anxiety, and decreased hot flashes. The reduction in hot flashes was comparable to an HRT group, who achieved hot flash reduction more rapidly but without improvements in emotional outcomes. (14) A study of women with more than five hot flashes per day revealed that the relaxation response training group had a significant decrease in hot flash intensity (P < 0.05), compared with the control group, and a significant decrease in tension, anxiety, and depression. (15) Wijma et al (16) used an intervention called applied relaxation, which was designed to teach the patient coping skills that enabled rapid relaxation, counteracting, or aborting anxiety reactions altogether. From baseline to the end of training, the six participants reduced the number of hot flashes by an average of 73% and had improved psychologic well being.

Younus et al (17) has looked at hypnosis for its possible effect on hot flashes, quality of life, and fatigue. Fourteen women having more than five hot flashes per week and not on medications other than tamoxifen participated in hypnosis classes. During the training period, hot flashes decreased in frequency, duration, and severity. At the end of training, they had improved quality of life and level of fatigue, and insomnia was improved. (17) This study is provocative, and future studies should look at long-term follow-up and compare hypnosis to a control group.

Mind-body therapies may be useful for women who are seeking an integrative approach to managing their menopause symptoms. Modalities shown to be helpful for some individuals include participating in group education, slow, deep breathing, and hypnosis.

Exercise

The literature is mixed about whether or not exercise is beneficial for menopausal symptoms. (18-20) There is certainly enough evidence that exercise is beneficial for prevention of obesity, osteoporosis, depression, and cardiovascular disease to make it a reasonable recommendation for almost all patients. One study found a significant improvement in moods of exercising women compared with those who did not exercise, independent of their menopausal status. (21) The same researchers also found that middle-aged women had a significant decrease in vasomotor symptoms immediately after aerobic exercise. Stadberg et al (22) reported that women who exercised regularly were more likely to be symptom free during the perimenopausal period. A yearlong study using exercise in overweight postmenopausal women not on HRT found that there was an increase in vasomotor symptoms in a small number of the participants. (23)

Diet

General dietary recommendations for menopausal women to maintain heart, bone, and breast health, as well as a healthy weight, include at least 5 servings daily of fruits and vegetables, 25 to 30 g of fiber, several servings of low-fat dairy, 25 g of soy protein, and fish several times each week (see Table 1). Following these recommendations by eating whole foods will provide adequate vitamin, mineral, antioxidant, omega-3 fatty acid, and isoflavone intake, which is associated with improved health and reduced risk of heart disease, osteoporosis, breast cancer, and obesity. Menopausal women may also want to reduce consumption of alcohol and caffeine. (24)

Controversy exists about the benefit of soy for reduction of hot flashes and protection from heart disease or osteoporosis. (25,26) Soy foods contain phytoestrogens. There are three classes of phytoestrogens: isoflavones, found primarily in soy products; lignans, found in most fiber-rich foods; and coumestans, found in many plants. Adding to the controversy about whether to recommend soy is the concern related to possible negative effects of phytoestrogens on endometrial hyperplasia and breast cancer. It is important to differentiate between studies done with soy protein versus those done with soy isoflavones versus those with soy whole foods in the diet.

Four studies on the effect of supplementation with soy isoflavones on menopausal symptoms have been reported. A randomized controlled trial (RCT) was done using 100 mg of soy isoflavone supplementation daily versus a purified soy protein and glucose placebo. Eighty women for 4 months showed a significant decrease for the isoflavone group in vasomotor complaints, insomnia, and depression. Two other investigators conducted placebo-controlled trials and found that both groups, isoflavone (80 to 90 mg/d) and placebo, had significant reductions in hot flashes after 3 or 6 months. (27) An uncontrolled trial documented reductions in hot flashes over a period of 4 months in 80% of the participants with just 35 mg/d of soy isoflavone. (25) Two 3-month studies of soy protein and soy flour showed similar mixed results. Soy protein was more effective than placebo in reducing hot flashes by 45% versus 30% (P < 0.01), (28) whereas soy flour and the placebo, wheat flour, both significantly reduced hot flashes and other menopausal symptoms in another study. (29) These data point out the high rate of placebo effect in menopause trials, which makes it difficult to sort out the difference in effects of soy isoflavones and soy protein. It does appear that higher doses (100 mg of soy isoflavones or 60 g of soy protein) may be beneficial in reducing menopausal symptoms and hot flashes.

Because of its estrogen-like effects, soy isoflavones, soy protein, and dietary soy have been examined for their effects on bone loss, cognition, and the cardiovascular system. An RCT of isoflavones and an epidemiologic study of dietary soy both showed that modest increases in bone mineral content were associated with higher soy intake. (30) Another RCT showed improved cognition with 110 mg of soy isoflavones daily. (31) It has been shown that 25 g of soy protein per day is sufficient to decrease serum cholesterol levels in those with initially high serum levels. Studies using isolated isoflavone supplements have not shown any effect on lipids. (32) In a case-control study involving 947 women, higher isoflavone and lignan intake lowered endometrial cancer risk. (33) It is reasonable to recommend whole food soy products in the diet for their probable benefit accompanied by low risk. Women with, or at risk for, breast cancer should limit soy intake because the benefit-to-risk ratio is not as favorable, based on preliminary animal studies (34) (see Table 2).

Dietary Supplements

Vitamin E

There is some subjective data that taking vitamin E in doses of 400 to 800 IU may help alleviate hot flashes, nervousness, and fatigue. These supportive studies are small or have methodologic flaws. Nonetheless, patients may want to add vitamin E to their daily regimen to see if it is beneficial. (35-37)

Calcium

Calcium intake is important for all women to prevent osteoporosis. Calcium supplementation has been associated with improved lipid profiles in the postmenopausal period, (40) although it has not been shown to alleviate symptoms associated with the perimenopausal period. One study showed better absorption of calcium citrate when compared with calcium carbonate. (38) Calcium citrate supplementation in post-menopausal women decreases serum markers for bone resorption significantly more than calcium carbonate. (39) One study showed that taking 400 mg of calcium citrate twice per day reduced bone loss in early postmenopause. (41,42) Total daily calcium doses should be divided because single doses greater than 500 mg lead to very small increases in absorption. (38) Nonpregnant premenopausal and postmenopausal women taking estrogen should take about 1,000 to 1,200 mg of calcium daily from both dietary and supplemental sources. Postmenopausal women not taking estrogen should consume about 1,500 mg of calcium daily.

Vitamin D

Vitamin D is produced when skin is exposed to sunlight. As aging occurs, the amount of vitamin D absorbed from skin decreases. Because of this and widespread use of sunscreen, 400 to 800 IU of vitamin D daily is recommended.

Magnesium

Fifty percent (50%) of magnesium is found in bone, and deficiency can lead to decreased calcium absorption and osteoporosis. The recommended intake is 600 mg daily.

Flaxseed 

Flaxseed is particularly high in lignan and phytoestrogens, and its daily intake of 40 g has been shown to be as effective as oral estrogen-progesterone therapy to control mild menopausal symptoms. It did not improve lipid profiles in women with hypercholesterolemia but did lower serum insulin and glucose levels. (43)

Botanicals

Black cohosh (Cimicifuga racemosa) has been used for both menstrual and menopausal conditions in Europe for more than 50 years. Four randomized trials of black cohosh, with a total of 345 menopausal women, lasting 3 to 6 months, supported its efficacy in reducing menopausal somatic complaints. (44-47) In one larger study, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, estradiol, and vaginal cell proliferation were not different between two doses of black cohosh and placebo, supporting its safety. (45) A fifth trial showed that black cohosh decreased LH but not FSH. (48)

Two studies have examined the effect of black cohosh in breast cancer survivors, many of whom had hot flashes as a side effect of taking tamoxifen. One study showed that both placebo and black cohosh improved symptoms. (49) Another larger trial using standardized black cohosh in the form of CR BNO 1055 (Menoem/Klimadynon) showed a significant reduction in percentage of women with severe hot flashes in the black cohosh group (24.4%) compared with the control group (73.9%, P < 0.01). (50) There were no serious adverse events, and there were only 11 minor adverse events in the latter study.

The most studied product, Remifemin, is currently standardized to 1 mg of triterpenes per 20 mg tablet. The recommended dose is 20 mg two times per day. No drug interactions have been identified. The most common side effect is gastrointestinal disturbance. A study in rats revealed no toxicity at 90 times the typical human dose. No mutagenicity or teratogenicity has been identified, but use during pregnancy can cause premature birth. (51,52) Multiple studies have attempted to determine whether black cohosh acts through estrogen receptors or through other mechanisms. (53) Black cohosh did not have estrogenic activity in a highly sensitive recombinant estrogen receptor system (54) and did not stimulate growth of human breast cancer cells but instead inhibited their growth. (55)

Red clover (Trifolium pretense) contains isoflavones similar to soy products. One large (n = 252) (56) and four small (n = 30 to 51) RCTs (57-60) have been conducted, with mixed results on hot flashes. Two of the trials showed reductions in number of hot flashes in the isoflavone groups. (58,60) The other two trials revealed no difference when compared with placebo. The large multicenter trial demonstrated a statistically significant 41% reduction in the number of hot flashes in the group taking a higher dose (82 mg isoflavones) compared with the lower-dose group (34%) or the placebo group (36%). (56) Others have shown that red clover isoflavones increased arterial compliance, (61) increased high-density lipoprotein, (62) increased bone density, (62) improved cognitive function, (63) and did not increase breast density. (64) Two forms of bioassay support estrogen receptor activity (54) and promotion of proliferation of estrogen-sensitive breast cancer cells. (55) Thus, red clover should be avoided by women with breast cancer or a family history of breast cancer.

Dong quai (Angelica sinensis) is commonly recommended as part of a mixture of other herbs. (36) Indications include menopausal symptoms, irregular menses, vaginal dryness, dysmenorrhea, and palpitations. A single RCT examined the 6-month administration of 4.5 g powdered root or placebo and found decreased hot flashes in both dong quai and placebo groups. (65) The lack of estrogenic effects in a trial on vaginal cytology, endometrial thickness, and serum estrogens is corroborated by a recent study that assayed estrogen activity using a highly sensitive human estrogen receptor and yeast recombinant system. (54) Dong quai contains psoralen, which can cause photodermatitis, and safrole, which is carcinogenic, as well as several coumarins. Dong quai should not be used by women taking anticoagulants or with heavy menstrual flow or with fibroids because of increased risk of bleeding.

Evening primrose oil (Oenothera biennis) (EPO) is often used for premenstrual symptoms as well as menopausal symptoms. A single RCT compared 500 mg EPO plus 10 mg natural vitamin E with placebo in 56 women over a period of 6 months. (66) EPO was no more effective than placebo for hot flashes except in decreasing the maximum number of night flashes. Side effects of nausea were relieved by taking the supplement with food. This appears to be a benign supplement that may benefit some women.

Chaste tree berries (Vitex agnus castus) are popular for premenstrual syndrome, menstrual irregularities, and secondary amenorrhea and are recommended for menopausal symptoms as well. Studies in the 1940s and 1950s established progestin-like effects, supporting the use for premenstrual symptoms. Others have demonstrated prolactin-inhibiting effects, based on dopaminergic actions. (2) Two small studies of essential oils from the leaf or berry have shown effectiveness for self-reported menopausal symptoms. (67,68) Side effects in trials of chaste tree berry include gastrointestinal symptoms, headache, rash, itching, and increased menstrual flow. No estrogen activity was found in a high-sensitivity, recombinant estrogen receptor system. (54) Therefore, the mechanism of action is more likely to be based on the progestin-like effects. This herb deserves further study.

Wild yam (Dioscorea villosa) creams have been touted for their effects on menopausal symptoms. Wild yam contains diosgenin, which can be converted into progesterone in the laboratory and was once a source of semisynthetic hormones. The human body cannot make this conversion, so it is unknown whether wild yam acts as a progestin in vivo. A single RCT of a 1-teaspoon mixture of 100 g wild yam, 2 g flax oil, 100 mg geranium oil, and 10 mg alpha-tocopherol applied twice per day versus placebo showed no difference in flushing, mood, breast symptoms, libido, or energy levels. There was also no difference in lipids, estradiol, FSH, or LH in the 3-month trial. (69) Almost half of the participants dropped out because of unrelieved symptoms, further suggesting that yam cream may not be useful for menopausal symptoms.

Bioidentical Hormones

It is important to differentiate between "synthetic" hormones, "natural" hormones, and "bioidentical" hormones. Synthetic hormones are formulated in a laboratory. Natural hormones come from another animal species, such as Premarin, from pregnant mares. They are processed with very few chemical changes and are not chemically identical with those found in humans. Bioidentical hormones are synthesized from plant sources, which are modified chemically to form products that are chemically identical with human hormones. Bioidentical hormones are preferable when HRT is necessary because they are identical with hormones produced by humans.

HRT is recommended by integrative providers when other lifestyle, nutritional, or herbal supplementations are not effective in controlling hot flashes. Perimenopausal women may complain of irregular menses and often require contraception as well. For these patients, one can use low-dose oral contraceptives in nonsmokers. Another approach for use with patients who do not require contraception is to provide progesterone during the last 2 weeks of their cycle to help control symptoms as well as inducing a predictable bleeding pattern. When hormones are necessary, it is best to use the smallest dose possible for the shortest period of time. It is important to discuss with the patient the expected risks, benefits, and the possibility of adverse outcomes. Also, data from the Women's Health Initiative trial can be provided, explaining that there have not been any long-term trials with bioidentical hormones for HRT. (70)

The most common bioidentical estrogen prescribed is 17-beta estradiol, which can be found in several formulations, including the oral micronized form, under the trade name Estrace and as transdermal patches and vaginal preparations in tablet, ring, and cream forms. To begin therapy with Estrace, it is used at the lowest dose of 1 mg daily and progesterone is added, if necessary, for endometrial protection. Compounded estrogen combinations are available in oral or troche forms from compounding pharmacies. These include Biest (80 to 90% estriol and 10 to 20% estradiol) and Triest (80% estriol, 10% estrone and 10% estradiol). Usual dosing for Biest and Triest are 1.25 to 5.0 mg per day. (70) The dose of estrogens can be titrated up as necessary to control symptoms. Some practitioners are proponents of serum or salivary testing to determine dosing. However, if hormone replacement is used only for symptom relief, then laboratory data will not be as effective for dose determination as patient report of symptoms. (37) There are very few data on the safety of compounded HRT. However, there are data showing that estradiol and estriol have the potential to stimulate the endometrium. (71) It is important to remember that endometrial protection with progesterone is indicated in all patients who retain their uterus and choose to take any form of estrogen therapy.

Bioidentical progesterone is available in micronized form under the trade name Prometrium. It can be dosed at 200 mg daily for 14 days per month to provide a reliable withdrawal bleeding pattern, which will gradually decrease in both duration and amount. Women generally do not become amenorrheic with cyclic progesterone. Prometrium can also be dosed continuously at 100 mg per day, which will cause unpredictable withdrawal bleeding. This will gradually decrease in frequency and duration until cessation. Each patient should be given the choice about which progesterone dosing regimen would be preferable for her situation, as endometrial protection appears to be similar in both cases. Bioidentical progesterone is also available in cream and troche forms, which can be obtained from a compounding pharmacy. (70) An RCT of one-quarter teaspoon of progesterone cream (supplying 20 mg of progesterone) versus placebo, applied for 1 year's time, had no effect on bone density but did show a statistically significant effect on hot flashes. Eighty-eight percent of the progesterone group versus 19% of the control group had a decrease in hot flashes (P < 0.001). Eight of 30 women in the progesterone group had vaginal spotting, one of which had biopsy-proven proliferative endometrium. (36) Another study that used 32 mg of progesterone in a cream found no difference in vasomotor symptoms, mood, or sexual feelings. (72) Caution is advised if using transdermal progesterone in opposition to estrogen, as three studies have shown that achieved serum levels of progesterone are too low to prevent estrogenic stimulation of the endometrium. (36) Oral or injected synthetic progesterones alone have repeatedly been shown to reduce vasomotor symptoms but also tend to elevate lipid profiles. Oral micronized natural progesterone has no adverse effects on mood or high-density lipoprotein. Side effects of fatigue or sedation can be avoided by taking the supplement at bedtime. (73)

Patients should take hormones for the shortest period of time necessary to control symptoms. (74,75) Timing of discontinuation should be individualized for each person, and tapering of hormones is recommended to avoid rebound hot flashes. Generally, one can begin tapering the hormones about 3 years after their initiation. Some patients may need to continue to take hormones for as long as 5 years.

Conclusion

Menopause is a natural transitional time for women; it provides an opportunity to adopt a healthier lifestyle. Physicians may help ease this transition with patient education, recommendations for mind-body activities, healthy diet, and exercise. If these measures are not sufficient to control symptoms, then supplementation with botanicals such as black cohosh and red clover may be of benefit. For cases that do not respond to these therapies, physicians can recommend bioidentical hormone therapy with progesterone alone or estrogen and progesterone at the lowest doses and shortest time possible to adequately control symptoms.

Table 1. General nutritional recommendations for daily intake with
examples and serving sizes (a)

       General Nutrition Guidelines for Women in their Menopausal Years
Daily recommendations           Examples of foods included  Serving size

Fruits and vegetables           Apple                       1 small, 4-5
  ([greater than or equal to]7                              oz
  servings) (c)
  * 2-3 fruit, 5+ vegetables    Berries                     3/4-1 C
  * Emphasis on rainbow of      Leafy greens, raw           1 C
    color
                                Cooked or raw chopped       1/2 C
                                  fruits or vegetables
Grains (4-8 servings)           Oatmeal                     1/2 C
  * Look for "whole" in         Brown rice, pasta           1/3 C
    ingredient labels
                                Whole grain breads          1 oz
  * Fiber >3 g per serving      Cereals                     1/4-1/2 C
  * Emphasis on whole grains
Legumes (1-2 servings)          Hummus (mashed chickpeas)   1/3 C
                                Cooked beans, peas,         1/2 C
                                  lentils
Whole soy foods (1-2 servings)  Soy milk                    1 C
  * Emphasis on whole foods vs  Tofu                        4 oz
    supplements
                                Soy beans                   1/2 C
                                Soy nuts                    1 oz
Low-fat dairy (b) (2-3          Yogurt, milk                1 C
  servings)
  * 0-3 g fat per serving       Cheese                      1 oz
Healthy fats (3-8) servings     Olive, canola oil           1 tsp
  * Emphasis on                 Almonds, cashews, peanut    6-7 nuts
    monounsaturated               butter
                                                            1/2 Tbsp
Animal protein (b) (up to 1
  serving/d)
  Lean meat (1-3 servings/wk)   Poultry
  * 3 g of fat per oz or less   Game                        3 oz
  * Remove skin from poultry    Pork
  * Loin and round cuts are     Lamb, beef
    leanest
  Fish and seafood (2-4
    servings/wk)
  * Grill, saute, broil, bake   Shellfish
    rather than fry
                                Salmon, anchovies,          4-6 oz
                                  sardines (highest in
                                  omega-3)
  * Emphasis on high omega-3    Tuna, cod, halibut
    fish at least 2 servings/
    wk

(a) oz, ounce; C, cup; tsp, teaspoon; g, gram; Tbsp, tablespoon.
(b) It is recommended to choose organic and hormone-free animal products
whenever possible to minimize exposure to potentially harmful
pesticides, residues, and hormones.
(c) Some recommend 9 to 11 servings of fruits and vegetables daily.

Table 2. Soy foods with serving sizes, grams of protein, and isoflavone
content (a)

Whole soy foods (74, 75)
                           Serving       Protein       Isoflavone
Food (b)                   size          (g)           content (mg)

Miso                       1/2 C         16            59
Soybeans, cooked           1/2 C         14            47
Soy milk                   1 C           11            24
Soy nuts, dry roasted      1 ounce       11            36
Soy yogurt                 1 C            9            43
Tempeh, cooked             1/2 C         18            53
Tofu, firm, cooked         1/2 C         20            40

(a) C, cup; g, grams; mg, milligrams.
(b) Recommended: 1-2 servings/d (25 g soy protein/d for cholesterol
lowering).

Acknowledgments

The authors wish to acknowledge the invaluable help of Jenna Wunder, MPH, RD, for assistance with the section of dietary changes, and Faye Harrington and Shirley Pearson for secretarial support.

Accepted December 13, 2004.

References

1. Stenchever M, Droegemueller W, Herbst A, et al. Comprehensive Gynecology. St Louis, MO, Mosby, 2001.

2. Kass-Annese B. Alternative therapies for menopause. Clin Obstet Gynecol 2000;43:162-183.

3. Bair Y, Gold E, Greendale G, et al. Ethnic differences in use of complementary and alternative medicine at midlife: longitudinal results from SWAN participants. Am Public Health Assoc 2002;11:1832-1840.

4. Kam I, Dennehy C, Tsourounis C. Dietary supplement use among menopausal women attending a San Francisco health conference. Menopause 2002;9:72-78.

5. Newton K, Buist D, Keenan N, et al. Use of alternative therapies for menopause symptoms: results of a population-based survey. Obstet Gynecol 2002;100:18-25.

6. Keenan N, Mark S, Fugh-Berman A, et al. Severity of menopausal symptoms and use of both conventional and complementary/alternative therapies. Menopause 2003;10:507-515.

7. Hunter M. Predictors of menopausal symptoms: psychosocial aspects. Baillieres Clin Endocrinol Metab 1993;7:33-45.

8. Hunter M, O'Dea I. An evaluation of a health education intervention for mid-aged women: five year follow-up of effects upon knowledge, impact of menopause and health. Patient Educ Counsel 1999;38:249-255.

9. Balk J. Mind-body approaches to menopausal symptoms. Altern Ther Womens Health 2003;5:9-12.

10. Swartzman L, Edelberg R, Kemmann E. Impact of stress on objectively recorded menopausal hot flushes and on flush report bias. Health Psychol 1990;9:529-545.

11. Geramaine L, Freedman R. Behavioral treatment for menopausal hot flashes: evaluation by objective methods. J Consult Clin Psychol 1984;52:1072-1079.

12. Stevenson D, Delprato DJ. Multiple component self-control program for menopausal hot flashes. J Behav Ther Exp Psychiatry 1983;14:137-140.

13. Freedman R, Woodward S. Behavioral treatment for menopausal hot flashes: evaluation by ambulatory monitoring. Am J Obstet Gynecol 1992;167:436-439.

14. Hunter M, Liao K-M. Determinants of treatment choice for menopausal hot flashes; hormonal versus psychological versus no treatment. J Psychosom Obstet Gynecol 1995;16:101-108.

15. Irvin J, Domar A, Clark C, et al. The effects of relaxation response training on menopausal symptoms. J Psychosom Obstet Gynecol 1996;17:202-207.

16. Wijma K, Melin A, Nedstrand E, et al. Treatment of menopausal symptoms with applied relaxation: a pilot study. Pergamon 1997;28:251-261.

17. Younus J, Simpson I, Collins A, et al. Mind control of menopause. Womens Health Issues 2003;13:74-78.

18. Bass S, Pearce G, Bradney M, et al. Exercise before puberty may confer residual benefits in bone density in adulthood: studies in active prepubertal and retired female gymnasts. J Bone Mineral Res 1998;13:500-507.

19. Beck B, Snow C. Bone health across the lifespan: exercising our options. Exerc Sport Sci Rev 2003;31:117-122.

20. Eden K, Orleans C, Mulrow C, et al. Does counseling by clinicians improve physical activity? A summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2002;137:E208-E215.

21. Slaven L, Lee C. Mood and symptom reporting among middle-aged women: the relationship between menopausal status, hormone replacement therapy, and exercise participation. Health Psychol 1997;16:203-208.

22. Stadberg E, Mattsson L, Milsom I. Factors associated with climacteric symptoms and the use of hormone replacement therapy. Acta Obstet Gynecol Scand 2000;79:286-292.

23. Aiello E, Yasui Y, Tworoger S, et al. Effect of a yearlong, moderate-intensity exercise intervention on the occurrence and severity of menopause symptoms in postmenopausal women. Menopause 2004;11:382-388.

24. Finn S. Women in Midlife: A nutritional perspective. J Womens Health Gender-Based Med 2000;9:351-356.

25. Albert A, Altabre C, Baro F, et al. Beneficial effects and good tolerability of soy for menopausal symptoms. Phytomedicine 2002;9:85-92.

26. Han X, Soares J, Haidar M, et al. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol 2002;99:389-394.

27. Van Patten C, Olivotto I, Chambers K, et al. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol 2002;20:1449-1455.

28. Albertazzi P, Pansini F, Bonaccorsi G, et al. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol 1998;91:6-10.

29. Murkies A, Lombard C, Strauss B, et al. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. Maturitus 1995;21:189-195.

30. Chen Y, Ho S, Lam S, et al. Soy Isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 2003;88:4740-4747.

31. Kritz-Silverstain D, Von Muhlen D, Barrett-Connor E, et al. Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health In Aging (SOPHIA) Study. Menopause 2003;10:196-202.

32. Cassidy A, Griffin B. Phyto-oestrogens: a potential role in the prevention of CHD? Proc Nutr Soc 1999;58:193-199.

33. Horn-Ross P, John E, Canchola A, et al. Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst 2003;95:1158-1164.

34. Kurzer M. Phytoestrogen Supplement Use by Women. Paper presented at NIH Dietary Supplement Use in Women: Current Status and Future Directions; January 28-29, 2002; Bethesda, MD.

35. Gass M, Taylor M. Alternatives for women through menopause. Alt J Obstet Gynecol 2001;185:S47-S56.

36. Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials. Ann Intern Med 2002;137:805-813.

37. Lowdog T. Menopause. Foundations Herb Med 2000;47-54.

38. Harvey J, Zobitz M, Pak C. Dose dependency of calcium absorption: a comparison of calcium carbonate and calcium citrate. J Bone Miner Res 1988;3:253-258.

39. Heaney R, Dowell M, Barger-Lux M. Absorption of calcium as the carbonate and citrate salts, with some observations on method. Osteoporos Int 1999;9:19-23.

40. Reid I. Therapy of osteoporosis: calcium, vitamin d, and exercise. Am J Med Sci 1996;312:278-286.

41. Sakhaee K, Poindexter J, Griffith C, et al. Stone forming risk of calcium citrate supplementation in healthy postmenopausal women. J Urol 2004;172:958-961.

42. Ruml L, Sakhaee K, Peterson R, et al. The effect of calcium citrate on bone density in the early and mid-postmenopausal period: a randomized placebo-controlled study. Am J Ther 1999;6:303-311.

43. Lemay A, Dodin S, Kadri N, et al. Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women. Obstet Gynecol 2002;100:495-504.

44. Lehmann-Willenbrock E, Riedel H. Clinical and endocrinologic examinations about therapy of climacteric symptoms following hysterectomy with remaining ovaries. Zentralbl Gynakol 1988;110:611-618.

45. Liske E, Wustenberg P. Therapy of climacteric complaints with cimicifuga racemosa: herbal medicine with clinically proven evidence. Menopause 1998;5:250.

46. Stoll W. phytopharmacon influences atrophic vaginal epithelium: double-blind study: cimicifuga vs estrogenic substances. Therapeuticum 1987;1:23-31.

47. Warnecke G. Influence of a phytopharmaceutical on climacteric complaints. Die Meizinisch Welt 1985;36:871-874.

48. Duker E, Kpanski L, Jarry H, et al. Effects of extracts from Cimicifuga racemosa on gonadotropin release in menopausal women and ovariectomized rats. Planta Med 1991;57:420-424.

49. Jacobson J, Troxel A, Evans J, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 2001;19:2739-2745.

50. Munoz G, Pluchino S. Cimicifuga racemosa for the treatment of hot flushes in women surviving breast cancer. Maturitas 2003;44(Suppl 1):S59-S65.

51. McKenna D, Jones K, Humphrey S, et al. Black cohosh: efficacy, safety, and use in clinical and preclinical applications. Altern Ther Health Med 2001;7:93-98.

52. Pepping J. Black cohosh: Cimicifuga racemosa. Am J Health Syst Pharm 1999;56:1400-1402.

53. Borrelli F, Izzo A, Ernst E. Pharmacological effects of Cimicifuga racemosa. Life Sci 2003;73:1215-1229.

54. Klein K, Janfaza M, Wong J, et al. Estrogen bioactivity in fo-ti and other herbs used for their estrogen-like effects as determined by a recombinant cell bioassay. J Clin Endocrinol Metab 2003;88:4077-4079.

55. Bodinet C, Freudenstin J. Influence of marketed herbal menopause preparations on MCF-7 cell proliferation. Menopause 2004;11:281-289.

56. Tice J, Ettinger B, Ensrud K, et al. Phytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) Study. JAMA 2003;290:207-214.

57. Baber R, Templeman C, Morton T, et al. Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric 1999;2:85-92.

58. Jeri A. the use of an isoflavone supplement to relieve hot flashes. Female Patient 2002;27:35-37.

59. Knight D, Howes J, Eden J. The effect of Promensil, and isoflavone extract, on menopausal symptoms. Climacteric 1999;2:79-84.

60. van de Weijer P, Barentsen R. Isoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas 2002;42:187-193.

61. Nestle P, Pomeroy S, Kay S, et al. Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women [erratum appears in J Clin Endocrinol Metab 1999;84:3647]. J Clin Endocrinol Metab 1999;84:895-898.

62. Clifton-Bligh P, Baber R, Fulcher G, et al. The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. Menopause 2001;8:259-265.

63. Howes J, Bray K, Lorenz L, et al. The effects of dietary supplementation with isoflavones from red clover on cognitive function in postmenopausal women. Climacteric 2004;7:70-77.

64. Atkinson C, Warren R, Sala E, et al. Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165]. Breast Cancer Res 2004;6:R170-R179.

65. Hirata J, Swiersz L, Zell B, et al. does dong quai have estrogenic effects in post menopausal women? Fertil Steril 1997;68:981-986.

66. Chenoy R, Hussain S, Tayob Y, et al. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ 1994;308:501-503.

67. Chopin L. Vitex agnus castus essential oil and menopausal balance: a research update. Comp Ther Nurs Midwife 2003;8:148-154.

68. Lucks B, Sorensen J, Veal L. Vitexagnus-castus essential oil and menopausal balance: a self-care survey. Comp Ther Nurs Midwife 2002;8:148-154.

69. Komesaroff P, Black C, Cable V, et al. Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women. Climacteric 2001;4:114-150.

70. Rakel D. Menopause, in Bralow L, Merahn S (eds): Integrative Medicine. Philadelphia, PA, Saunders, 2003, pp 367-370.

71. Taylor M. Unconventional estrogens: Estriol, Biest, and Triest. Clin Obstet Gynecol 2001;44:864-879.

72. Fugate S, Church C. Nonestrogen treatment modalities for vasomotor symptoms associated with menopause. Ann Pharmacother 2004;38:1482-1499.

73. Morelli V, Naquin C. alternative therapies for traditional disease states: menopause. Am Fam Physician 2002;66:129-134.

74. USDA, Iowa State University. Database on the Isoflavone Content of Foods. http://www.nal.usda.gov/fnic/foodcomp/Data/isoflav/isfl_tbl.pdf. Accessed November 9, 2004.

75. USDA, Iowa State University. Database on the Protein Content of Foods. http://www.nal.usda.gov/fnic/foodcomp. Accessed November 9, 2004.

RELATED ARTICLE: Key Points

* This report is a topical review of several therapeutic approaches to menopausal symptoms.

* The focus is on holistic and integrative medicine therapies, including mind-body skills, exercise, dietary changes, nutritional supplements, botanicals, and bioidentical hormones.

Julie McKee, MD, and Sara L. Warber, MD

From the Family Medicine Department, University of Texas Medical Branch, Galveston, TX; and Michigan Integrative Medicine, Department of Family Medicine, University of Michigan Medical School, Ann Arbor, MI.

Supported by grant IR25AT00586-01 from National Center for Complementary and Alternative Medicine (to Dr. McKee).

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or the National Center for Complementary and Alternative Medicine.

Reprint requests to Dr. Julie McKee, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1123. Email: [e-mail]