Prospective clinical trials
Ten prospective clinical trials have assessed the effectiveness of soy foods in ameliorating vasomotor symptoms and/or changes in the vaginal epithelium (Table 1).
Clinical trials testing soy foods
A 6-wk trial conducted in Australia enrolled 25 postmenopausal women who received a diet supplemented with soy flour, red clover sprouts, or linseed, each for 2 wk in turn (18). Vaginal MV increased after the 2-wk soy-rich diet (P < 0.05) but not after red clover or linseed.
In a U.S. study, 19 postmenopausal women 45–65 y old were randomized to soy foods, substituting one-third of their caloric intake, or usual diet for 4 wk (19). One main dish made from whole soybeans or texturized vegetable soy protein was supplied by the study to provide a daily intake of 165 mg of conjugated isoflavones. Compliance with the soy diet was 73%. In 68% of the women consuming soy foods, the percentage of superficial cells, an indication of estrogenicity, did not change; it increased in 19% and decreased in 13%. Among the women in the control group, 71% showed no change, 8% had an increase, and 21% had a decrease. These differences were not significant.
In a study from Australia, 58 postmenopausal women ages 30–70 y were randomized to receive soy flour or wheat flour over 12 wk (20). The flour was mixed in a drink or cereal or cooked in a muffin. Participants recorded their vasomotor symptoms and had assessments of their vaginal cytology at baseline and at 6 and 12 wk. Vasomotor symptoms decreased in both groups by 12 wk, with no significant difference between groups. The vaginal MI did not change over time in either group.
A study conducted in Israel recruited 145 women ages 43–65 y to receive a soy-rich diet or usual diet in a 2:1 ratio (21) for 12 wk. The dietary intervention consisted of daily consumption of foods known to contain high concentrations of soy isoflavones and included tofu, soy drink, and miso plus flaxseed, substituting one-fourth of their caloric intake. Participants were evaluated with the Menopause Symptom Questionnaire, which includes questions on vasomotor and genitourinary symptoms. Although 82% of the women reported eating all or part of their assigned foods, the study does not report the actual amount consumed. Hot flashes and vaginal dryness scores were significantly reduced in both groups.
In another study from Australia, 52 postmenopausal were assigned to 1 of 3 dietary regimens (soy, wheat, or linseed) for 12 wk and after a 4-wk washout period, they crossed over to a another diet (22). The soy group ingested 4 slices of bread daily containing 45 g of soy grits (52.6 ± 8.7 mg of isoflavones). Participants consuming the soy diet had an increase of 103% in vaginal cytology MI from baseline (P < 0.03), but the rate of hot flashes did not change.
An Italian study evaluated the effects of a 6-mo soy-rich diet on the vaginal epithelium of 187 menopausal women 39–60 y old. Participants were randomized to soy, estrogen therapy, or placebo (23). With the goal of providing 20–30 mg/d of soy isoflavones, an intake comparable to the average consumption in Asian women, participants in the diet group were asked to add 1 soy food serving daily (soymilk, miso, soup, tofu, etc.) and a phytoestrogen-rich food twice per week. The size of the servings was not reported. The trial had a high drop-out in the diet group (42%), probably because soy products are not usual components of the Italian diet. Food diaries kept by the participants indicated a daily isoflavone consumption of 47 mg, mostly from soy milk. Compliance in the participants who remained in the study, assessed from pooled morning urine collected over 14 d, showed significantly higher urinary daidzein concentrations in the soy-rich diet group. The biggest increase in MV and KI was in the estrogen therapy group; these indices had a smaller but significant increase in the diet group and no change in the control group.
The Herbal Alternatives for Menopause Study was conducted in the US and recruited 351 menopausal women between the ages of 45 and 55 y who had ≥2 vasomotor symptoms/d; 52% were in the menopausal transition and 48% were postmenopausal (24, 25). Participants were randomized to 1 of 5 interventions: multibotanical plus soy dietary counseling vs. multibotanical vs. black cohosh vs. estrogen therapy vs. placebo. The women in the soy food intervention group reported an average of 0.6 servings/d of soy at baseline and increased dietary soy by 1.1 servings/d between baseline and 3 mo. A serving was defined as 240 mL of soy milk or 1/4 cup (60 mL) of soy nuts. At 12 mo, the multibotanical plus soy intervention group had higher (worse) symptoms relative to placebo (P = 0.016). The study did not detect differences < 1.5 vasomotor symptoms/d between treatment groups.
In Canada, 99 women aged 45–60 y and menopausal for 1–8 y were enrolled in a 16-wk study of quality of life and hot flash frequency and severity (26). They received 1 muffin daily containing soy, wheat, or flaxseed flour. Soy muffins contained 25 g of soy flour, supplying 42 mg of isoflavones daily. Among the 87 women who completed the trial, there was no significant difference in the frequency and severity of hot flashes between treatment groups.
A study in Thailand enrolled 42 women ages 45–70 y with at least 3 mo of amenorrhea and 1 or more symptom of urogenital atrophy (27). The study had a cross-over design of two 12-wk periods and two 4-washout periods, where participants were randomized to a soy-rich diet of 25 g of various soy foods such as soy milk or soft tofu containing >50 mg daily of isoflavones or an equivalent amount of animal protein. The groups did not differ before or after treatment.
In the US, 82 women with irregular menses or in amenorrhea for at least 12 mo were randomized in a cross-over design between 2 diet sequences: therapeutic lifestyle changes diet with soy or without soy (28). Participants received 1/2 cup of soy nuts (roasted soybeans) containing 25 g of soy protein and 101 mg aglycone isoflavones daily to be eaten throughout the day. The main outcome of this study was changes in blood pressure. Of the 60 women who finished the study, 39 had hot flashes. Participants recorded the number of hot flashes in calendars and were asked to complete the Menopause-Specific Quality of Life Questionnaire at the end of each 8-wk period. Soy nut ingestion was associated with a 45% decrease in hot flashes in women with >4.5 hot flashes/d at baseline (P < 0.001) and a 41% decrease in those with ≤4.5 hot flashes/d. The reduction in hot flashes was apparent at 2 wk in both groups, although there was some attenuation in the benefit of soy nuts over time in the low-hot flash group. When hot flashes were assessed by the menopausal symptom quality of life questionnaire, the group consuming soy nuts reported a 19% decrease in vasomotor score (P = 0.004).
The limitations of these studies include small sample size, short duration, the use of different soy foods that contain varying amounts of isoflavones, and enrollment of women in a wide age range or who differed in the number and severity of menopausal symptoms. Studies evaluating vasomotor symptoms commonly observe a significant placebo effect, with up to 30% reduction in hot flashes in the placebo group; therefore, trials longer than 12 wk are necessary to evaluate the sustainability of effects.
In conclusion, menopausal symptoms are common, although their incidence varies according to the population that is studied. The findings of the WHI have resulted in a sharp decline in the use of estrogen therapy among menopausal women and an increase in the consumption of soy foods and soy supplements for the management of menopausal symptoms. Studies evaluating the effectiveness of soy foods in ameliorating vasomotor and vaginal symptoms have been conducted worldwide and have utilized a variety of soy foods containing different amounts of isoflavones. Among the 10 studies published in the last 20 y, 4 have had negative results and 1 reported worsening of symptoms in the group consuming soy food. Of the 4 studies that assessed only vaginal cytology, 3 reported beneficial effects. Only 1 of the 4 studies exclusively assessing vasomotor symptoms reported a reduction in symptoms. Two studies evaluated both outcomes, with opposite findings. In conclusion, considering the conflicting results provided by a small number of studies, the efficacy of soy foods in improving menopausal symptoms remains unclear.