Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women

Abstract

Objective-The aim of this study was to determine the effect of DRIs on hot flash symptoms in menopausal women.Design-This was a randomized, double-blind, placebo-controlled trial of menopausal women, aged 38 to 60 years, who experienced 4 to 14 hot flashes per day. After a 1-week run-in period, a total of 190 menopausal women were randomized to receive a placebo or 40 or 60 mg/day of a DRI for 12 weeks. The primary outcome was the mean changes from baseline to week 12 in the frequency of hot flashes recorded in the participant diary. The secondary outcomes included changes in quality of life and hormonal profiles.Results-A total of 147 women (77%) completed the study. It was found that 40 and 60 mg of DRI improved hot flash frequency and severity equally. At 8 weeks hot flash frequency was reduced by 43% in the 40-mg DRI group and by 41% in the 60-mg DRI group, compared with 32% in the placebo group (P = not significant vs placebo). The corresponding numbers for 12 weeks were 52%, 51%, and 39%, respectively (P = 0.07 and 0.09 vs placebo). When comparing the two treatment groups with the placebo group, there were significant reductions in mean daily hot flash frequency. The supplement (either 40 or 60 mg) reduced hot flash frequency by 43% at 8 weeks (P = 0.1) and 52% at 12 weeks (P = 0.048) but did not cause any significant changes in endogenous sex hormones or thyroid hormones. Menopausal quality of life improved in all three groups, although there were no statistically significant differences between groups.Conclusions-DRI supplementation may be an effective and acceptable alternative to hormone treatment for menopausal hot flashes. Although hormone therapy (HT) is the most effective treatment for the relief of hot flashes to date, evidence suggests that long-term use of HT may increase the risk of developing certain medical disorders. The data from the Women's Health Initiative showed an increased risk of coronary heart disease, stroke, pulmonary embolism, and breast cancer with estrogen + progestogen therapy (conjugated equine estrogens + medroxyprogesterone acetate) after a mean of 5.2 years of follow-up. 3 Estrogen+ progestogen therapy was associated with a 24% increased risk of coronary heart disease. 4 Thus, safe and effective alternatives are needed. KeywordsRecently interest has arisen in isoflavones as a potential therapy for menopausal hot flashes.Isoflavones are one of several classes of phytoestrogens, compounds that exert both estrogenic and antiestrogenic properties. Daidzein and genistein are isoflavones that are found in rich supply in soybeans and soy products. Available data on isoflavones for the treatment of menopausal symptoms have been inconclusive; studies with positive results have reported only a slight improvement. Nonetheless, there are no studies showing harmful effects of isoflavones on menopausal symptoms. This inconsistency may, in part, be due to differences in methods used to isolate isoflavones, concentrations of bioavailable isoflavones, and the composition of isoflav...

Scientific Opinion on the substantiation of health claims related to soy isoflavones and protection of DNA, proteins and lipids from oxidative damage (ID 1286, 4245), maintenance of normal blood LDL cholesterol concentrations (ID 1135, 1704a, 3093a), reduction of vasomotor symptoms associated with menopause (ID 1654, 1704b, 2140, 3093b, 3154, 3590), maintenance of normal skin tonicity (ID 1704a), contribution to normal hair growth (ID 1704a, 4254), “cardiovascular health” (ID 3587), treatment of prostate c

“…The Panel notes that from the 12 human intervention studies provided from which conclusions can be drawn for the scientific substantiation of the claim, most of which have some methodological limitations and/or inadequate reporting, five studies (n=498 subjects analysed; range: 25-115 per group) with a duration of 12 weeks to 12 months using doses from 27 mg genistein to 100 mg of total isoflavones showed a statistically significant effect of soy isoflavones on vasomotor symptoms after one month , three months (Cheng et al, 2007;Crisafulli et al, 2004), four months (Han et al, 2002) and 10 months , whereas six studies (n=463 subjects analysed, range: 12-99 per group/period) with a duration of six weeks to six months using doses from 40 mg to 118 mg of total isoflavones did not show a statistically significant effect of soy isoflavones on vasomotor symptoms (Albertazzi et al, 2005;Faure et al, 2002;Khaodhiar et al, 2008;Knight et al, 2001;Kotsopoulos et al, 2000;St Germain et al, 2001), and that one study in 122 analysed subjects using a dose of 50 mg isoflavones for four months led to inconsistent results with regard to the effect soy isoflavones on vasomotor symptoms.…”

“…From the remaining human intervention studies provided, either separately in the consolidated list or in the systematic reviews, seven investigated the effect of soy isoflavones on both frequency and severity of hot flushes (Albertazzi et al, 2005;D'Anna et al, 2007;Khaodhiar et al, 2008;Knight et al, 2001;Nahas et al, 2007;St Germain et al, 2001;Upmalis et al, 2000), two investigated frequency only (Crisafulli et al, 2004;Faure et al, 2002) and three severity only (Cheng et al, 2007;Han et al, 2002;Kotsopoulos et al, 2000). Three of these studies also investigated the effect of soy isoflavones on night sweats (Cheng et al, 2007;St Germain et al, 2001;Upmalis et al, 2000).…”

“…In the 10 studies which investigated the effect of soy isoflavones on severity of hot flushes, severity of hot flushes was assessed by self-rating scales in five studies (Cheng et al, 2007;D'Anna et al, 2007;Khaodhiar et al, 2008;Nahas et al, 2007;Upmalis et al, 2000), by the vasomotor sub-scale of the Greene Climacteric Scale in two studies (Albertazzi et al, 2005;Knight et al, 2001), by the vasomotor symptom score of the Kupperman Index in one study (Han et al, 2002), by an interviewer-administered menopausal index in one study (St Germain et al, 2001), and by a validated questionnaire in the remaining study (Kotsopoulos et al, 2000). In the three of the aforementioned studies which investigated night sweats, one study (Cheng et al, 2007) assessed the severity of night sweats only, one study (Upmalis et al, 2000) assessed the frequency of night sweats only, while St Germain et al (2001) assessed both of these measures of night sweats.…”

“…In the double-blind, randomised, placebo-controlled study by Khaodhiar et al (2008) 191 post-menopausal women (aged 38-60 years) experiencing at least four hot flushes (mean frequency: approx. 8, mean severity approx.…”

Scientific Opinion on the substantiation of health claims related to soy isoflavones and maintenance of bone mineral density (ID 1655) and reduction of vasomotor symptoms associated with menopause (ID 1654, 1704, 2140, 3093, 3154, 3590) (further assessmen

“…In a previous assessment of this claim (EFSA Panel on Dietetic Products Nutrition and Allergies (NDA), 2011), 12 RCTs (Albertazzi et al, 2005;Cheng et al, 2007;Crisafulli et al, 2004;D'Anna et al, 2007;Faure et al, 2002;Han et al, 2002;Khaodhiar et al, 2008;Knight et al, 2001;Kotsopoulos et al, 2000;Nahas et al, 2007;St Germain et al, 2001;Upmalis et al, 2000) were evaluated for the scientific substantiation of the claim. RCTs evaluating outcomes other than vasomotor symptoms, assessing the effect of foods other than soy isoflavones, or RCTs for which confounding could not be excluded or which showed considerable limitations in methodology or reporting, or meta-analyses which included these studies, were not considered pertinent to the evaluation of the claim.…”