Herbal Science Research - menopause

Black cohosh (Cimicifuga racemosa [L.] Nutt.): safety and efficacy for cancer patients.

Site Editor — Fri, 02 Nov 2007 05:52:36 -0700

Black cohosh (Cimicifuga racemosa [L.] Nutt.): safety and efficacy for cancer patients.: Support Care Cancer. 2007 Aug;15(8):913-21 Authors: Walji R, Boon H, Guns E, Oneschuk D, Younus J

GOALS OF WORK: Black cohosh is commonly used to treat hot flashes and other symptoms associated with menopause. It is thought to have multiple mechanisms of action, including potential phytoestrogenic properties. This has caused some concern about its use by patients with hormone-sensitive cancer. This paper will present the results of a systematic review of the safety and efficacy of black cohosh (Cimicifuga racemosa [L.] Nutt.) in patients with cancer. MATERIALS AND METHODS: A critical assessment of clinical (n = 5) and preclinical (n = 21) studies of black cohosh and cancer (breast and prostate) to treat hot flashes and other related symptoms is presented. In addition, clinical studies, case reports, animal studies, and in vitro assessments of the safety of black cohosh for patients with hormonally sensitive cancers is summarized and interpreted. MAIN RESULTS: In general, the research assessing efficacy of black cohosh for the treatment of hot flashes in women with breast cancer is inconclusive. There is laboratory evidence of antiproliferative properties but no confirmation from clinical studies for a protective role in cancer prevention. Black cohosh seems to have a relatively good safety profile. Concerns about liver toxicity are inconclusive. With relevance to cancer patients, black cohosh also seems not to exhibit phytoestrogenic activity and is in fact possibly an inhibitor of tumor growth. CONCLUSIONS: The use of black cohosh appears to be safe in breast cancer patients without risk for liver disease, although further research is needed in this and other populations.

PMID: 17602247 [PubMed - indexed for MEDLINE]

[...] the effects of naturopathic botanical and dietary interventions on sex steroid hormone metabolism in premenopausal women.

Site Editor — Sun, 14 Oct 2007 01:17:38 -0700

A pilot and feasibility study on the effects of naturopathic botanical and dietary interventions on sex steroid hormone metabolism in premenopausal women.: Cancer Epidemiol Biomarkers Prev. 2007 Aug;16(8):1601-9 Authors: Greenlee H, Atkinson C, Stanczyk FZ, Lampe JW

Naturopathic physicians commonly make dietary and/or dietary supplement recommendations for breast cancer prevention. This placebo-controlled, parallel-arm, pilot study tested the effects of two naturopathic interventions over five menstrual cycles on sex steroid hormones and metabolic markers in 40 healthy premenopausal women. The intervention arms were as follows: combination botanical supplement (Curcuma longa, Cynara scolymus, Rosmarinus officinalis, Schisandra chinensis, Silybum marinum, and Taraxacum officinalis; n = 15), dietary changes (3 servings/d crucifers or dark leafy greens, 30 g/d fiber, 1-2 liters/d water, and limiting caffeine and alcohol consumption to 1 serving each/wk; n = 10), and placebo (n = 15). Early-and late-follicular phase serum samples from cycles 1 and 5 were analyzed for estrogens (estrone, estrone-sulfate, total estradiol, and free estradiol), androgens (dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, total testosterone, and free testosterone), sex hormone-binding globulin, and metabolic markers (insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and leptin). Serum samples collected during the mid-luteal phase of cycles 1 and 5 were analyzed for total estradiol, free estradiol, and sex hormone-binding globulin. Urine samples collected during the late follicular phase of cycles 1 and 5 were analyzed for 2-hydroxyestrone and 16alpha-hydroxyestrone. During the early follicular phase, compared with placebo, the botanical supplement decreased dehydroepiandrosterone (-13.2%; P = 0.02), dehydroepiandrosterone-sulfate (-14.6%; P = 0.07), androstenedione (-8.6%; P = 0.05), and estrone-sulfate (-12.0%; P = 0.08). No other trends or statistically significant changes were observed. When comparing dietary changes with placebo, no statistically significant differences were observed. Overall, in this pilot study, the naturopathic interventions had no substantial effects on estrogen measures. Early-follicular phase androgens decreased with the botanical supplement.

PMID: 17684134 [PubMed - indexed for MEDLINE]

Challenges in the conduct of Thai herbal scientific study: efficacy and safety of phytoestrogen, pueraria mirifica [...]

Site Editor — Sat, 22 Sep 2007 18:02:00 -0700

Challenges in the conduct of Thai herbal scientific study: efficacy and safety of phytoestrogen, pueraria mirifica (Kwao Keur Kao), phase I, in the alleviation of climacteric symptoms in perimenopausal women.: J Med Assoc Thai. 2007 Jul; 90(7): 1274-80 Chandeying V, Lamlertkittikul S

OBJECTIVE: To evaluate the preliminary efficacy and safety of Pueraria mirifica (Kwao Keur Kao), phytoestrogen, for the alleviation of climacteric symptoms. MATERIAL AND METHOD: Perimenopausal women attending with climacteric symptoms, such as hot flushes and night sweats, were invited to join the present study, conducted at the Menopausal Clinic, Hat Yai Regional Hospital. The patients were voluntarily enrolled and randomly received the raw material of Pueraria mirifica, oral 50 and 100 mg capsule, once daily for six months, as an open-label study. RESULTS: Of the 10 enrolled patients, 8 cases were completely evaluated. The modified Greene climacteric scale (MGCS) was satisfactorily decreased in both groups. The average scale declined from 44.1 at baseline, to be 26, 17, and 11.1 at 1-, 3-, and 6- month follow-up respectively. No other laboratory abnormalities, except one case had transiently increased the creatinine level, and one case of increased blood urea nitrogen. The mean serum estradiol was slightly increased, while the mean serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were nearly stable. CONCLUSION: Pueraria mirifica is relatively safe and preliminarily alleviates the climacteric symptoms in perimenopausal. women, but the data is insufficient to draw definite conclusions regarding the estrogenic effect.

[...] Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women.

Site Editor — Sat, 23 Jun 2007 05:37:43 -0700

The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women.:

The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women.

Menopause. 2007 Mar-Apr;14(2):270-83

Authors: Kaszkin-Bettag M, Ventskovskiy BM, Kravchenko A, Rettenberger R, Richardson A, Heger PW, Heger M

OBJECTIVE: To investigate the efficacy of the special extract ERr 731 from the roots of Rheum rhaponticum compared with placebo on anxiety, health state, and general well-being in perimenopausal women. DESIGN: This study is a multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial, in which 109 perimenopausal women with climacteric complaints and anxiety received either 1 enteric coated tablet of ERr 731 (n=54) or placebo (n=55) daily for 12 weeks. The Hamilton Anxiety Scale, the Menopause Rating Scale II, the Women's Health Questionnaire, and the Psychological General Well-Being Index were used to measure anxiety, health state, and subjective psychological well-being. RESULTS: The results demonstrate that ERr 731 is highly effective in reducing anxiety in perimenopausal women compared with placebo. After 12 weeks, the Hamilton Anxiety Scale total score decreased significantly with ERr 731 (from 27.5+/-6.8 to 9.4+/-4.2 points) compared with placebo (from 25.1+/-6.0 to 21.6+/-8.6 points). ERr 731 also reduced the Hamilton Anxiety Scale factor scores for somatic and psychic anxiety. After 12 weeks, a reduction in the severity of anxiety from "moderate" or "severe" to "slight" was observed in 33 of 39 ERr 731 women completing the double-blind phase, which correlated well with the reduction in number and severity of hot flushes. This was reflected by a high rate of ERr 731 women reporting a marked improvement in health state and general well-being. CONCLUSIONS: ERr 731 is an effective medication for women with menopause-related anxiety and improves their health state and general well-being.

PMID: 17213754 [PubMed - indexed for MEDLINE]

Gene expression analysis of the mechanisms whereby black cohosh inhibits human breast cancer cell growth.

Site Editor — Fri, 11 May 2007 15:55:23 -0700

Gene expression analysis of the mechanisms whereby black cohosh inhibits human breast cancer cell growth.: Anticancer Res. 2007 Mar-Apr;27(2):697-712 Authors: Einbond LS, Su T, Wu HA, Friedman R, Wang X, Jiang B, Hagan T, Kennelly EJ, Kronenberg F, Weinstein IB

BACKGROUND: Previous studies indicate that specific extracts and the pure triterpene glycoside actein obtained from black cohosh inhibit growth of human breast cancer cells. Our aim is to identify alterations in gene expression induced by treatment with a methanolic extract (MeOH) of black cohosh. MATERIALS AND METHODS: We treated MDA-MB-453 human breast cancer cells with the MeOH extract at 40 microg/ml and collected RNA at 6 and 24 h; we confirmed the microarray results with real-time RT-PCR for 18 genes. RESULTS: At 6 h after treatment there was significant increase in expression of ER stress (GRP78), apoptotic (GDF15), lipid biosynthetic (INSIG1 and HSD17B7) and Phase 1 (CYP1A1) genes and, at 24 h, decrease in expression of cell cycle (HELLS and PLK4) genes. CONCLUSION: Since the MeOH extract activated genes that enhance apoptosis and repressed cell cycle genes, it may be useful in the prevention and therapy of breast cancer.

Pharmacokinetics and systemic endocrine effects of [...] 8-prenylnaringenin after single oral doses postmenopausal women

Site Editor — Fri, 11 May 2007 15:41:22 -0700

Pharmacokinetics and systemic endocrine effects of the phyto-oestrogen 8-prenylnaringenin after single oral doses to postmenopausal women.: Br J Clin Pharmacol. 2006 Sep;62(3):288-96 Authors: Rad M, Hümpel M, Schaefer O, Schoemaker RC, Schleuning WD, Cohen AF, Burggraaf J

AIMS: Pre-clinical data suggest that the racemic phyto-oestrogen 8-prenylnaringenin (8-PN) may have beneficial effects in postmenopausal women and may become an alternative to classical hormone replacement therapy (HRT) treatment regimes. The aim of this study was to investigate the pharmacokinetics, endocrine effects and tolerability of chemically synthesized 8-PN in postmenopausal women. METHODS: The study was performed using a randomized, double-blind, placebo-controlled, dose-escalation design with three groups of eight healthy postmenopausal women. In each group six subjects received 8-PN and two subjects placebo. 8-PN was given orally in doses of 50, 250 or 750 mg. Drug concentrations in serum, urine and faeces were measured up to 48 h and follicle-stimulating hormone/luteinizing hormone (LH) concentrations up to 24 h. RESULTS: All treatments were well tolerated and associated with a low incidence of (drug unrelated) adverse events. Serum concentrations of free 8-PN showed rapid drug absorption and secondary peaks suggestive of marked enterohepatic recirculation. Independent of the treatment group, approximately 30% of the dose was recovered in excreta as free compound or conjugates over the 48-h observation period. The first C(max) and AUC(0-48 h) showed dose linearity with ratios of 1 : 4.5 : 13.6 (C(max)) and 1 : 5.2 : 17.1 (AUC). The750- mg dose decreased LH concentrations by 16.7% (95% confidence interval 0.5, 30.2). CONCLUSION: Single oral doses of up to 750 mg 8-PN were well tolerated by postmenopausal women. The pharmacokinetic profile of 8-PN was characterized by rapid and probably complete enteral absorption, high metabolic stability, pronounced enterohepatic recirculation and tight dose linearity. The decrease in LH serum concentrations found after the highest dose demonstrates the ability of 8-PN to exert systemic endocrine effects in postmenopausal women.

Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status.

Site Editor — Sat, 20 Jan 2007 16:28:29 -0800

Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status.: Breast Cancer Res Treat. 2006 Oct;99(3):309-11 Authors: McCann SE, Kulkarni S, Trevisan M, Vito D, Nie J, Edge SB, Muti P, Freudenheim JL

We examined the association of dietary lignan intake with estrogen receptor negative (ER-) and ER positive (ER+) breast cancer risk in a breast cancer case-control study. Among premenopausal women only, there was a reduced risk of ER- breast cancer for those in the highest compared to the lowest quartile of lignan intake suggesting that the observed negative association of lignans with breast cancer may be limited to ER- tumors.

The use of herbs and dietary supplements in gynecology: an evidence-based review.

Site Editor — Fri, 19 Jan 2007 18:43:30 -0800

The use of herbs and dietary supplements in gynecology: an evidence-based review.: J Midwifery Womens Health. 2006 Nov-Dec;51(6):402-9 Authors: Dennehy CE

Consumers frequently use herbs and dietary supplements to treat chronic conditions that are poorly responsive to prescription drugs or when prescription drugs carry a high side effect burden. Women may use herbs and supplements for chronic gynecologic conditions, such as menopause, premenstrual syndrome, dysmenorrhea, cyclic mastalgia, and infertility. This review is an evidence-based evaluation of herbs and supplements for these conditions. Therapies that carry a higher level of support from randomized controlled trial evidence include black cohosh for menopause; vitamins B(1) and E for dysmenorrhea; calcium, vitamin B(6), and chasteberry for premenstrual syndrome; and chasteberry for cyclic mastalgia. There were too few trials involving herbs and supplements in infertility to warrant a solid recommendation, but chasteberry, antioxidants, and Fertility Blend have some preliminary support. Midwives may want to consider these alternatives in addition to more traditional treatment options when meeting with patients.

[Effectiveness and safety of the treatment of menopausal syndrome with Cimicifuga racemosa dry extract]

Site Editor — Wed, 17 Jan 2007 06:30:11 -0800

[Effectiveness and safety of the treatment of menopausal syndrome with Cimicifuga racemosa dry extract]: Ginekol Pol. 2006 Sep;77(9):678-83 Authors: Radowicki S, Skórzewska K, Rudnicka E, Szlendak-Sauer K, Wierzba W

OBJECTIVES: Phytoestrogens could be an alternative method of the treatment of menopausal syndrome in women with contraindications to hormonal replacement therapy. Design: The aim of the study was to evaluate efficacy and safety of the therapy with Cimicifuga racemosa dry extract. MATERIAL AND METHODS: Twenty women aged mean 52.4 +/- 4.9 years with climacteric syndrome were treated with Cimicifuga racemosa dry extract in a dose of 40 mg a day during 6 months. Kupperman's Index, biochemical parameters and hormonal profile were estimated before and after 3 and 6 months of the therapy. RESULTS: Mean values of Kuppermen's Index were decreased from 30.2 +/- 5.7 points before the therapy to 8.5 +/- 6.3 points after 3 months and to 2.6 +/- 2.1 points after 6 months of the therapy (p < 0.05). No statistical differences in biochemical parameters' concentrations and hormonal profile were observed. CONCLUSIONS: Cimicifuga racemosa dry extract was an effective and safe therapy of climacteric women with contraindications to hormonal replacement therapy.

A retrospective case-control study of the use of hormone-related supplements and association with breast cancer.

Site Editor — Sat, 06 Jan 2007 19:01:39 -0800

A retrospective case-control study of the use of hormone-related supplements and association with breast cancer.: Int J Cancer. 2007 Jan 4; Authors: Rebbeck TR, Troxel AB, Norman S, Bunin GR, Demichele A, Baumgarten M, Berlin M, Schinnar R, Strom BL

Hormone-related supplements (HRS), many of which contain phytoestrogens, are widely used to manage menopausal symptoms, yet their relationship with breast cancer risk has generally not been evaluated. We evaluated whether use of HRS was associated with breast cancer risk, using a population-based case-control study in 3 counties of the Philadelphia metropolitan area consisting of 949 breast cancer cases and 1,524 controls. Use of HRS varied significantly by race, with African American women being more likely than European American women to use any herbal preparation (19.2% vs. 14.7%, p = 0.003) as well as specific preparations including black cohosh (5.4% vs. 2.0%, p = 0.003), ginseng (12.5% vs. 7.9%, p < 0.001) and red clover (4.7% vs. 0.6%, p < 0.001). Use of black cohosh had a significant breast cancer protective effect (adjusted odds ratio 0.39, 95% CI: 0.22-0.70). This association was similar among women who reported use of either black cohosh or Remifemin (an herbal preparation derived from black cohosh; adjusted odds ratio 0.47, 95% CI: 0.27-0.82). The literature reports that black cohosh may be effective in treating menopausal symptoms, and has antiestrogenic, antiproliferative and antioxidant properties. Additional confirmatory studies are required to determine whether black cohosh could be used to prevent breast cancer. (c) 2006 Wiley-Liss, Inc.

Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo...

Site Editor — Wed, 03 Jan 2007 19:07:14 -0800

Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial.: Ann Intern Med. 2006 Dec 19;145(12):869-79 Authors: Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J

BACKGROUND: Herbal supplements are widely used for vasomotor symptoms. OBJECTIVE: To test the efficacy of 3 herbal regimens and hormone therapy for relief of vasomotor symptoms compared with placebo. DESIGN: 1-year randomized, double-blind, placebo-controlled trial conducted from May 2001 to September 2004. SETTING: Group Health, Washington State. PARTICIPANTS: 351 women age 45 to 55 years with 2 or more vasomotor symptoms per day; 52% of the women were in menopausal transition and 48% were postmenopausal. MEASUREMENTS: Rate and intensity of vasomotor symptoms (1 = mild to 3 = severe), and Wiklund Vasomotor Symptom Subscale. INTERVENTIONS: 1) Black cohosh, 160 mg daily; 2) multibotanical with black cohosh, 200 mg daily, and 9 other ingredients; 3) multibotanical plus dietary soy counseling; 4) conjugated equine estrogen, 0.625 mg daily, with or without medroxyprogesterone acetate, 2.5 mg daily; or 5) placebo. RESULTS: Vasomotor symptoms per day, symptom intensity, Wiklund Vasomotor Symptom Subscale score did not differ between the herbal interventions and placebo at 3, 6, or 12 months or for the average over all the follow-up time points (P > 0.05 for all comparisons) with 1 exception: At 12 months, symptom intensity was significantly worse with the multibotanical plus soy intervention than with placebo (P = 0.016). The difference in vasomotor symptoms per day between placebo and any of the herbal treatments at any time point was less than 1 symptom per day; for the average over all the follow-up time points, the difference was less than 0.55 symptom per day. The difference for hormone therapy versus placebo was -4.06 vasomotor symptoms per day for the average over all the follow-up time points (95% CI, -5.93 to -2.19 symptoms per day; P < 0.001). LIMITATIONS: The trial did not simulate the whole-person approach used by naturopathic physicians. Differences between treatment groups smaller than 1.5 Vasomotor symptoms per day cannot be ruled out. CONCLUSION: Black cohosh used in isolation, or as part of a multibotanical regimen, shows little potential as an important therapy for relief of vasomotor symptoms. Clinical Trials Registration number: NCT00169299.

Black Cohosh...Behaves as a Mixed Competitive Ligand and Partial Agonist at the Human mu Opiate Receptor

Site Editor — Wed, 03 Jan 2007 18:57:06 -0800

Black Cohosh (Actaea racemosa, Cimicifuga racemosa) Behaves as a Mixed Competitive Ligand and Partial Agonist at the Human mu Opiate Receptor.: J Agric Food Chem. 2006 Dec 27;54(26):9852-9857 Authors: Rhyu MR, Lu J, Webster DE, Fabricant DS, Farnsworth NR, Wang ZJ

Black cohosh is a commonly used botanical dietary supplement for the treatment of climacteric complaints. Because the opiate system in the brain is intimately associated with mood, temperature, and sex hormonal levels, the activity of black cohosh extracts at the human &mgr; opiate receptor (hMOR) expressed in Chinese hamster ovary cells was investigated. The 100% methanol, 75% ethanol, and 40% 2-propanol extracts of black cohosh effectively displaced the specific binding of [3H]DAMGO to hMOR. Further studies of the clinically used ethanol extract indicated that black cohosh acted as a mixed competitive ligand, displacing 77 +/- 4% [3H]DAMGO to hMOR (Ki = 62.9 &mgr;g/mL). Using the [35S]GTP&ggr;S assay, the action of black cohosh was found to be consistent with an agonist, with an EC50 of 68.8 +/- 7.7 &mgr;g/mL. These results demonstrate for the first time that black cohosh contains active principle(s) that activate hMOR, supporting its beneficial role in alleviating menopausal symptoms. Keywords: Black cohosh; menopause; hot flashes; opiate; botanical dietary supplement.

Management of postmenopausal symptoms in breast cancer survivors.

Site Editor — Wed, 03 Jan 2007 18:41:34 -0800

Management of postmenopausal symptoms in breast cancer survivors.: Management of postmenopausal symptoms in breast cancer survivors. Semin Oncol. 2006 Dec;33(6):696-707 Authors: Bruno D, Feeney KJ

With the increasing numbers of breast cancers survivors, menopause, its symptoms, and its physical complications are becoming more prevalent problems in this patient population. Hormonal replacement, which has been the cornerstone therapy of menopausal related symptoms for decades, recently has been shown to increase breast cancer incidence as well as risk of recurrence and no longer should be recommended. Menopausal symptoms and complications such as hot flashes, vaginal dryness, dyspareunia, and osteoporosis leading to fractures have a negative impact on the quality of life of both breast cancer survivors and the general postmenopausal population. The purpose of this review is to discuss the evidence for the use of alternative therapies for menopausal symptoms, thus providing guidance and recommendations that should facilitate therapeutic decisions in the daily practice of medical oncologists and primary care physicians.

Circulating enterolactone and risk of endometrial cancer.

Site Editor — Wed, 04 Oct 2006 18:40:01 -0700

Circulating enterolactone and risk of endometrial cancer.: Int J Cancer. 2006 Aug 23; Zeleniuch-Jacquotte A, Lundin E, Micheli A, Koenig KL, Lenner P, Muti P, Shore RE, Johansson I, Krogh V, Lukanova A, Stattin P, Afanasyeva Y, Rinaldi S, Arslan AA, Kaaks R, Berrino F, Hallmans G, Toniolo P, Adlercreutz H

It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer. (c) 2006 Wiley-Liss, Inc.

Femal, a herbal remedy made from pollen extracts, reduces hot flushes and improves quality of life in menopausal women...

Site Editor — Fri, 09 Jun 2006 07:21:12 -0700

Femal, a herbal remedy made from pollen extracts, reduces hot flushes and improves quality of life in menopausal women: a randomized, placebo-controlled, parallel study.: Climacteric. 2005 Jun;8(2):162-70 Authors: Winther K, Rein E, Hedman C

BACKGROUND: The fact that hormone replacement therapy has been claimed to increase the risk of breast cancer has made it relevant to search for new non-hormonal treatments of menopausal symptoms. OBJECTIVES: This study aimed to evaluate whether Femal, a herbal remedy made from pollen extracts, alleviates the symptoms of the menopause, especially hot flushes. DESIGN: A randomized, double-blind, placebo-controlled, parallel trial of 64 menopausal women, of whom 54 completed the trial. After an initial run-in phase of 1 month, the women were randomly given either two Femal tablets each morning, or two identical placebo tablets, for 3 months of treatment. On inclusion, and then at 4-week intervals, the patients were asked to evaluate 16 symptoms of the menopause using Menopause Rating Scales (MRS). In addition, every day throughout the study, certain menopausal symptoms were recorded in a diary. RESULTS: The two treatment groups were identical regarding demographic data and the initial symptom scores. In the active-treatment group, 65% responded with a reduction in hot flushes compared with 38% in the placebo group (p<0.006) and, in this group, the number of hot flushes registered in diaries declined after 3 months by 27% as compared to the placebo group (p<0.026). MRS evaluation of hot flushes yielded similar results (p<0.031). There were 23% and 22% decreases in hot flushes after 2 and 3 months of treatment, respectively, and after both intervals of time the inter-group comparisons were significantly affected. An overall evaluation of the trend in 15 other 'quality-of-life' parameters showed likewise in favor of the pollen extract (p<0.031). CONCLUSION: The pollen extract Femal significantly reduces hot flushes and certain other menopausal symptoms when compared to placebo.

Effect of pure genistein on bone markers and hot flushes.

Site Editor — Fri, 09 Jun 2006 04:26:55 -0700

Effect of pure genistein on bone markers and hot flushes.: Climacteric. 2005 Dec;8(4):371-9 Authors: Albertazzi P, Steel SA, Bottazzi M

OBJECTIVE: To evaluate the effect of 90 mg of daily genistein on markers of bone turnover and menopausal symptoms. DESIGN: This was a cross-over, placebo-controlled study involving 100 postmenopausal women. Subjects were randomly assigned to daily genistein or placebo for 6 weeks and crossed over to the alternative preparation for the following 6 weeks. Pure genistein was processed and encapsulated in accordance with British Pharmacopoeia standards. Each capsule contained 90 mg of pure genistein while the placebo contained just the recipients. RESULTS: In women with significant hot flushes (score (intensity x number) > or = 9), genistein reduced symptoms by 30% compared to baseline and the difference compared to placebo was statistically significant. No effect was observed on biochemical markers of bone turnover, possibly due to the short duration of each arm of the study. Genistein reduced osteocalcin, a marker of bone formation, by 3.6% compared to baseline and 0.31% compared to placebo (p = 0.81 and 0.40, respectively). Genistein increased cross-link telopeptide, a marker of bone resorption, by 1.8% compared to baseline and 0.29% compared to placebo; both differences were not statistically significant (p = 0.078 and 0.88, respectively). CONCLUSION: Pure genistein at a dose of 90 mg per day appears to reduce the number of hot flushes in postmenopausal women but the effect is mild.

Pharmacokinetics of isoflavones, daidzein and genistein, after ingestion of soy beverage...

Site Editor — Fri, 09 Jun 2006 04:22:40 -0700

Pharmacokinetics of isoflavones, daidzein and genistein, after ingestion of soy beverage compared with soy extract capsules in postmenopausal Thai women.: BMC Clin Pharmacol. 2005;5(1):2 Authors: Anupongsanugool E, Teekachunhatean S, Rojanasthien N, Pongsatha S, Sangdee C

BACKGROUND: Isoflavones from soybeans may provide some beneficial impacts on postmenopausal health. The purpose of this study was to compare the pharmacokinetics and bioavailability of plasma isoflavones (daidzein and genistein) after a single dose of orally administered soy beverage and soy extract capsules in postmenopausal Thai women. METHODS: We conducted a randomized two-phase crossover pharmacokinetic study in 12 postmenopausal Thai women. In the first phase, each subject randomly received either 2 soy extract capsules (containing daidzin : genistin = 7.79 : 22.57 mg), or soy beverage prepared from 15 g of soy flour (containing daidzin : genistin = 9.27 : 10.51 mg). In the second phase, the subjects received an alternative preparation in the same manner after a washout period of at least 1 week. Blood samples were collected immediately before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24 and 32 h after administration of the soy preparation in each phase. Plasma daidzein and genistein concentrations were determined by using high performance liquid chromatography (HPLC). The pharmacokinetic parameters of daidzein and genistein, i.e. maximal plasma concentration (Cmax), time to maximal plasma concentration (Tmax), area under the plasma concentration-time curve (AUC) and half-life (t1/2), were estimated using the TopFit version 2.0 software with noncompartmental model analysis. RESULTS: There were no significant differences in the mean values of Cmax/dose, AUC0-32/dose, AUC0- proportional, variant/dose, Tmax, and t1/2 of genistein between both preparations. For pharmacokinetic parameters of daidzein, the mean values of Cmax/dose, Tmax, and t1/2 did not significantly differ between both preparations. Nonetheless, the mean AUC0-32/dose and AUC0- proportional, variant/dose after administration of soy extract capsules were slightly (but significantly, p < 0.05) higher than those of soy beverage. CONCLUSION: The bioavailability of daidzein, which was adjusted for the administered dose (AUC/dose), following a single oral administration of soy beverage was slightly (but significantly) less than that of soy extract capsules, whereas, the bioavailability adjusted for administered dose of genistein from both soy preparations were comparable. The other pharmacokinetic parameters of daidzein and genistein, including Cmax adjusted for the dose, Tmax and t1/2, were not different between both soy preparations.

The red wine phenolics piceatannol and myricetin act as agonists for estrogen receptor alpha in human breast cancer cells.

Site Editor — Fri, 09 Jun 2006 04:21:37 -0700

The red wine phenolics piceatannol and myricetin act as agonists for estrogen receptor alpha in human breast cancer cells.: J Mol Endocrinol. 2005 Oct;35(2):269-81 Authors: Maggiolini M, Recchia AG, Bonofiglio D, Catalano S, Vivacqua A, Carpino A, Rago V, Rossi R, Andò S

Previous epidemiological reports have suggested that red wine intake is associated with beneficial health effects due to the ability of certain phytochemical components to exert estrogen-like activity. It has been also documented that estrogens induce the proliferation of hormone-dependent breast cancer cells by binding to and transactivating estrogen receptor (ER) alpha, which in turn interacts with responsive DNA sequences located within the promoter region of target genes. In order to provide further insight into the positive association between wine consumption and the incidence of breast carcinoma in postmenopausal women, we have evaluated the estrogenic properties of two abundant wine-derived compounds, named piceatannol (PIC) and myricetin (MYR), using as model systems the hormone-sensitive MCF7 and the endocrine-independent SKBR3 breast cancer cells. On the basis of our experimental evidence PIC and MYR may contribute to the estrogenicity of red wine since: (1) they transactivate endogenous ER alpha; (2) they activate the agonist-dependent activation function (AF) 2 of ER alpha and ER beta in the context of the Gal4 chimeric proteins; (3) they rapidly induce the nuclear immunodetection of ER alpha; (4) they regulate the expression of diverse estrogen target genes; (5) they compete with 17beta-estradiol for binding to ER alpha and ER beta; and--as a biological counterpart of the aforementioned abilities--(6) they exert stimulatory effects on the proliferation of MCF7 cells. Hence, the estrogenic activity of PIC and MYR might be considered at least as a potential factor in the association of red wine intake and breast tumors, particularly in postmenopausal women.

Menopause: a review of botanical dietary supplements.

Site Editor — Fri, 09 Jun 2006 04:14:55 -0700

Menopause: a review of botanical dietary supplements.: Am J Med. 2005 Dec 19;118(12 Suppl 2):98-108 Authors: Low Dog T

Since the release of the Women's Health Initiative (WHI) findings, an increasing number of dietary supplement products specifically targeting women in menopause have appeared in the American marketplace. This growth highlights the need for a critical evaluation of the tolerability and effectiveness of these products. The purpose of this article is to assess the evidence for safety and benefit of botanical monopreparations used for relief of menopause-related symptoms. The Cochrane Library and Medline databases were searched from January 1966 to October 2004, using a detailed list of terms related to botanicals and menopausal symptoms. Studies were considered eligible (1) if they were controlled trials of a botanical monopreparation administered orally for a minimum of 6 weeks to perimenopausal or postmenopausal women with hot flashes and (2) if they included a placebo or comparative treatment arm. Topical preparations, botanical combinations, and dietary interventions, such as soy food or protein, were not included. No language restrictions were imposed on the search. A total of 19 studies met the inclusion criteria. The majority of studies indicate that extract of black cohosh (Actaea racemosa L.) improves menopause-related symptoms; however, methodologic shortcomings in the trials were identified. To date, 4 case reports of possible hepatotoxicity have been published, although previous safety reviews suggest that black cohosh is well tolerated and that adverse events are rare when it is used appropriately. The results of 6 clinical studies on soy (Glycine max L.) isoflavone extracts are mixed. Moreover, the composition and dose of soy supplements varies widely across studies, making comparisons and definitive conclusions difficult. One study challenged the long-term safety of high-dose soy isoflavone extract (150 mg/day for 5 years) on the uterine endometrium. Clinical data from 5 controlled trials assessing the efficacy of semipurified isoflavone red clover (Trifolium pratense L.) leaf extracts to reduce hot flash frequency and severity or to relieve symptoms associated with the domains of the Greene Menopausal Symptom Scale are contradictory. The largest study showed no benefit for reducing symptoms associated with menopause for 2 different red clover isoflavone products compared with placebo. No significant adverse events have been reported in the literature. Single clinical trials do not support the use of dong quai (Angelica sinensis L.), ginseng (Panax ginseng C.A. Mey), or evening primrose seed oil (Oenothera biennis L.) for improving menopausal symptoms. We conclude that black cohosh extracts appear to ease menopausal symptoms; ongoing studies funded by the National Institutes of Health (NIH) will provide more definitive safety and efficacy data. Soy isoflavone extracts appear to have minimal to no effect, although definitive conclusions are difficult given the wide variation in product composition and dose. Long-term safety of higher dosage (150 mg/day) soy isoflavone extracts is uncertain. Semipurified isoflavone red clover leaf extracts have minimal to no effect in reducing menopausal symptoms. Dong quai, ginseng extract, and evening primrose seed oil appear to be ineffective in ameliorating menopausal symptoms at the dosages and in the preparations used in these studies.

Menopause: a review of botanical dietary supplements.

Site Editor — Fri, 09 Jun 2006 04:14:38 -0700

Menopause: a review of botanical dietary supplements.: Am J Med. 2005 Dec 19;118(12 Suppl 2):98-108 Authors: Low Dog T

Research opportunities for reducing the burden of menopause-related symptoms.

Site Editor — Fri, 09 Jun 2006 04:14:27 -0700

Research opportunities for reducing the burden of menopause-related symptoms.: Am J Med. 2005 Dec 19;118(12 Suppl 2):166-71 Authors: Sherman S, Miller H, Nerurkar L, Schiff I

The National Institutes of Health (NIH) State-of-the-Science (SoS) Conference on the Management of Menopause-Related Symptoms identified a number of important gaps in our understanding of the natural history of the menopausal transition and the etiology and course of menopause-related symptoms. Updated information is needed from prospective studies of reproductive aging in diverse populations of women, especially of younger women in their mid reproductive years, to better understand the underlying biology of ovarian aging as well as the etiology of conditions leading to premature spontaneous or surgical menopause. To facilitate this goal, a number of methodologic issues must be addressed, including the development of (1) consensus definitions of menopause-related terms and stages, and (2) standard measures and methods for assessing progression through the menopausal transition and related symptoms and outcomes. Estrogen therapy is highly efficacious in relieving menopausal symptoms and was the treatment of choice until 2002, when findings of unexpected harm from the Women's Health Initiative (WHI) were published. Consequently, there has been a burgeoning interest in a number of botanical products as well as other complementary and alternative medicine strategies, such as acupuncture, magnets, homeopathy, and behavioral regimens. However the benefits of most of these strategies are either very limited or equivocal, and related safety issues are poorly understood. Future research is needed to identify new efficacious strategies, to understand side effects and safety issues, and to provide new options to women who are burdened by bothersome menopause-related symptoms.

Alternative therapies for postmenopausal women.

Site Editor — Fri, 09 Jun 2006 04:12:39 -0700

Alternative therapies for postmenopausal women.: Int J Fertil Womens Med. 2005 May-Jun;50(3):101-14 Authors: Speroff L

Alternative therapies are being used by postmenopausal women in attempts to treat all of the complaints and medical conditions of the menopause. One-fifth of those who take prescription drugs for these indications also take herbal remedies and/or high-dose vitamins, most often without disclosing the fact to the physician. Although studies of alternative therapies are short-term and rarely focused on safety--let alone efficacy--in the long-term, there are many studies spread over the large number of substances involved. More than 130 studies, including meta-analyses, are reviewed in this article under the headings of phytoestrogens, especially from soy; therapies for hot flushes; and preventives for cardiovascular disease, osteoporosis, and breast cancer. Special attention is given to the recently recognized daidzein metabolite equol, and for the sake of completeness there are reviews of the unconventional, but not botanical, treatments estriol, transdermal progesterone, and dehydroepiandrosterone. The total picture produced by conscientious review of the studies is bleak overall, but there seems to be good reason to pursue the possibilities inherent in soy protein with phytoestrogens in populations of women who endogenously produce equol.

The Herbal Alternatives for Menopause (HALT) Study: background and study design.

Site Editor — Fri, 09 Jun 2006 04:12:22 -0700

The Herbal Alternatives for Menopause (HALT) Study: background and study design.: Maturitas. 2005 Oct 16;52(2):134-46 Authors: Newton KM, Reed SD, Grothaus L, Ehrlich K, Guiltinan J, Ludman E, Lacroix AZ

We designed a randomized double-blind randomized trial to examine the short and long-term effects of alternative approaches commonly used to manage menopause symptoms. Women were randomly assigned to: (1) black cohosh 160 mg daily; (2) multibotanical (50 mg black cohosh, alfalfa, chaste tree, dong quai, false unicorn, licorice, oats, pomegranate, Siberian ginseng, boron) four capsules daily; (3) multibotanical plus telephone counseling to increase dietary soy; (4) conjugated equine estrogen 0.625 mg +/- 2.5 mg medroxyprogesterone acetate; or (5) placebo. Working with a skilled CAM provider helped us choose interventions that reflected naturopathic practices worthy of study. Mass mailing, with careful tracking and rapid responses to recruitment rates, was an effective and cost-effective recruitment strategy. Creativity was necessary to construct methods for blinding capsules and the dietary soy intervention. Independent testing of herbal products was vital to confirming their constituents. The Data and Safety and Monitoring Committee, and project officers at the funding agency, were critical partners in designing responses to unanticipated Women's Health Initiative findings published during the HALT trial. Careful monitoring of adverse events may provide much needed information about side effects of herbal products and supplements. Despite inherent challenges, the study of alternative therapies for menopause symptoms is a rewarding and important area deserving of further inquiry.

Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women.

Site Editor — Fri, 09 Jun 2006 04:03:28 -0700

Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production.: Am J Clin Nutr. 2005 Dec;82(6):1260-8; quiz 1365-6 Authors: Hall WL, Vafeiadou K, Hallund J, Bügel S, Koebnick C, Reimann M, Ferrari M, Branca F, Talbot D, Dadd T, Nilsson M, Dahlman-Wright K, Gustafsson JA, Minihane AM, Williams CM

BACKGROUND: Dietary isoflavones are thought to be cardioprotective because of their structural similarity to estrogen. The reduction of concentrations of circulating inflammatory markers by estrogen may be one of the mechanisms by which premenopausal women are protected against cardiovascular disease. OBJECTIVE: Our aim was to investigate the effects of isolated soy isoflavones on inflammatory biomarkers [von Willebrand factor, intracellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), E-selectin, monocyte chemoattractant protein 1, C-reactive protein (CRP), and endothelin 1 concentrations]. Differences with respect to single-nucleotide polymorphisms in selected genes [estrogen receptor alpha (XbaI and PvuII), estrogen receptor beta [ERbeta (AluI) and ERbeta[cx] (Tsp509I), endothelial nitric oxide synthase (Glu298Asp), apolipoprotein E (Apo E2, E3, and E4), and cholesteryl ester transfer protein (TaqIB)] and equol production were investigated. DESIGN: One hundred seventeen healthy European postmenopausal women participated in this randomized, double-blind, placebo-controlled, crossover dietary intervention trial. Isoflavone-enriched (genistein-to-daidzein ratio of 2:1; 50 mg/d) or placebo cereal bars were consumed for 8 wk, with a washout period of 8 wk between the crossover. Plasma inflammatory factors were measured at 0 and 8 wk of each study arm. RESULTS: Isoflavones improved CRP concentrations [odds ratio (95% CI) for CRP values >1 mg/L for isoflavone compared with placebo: 0.43 (0.27, 0.69)]; no significant effects of isoflavone treatment on other plasma inflammatory markers were observed. No significant differences in the response to isoflavones were observed according to subgroups of equol production. Differences in the VCAM-1 response to isoflavones and to placebo were found with ERbeta AluI genotypes. CONCLUSION: Isoflavones have beneficial effects on CRP concentrations, but not on other inflammatory biomarkers of cardiovascular disease risk in postmenopausal women, and may improve VCAM-1 in an ERbeta gene polymorphic subgroup.

[Primary and secondary prevention of cardiovascular events through hormone replacement therapy (HRT)]

Site Editor — Fri, 09 Jun 2006 04:02:47 -0700

[Primary and secondary prevention of cardiovascular events through hormone replacement therapy (HRT)]: Wien Med Wochenschr. 2005 Sep;155(17-18):397-403 Authors: Pilz H

A recently (2002) published, randomised, double blind placebo controlled trial of hormone replace ment therapy (HRT), the Women's Health Initiative (WHI), is not consistent with the decrease in cardiovascular disease under CEE/HPA seen in observational primary prevention studies like the Nurses' Health Study. Baseline characteristics of participants like age, body mass index, years since menopause and preexistent cardiovascular diseases may be responsible for the lack of benefit seen in this trial. Clinical outcome data of HRT from randomised trials in secondary prevention of cardiovasular diseases are limited. The first prospective, randomised placebo controlled trial, the Heart and Estrogen/Progestin Replacement Study (HERS) in secondary prevention did not show any difference in CHD events between treatment groups and placebo during a follow up of 4.1 years. However, an increased risk of CHD was seen especially during the first year on HRT, subsequent years showed a decrease in event rate compared with never-users. One explanation for this lack of benefit may be a bi-directional effect of estrogen - early risk and late benefit - especially in an elderly study population with established atherosclerotic lesions. In postmenopausal women, estrogen replacement therapy affects LDL- and HDL-cholesterol levels favorably, causes vasodilatation by activating NOS, inhibits platelet aggregation and proinflammatory cell adhesion on endothelial cells of vascular wall. Estrogen can affect the cardiovascular system adversely by increasing triglycerid levels, CPR and proinflammatory cytokines like tumor necrosis factor alpha (TNF-alpha). Alternatives to HRT like phytoestrogens act via estrogen alpha and beta receptor modulation. Phytoestrogens may lower LDL-cholesterol levels without increasing triglyceride levels, they have shown antioxidannt properties as well as favorable effects on vascular reactivity. The importance of HRT and phytoestrogens in primary and secondary prevention of cardiovascular disease remains to be established.

Muscle damage induced by black cohosh (Cimicifuga racemosa).

Site Editor — Fri, 09 Jun 2006 03:53:42 -0700

Muscle damage induced by black cohosh (Cimicifuga racemosa).: Phytomedicine. 2006 Jan; 13(1-2): 115-8 Minciullo PL, Saija A, Patafi M, Marotta G, Ferlazzo B, Gangemi S

Extracts of black cohosh (Cimicifuga racemosa) are commonly used for the treatment of symptoms associated with menopause. Adverse events with black cohosh are rare, mild and reversible. A few number of serious adverse events, including hepatic and circulatory conditions, have been also reported, but without a clear causality relationship. We report the case of a woman with severe asthenia and very high blood levels of creatine phosphokinase and lactate dehydrogenase. The patient referred to take a dietary supplement derived from black cohosh for ameliorating menopause vasomotor symptoms. To exclude a possible involvement of this product, the patient was suggested to discontinue this therapy. After suspicion the patient showed a progressive normalization of biochemical parameters and improvement of clinical symptoms. We can hypothesise a causative role for black cohosh in the muscle damage observed in this patient. Factors suggesting an association between black cohosh and the observed myopathy included the temporal relationship between use of herbal product and asthenia and the absence of other identified causative factors. Rechallenge with the suspected agent was inadvisable for ethic reasons because of the risk of a serious relapse. This is the first time that asthenia associated with high muscle enzymes serum levels by black cohosh has been reported. In our opinion, this report is of interest because of the widespread diffusion of use of black cohosh as an alternative medicine for relief from menopausal symptoms.

Do soy isoflavones cause endometrial hyperplasia?

Site Editor — Fri, 09 Jun 2006 03:50:12 -0700

Do soy isoflavones cause endometrial hyperplasia?: Nutr Rev. 2005 Nov;63(11):392-7 Authors: Mahady GB

For many years, hormone replacement therapy (HRT) was considered the gold standard for the symptomatic treatment of menopause. Clinical trials have found that HRT reduces the symptoms of hot flashes and sweating, while also decreasing vaginal dryness and urinary tract infections. HRT has also been shown to be protective against colon cancer (37%) and hip fractures (34%). However, recent findings from the Women's Health Initiative (WHI) have revealed that long-term HRT may actually lead to an increase in heart disease (29%), breast cancer (26%) and other adverse events, such as stroke (41%). Consequently, many women in the United States and abroad are actively looking for alternative treatments for menopause, including botanical dietary supplements.

The pharmacognosy of Humulus lupulus L. (hops) with an emphasis on estrogenic properties.

Site Editor — Fri, 09 Jun 2006 03:45:41 -0700

The pharmacognosy of Humulus lupulus L. (hops) with an emphasis on estrogenic properties.: Phytomedicine. 2006 Jan;13(1-2):119-31 Authors: Chadwick LR, Pauli GF, Farnsworth NR

As the population ages, there is an ever-increasing need for therapeutic agents that can be used safely and efficaciously to manage symptoms related to postmenopausal estrogen deficiency. Endogenous estrogens, e.g., 17beta-estradiol, of exogenous mammalian origin, e.g., horses, have long been used to manage such symptoms. There are more than 20 different classes of phytochemicals that have demonstrated affinity for human estrogen receptors in vitro. Some studies on exogenous estrogenic substances of botanical origin (phytoestrogens), such as standardized formulations of plant extracts with in vitro and in vivo estrogenic activity from soy (Glycine max Merill.) and red clover (Trifolium pratense L.), suggest clinical efficacy. Few clinical data for phytoestrogens other than isoflavonoids are available. In an exhaustive review of the literature through 2003, only two clinical trials were identified that were designed to evaluate the effect of hops (Humulus lupulus L.) on symptoms related to menopause. Folkloric, chemical, and biological literature relating primarily to the use of hops for their estrogenic activity, and two human clinical trials, are reviewed.

Uncommon trajectories: steroid hormones, Mexican peasants, and the search for a wild yam.

Site Editor — Fri, 09 Jun 2006 03:29:20 -0700

Uncommon trajectories: steroid hormones, Mexican peasants, and the search for a wild yam.: Stud Hist Philos Biol Biomed Sci. 2005 Dec;36(4):743-760 Authors: Soto Laveaga G

This article analyzes how evolving pharmaceutical technology, chemical advances, and world politics created the need for an abundant and cheap supply of steroids, and how decisions made in faraway laboratories ultimately determined that a Mexican yam, barbasco, was the best possible raw material. Following this discovery, this article explores how barbasco's exploitation impacted on the Mexican countryside and specifically the men and women hired to gather wild yams. In analyzing, for example, the peasant organizations that emerged, the use of chemical terms by barely literate peasants, and the Mexican government's political strategy to control rural unrest by controlling barbasco production one begins to understand the unexpected consequences of the global search for medicinal plants. In this particular case, the merging of science and peasant life reshuffled social hierarchies in the countryside, granted monetary value to an erstwhile 'weed', and gave a novel reinterpretation to laboratory knowledge and its (social) uses.

Hypertensive crisis associated with high dose soy isoflavone supplementation in a post-menopausal woman: a case report

Site Editor — Fri, 09 Jun 2006 03:26:05 -0700

Hypertensive crisis associated with high dose soy isoflavone supplementation in a post-menopausal woman: a case report:

Background: Isoflavones are gaining popularity as alternatives to hormone replacement therapy. However, few guidelines exist to inform the public as to an appropriate dose. This case involves a postmenopausal woman who experienced a hypertensive crisis while consuming a high-dose isoflavone supplement as part of a research protocol.Case PresentationThe participant was part of a placebo-controlled crossover trial to investigate the potential synergism of the antioxidant activity of soy isoflavones and vitamin C. Upon entry into the study, this healthy, well-nourished, normotensive postmenopausal woman (51 years old), consumed the first of four randomly assigned treatments (500 mg vitamin C plus 5 mg/kg body weight soy isoflavones). During this treatment, the participant's systolic blood pressure spiked to a recorded 226/117 mmHg, necessitating medical intervention and discontinuation of study participation. Two plausible mechanisms for this hypertensive crisis are discussed.
Conclusion: Due to the availability and increasing popularity of soy supplements, practitioners should be aware of the potential side effects associated with their use. Practitioners counseling clients who are consuming soy isoflavone supplements should advise them that elevated blood pressure may be a potential side-effect to consider and monitor.