Effects of Dietary Phytoestrogens on Hormones throughout a Human Lifespan: A Review.

Dietary phytoestrogens are bioactive compounds with estrogenic activity. With the growing popularity of plant-based diets, the intake of phytoestrogen-rich legumes (especially soy) and legume-derived foods has increased. Evidence from preclinical studies suggests these compounds may have an effect on hormones and health, although the results of human trials are unclear. The effects of dietary phytoestrogens depend on the exposure (phytoestrogen type, matrix, concentration, and bioavailability), ethnicity, hormone levels (related to age, sex, and physiological condition), and health status of the consumer. In this review, we have summarized the results of human studies on dietary phytoestrogens with the aim of assessing the possible hormone-dependent outcomes and health effects of their consumption throughout a lifespan, focusing on pregnancy, childhood, adulthood, and the premenopausal and postmenopausal stages. In pregnant women, an improvement of insulin metabolism has been reported in only one study. Sex hormone alterations have been found in the late stages of childhood, and goitrogenic effects in children with hypothyroidism. In premenopausal and postmenopausal women, the reported impacts on hormones are inconsistent, although beneficial goitrogenic effects and improved glycemic control and cardiovascular risk markers have been described in postmenopausal individuals. In adult men, different authors report goitrogenic effects and a reduction of insulin in non-alcoholic fatty liver patients. Further carefully designed studies are warranted to better elucidate the impact of phytoestrogen consumption on the endocrine system at different life stages.

Predictive Value of Molecular Subtypes in Premenopausal Women with Hormone Receptor-positive Early Breast Cancer: Results from the ABCSG Trial 5.

PURPOSE: To assess the predictive value of molecular breast cancer subtypes in premenopausal patients with hormone receptor-positive early breast cancer who received adjuvant endocrine treatment or chemotherapy. EXPERIMENTAL DESIGN: Molecular breast cancer subtypes were centrally assessed on whole tumor sections by IHC in patients of the Austrian Breast and Colorectal Cancer Study Group Trial 5 who had received either 5 years of tamoxifen/3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Luminal A disease was defined as Ki67 <20% and luminal B as Ki67 ≥20%. The luminal B/HER2-positive subtype displayed 3+ HER2-IHC or amplification by ISH. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic factors. RESULTS: 185 (38%), 244 (50%), and 59 (12%) of 488 tumors were classified as luminal A, luminal B/HER2-negative and luminal B/HER2-positive, respectively. Luminal B subtypes were associated with poor outcome. Patients with luminal B tumors had a significantly shorter RFS [adjusted HR for recurrence: 2.22; 95% confidence interval (CI), 1.41-3.49; P = 0.001] and OS (adjusted HR for death: 3.51; 95% CI, 1.80-6.87; P < 0.001). No interaction between molecular subtypes and treatment was observed (test for interaction: P = 0.84 for RFS; P = 0.69 for OS). CONCLUSIONS: Determination of molecular subtypes by IHC is an independent prognostic factor for recurrence and death in premenopausal women with early-stage, hormone receptor-positive breast cancer but is not predictive for outcome of adjuvant treatment with tamoxifen/goserelin or CMF.See related commentary by Hunter et al., p. 5543.

Changes in bone mineral density during 5 years of adjuvant treatment in premenopausal breast cancer patients.

PURPOSE: Adjuvant treatment for breast cancer in postmenopausal women is a risk factor for bone loss. However, the association between bone mineral density (BMD) changes in premenopausal breast cancer patients and various adjuvant treatment regimens is not well characterized. In this study, we evaluated the changes in BMD according to adjuvant treatment in premenopausal women with breast cancer. METHODS: Between 2006 and 2010, BMD data of 910 premenopausal women with breast cancer before operation and 1, 2, 3.5, and 5 years post-operation were retrospectively analyzed. The patients were divided according to the type of treatment: observation (O), tamoxifen (T), chemotherapy (C), C followed by T (C → T), and gonadotropin-releasing hormone (GnRH) agonist with T (G + T). RESULTS: After 5 years of follow-up, BMD changes were similar between the T and O groups (all p > 0.05). Within 1 year of treatment, the C group showed the most significant BMD loss. The C → T and G + T groups showed more significant BMD loss in the lumbar spine and femur than the O and T groups (both p < 0.001, both). After 1 year of treatment, BMD loss in the lumbar spine was significantly greater in the C → T and G + T groups than in the T group; this tendency was maintained for 5 years of treatment (all p < 0.005). CONCLUSION: Premenopausal women who received adjuvant treatment which induced menopause showed significant bone loss which lasted for 5 years. Although no significant difference was observed between the O and T groups, tamoxifen treatment during chemotherapy or GnRH agonist treatment might prevent bone loss.

Prevention of breast cancer treatment-induced bone loss in premenopausal women treated with zoledronic acid: Final 5-year results from the randomized, double-blind, placebo-controlled ProBONE II trial.

PURPOSE: Premenopausal women receiving chemotherapy or endocrine treatment for early breast cancer are at increased risk for cancer treatment induced bone loss (CTIBL). The aim of the randomized, double-blind ProBONE II trial was to investigate whether a 2-year adjuvant treatment with 4 mg intravenous zoledronic acid (ZOL) every 3 months versus placebo would prevent CTIBL after a five-year period. METHODS: Thirty-one of the 34 participants in the ZOL arm and thirty-four of the 36 participants in the placebo arm were followed-up to the 5-year visit and completed the study as planned. The changes in Bone Mass Density (BMD) were assessed at baseline and each visit after treatment initiation. RESULTS: After 24 months, BMD at the lumbar spine showed a 2.9% increase in patients treated with ZOL vs. a 7.1% decrease in placebo-treated participants compared to baseline (p < 0.001). Over the 60-month study period, we found a decrease of 2.2% vs. 7.3% in the BMD at the lumbar spine in patients receiving ZOL and placebo respectively (p < 0.001). Over the 60-month study period, BMD in the placebo arm showed a continuous decrease at all sites (p < 0001), whereas patients treated with ZOL reached baseline BMD-values at the femoral neck and total hip. CONCLUSIONS: In ProBone II, a 2-year treatment with ZOL 4 mg intravenous every 3 months prevented cancer treatment induced bone loss in premenopausal women with breast cancer and maintained the BMD up to 3 years post-treatment.

Uncertainty on the effectiveness and safety of rivaroxaban in premenopausal women with atrial fibrillation: empirical evidence needed.

BACKGROUND: Novel anticoagulations (NOACs) are increasingly prescribed for the prevention of stroke in premenopausal women with atrial fibrillation. Small studies suggest NOACs are associated with a higher risk of abnormal uterine bleeds than vitamin K antagonists (VKAs). Because there is no direct empirical evidence on the benefit/risk profile of rivaroxaban compared to VKAs in this subgroup, we synthesize available indirect evidence, estimate decision uncertainty on the treatments, and assess whether further research in premenopausal women is warranted. METHODS: A Markov model with annual cycles and a lifetime horizon was developed comparing rivaroxaban (the most frequently prescribed NOAC in this population) and VKAs. Clinical event rates, associated quality adjusted life years, and health care costs were obtained from different sources and adjusted for gender, age, and history of stroke. A Monte Carlo simulation with 10,000 iterations was then performed for a hypothetical cohort of premenopausal women, estimated to be reflective of the population of premenopausal women with AF in The Netherlands. RESULTS: In the simulation, rivaroxaban is the better treatment option for the prevention of ischemic strokes in premenopausal women in 61% of the iterations. Similarly, this is 98% for intracranial hemorrhages, 24% for major abnormal uterine bleeds, 1% for minor abnormal uterine bleeds, 9% for other major extracranial hemorrhages, and 23% for other minor extracranial hemorrhages. There is a 78% chance that rivaroxaban offers the most quality-adjusted life years. The expected value of perfect information in The Netherlands equals 122 quality-adjusted life years and 22 million Euros. CONCLUSIONS: There is a 22% risk that rivaroxaban offers a worse rather than a better benefit/risk profile than vitamin K antagonists in premenopausal women. Although rivaroxaban is preferred over VKAs in this population, further research is warranted, and should preferably take the shape of an internationally coordinated registry study including other NOACs.

Evaluation of Antioxidant Intakes in Relation to Inflammatory Markers Expression Within the Normal Breast Tissue of Breast Cancer Patients.

Chronic inflammation may be a causative factor in breast cancer. One possible underlying mechanism is the generation of oxidative stress, which may favor tumorigenic processes. Antioxidant consumption may, therefore, help reduce tissue inflammation levels. However, few studies have explored this relation in breast tissue. We aimed to evaluate correlations between antioxidant (vitamin A/retinol, vitamin C, vitamin E, ß-carotene, α-carotene, lycopene, lutein/zeaxanthin, ß-cryptoxanthin, selenium, and zinc) intakes and protein expression levels of interleukin (IL)-6, tumor necrosis factor-α, C-reactive protein, cyclooxygenase-2, leptin, serum amyloid A1, signal transducer and activator of transcription 3, IL-8, IL-10, lactoferrin, and transforming growth factor-ß measured in the normal breast tissue of 160 women diagnosed with breast cancer. Antioxidant intakes were collected using a self-administered food frequency questionnaire. Inflammation marker expression was assessed by immunohistochemistry. Correlations between antioxidant intakes and inflammatory marker expression were evaluated using Spearman's partial correlation coefficients ( r) for all women and for premenopausal and postmenopausal women separately. After Bonferroni correction, negative correlations were observed between dietary ß-tocopherol and IL-10 expression in all women combined ( r = -0.26, P = .003) and among postmenopausal women ( r = -0.39, P = .003). For all women, a negative correlation was found between total zinc intakes and IL-10 ( r = -0.26, P = .002). Among postmenopausal women, dietary selenium intake was negatively correlated with the expression of lactoferrin ( r = -0.39, P = .003). No associations were observed in premenopausal women. Our findings suggest that consumption of specific antioxidants, including ß-tocopherol, zinc, and selenium, may act on the breast tissue through mechanisms affecting the expression of some inflammation markers, particularly among postmenopausal women.

FSH Levels Predict Bone Loss in Premenopausal Women Treated for Breast Cancer More Than One Year After Treatment.

CONTEXT: Biomarkers to predict bone loss in premenopausal women after breast cancer treatment have not been examined. OBJECTIVE: To determine whether baseline FSH predicts subsequent bone loss. DESIGN: Secondary data analysis of the Exercise for Bone Health: Young Breast Cancer Survivors study, in which women were randomized to a 12-month exercise program or monthly health newsletter. SETTING: Community dwelling women. PARTICIPANTS: A total of 206 women age less than or equal to 55 years at breast cancer diagnosis who had received adjuvant chemotherapy and were at least 1 year after diagnosis. INTERVENTION: Serum collected at baseline (an average of 302 ± 148 d after completing chemotherapy) was analyzed for FSH. MAIN OUTCOME MEASURE: Change in bone mineral density. RESULTS: In linear regression models, baseline FSH levels predicted bone loss over the ensuing 12 months at the lumbar spine and femoral neck including after adjustment for age, ethnicity, treatment group (exercise vs control), baseline bone density, and high-sensitivity C-reactive protein (P < .001). In multiply adjusted models, the 12-month rate of change in bone density was +0.007% in the lowest tertile of FSH (FSH = 9 ± 7 IU/L, mean ± SD), -0.96% in the middle tertile (mean FSH = 41 ± 11 IU/L), and -2.2% in the highest tertile (mean FSH = 86 ± 19 IU/L), P for trend <.001. CONCLUSIONS: Among premenopausal women with breast cancer treated with chemotherapy, baseline FSH levels are strongly associated with subsequent bone loss. Further studies are needed to establish the optimal timing of FSH measurement in relation to breast cancer treatment and to investigate potential strategies to prevent bone loss.

Efficacy and safety of Labisia pumila var alata water extract among pre- and postmenopausal women.

This study evaluated the effectiveness and safety of Labisia pumila var alata (L. pumila) water extract for improving quality of life, cardiovascular and hormonal balance. A randomized, double-blind, placebo-controlled, parallel group, 16-week study in healthy pre- and postmenopausal women aged 40-60 years was conducted in Kelantan, Malaysia. The subjects were randomized to 400 mg propriety extract of L. pumila or placebo. A Women's Health Questionnaire was used to assess quality of life. Repeated-measures analysis of variance was used to evaluate the data. A total of 197 subjects (L. pumila: n=102 and placebo: n=95) were analyzed. Subjects in the herbal group showed improved memory/concentration, vasomotor symptoms, menstrual symptoms, and sleep problems by 8.3%, 15.9%, 11.8%, and 31.0%, respectively. The greatest improvement was observed for the question: "I get frightened or panic feelings for apparently no reason at all" with a 53% decrease as compared with placebo. Improvements were also seen in the cardiovascular parameters, and the safety profiles were normal. Postmenopausal women supplemented with L. pumila showed no changes in gynecological relevant hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), and 17ß-Estradiol. Water extract of L. pumila was shown to be safe and effective for improving several parameters of quality of life and cardiovascular risks factors (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C]).

Effect of adjuvant endocrine therapy on hormonal levels in premenopausal women with breast cancer: the ProBONE II study.

Endocrine therapy (ET) is a key treatment modality in hormone receptor positive (HR+) early breast cancer (BC) patients. Although the anticancer activity of adjuvant ET + zoledronic acid (ZOL) has been investigated, the potential effects of ET ± ZOL on endocrine hormones in premenopausal women with HR+ early BC are not well understood. ProBONE II was prospective, double-blind, randomized controlled trial. Premenopausal patients with histologically confirmed invasive BC with no evidence of metastases and a T score >-2.5 received ET ± ZOL 4 mg every 3 months for 2 years. Serum levels of estradiol (E2), follicle-stimulating hormone, anti-muellerian hormone (AMH), inhibins A and B, sex hormone-binding globulin, parathyroid hormone, total testosterone, and vitamin D were evaluated at baseline and at every scheduled visit. Of 71 women enrolled, 70 were evaluable (n = 34, ZOL; n = 36, placebo). No statistically significant differences were observed in hormone levels, except E2 and AMH, which showed minor differences. These included decreases in serum E2 levels, which reached a nadir after 3 and 9 months in placebo and ZOL groups, respectively, and decrease in serum AMH levels throughout the study with ZOL, but remained constant with placebo after 6 months. Adverse events in ZOL-treated group were influenza-like illness (32.4 %), bone pain (32.4 %), chills (20.6 %), and nausea (23.5 %). ET ± ZOL was well tolerated. This study showed no influence of ZOL on hormonal level changes that accompany ET, supporting inclusion of ZOL in adjuvant therapy for premenopausal women with HR + BC.

Bone mineral density following surgical oophorectomy and tamoxifen adjuvant therapy for breast cancer.

BACKGROUND: In premenopausal women treated for breast cancer, loss of bone mineral density (BMD) follows from menopause induced by chemotherapy or loss of ovarian function biochemically or by surgical oophorectomy. The impact on BMD of surgical oophorectomy plus tamoxifen therapy has not been described. METHODS: In 270 Filipino and Vietnamese premenopausal patients participating in a clinical trial assessing the impact of the timing in the menstrual cycle of adjuvant surgical oophorectomy on breast cancer outcomes, BMD was measured at the lumbar spine and femoral neck before this treatment, and at 6, 12, and 24 months after surgical and tamoxifen therapies. RESULTS: In women with a pretreatment BMD assessment and at least 1 other subsequent BMD assessment, no significant change in femoral neck BMD was observed over the 2-year period (-0.006 g/cm2 , -0.8%, P = .19), whereas in the lumbar spine, BMD fell by 0.045 g/cm2 (4.7%) in the first 12 months (P < .0001) and then began to stabilize. CONCLUSIONS: Surgically induced menopause with tamoxifen treatment is associated with loss of BMD at a rate that lessens over 2 years in the lumbar spine and no significant change of BMD in the femoral neck.

Incidence of chemotherapy-induced amenorrhea in premenopausal women treated with adjuvant FOLFOX for colorectal cancer.

BACKGROUND: Studies indicate that the incidence of young women diagnosed with colorectal cancer is rising, thus there is an increasing number of female colorectal cancer survivors of premenopausal and child-bearing age. Adjuvant FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy is the most widely used standard treatment for stage III and high-risk stage II colon cancer. We evaluated the incidence of FOLFOX-induced amenorrhea in women age 50 and younger treated with adjuvant therapy for colorectal cancer. PATIENTS AND METHODS: A search of pharmacy records identified 119 women age 50 or younger who received adjuvant FOLFOX chemotherapy at Memorial Sloan-Kettering for stage II or III colorectal cancer from January 2002 and January 2011. Eligible patients were mailed an anonymous questionnaire. The returned surveys were reviewed and the results tallied. RESULTS: Seventy-three patients returned the questionnaire. Twenty-four patients were excluded from analysis: 19 were treated with pelvic radiotherapy, 2 patients had undergone bilateral oophorectomy, 2 had a hysterectomy, and 1 stopped menstruating before diagnosis. Forty-nine patient responses were analyzed. In total, 41% (n = 20) experienced amenorrhea during chemotherapy. Sixteen percent had persistent amenorrhea 1 year after completion of chemotherapy. The incidence of amenorrhea during chemotherapy trended higher in patients aged older than 40 compared with patients aged 40 and younger (59% vs. 31% [P = .075]). There was no statistically significant difference in persistent amenorrhea between the 2 age groups (24% vs. 13%; P = .42). CONCLUSION: In this retrospective series, there appears to be a trend toward FOLFOX induced amenorrhea during chemotherapy increasing with age. Twenty-four percent of women older than the age of 40 were found to have persistent amenorrhea after FOLFOX therapy. Because of the small sample size, the study is underpowered to detect a statistically significant difference between older and younger patients. Prospective studies are planned to further characterize the effect of FOLFOX on early menopause and fertility.

The effect of vitamin A supplementation on thyroid function in premenopausal women.

OBJECTIVE: Vitamin A and its retinoid derivates play an important role in regulation of normal growth and development. Vitamin A has been shown to regulate thyroid hormone metabolism and inhibit thyroid-stimulating hormone (TSH) secretion via down regulation of TSH-ß gene expression; however, the effect of vitamin A on thyroid function in obese individuals who are at higher risk of subclinical hypothyroidism is still unclear. In the present study we investigate the impact of vitamin A supplementation on thyroid function in obese women. METHOD: A 4-month randomized, double blind controlled trial was conducted among 84 healthy women aged 17-50 years old: 56 were obese (body mass index [BMI] 30-35 kg/m(2)) and 28 were nonobese (BMI 18.5-24.9 kg/m(2)). Obese women were randomly allocated to receive either vitamin A (25,000 IU/d retinyl palmitate) or placebo. Nonobese women received vitamin A. At baseline and 4 months after intervention, serum concentrations of TSH, total thyroxine (T4), total triiodothyronine (T3), retinol-binding protein (RBP), and transthyretin (TTR) were measured. RESULTS: Baseline concentrations of thyroid hormones, RBP and TTR were not significantly different between groups. Vitamin A caused a significant reduction in serum TSH concentrations in obese (p = 0.004) and nonobese (p = 0.001) groups. Serum T3 concentrations also increased in both obese and nonobese vitamin A-treated groups (p < 0.001). Serum T4 decreased in all 3 groups after treatment. The results showed a significant reduction in serum RBP in the obese group after vitamin A supplementation (p = 0.007), but no significant change was seen in serum TTR. CONCLUSIONS: Serum TSH concentrations in vitamin A-treated subjects were significantly reduced; therefore, vitamin A supplementation might reduce the risk of subclinical hypothyroidism in premenopausal women.

Red clover (Trifolium pratense) isoflavones and serum homocysteine in premenopausal women: a pilot study.

BACKGROUND: There is limited information on the effect of isoflavones on homocysteine concentrations, a risk factor for a number of chronic diseases. METHODS: Twenty-three premenopausal women participated in a double-blind, randomized, parallel study for four menstrual cycles. Subjects consumed either placebo or purified red clover (Trifolium pratense) isoflavone (86 mg/day) tablets. Blood samples were collected weekly during cycles 1, 3, and 4 for determination of serum folate and total homocysteine concentrations. Dietary intake was monitored monthly. RESULTS: Concentrations of folate and homocysteine in serum did not change significantly in either group, and there were no significant differences observed between the follicular and luteal phases of the menstrual cycle. The participants' dietary records indicated that nutrient intake was constant, and compliance was confirmed by analysis of urinary isoflavone concentrations and tablet counts in returned containers. CONCLUSIONS: These results suggest that in the absence of any dietary modification, supplementation with purified isoflavones that are predominantly methoxylated has no effect on serum homocysteine or folate in premenopausal women.

Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer.

OBJECTIVE: To assess the safety and tolerability of a standardized 40 mg red clover isoflavone dietary supplement (Promensil, Novogen) in women with a family history of breast cancer to evaluate the feasibility of using the supplement for prevention of breast cancer in healthy women. STUDY DESIGN: Healthy women aged 35-70 years (n = 401) with at least one first-degree relative with breast cancer received red clover isoflavones or placebo for three years in a randomized, double-blind, placebo-controlled pilot trial. Participants were assessed clinically and blood samples taken for biochemical analysis every six months. In addition, study participants underwent mammography, bone density and transvaginal ultrasound (postmenopausal women only) once per year. RESULTS: No significant differences in breast density, endometrial thickness, serum cholesterol, follicle stimulating hormone levels and bone mineral density were detected between those taking red clover isoflavones and placebo. In postmenopausal women, some significant differences in bone marker levels were seen between active and placebo groups, at six months and at 12 months. The adverse event profile was similar across all red clover isoflavone and placebo groups. CONCLUSION: This three-year study supports the growing body of evidence that treatment with red clover isoflavones is safe and well tolerated in healthy women. Supplements containing red clover isoflavones did not adversely affect breast density, skeletal strength or cardiovascular status. In postmenopausal women, endometrial status was not adversely affected. The adverse event profile was similar between red clover isoflavones, and placebo and endocrine status did not differ.

Effect of herbal Ephedra sinica and Evodia rutaecarpa on body composition and resting metabolic rate: a randomized, double-blind clinical trial in Korean premenopausal women.

BACKGROUND: As obesity is becoming an epidemic, diet programs, including low-calorie diets, are continuously being developed. It is generally believed that a low-calorie diet is commonly followed by a resting metabolic rate decrease and ultimate weight regain. Ephedra sinica and evodia rutaecarpa are known to have sympathomimetic and anti-obesity effects. DESIGN AND OBJECTIVE: This study was a prospective; double-blinded, randomized and placebo-controlled clinical trial to evaluate the effects of ephedra sinica and evodia rutaecarpa on resting metabolic rate (RMR), body composition and short-term safety in obese Korean premenopausal women on a low-calorie diet. METHODS: One hundred and twenty-five otherwise healthy obese women (body mass index > or =25 kg/m(2)) were recruited and randomly assigned to three groups: ephedra group (n = 41), evodia group (n = 45) and placebo group (n = 39). Subjects were administered ephedra extract in capsules (pseudo-ephedrine 31.52 mg) or evodia extract in capsules (evodiamine 6.75 mg, rutaecarpine 0.66 mg) or placebo capsules as well as participating in a low-calorie diet for 8 weeks. Resting metabolic rate and body composition were measured at baseline, 4 and 8 weeks. Basic serum tests were performed to evaluate the short-term safety and lipid-lowering effects of the herbs. RESULTS: All three groups showed significant body mass index (BMI) decreases, probably due to the low-calorie diet. Among the groups, the most prominent BMI-reducing effect was seen in the ephedra group. In RMR, no significant change in any group or significant difference among the groups was found. No significant adverse effects were observed in serum tests or in the self-questionnaire. CONCLUSION: Ephedra combined with a low-calorie diet was effective in reducing BMI. RMR change was not compensated for by the herbal medicines tried. RMR change seemed to be affected by constitution and body composition rather than by medicine. Ephedra and evodia were proven to be safe for short-term use in the herbal form.

The use of herbal and other non-vitamin, non-mineral supplements among pre- and post-menopausal women in Ontario.

BACKGROUND: Herbal or other non-vitamin, non-mineral (NVNM) supplements are used by many Canadians, and are of public health significance given potential health effects. The majority of supplement users are women, yet there are limited data on their pattern of use. Ontario women were surveyed about their use of NVNM supplements, including those for women's health, and characteristics associated with use were examined. METHODS: 3,423 randomly selected Ontario households were telephoned to identify eligible women (25-65 years). Of the 1,741 identified, 800 agreed to participate and were mailed a self-administered questionnaire querying NVNM supplement use and health-related characteristics. Prevalence of use, duration, and reasons for use were calculated; distributions of respondent characteristics were tabulated and associations with supplement use were assessed. RESULTS: 478 women (27%) completed questionnaires; 64% reported ever, and 34% reported current use of NVNM supplements. Echinacea was the most frequently used, followed by evening primrose, garlic, and camomile; supplements were used for less than one year. Alleviation of symptoms and prevention of illness were two primary reasons for taking NVNM supplements. 49% reported ever, and 37% reported current use of supplements for women's health, and for reasons similar to other NVNM supplements. High body mass index (> or =30.0 kg/m2) was associated with more supplement use, and visiting a physiotherapist in the past year was associated with less. CONCLUSION: Findings suggest a high level of NVNM supplement use among Ontario women, possibly associated with certain health-related characteristics. This has important public health implications considering possible benefits and/or interactions with conventional medications.

Implications of phytoestrogen intake for breast cancer.

Phytoestrogens are a group of plant-derived substances that are structurally or functionally similar to estradiol. Interest in phytoestrogens has been fueled by epidemiologic data that suggest a decreased risk of breast cancer in women from countries with high phytoestrogen consumption. Women with a history of breast cancer may seek out these "natural" hormones in the belief that they are safe or perhaps even protective against recurrence. Interpretation of research studies regarding phytoestrogen intake and breast cancer risk is hampered by differences in dietary measurement, lack of standardization of supplemental sources, differences in metabolism amongst individuals, and the retrospective nature of much of the research in this area. Data regarding the role of phytoestrogens in breast cancer prevention is conflicting, but suggest early exposure in childhood or early adolescence may be protective. In several placebo-controlled randomized trials among breast cancer survivors, soy has not been found to decrease menopausal symptoms. There is very little human data on the role of phytoestrogens in preventing breast cancer recurrence, but the few studies conducted do not support a protective role. There is in vivo animal data suggesting the phytoestrogen genistein may interfere with the inhibitive effects of tamoxifen on breast cancer cell growth.

A pilot and feasibility study on the effects of naturopathic botanical and dietary interventions on sex steroid hormone metabolism in premenopausal women.

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.

Breast cancer adjuvant endocrine therapy.

Adjuvant endocrine therapy with the selective estrogen receptor modulator, tamoxifen, has significantly improved mortality from early-stage breast cancer for both pre- and postmenopausal women with hormone receptor-positive breast cancer. Recent large clinical trials have demonstrated a clear and consistent benefit for the incorporation of aromatase inhibitor (AI) therapy within adjuvant endocrine regimens for postmenopausal women. The AIs, which are associated with myalgias, arthralgias, and a reduction in bone mineral density, are generally well tolerated and have lower risks of endometrial carcinoma and thromboembolic events than tamoxifen. Data are awaited from ongoing trials to better define the optimal sequencing strategy, duration, and AI agent. Attempts to further optimize adjuvant endocrine therapy by identifying predictive biomarkers of response, as well as by developing strategies to overcome endocrine resistance are underway. In premenopausal women AI monotherapy is currently contraindicated and tamoxifen remains the standard of care. The role of ovarian function suppression in addition to tamoxifen or combined with AI therapy is being explored. The hope is that continued advances in endocrine therapy will translate into improved survival among both pre- and postmenopausal women with receptor-positive breast cancer.