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Botanicals in Postmenopausal Osteoporosis.
Słupski, W, Jawień, P, Nowak, B
Nutrients. 2021;13(5)
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One of the main age-associated hormonal imbalances women experience during peri- and post-menopause is osteoporosis. Oestrogen plays a protective role in maintaining bone mineral density, so a decrease in this hormone that naturally occurs with menopause leads to an increased risk of osteoporosis. Due to the various side effects associated with pharmaceutical drugs, many women seek complementary or alternative treatments during menopause. The aim of this review is to present the current information on the efficacy and mechanism of plant-derived compounds in modulating menopause-associated bone metabolism. The main plant compounds that have been studied in detail are phytoestrogens, specifically isoflavones. The literature shows these compounds not only prevent bone resorption, but also promote bone formation. This review also highlights the many biologically plausible mechanisms by which these compounds influence bone metabolism. According to these findings, the authors conclude there are many bioactive, plant-based compounds that may be useful alternative therapies for peri- and post-menopausal women experiencing osteoporosis. While there is promising potential therapeutic use for these botanicals, further clinical research is needed.
Abstract
Osteoporosis is a systemic bone disease characterized by reduced bone mass and the deterioration of bone microarchitecture leading to bone fragility and an increased risk of fractures. Conventional anti-osteoporotic pharmaceutics are effective in the treatment and prophylaxis of osteoporosis, however they are associated with various side effects that push many women into seeking botanicals as an alternative therapy. Traditional folk medicine is a rich source of bioactive compounds waiting for discovery and investigation that might be used in those patients, and therefore botanicals have recently received increasing attention. The aim of this review of literature is to present the comprehensive information about plant-derived compounds that might be used to maintain bone health in perimenopausal and postmenopausal females.
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Role of Calcium and Low-Fat Dairy Foods in Weight-Loss Outcomes Revisited: Results from the Randomized Trial of Effects on Bone and Body Composition in Overweight/Obese Postmenopausal Women.
Ilich, JZ, Kelly, OJ, Liu, PY, Shin, H, Kim, Y, Chi, Y, Wickrama, KKAS, Colic-Baric, I
Nutrients. 2019;11(5)
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A woman’s menopausal years are believed to bring about weight gain due to various biological mechanisms, such as depletion of oestrogen. Many women undertake weight loss diets, in an attempt to control the weight gain, and although weight loss can reduce the risk factors for metabolic and cardiovascular disease etc, it can also lead to accelerated loss bone density and muscle mass. The objective of this study was to investigate whether by complementing a low-calorie diet with 4 to 5 servings of low-fat dairy foods per day and/or supplementing with calcium and vitamin D supplements would aid weight loss and preserve either/both bone and muscle mass. The study was conducted on 189 early postmenopausal, obese women. It was a randomized, placebo-controlled clinical trial conducted over 6 months. Researchers found that results were better for the participants on the low-fat dairy foods and those supplementing with calcium and vitamin D when compared to the placebo group (who only had placebo pills). They suggest that when embarking on a weight loss program it is beneficial to include 4 to 5 servings of low-fat dairy foods each day and take calcium and vitamin D supplements will have a positive impact on weight loss, bone density and muscle mass in post-menopausal women.
Abstract
Several studies have investigated the possibility of dairy foods and calcium (Ca) mediating weight and body composition, but a consensus has not been reached. We aimed to investigate weight-loss-related outcomes during intervention with low-fat dairy foods or Ca + vitamin D supplements, both as complements to hypocaloric diets. Overweight/obese Caucasian, early-postmenopausal women (n = 135) were recruited for a 6 month energy-restricted weight loss study complemented with either low-fat dairy foods (D; 4-5 servings/day), or Ca + vitamin D supplements (S); both to amount a total of ~1500 mg/day and 600 IU/day of Ca and vitamin D, respectively, or placebo pills (C). Bone mineral density (BMD) and lean and fat tissue were measured by Lunar iDXA. Serum and urinary markers of bone turnover were analyzed. Diet and physical activity were assessed with 3-day records. Participants on average lost ~4%, ~3%, and ~2% of body weight, fat, and lean tissue, respectively. The significantly better outcomes were noticed in participants in the D group regarding body composition (fat loss/lean tissue preservation) and in participants in the S group regarding the BMD outcomes, compared to those in the C group. Therefore, increasing low-fat dairy foods to 4-5 servings/day and/or increasing Ca & vitamin D intake by supplements (in those who are at the borderline dietary intake) may be beneficial for weight loss/maintenance and may lead to more favorable bone and body composition outcomes in postmenopausal women during moderate weight loss.
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Association between the Dietary Inflammatory Index and Risk for Cancer Recurrence and Mortality among Patients with Breast Cancer.
Jang, H, Chung, MS, Kang, SS, Park, Y
Nutrients. 2018;10(8)
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There is evidence of a role for inflammation in cancer, and certain dietary factors may promote inflammation in the body. The dietary inflammatory index (DII) is a tool for assessing the inflammatory potential of a diet, where a lower DII score indicates a higher consumption of anti-inflammatory foods, and a higher DII score shows a higher consumption of pro-inflammatory foods. This study aimed to investigate the association between DII and the risk for cancer recurrence and death rate among patients with breast cancer in Korea. Out of 511 women, average age 52, who underwent breast cancer surgery, 88 had cancer recurrence, and 44 died during the follow–up period of 18 years. The DII was significantly higher in patients with recurrence than those without recurrence, and women with the highest DIIs were 2.3 more likely to have recurrence and 3 times more likely to die than those with the lowest DIIs. The association was significant in patients aged under 50 years, who were premenopausal, had a BMI ≥25 kg/m2, hormone receptor positive (HR+) breast cancer, tumour size >2 cm, and where the cancer had spread to the lymph nodes. The authors concluded that pro-inflammatory diets may be associated with the risk of cancer recurrence and death rate in patients with breast cancer. However, further studies must be conducted to investigate whether dietary intervention that is focused on inflammation could reduce the risk of cancer recurrence and death.
Abstract
The dietary inflammatory index (DII) has been associated with breast cancer incidence and survival. However, the association between DII and cancer recurrence and mortality among patients with breast cancer has not been investigated. Therefore, the present study aimed to investigate whether DII was positively associated with risk for cancer recurrence and overall mortality among patients with breast cancer. Among 511 women (51.9 ± 10.7 years; stage 0⁻3) who underwent breast cancer surgery, 88 had cancer recurrence, and 44 died during follow⁻up until 213 months (average disease free survival of 84.3 ± 42.4 months and overall survival of 69.3 ± 38.9 months). The DII assessed after surgery (5.4 ± 5.2 months after diagnosis) was significantly higher in patients with recurrence than those without recurrence, and Cox proportional hazards regression analysis showed that it was positively associated with the risk for cancer recurrence (hazard ratio (HR) 2.347, confidence interval (CI) 1.17⁻4.71) and overall mortality (HR 3.049, CI 1.08⁻8.83) after adjusting for confounding factors. Disease-free survival and overall survival rates were significantly lower in patients with higher DII scores. In addition, the DII was positively associated with the risk for cancer recurrence according to prognostic factors, such as age (<50 years), premenopausal status, body mass index (≥25 kg/m²), HR+, tumor size (>2 cm), and presence of lymph node metastasis. The present study showed that anti-inflammatory diets may decrease the risk of cancer recurrence and overall mortality in patients with breast cancer, particularly those with prognostic factors, such as younger age, premenopausal status, obesity, HR+ breast cancer, tumor size >2 cm, and presence of lymph node metastasis.
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Physiologic and behavioral indicators of energy deficiency in female adolescent runners with elevated bone turnover.
Barrack, MT, Van Loan, MD, Rauh, MJ, Nichols, JF
The American journal of clinical nutrition. 2010;92(3):652-9
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Young female runners are more likely to have a low bone mass for their age. It is thought that this might be partly due to them using more energy (calories) than they consume. This study looked at the relationship between nutrition intake and biomarkers of bone turnover in young female runners. Participants were competitive cross-country runners, aged 14-17. The girls ate their usual diet and kept a food diary for a week, to allow the researchers to analyse their nutritional intakes. Runners that had an elevated bone turnover consumed significantly less calories and calcium than the runners with a normal bone turnover. They were also more likely to have a lower body mass, fewer menstrual cycles, lower oestrogen and vitamin D levels, lower BMI and lower bone mass. The authors concluded that nutritional support to increase energy and calcium intake, and vitamin D levels may improve bone growth in young female runners.
Abstract
BACKGROUND Female adolescent runners have an elevated prevalence of low bone mass for agemdashan outcome that may be partially due to inadequate energy intake. OBJECTIVE The objective was to evaluate diet, menstrual history, serum hormone concentrations, and bone mass in female adolescent runners with normal or abnormal bone turnover. DESIGN Thirty-nine cross-country runners (age: 15.7 plusmn 0.2 y) participated in the study, which included a 7-d dietary assessment with the use of a food record and daily 24-h dietary recalls; serum measures of insulin-like growth factor I, estradiol, leptin, parathyroid hormone, progesterone, triiodothyronine, 25-hydroxycholecalciferol, bone-specific alkaline phosphatase (BAP), and cross-linked C-telopeptides of type I collagen (CTX); an evaluation of height, weight, bone mass, and body composition with the use of dual-energy X-ray absorptiometry; and a questionnaire to assess menses and sports participation. Age- and sex-specific BAP and CTX concentrations of at least the 97th percentile and no greater than the third percentile, respectively, were considered abnormal. RESULTS All abnormal BAP and CTX concentrations fell within the elevated ( ge 97%) range. Runners with an elevated bone turnover (EBT) (n = 13) had a lower body mass, fewer menstrual cycles in the past year, lower estradiol and 25-hydroxycholecalciferol concentrations, and a higher prevalence of body mass index lt 10% for age, vitamin D insufficiency, amenorrhea, and low bone mass. Girls with EBT consumed less than the recommended amounts of energy and had a higher prevalence of consuming lt 1300 mg Ca than did those with normal bone turnover. CONCLUSIONS Runners with EBT had a profile consistent with energy deficiency. Nutritional support to increase energy, calcium intake, and 25-hydroxycholecalciferol concentrations may improve bone mineral accrual in young runners with EBT. This trial was registered at clinicaltrials.gov as NCT01059968.
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Estrogen and progesterone exposure is reduced in response to energy deficiency in women aged 25-40 years.
Williams, NI, Reed, JL, Leidy, HJ, Legro, RS, De Souza, MJ
Human reproduction (Oxford, England). 2010;25(9):2328-39
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Diet and exercise are related to a reduction in breast cancer risk, and it is thought that this is at least partly due to their impact on levels of female sex hormones. This study aimed to test the effect that exercise and calorie restriction have on menstruation and sex hormones in premenopausal women. Inactive women aged 25-40 years were recruited for the study, and allocated to two groups. One group was assigned a low-calorie diet that provided 20-35% lower calories than baseline energy needs, plus 4 sessions of moderate-intensity exercise per week. The control group followed a diet designed to ensure weight maintenance, and took part in shorter exercise sessions twice a week. Women in the low-calorie group experienced a 15% reduction in levels of oestradiol and a 20% reduction in the levels of oestrogen metabolite oestrone glucuronide. Larger reductions in oestrone glucuronide were related to higher energy deficits, suggesting that hormone production is sensitive to day-to-day fluctuations in energy balance. There was no change in the menstrual cycles of the participants. The researchers concluded that an energy deficit is a more important factor in reducing oestrogen exposure than losing weight.
Abstract
BACKGROUND Alterations in circulating steroids are believed to be important mediators of the impact that diet and exercise have on breast cancer risk and changes in bone density. This study aimed to test the hypothesis that moderate exercise training combined with caloric restriction would produce significant menstrual disturbances and alterations in ovarian steroids in premenopausal women. METHODS Sedentary premenopausal women (25-40 years; body mass index: 23.6 +/- 0.6 kg/m(2)) assigned to either a light conditioning (LC, n = 9) or an exercise combined with caloric restriction group (EX + CR, n = 24) were studied for one screening, one baseline and four intervention periods equivalent to the length of subjects' menstrual cycles. Exercise consisted of supervised training sessions, i.e. two LC or four EX + CR times per week, 30-60 min at a moderate intensity. The EX + CR group was prescribed a diet representing a caloric restriction of 20-35% below baseline energy requirements, whereas the LC group remained eucaloric. Ovarian steroid exposure was determined with daily urinary estrone-1- and pregnanediol glucuronides (E1G and PdG, respectively) and mid-cycle urinary LH measures. Fitness, body composition, and serum sex hormone binding globulin (SHBG) and serum estradiol (E2) were assessed repeatedly. RESULTS The intervention produced significant increases in VO(2) max and decreases in both body weight (-3.7 +/- 0.5 kg; ranged from -8.8 to +1.8 kg) and percent body fat (-4.5 +/- 0.7%; ranged from -12 to +0.3%), which were attributable primarily to changes in the EX + CR subjects (time x group; P < 0.05). Serum E2 and urinary E1G and PdG concentrations declined significantly across the intervention period (time; P < 0.05), whereas SHBG increased transiently (time; P < 0.05) in the EX + CR subjects, with no significant changes observed in the LC group. The decrease in E1G area under the curve was significantly related to the daily energy deficit (R =0.61; P = 0.003), not the amount of weight lost. There was no significant impact of the intervention on menstrual cyclicity or the incidence of menstrual disturbances in either group. CONCLUSIONS A moderate aerobic exercise training program combined with modest weight loss in accordance with recommended guidelines produces significant reductions in ovarian steroid exposure without disrupting menstrual cyclicity in premenopausal women aged 25-40 years. Exposure to a daily energy deficit is a stronger predictor of the decline in estrogen exposure than decreases in body weight.
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Effects of dehydroepiandrosterone (DHEA) on cardiovascular risk factors in older women with frailty characteristics.
Boxer, RS, Kleppinger, A, Brindisi, J, Feinn, R, Burleson, JA, Kenny, AM
Age and ageing. 2010;39(4):451-8
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Older women have the highest incidence of cardiovascular disease. This is thought to be partly due to declining hormone levels and changes in body composition with age. Dehydroepiandrosterone (DHEA) is a hormone that is associated with improved body composition and sense of wellbeing, and naturally declines with age. The aim of this double-blind, randomised, placebo-controlled trial was to examine the effects of DHEA supplementation on cardiovascular risk factors in older frail women. 88 women with low DHEA levels and an average age of 76 completed the 6-month study. Participants received either 50mg/day DHEA or a placebo for 6 months, along with exercise in the form of either yoga or chair aerobics. All participants also received calcium and vitamin D3 supplementation. Whilst DHEA supplementation increased the levels of sex hormones studied, cardiovascular risk factors such as abdominal fat, blood pressure, cholesterol levels and fasting glucose levels did not change. The authors concluded that short-term DHEA supplementation in older women increases levels of oestrogen and testosterone, but these changes may not have any impact on cardiovascular disease risk.
Abstract
OBJECTIVE this analysis was to investigate the effects of dehydroepiandrosterone (DHEA) on cardiovascular risk factors in older women with frailty characteristics. DESIGN, SETTING AND PARTICIPANTS the study was a double-blind, randomised, placebo-controlled trial of 99 women (mean 76.6 +/- 6.0 year) with the low DHEA-S level and frailty. INTERVENTION participants received 50 mg/day DHEA or placebo for 6 months; all received calcium (1,000-1,200 mg/day diet) and supplement (combined) and cholecalciferol (1,000 IU/day). Women participated in 90-min twice weekly exercise regimens, either chair aerobics or yoga. MAIN OUTCOME MEASURES assessment of outcome variables included hormone levels (DHEA-S, oestradiol, oestrone, testosterone and sex hormone-binding globulin (SHBG)), lipid profiles (total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides), body composition measured by dual energy absorptiometry, glucose levels and blood pressure (BP). RESULTS eighty-seven women (88%) completed 6 months of study; 88% were pre-frail demonstrating 1-2 frailty characteristics and 12% were frail with > or =3 characteristics. There were significant changes in all hormone levels including DHEA-S, oestradiol, oestrone and testosterone and a decline in SHBG levels in those taking DHEA supplements. In spite of changes in hormone levels, there were no significant changes in cardiovascular risk factors including lipid profiles, body or abdominal fat, fasting glucose or BP. CONCLUSION research to date has not shown consistent effects of DHEA on cardiovascular risk, and this study adds to the literature that short-term therapy with DHEA is safe for older women in relation to cardiovascular risk factors. This study is novel in that we recruited women with evidence of physical frailty.
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Adolescent diet and subsequent serum hormones, breast density, and bone mineral density in young women: results of the Dietary Intervention Study in Children follow-up study.
Dorgan, JF, Liu, L, Klifa, C, Hylton, N, Shepherd, JA, Stanczyk, FZ, Snetselaar, LG, Van Horn, L, Stevens, VJ, Robson, A, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2010;19(6):1545-56
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Population and animal studies suggest that fat in the diet may have an influence on the development of breast cancer, but the results of studies in humans are inconsistent. This randomised controlled trial aimed to determine the effects of a lower-fat diet during childhood and adolescence on markers associated with breast cancer risk in adults. Female participants were initially recruited at age 8-10 years old, as part of a study to test the effects of lower-fat diets on cholesterol levels in children. The study diet limited total fat intake to 28% of calories (<8% saturated fat, <9% polyunsaturated fat, remainder monounsaturated), cholesterol was limited to 150mg/day and consumption of fibre was encouraged. The children followed the diet for 7 years, when the trial was terminated. This follow-up study was conducted 9 years later, when the participants were aged 25 to 29 years old. After adjusting for current diet, the lower-fat diet group had significantly higher oestradiol levels and bone mineral density. Progesterone concentrations and breast density did not differ between the two groups. The authors concluded that consumption of a lower-fat diet during adolescence does not appear to affect factors associated with breast cancer risk. Current diet may be more important than adolescent diet in determining hormone levels in premenopausal women.
Abstract
BACKGROUND Adolescent diet is hypothesized to influence breast cancer risk. We evaluated the long-term effects of an intervention to lower fat intake among adolescent girls on biomarkers that are related to breast cancer risk in adults. METHODS A follow-up study was conducted on 230 girls who participated in the Dietary Intervention Study in Children (DISC), in which healthy, prepubertal, 8 to 10 year olds were randomly assigned to usual care or to a behavioral intervention that promoted a reduced fat diet. Participants were 25 to 29 years old at follow-up visits. All tests of statistical significance are two-sided. RESULTS In analyses that did not take account of diet at the time of the follow-up visit, the only statistically significant treatment group difference was higher bone mineral content in intervention group participants compared with usual care group participants; their mean bone mineral contents were 2,444 and 2,377 g, respectively. After adjustment for current diet, the intervention group also had statistically significantly higher bone mineral density and luteal phase serum estradiol concentrations. Serum progesterone concentrations and breast density did not differ by treatment group in unadjusted or adjusted analyses. CONCLUSIONS Results do not support the hypothesis that consumption of a lower fat diet during adolescence reduces breast cancer risk via effects on subsequent serum estradiol and progesterone levels, breast density, or bone mineral density. It remains unclear, however, if the results are specific to the DISC intervention or are more broadly applicable. IMPACT Modest reductions in fat intake during adolescence are unlikely to lower later breast cancer risk via long-term effects on the biomarkers measured.
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Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer.
Thompson, LU, Chen, JM, Li, T, Strasser-Weippl, K, Goss, PE
Clinical cancer research : an official journal of the American Association for Cancer Research. 2005;11(10):3828-35
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High levels of the hormone oestrogen are linked with an increased risk of developing breast cancer. Plant lignans have similar chemical structures to oestrogen and may block the action of oestrogen in breast cancer cells. Flaxseed (also known as linseed) is a rich source of lignan precursors and has been shown to reduce tumour growth in rats. Therefore, it is thought that flaxseed might be effective in cancer treatment and prevention. This randomised, double-blind, placebo-controlled trial examined the effects of dietary flaxseed on tumour growth in postmenopausal women with newly diagnosed breast cancer. Patients were given either a muffin containing 25g of flaxseed or a control muffin, every day from the time of the initial biopsy until undergoing surgery to remove the tumours. They continued to eat their normal diet. The group that ate the flaxseed muffins experienced significant reductions of between 34 and 71% in various markers of tumour growth, and a significant increase in apoptosis of 30%. The control group did not experience any significant changes in these markers. The authors concluded that eating flaxseed has the potential to reduce tumour growth in patients with breast cancer.
Abstract
PURPOSE Flaxseed, the richest source of mammalian lignan precursors, has previously been shown to reduce the growth of tumors in rats. This study examined, in a randomized double-blind placebo-controlled clinical trial, the effects of dietary flaxseed on tumor biological markers and urinary lignan excretion in postmenopausal patients with newly diagnosed breast cancer. EXPERIMENTAL DESIGN Patients were randomized to daily intake of either a 25 g flaxseed-containing muffin (n = 19) or a control (placebo) muffin (n = 13). At the time of diagnosis and again at definitive surgery, tumor tissue was analyzed for the rate of tumor cell proliferation (Ki-67 labeling index, primary end point), apoptosis, c-erbB2 expression, and estrogen and progesterone receptor levels. Twenty-four-hour urine samples were analyzed for lignans, and 3-day diet records were evaluated for macronutrient and caloric intake. Mean treatment times were 39 and 32 days in the placebo and flaxseed groups, respectively. RESULTS Reductions in Ki-67 labeling index (34.2%; P = 0.001) and in c-erbB2 expression (71.0%; P = 0.003) and an increase in apoptosis (30.7%; P = 0.007) were observed in the flaxseed, but not in the placebo group. No significant differences in caloric and macronutrient intake were seen between groups and between pre- and posttreatment periods. A significant increase in mean urinary lignan excretion was observed in the flaxseed group (1,300%; P < 0.01) compared with placebo controls. The total intake of flaxseed was correlated with changes in c-erbB2 score (r = -0.373; P = 0.036) and apoptotic index (r = 0.495; P < 0.004). CONCLUSION Dietary flaxseed has the potential to reduce tumor growth in patients with breast cancer.
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Effects of a 2-year randomized soy intervention on sex hormone levels in premenopausal women.
Maskarinec, G, Franke, AA, Williams, AE, Hebshi, S, Oshiro, C, Murphy, S, Stanczyk, FZ
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2004;13(11 Pt 1):1736-44
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Countries that have a high consumption of soy, such as Japan and China, tend to have lower breast cancer rates. Soy contains isoflavones, phytoestrogens which may have oestrogenic and antieostrogenic effects. The aim of this trial was to examine the effect of soy foods on menstrual cycle length and circulating sex hormone levels. 189 healthy premenopausal women completed the 2-year study, during which the treatment group consumed two daily servings of soy foods (tofu, soy milk, roasted soy nuts, soy protein powder or soy protein bars) containing a total of 50 mg of isoflavones. The control group maintained their regular diet. Blood samples were taken 5 days after ovulation in months 0, 3, 6, 12 and 24. Soy did not have any significant effects on the levels of circulating sex hormones or length of menstrual cycle. The authors concluded that any preventative effects of soy on breast cancer risk may be mediated by mechanisms other than its effect on circulating sex hormone levels.
Abstract
OBJECTIVE Several epidemiologic studies have described protective effects of soy consumption against breast cancer. The goal of this trial among premenopausal women was to examine the effect of soy foods on menstrual cycle length and circulating sex hormone levels. METHODS This 2-year dietary intervention randomized 220 healthy premenopausal women. The intervention group consumed two daily servings of soy foods containing approximately 50 mg of isoflavones; the control group maintained their regular diet. Five blood samples (obtained in months 0, 3, 6, 12, and 24) were taken 5 days after ovulation as determined by an ovulation kit. The serum samples were analyzed for estrone, estradiol, sex hormone binding globulin, androstenedione, and progesterone by immunoassay. RESULTS At baseline, both groups had similar demographic, anthropometric, and nutritional characteristics. The dropout rates of 15.6% (17 of 109) in the intervention group and 12.6% (14 of 111) in the control group did not differ significantly. According to soy intake logs, 24-hour recalls, and urinary isoflavone excretion, the women closely adhered to the study regimen. Menstrual cycles became slightly shorter in both groups but did not differ by group. Mixed general linear models indicated no significant intervention effect on any of the serum hormones. However, androstenedione and progesterone decreased significantly over time in both groups. CONCLUSIONS The results of this study suggest that the preventive effects of soy on breast cancer risk in premenopausal women may not be mediated by circulating sex hormone levels. Different mechanisms of actions or effects of exposure earlier in life are alternate hypotheses that require further investigation.