[show abstract][hide abstract] ABSTRACT: It is hypothesized that exercise can lead to a decrease in breast cancer risk through several hormonal and nonhormonal mechanisms. The WISER (Women In Steady Exercise Research) study investigated the effects of aerobic exercise on premenopausal sex hormone levels.
Three hundred ninety-one sedentary, healthy, young eumenorrheic women were randomized either into an exercise intervention of 30 minutes of aerobic exercise 5 times a week for approximately 16 weeks (n = 212) or into a control group (n = 179). Serum levels of estradiol, estrone sulfate, testosterone, and sex hormone-binding globulin (SHBG), all in the midfollicular phase, and of progesterone, in the midluteal phase, were measured at baseline and at the end of the 16-week period.
Compared with the controls (n = 153), exercisers (n = 166) experienced significant increases in aerobic fitness, lean body mass, and decreases in percent body fat. There were no significant changes in body weight and menstrual cycle length between or within groups. Progesterone decreased significantly in exercisers; however, this reduction was similar to that of the control group. No significant changes between or within groups were found for any of the other sex hormones or SHBG.
In premenopausal women, 16 weeks of 150 minutes per week of moderate aerobic exercise in young women did not significantly alter sex hormone or SHBG levels.
Any favorable effects that moderate aerobic exercise without an associated weight change may have on breast cancer risk in premenopausal women are unlikely to be a consequence of changes in levels of sex hormones or SHBG.
[show abstract][hide abstract] ABSTRACT: BACKGROUND Hormonal effects of soy and isoflavones have been investigated in numerous trials with equivocal findings. We aimed to systematically assess the effects of soy and isoflavones on circulating estrogen and other hormones in pre- and post-menopausal women. METHODS The Cochrane Library, MEDLINE and EMBASE (plus reviews and experts) were searched to December 2007. Inclusion of randomized or residential crossover trials of soy or isoflavones for 4 or more weeks on estrogens, SHBG, FSH, LH, progesterone and thyroid hormones in women was assessed independently in duplicate. Six percent of papers assessed were included. Data concerning participants, interventions, outcomes, potential effect modifiers and trial quality characteristics were extracted independently in duplicate. RESULTS Forty-seven studies (11 of pre-, 35 of post- and 1 of perimenopausal women) were included. In premenopausal women, meta-analysis suggested that soy or isoflavone consumption did not affect primary outcomes estradiol, estrone or SHBG concentrations, but significantly reduced secondary outcomes FSH and LH [by approximately 20% using standardized mean difference (SMD), P = 0.01 and 0.05, respectively]. Menstrual cycle length was increased by 1.05 days (95% CI 0.13, 1.97, 10 studies). In post-menopausal women, there were no statistically significant effects on estradiol, estrone, SHBG, FSH or LH, although there was a small statistically non-significant increase in total estradiol with soy or isoflavones ( approximately 14%, SMD, P = 0.07, 21 studies). CONCLUSIONS Isoflavone-rich soy products decrease FSH and LH in premenopausal women and may increase estradiol in post-menopausal women. The clinical implications of these modest hormonal changes remain to be determined.
Human Reproduction Update 04/2009; 15(4):423-40. · 9.23 Impact Factor
[show abstract][hide abstract] ABSTRACT: To review current research on the effects of soy consumption on menopausal symptoms.
To review results of recent meta-analyses and individual clinical trials.
One recent meta-analysis reported that isoflavone supplementation was associated with a 34% reduction in hot flashes, with increased efficacy as the baseline number of flashes and isoflavone dose increased. A second review concluded that consumption of at least 15 mg genistein, rather than total isoflavones, is responsible for the reduction in symptoms. Results of these two reviews are supported by most subsequent randomized controlled trials.
Consumption of 30 mg/day of soy isoflavones (or at least 15 mg genistein) reduces hot flashes by up to 50 %. This total reduction includes that provided by "the placebo effect". The greatest benefit may be realized when the isoflavone-rich food or supplement is taken in divided doses by subjects who experience at least four hot flashes/day.
[show abstract][hide abstract] ABSTRACT: To investigate the effect of probiotic capsules on plasma lipids.
A randomized, single-blinded, placebo-controlled, parallel-arm trial.
Fifty-five normocholesterolemic subjects ages 18-36 (33 premenopausal women and 22 men).
Each subject consumed either three probiotic capsules each containing a total of 10(9) colony-forming units Lactobacillus acidophilus and Bifidobacterium longum and 10-15 mg fructo-oligosaccharide or three placebo capsules daily for 2 months (men) or two menstrual cycles (women). Plasma lipids were measured before and following the intervention (during the early follicular phase for women).
Plasma concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride were not altered by consumption of probiotic or placebo capsules and were not different between treatment groups following the intervention.
These results do not support a beneficial effect of Lactobacillus acidophilus strain DDS-1 and Bifidobacterium longum strain UABL-14 on plasma lipids in normocholesterolemic young women and men.
Supported by the Minnesota Agricultural Experiment Station and UAS Laboratories.
European Journal of Clinical Nutrition 03/2008; 62(2):232-7. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the effect of soy protein containing isoflavones on homocysteine (Hcy), C-reactive protein (CRP), soluble E-selectin (sE-selectin), soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1).
In a randomized crossover design, 34 postmenopausal women consumed soy protein isolate (26+/-5 g protein containing 44+/-8 mg isoflavones per day) or milk protein isolate (26+/-5 g protein per day) for 6 weeks each. Fasting blood samples were collected at the end of each diet period and end points analyzed by enzyme-linked immunosorbent assay.
Concentrations of Hcy, CRP, sE-selectin, sVCAM-1 and sICAM-1 were not different between soy and milk diet treatments. Results did not differ by equol production status or by baseline lipid concentration. Adjustment for intake of folate and methionine did not alter the Hcy results.
These data suggest that decreasing vascular inflammation and Hcy concentration are not likely mechanisms by which soy consumption reduces coronary heart disease risk.
European Journal of Clinical Nutrition 10/2007; 62(12):1419-25. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: To confirm the results of an earlier study showing premenopausal equol excretors to have hormone profiles associated with reduced breast cancer risk, and to investigate whether equol excretion status and plasma hormone concentrations can be influenced by consumption of probiotics.
A randomized, single-blinded, placebo-controlled, parallel-arm trial.
In all, 34 of the initially enrolled 37 subjects completed all requirements.
All subjects were followed for two full menstrual cycles and the first seven days of a third cycle. During menstrual cycle 1, plasma concentrations of estradiol (E(2)), estrone (E(1)), estrone-sulfate (E(1)-S), testosterone (T), androstenedione (A), dehydroepiandrosterone-sulfate (DHEA-S), and sex-hormone-binding globulin (SHBG) were measured on cycle day 2, 3, or 4, and urinary equol measured on day 7 after a 4-day soy challenge. Subjects then received either probiotic capsules (containing Lactobacillus acidophilus and Bifidobacterium longum) or placebo capsules through day 7 of menstrual cycle 3, at which time both the plasma hormone concentrations and the post-soy challenge urinary equol measurements were repeated.
During menstrual cycle 1, equol excretors and non-excretors were not significantly different with respect to subject characteristics, diet, or hormone concentrations. Significant inverse correlations were found between E(2) and body mass index (BMI) (P=0.02), SHBG and BMI (P=0.01), DHEA-S and dietary fiber (P=0.04), and A and protein:carbohydrate ratio (P=0.02). Probiotic consumption failed to significantly alter equol excretor status or hormone concentrations during menstrual cycle 3, although there were trends towards decreased concentrations of T (P=0.14) and SHBG (P=0.10) in the probiotic group.
We were unable to verify a previously reported finding of premenopausal equol excretors having plasma hormone concentrations different from those of nonexcretors. Furthermore, a 2-month intervention with probiotic capsules did not significantly alter equol excretion or plasma hormone concentrations.
European Journal of Clinical Nutrition 01/2005; 58(12):1635-42. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Sex steroid concentrations in urine samples from post-menopausal women have been associated with risk of various chronic diseases. The basic requirement for the assessment of risk in such large-scale epidemiological studies is that subjects be ranked accurately by their average, long-term hormone levels. We examined the reproducibility over time of measurements of urinary testosterone (T), 5alpha-androstane-3alpha, 17beta-diol (ADIOL), estrone (E1), estradiol (E2), 2-hydroxy estrone and 2-hydroxy estradiol, (2(OH)-E), 16alpha-hydroxyestrone (16alpha(OH)-E1) and the ratio of 2(OH)-E and 16alpha(OH)-E1, in a representative sub-sample of post-menopausal women (n = 43) participating in an ongoing prospective cohort study. Women collected three first morning urine voids on different occasions, with average time difference between the first and the third urine sample of 5.1 years. T, ADIOL, E1 and E2 were measured by radio immunoassay after enzymatic hydrolysis, solid-phase extraction and HPLC purification of the samples, while 2(OH)-E and 16alpha(OH)-E1 were assayed by solid-phase enzyme immunoassay after enzymatic hydrolysis. Intra-class correlation co-efficients (ICCs) over time were very good for T (r = 0.85), acceptable for E2, E1 and ADIOL (r > 0.55), but low for 2(OH)-E, 16alpha(OH)-E1 and their ratio (r < 0.46). The adjustment for creatinine concentrations did not increase these correlations.
European Journal of Epidemiology 01/2003; 18(5):417-24. · 5.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: Soy-protein consumption is known to reduce plasma total and LDL cholesterol concentrations. However, the responsible soy component or components and the magnitude of effects in normocholesterolemic and mildly hypercholesterolemic subjects are unclear.
The present study examined the effects of soy isoflavone consumption on plasma concentrations of triacylglycerol, apolipoprotein (apo) A-I, apo B, lipoprotein(a), and total, LDL, and HDL cholesterol and on LDL peak particle diameter in normocholesterolemic and mildly hypercholesterolemic postmenopausal women.
In a randomized crossover trial, fasting plasma samples were obtained from 18 postmenopausal women throughout three 93-d periods of daily isolated soy protein (ISP) consumption providing an average of 7.1 +/- 1.1 (control), 65 +/- 11 (low isoflavone), or 132 +/- 22 (high isoflavone) mg isoflavones/d.
Compared with values measured during the control diet, the plasma LDL cholesterol concentration was 6.5% lower (P < 0.02) during the high-isoflavone diet and the ratio of LDL to HDL cholesterol was 8.5% and 7.7% lower during the low- and high-isoflavone diets, respectively (P < 0.02). Isoflavone consumption did not significantly affect plasma concentrations of total or HDL cholesterol, triacylglycerol, apo A-I, apo B, or lipoprotein(a) or the LDL peak particle diameter.
Consumption of isoflavones as a constituent of ISP resulted in small but significant improvements in the lipid profile in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. Although the effects were small, it is possible that isoflavones may contribute to a lower risk of coronary heart disease if consumed over many years in conjunction with other lipid-lowering strategies.
American Journal of Clinical Nutrition 02/2001; 73(2):225-31. · 6.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Soy isoflavones are hypothesized to exert hormonal effects in women and thus may play a role in bone metabolism throughout life. In 2 randomized, cross-over studies, 14 pre- and 17 postmenopausal women were given 3 soy protein isolates containing different amounts of isoflavones [control, 0.13; low isoflavone (low-iso), 1.00; and high-iso, 2.01 mg/kg body wt/day, averaging 8, 65, and 130 mg/day, respectively], for over 3 months each. Food records, blood samples, and 24-h urine collections were obtained throughout the studies. The endpoints evaluated included plasma or serum concentrations of bone-specific alkaline phosphatase, osteocalcin, insulin-like growth factor-I (IGFI), IGF binding protein-3 (IGFBP3), and urine concentrations of deoxypyridinoline cross-links and carboxy-terminal telopeptide of type I collagen. In premenopausal women, IGFI and IGFBP3 concentrations were increased by the low-iso diet, and deoxypyridinoline cross-links was increased by both the low- and high-iso diets during certain phases of the menstrual cycle. In postmenopausal women, bone-specific alkaline phosphatase was decreased by both the low- and high-iso diets, and there were trends toward decreased osteocalcin, IGFI, and IGFBP3 concentrations with increasing isoflavone consumption. Although soy isoflavones do affect markers of bone turnover, the changes observed were of small magnitude and not likely to be clinically relevant. These data do not support the hypothesis that dietary isoflavones per se exert beneficial effects on bone turnover in women.
[show abstract][hide abstract] ABSTRACT: Isoflavones are soy phytoestrogens that have been suggested to be anticarcinogenic. Our previous study in premenopausal women suggested that the mechanisms by which isoflavones exert cancer-preventive effects may involve modulation of estrogen metabolism away from production of potentially carcinogenic metabolites [16alpha-(OH) estrone, 4-(OH) estrone, and 4-(OH) estradiol] (X. Xu et al., Cancer Epidemiol. Biomark. Prev., 7: 1101-1108, 1998). To further evaluate this hypothesis, a randomized, cross-over soy isoflavone feeding study was performed in 18 healthy postmenopausal women. The study consisted of three diet periods, each separated by a washout of approximately 3 weeks. Each diet period lasted for 93 days, during which subjects consumed their habitual diets supplemented with soy protein isolate providing 0.1 (control), 1, or 2 mg isoflavones/kg body weight/day (7.1 +/- 1.1, 65 +/- 11, or 132 +/- 22 mg/day). A 72-h urine sample was collected 3 days before the study (baseline) and days 91-93 of each diet period. Urine samples were analyzed for 10 phytoestrogens and 15 endogenous estrogens and their metabolites by a capillary gas chromatography-mass spectrometry method. Compared with the soy-free baseline and very low isoflavone control diet, consumption of 65 mg isoflavones increased the urinary 2/16alpha-(OH) estrone ratio, and consumption of 65 or 132 mg isoflavones decreased excretion of 4-(OH) estrone. When compared with baseline values, consumption of all three soy diets increased the ratio of 2/4-(OH) estrogens and decreased the ratio of genotoxic: total estrogens. These data suggest that both isoflavones and other soy constituents may exert cancer-preventive effects in postmenopausal women by altering estrogen metabolism away from genotoxic metabolites toward inactive metabolites.
[show abstract][hide abstract] ABSTRACT: Soy consumption is known to reduce plasma total cholesterol and LDL cholesterol in hypercholesterolemic subjects, but the responsible soy components and the effects in normocholesterolemic subjects remain unclear.
The effects of soy isoflavone consumption on plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerol, apolipoprotein A-I, apolipoprotein B, and lipoprotein(a) concentrations and on LDL peak particle diameter were examined in normocholesterolemic, premenopausal women.
Thirteen healthy, normocholesterolemic, free-living, premenopausal female volunteers took part in this randomized, crossover-controlled trial. Each subject acted as her own control. Three soy isoflavone intakes (control: 10.0 +/- 1.1; low: 64.7 +/- 9.4; and high: 128.7 +/- 15.7 mg/d), provided as soy protein isolate, were consumed for 3 menstrual cycles each. Total cholesterol, HDL cholesterol, LDL cholesterol, and triacylglycerol were measured over the menstrual cycle. Apolipoprotein A-I, apolipoprotein B, lipoprotein(a), and LDL peak particle diameter were evaluated in the midluteal phase.
Total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations changed significantly across menstrual cycle phases (P < 0.005). During specific phases of the cycle, the high-isoflavone diet lowered LDL cholesterol by 7.6-10.0% (P < 0.05), the ratio of total cholesterol to HDL cholesterol by 10.2% (P < 0.005), and the ratio of LDL to HDL cholesterol by 13.8% (P < 0.002).
Isoflavones significantly improved the lipid profile across the menstrual cycle in normocholesterolemic, premenopausal women. Although of small magnitude, these effects could contribute to a lower risk of developing coronary heart disease in healthy people who consume soy over many years.
American Journal of Clinical Nutrition 07/2000; 71(6):1462-9. · 6.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Increased urinary excretion of equol, a metabolite of the isoflavone daidzein, has been associated with a reduced risk of breast cancer. This risk reduction has generally been presumed to be a consequence of increased isoflavone consumption. However, only 30-40% of the population excretes more than trace amounts of equol, regardless of isoflavone intake. Accordingly, we hypothesized that the observed apparent protective effect of equol is at least in part attributable to hormonal differences between equol excretors and non-excretors, and that these differences are largely independent of isoflavone intake. We measured plasma hormone and sex hormone binding globulin (SHBG) concentrations in 14 normally cycling premenopausal women during each of three diet periods in which they consumed differing isoflavone doses (0.15, 1.0, and 2.0 mg/kg of body weight/day) as a component of soy protein isolate. The plasma hormone and SHBG concentrations of equol excretors (n = 5) were then compared with those of the non-excretors (n = 9). Results showed that even at the lowest dose, urinary equol excretion values for excretors far exceeded those for non-excretors consuming the highest dose. At all doses, equol excretors generally had lower concentrations of estrone, estrone-sulfate, testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA-sulfate, and cortisol and higher concentrations of SHBG and midluteal progesterone, a hormonal pattern overall consistent with lowered breast cancer risk. In conclusion, the association of equol excretion and lowered breast cancer risk may largely reflect the tendency of equol excretors to have more favorable hormonal profiles, as opposed to merely reflecting increased isoflavone intake. Equol may be a marker for the presence of colonic bacterial enzymatic activity that increases fecal steroid excretion. Alternatively, equol itself, even with very modest isoflavone intake, may exert beneficial effects on the regulation of endogenous hormones.
[show abstract][hide abstract] ABSTRACT: Endogenous estrogen metabolism may play an important role in the pathogenesis of hormone-related cancers, most notably breast cancer. Despite the importance of estrogen metabolism, little is known about estrogen metabolite profiles during different phases of the menstrual cycle. This study was performed to evaluate the effects of the menstrual cycle on endogenous estrogen metabolism. Twenty-four-hour urine samples were collected daily during 4 precisely defined phases of the menstrual cycle (early follicular, midfollicular, periovulatory, and midluteal phases) from 6 healthy premenopausal women. Urine samples were analyzed for 15 endogenous estrogens and their metabolites by an ion exchange chromatography and the capillary gas chromatography-mass spectrometry method. The patterns of urinary estrogen metabolites (including potentially genotoxic 16alpha-hydroxyestrone, 4-hydroxyestradiol, and 4-hydroxyestrone) followed those of plasma estradiol and estrone, showing significant increases in the periovulatory and midluteal phases. Compared to the early and midfollicular phases, the ratios of 2-hydroxyestrogens/16alpha-hydroxyestrogens and 2-hydroxyestrogens/4-hydroxyestrogens were significantly increased during the periovulatory and midluteal phases (by 28% and 72%, respectively; P < 0.05), suggesting that estrogen metabolism is significantly affected by menstrual cycle phase. These data indicate that menstrual cycle phase must be considered in studies of estrogen metabolism in premenopausal women.
[show abstract][hide abstract] ABSTRACT: Soy isoflavones have been hypothesized to exert hormonal effects in postmenopausal women. To test this hypothesis, we studied the effects of three soy powders containing different levels of isoflavones in 18 postmenopausal women. Isoflavones were consumed relative to bodyweight [control: 0.11 +/- 0.01; low isoflavone (low-iso): 1.00 +/- 0.01; high isoflavone (high-iso): 2.00 +/- 0.02 mg/kg/day] for 93 days each in a randomized crossover design. Blood was collected on day 1 of the study (baseline) and days 36-38, 64-66, and 92-94 of each diet period, for analysis of estrogens, androgens, gonadotropins, sex hormone binding globulin (SHBG), prolactin, insulin, cortisol, and thyroid hormones. Vaginal cytology specimens were obtained at baseline and at the end of each diet period, and endometrial biopsies were performed at baseline and at the end of the high-iso diet period, to provide additional measures of estrogen action. Overall, compared with the control diet, the effects of the low-iso and high-iso diets were modest in degree. The high-iso diet resulted in a small but significant decrease in estrone-sulfate (E1-S), a trend toward lower estradiol (E2) and estrone (E1), and a small but significant increase in SHBG. For the other hormones, the few significant changes noted were also small and probably not of physiological importance. There were no significant effects of the low-iso or high-iso diets on vaginal cytology or endometrial biopsy results. These data suggest that effects of isoflavones on plasma hormones per se are not significant mechanisms by which soy consumption may exert estrogen-like effects in postmenopausal women. These data also show that neither isoflavones nor soy exert clinically important estrogenic effects on vaginal epithelium or endometrium.
[show abstract][hide abstract] ABSTRACT: Soy isoflavones are hypothesized to be responsible for changes in hormone action associated with reduced breast cancer risk. To test this hypothesis, we studied the effects of isoflavone consumption in 14 premenopausal women. Isoflavones were consumed in soy protein powders and provided relative to body weight (control diet, 10 +/- 1.1; low isoflavone diet, 64 +/- 9.2; high isoflavone diet, 128 +/- 16 mg/day) for three menstrual cycles plus 9 days in a randomized cross-over design. During the last 6 weeks of each diet period, plasma was collected every other day for analysis of estrogens, progesterone, LH, and FSH. Diet effects were assessed during each of four distinctly defined menstrual cycle phases. Plasma from the early follicular phase was analyzed for androgens, cortisol, thyroid hormones, insulin, PRL, and sex hormone-binding globulin. The low isoflavone diet decreased LH (P = 0.009) and FSH (P = 0.04) levels during the periovulatory phase. The high isoflavone diet decreased free T3 (P = 0.02) and dehydroepiandrosterone sulfate (P = 0.02) levels during the early follicular phase and estrone levels during the midfollicular phase (P = 0.02). No other significant changes were observed in hormone concentrations or in the length of the menstrual cycle, follicular phase, or luteal phase. Endometrial biopsies performed in the luteal phase of cycle 3 of each diet period revealed no effect of isoflavone consumption on histological dating. These data suggest that effects on plasma hormones and the menstrual cycle are not likely to be the primary mechanisms by which isoflavones may prevent cancer in premenopausal women.
[show abstract][hide abstract] ABSTRACT: Isoflavones and lignans are soy phytoestrogens that have been suggested to be anticarcinogenic. The mechanisms by which they exert cancer-preventive effects may involve modulation of estrogen synthesis and metabolism. To evaluate this hypothesis, a randomized, cross-over soy isoflavone feeding study was performed in 12 healthy premenopausal women. The study consisted of three diet periods, each separated by a washout of approximately 3 weeks. Each diet period lasted for three menstrual cycles plus 9 days (averaging approximately 100 days), during which subjects consumed their habitual diets supplemented with soy protein powder providing 0.16 (control diet), 1.01, or 2.01 mg of total isoflavones per kg of body weight per day (10+/-1.1, 65+/-9.4, or 129+/-16 mg/day, respectively). A 72-h urine sample was collected during the midfollicular phase (days 7-9) of the fourth menstrual cycle in each diet period. Urine samples were analyzed for 10 phytoestrogens and 15 endogenous estrogens and their metabolites by a capillary gas chromatography-mass spectrometry method. Urinary excretion of isoflavonoids and lignans significantly increased with increased isoflavone consumption. Compared with the control diet, increased isoflavone consumption decreased urinary excretion of estradiol, estrone, estriol, and total estrogens, as well as excretion of the hypothesized genotoxic estrogen metabolites, 16alpha-hydroxyestrone, 4-hydroxyestrone, and 4-hydroxyestradiol. Of importance are the observations of a significant increase in the 2-hydroxyestrone/16alpha-hydroxyestrone ratio and a decrease in the genotoxic/total estrogens ratio. These data suggest that soy isoflavone consumption may exert cancer-preventive effects by decreasing estrogen synthesis and altering metabolism away from genotoxic metabolites toward inactive metabolites.