Pomegranate is a rich source of polyphenols. Laboratory studies suggest polyphenols may exert breast cancer preventive effects through modulation of endogenous sex hormone levels. The aim of this ...study was to determine the effect of pomegranate juice consumption on serum levels of estradiol, estrone, testosterone, androstenedione, and sex hormone binding globulin (SHBG). Sixty-four healthy postmenopausal women were randomly assigned to drink 8 ounces of either 100% commercial pomegranate juice (intervention) or apple juice (control) for 3 weeks. Overall, women in the intervention group did not experience any significant decline in serum sex hormones or SHBG compared to women in the control group. In subgroup analyses restricted to 38 normal weight women, women in the intervention group compared to control group had a significant decline in estrone (pg/mL) and testosterone levels (pg/mL): pomegranate: −61.6 95% confidence interval (CI): −175.8 to 52.6), apple: 1.1 (95% CI: −5.4 to 7.7), P = 0.05, and pomegranate: −289.1 (95% CI: −630.7 to 52.5), apple: 79.6 (95% CI: −77.8 to 236.9), P = 0.03, respectively. Because of several study limitations, results should be considered preliminary. Additional larger trials would be needed to determine effects in normal versus overweight/obese women.
Breast density is one of the strongest risk factors for breast cancer, but determinants of breast density in young women remain largely unknown.
Associations of height, adiposity and body fat ...distribution with percentage dense breast volume (%DBV) and absolute dense breast volume (ADBV) were evaluated in a cross-sectional study of 174 healthy women, 25 to 29 years old. Adiposity and body fat distribution were measured by anthropometry and dual-energy X-ray absorptiometry (DXA), while %DBV and ADBV were measured by magnetic resonance imaging. Associations were evaluated using linear mixed-effects models. All tests of statistical significance are two-sided.
Height was significantly positively associated with %DBV but not ADBV; for each standard deviation (SD) increase in height, %DBV increased by 18.7% in adjusted models. In contrast, all measures of adiposity and body fat distribution were significantly inversely associated with %DBV; a SD increase in body mass index (BMI), percentage fat mass, waist circumference and the android:gynoid fat mass ratio (A:G ratio) was each associated significantly with a 44.4 to 47.0% decrease in %DBV after adjustment for childhood BMI and other covariates. Although associations were weaker than for %DBV, all measures of adiposity and body fat distribution also were significantly inversely associated with ADBV before adjustment for childhood BMI. After adjustment for childhood BMI, however, only the DXA measures of percentage fat mass and A:G ratio remained significant; a SD increase in each was associated with a 13.8 to 19.6% decrease in ADBV. In mutually adjusted analysis, the percentage fat mass and the A:G ratio remained significantly inversely associated with %DBV, but only the A:G ratio was significantly associated with ADBV; a SD increase in the A:G ratio was associated with an 18.5% decrease in ADBV.
Total adiposity and body fat distribution are independently inversely associated with %DBV, whereas in mutually adjusted analysis only body fat distribution (A:G ratio) remained significantly inversely associated with ADBV in young women. Research is needed to identify biological mechanisms underlying these associations.
Adiposity and sex hormones in girls Baer, Heather J; Colditz, Graham A; Willett, Walter C ...
Cancer epidemiology, biomarkers & prevention,
09/2007, Volume:
16, Issue:
9
Journal Article
Peer reviewed
Greater body fatness during childhood is associated with reduced risk of premenopausal breast cancer, but few studies have addressed the relation of adiposity with sex hormones in girls. We ...prospectively examined associations between adiposity and circulating levels of sex hormones and sex hormone-binding globulin (SHBG) among 286 girls in the Dietary Intervention Study in Children. Participants were 8 to 10 years old at baseline and were followed for an average of 7 years. Anthropometric measurements were taken at baseline and at subsequent annual visits, and blood samples were collected every 2 years. Concentrations of dehydroepiandrosterone sulfate (DHEAS) during follow-up were higher among girls with greater body mass index (BMI) at baseline. The mean for the lowest BMI quartile was 63.0 microg/dL compared with 78.8 microg/dL for the highest quartile, and each kg/m(2) increment in baseline BMI was associated with a 4.3% increase (95% confidence interval, 1.6-7.0%) in DHEAS levels during follow-up (P(trend) = 0.002). Concentrations of SHBG during follow-up were lower among girls with greater BMI at baseline. The mean for the lowest BMI quartile was 94.8 nmol compared with 57.5 nmol for the highest quartile, and each kg/m(2) increment in baseline BMI was associated with an 8.8% decrease (95% confidence interval, 7.0-10.6%) in SHBG levels during follow-up (P(trend) < 0.0001). Estrogen and progesterone concentrations were similar across BMI quartiles. These findings suggest that adiposity may alter DHEAS and SHBG levels in girls. Whether and how these differences affect breast development and carcinogenesis requires further research.
Breast density is an established predictor of breast cancer risk, and there is considerable interest in associations of modifiable lifestyle factors, such as diet, with breast density.
To determine ...whether dietary energy density (ED) is associated with percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) in young women.
A cross-sectional analysis was conducted with women who participated in the Dietary Intervention Study in Children Follow-Up Study. %DBV and ADBV were measured by magnetic resonance imaging. Diet was assessed by three 24-hour recalls. Dietary ED (kilocalories/gram) was calculated using three methods: food only, food and caloric beverages, and food and all beverages.
One hundred seventy-two women (aged 25 to 29 years) who were enrolled in the Dietary Intervention Study in Children Follow-Up Study. Participants who reported breast augmentation or reduction surgery or were pregnant or lactating within 3 months before breast density assessment were excluded.
ADBV and %DBV.
Multivariable linear mixed effects models were used. Final models were adjusted for race, smoking status, education, parity, duration of sex hormone use, whole body percent fat, childhood body mass index z score, and energy from beverages.
After adjustment, each 1 kcal/g unit increase in food-only ED was associated with a 25.9% (95% CI 6.2% to 56.8%) increase in %DBV (P=0.01). Childhood body mass index z score modified the association between food-only ED and %DBV such that a significant positive association was observed only in women who were heavier as children. Food-only ED was not associated with ADBV in all women, but a borderline significant positive association was observed in women who had higher childhood body mass index z scores.
This is the first report to suggest a potential role for dietary ED in breast density; the effects of long-term exposure to high-ED diets on breast cancer risk remain unknown.
Animal and experimental data suggest that anti‐Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have ...examined the association between AMH and ovarian cancer risk. We conducted a nested case‐control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme‐linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable‐adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable‐adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59–1.67) (Ptrend: 0.91). The association did not differ by age at blood draw or oral contraceptive use (all Pheterogeneity: ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all Pheterogeneity: ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.
What's new?
As the anti‐Müllerian hormone (AMH) inhibits Müllerian duct formation during sexual differentiation, an inhibitory role of the AMH in ovarian cancer development was proposed. Here the authors performed a pooled analysis of nine cohorts of mostly late premenopausal women testing a potential protective role of AMH against ovarian carcinogenesis. Contrary to animal and experimental studies, the authors found no associations between AMH and ovarian cancer risk, pointing to future studies in younger women with overall higher AMH concentrations to conclusively establish whether AMH reduces ovarian cancer risk.
Abstract The perinatal period, childhood, and adolescence are important intervals for breast cancer risk development. Endogenous estrogen exposure is thought to be highest in utero, and exposure to ...estrogens throughout life plays an important role in increasing breast cancer risk. Some evidence suggests that breast tissue is not fully differentiated until after the first full-term pregnancy; thus, breast tissue might be more susceptible to carcinogenic influences during early life and adolescence. Birth characteristics of the daughter, including gestational age, birth weight, and birth length are associated with maternal hormone levels during the index pregnancy, and birth size has been related to daughter's timing of puberty and adult breast cancer incidence. Furthermore, early life and adolescence are critical times for maturation of the hypothalamic pituitary ovarian axis, which regulates production of ovarian hormones including estrogen and progesterone. Childhood height, growth, diet, and body mass index (BMI) have also been associated with breast cancer risk later in life. Of the examined characteristics, we conclude that the available evidence is suggestive of a positive relationship of breast cancer risk with birth weight, birth length, and adolescent height, and an inverse relationship with gestational age and childhood BMI, although several inconsistencies exist in the literature. The best evidence for a relationship of adolescent diet and adult breast cancer risk is indirect, and the relationship of diet, weight status, and weight gain in childhood deserves further attention. The interaction of birth characteristics with established risk factors over the life course, such as age at menarche, in addition to gene-environment interactions, require more research. Further study is also needed to clarify the biologic mechanisms influencing the observed associations.
Both obesity and sex hormones are known risk factors for postmenopausal breast cancer. Although adiposity and sex hormones have been studied in the past, previous reports in postmenopausal women have ...not been conducted under carefully controlled dietary conditions. In this study, we investigated the usefulness of body mass index (BMI) as a sufficient adiposity measurement to assess associations with sex hormone levels.
This study was conducted as a cross-sectional analysis within the control segment (0 g alcohol group) of a randomized, crossover design, in which 51 postmenopausal women consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks each as part of a controlled diet. Dual-energy X-ray absorptiometry scans were administered to the women during the control (0 g alcohol) segment, and a blood sample was drawn at the end of that diet period for hormone analysis.
In multivariate analysis (adjusted for age, race, family history of breast cancer, parity, and menarche <12 years), women who were overweight or obese had significantly higher serum concentrations of estradiol, bioavailable estradiol, estrone, and estrone sulfate and lower sex hormone-binding globulin than normal weight women (all P < 0.05). In models adjusted for BMI and the covariates above, none of the dual-energy X-ray absorptiometry adiposity measures added further information (all P > 0.10) for these five analytes beyond that of BMI alone.
In this population of postmenopausal women, under carefully controlled dietary conditions, we confirmed previous findings that higher levels of adiposity were associated with higher concentrations of estrogens and lower sex hormone-binding globulin, and we found that the use of the epidemiology-friendly BMI seems sufficient to assess associations with these hormone levels.
The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual ...differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk.
We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. Anti-Mullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (OR
). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics.
Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (OR
: 1.07 (0.99-1.17)), or with any of the examined subgroups.
Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.
Background: Alcohol ingestion is associated with an increased risk of breast cancer in most epidemiologic studies. Results, however, are heterogeneous at lower levels of alcohol intake, and a ...biologic mechanism for the association has not been clearly identified. To determine whether alcohol consumption by postmenopausal women elevates serum levels of hormones associated with an increased risk of breast cancer, we performed a controlled feeding study. Methods: Participants were 51 healthy postmenopausal women not using hormone replacement therapy. Each participant rotated through three 8-week dietary periods in which she consumed 15 or 30 g of alcohol per day or an alcohol-free placebo beverage. The order of assignment to the three alcohol levels was random. During the dietary periods, all food and beverages were supplied by the study, and energy intake was adjusted to keep body weight constant. Levels of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and androstenediol were measured by radioimmunoassays in serum collected at the end of each dietary period. All statistical tests are two-sided. Results: When women consumed 15 or 30 g of alcohol per day, respectively, estrone sulfate concentrations increased by 7.5% (95% confidence interval CI = −0.3% to 15.9%; P = .06) and 10.7% (95% CI = 2.7% to 19.3%; P = .009) and DHEAS concentrations increased by 5.1% (95% CI = 1.4% to 9.0%; P = .008) and 7.5% (95% CI = 3.7% to 11.5%; P<.001) relative to levels when women consumed placebo. None of the other hormones measured changed statistically significantly when women consumed alcohol. Conclusions: Results suggest a possible mechanism by which consumption of one or two alcoholic drinks per day by postmenopausal women could increase their risk of breast cancer.
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