Urinary estrogen metabolites and prostate cancer : a case-control study and meta-analysis

Objective: To investigate prostate cancer (Pca) risk in relation to estrogen metabolism, expressed as urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1) and 2-OHE1 to 16α-OHE1 ratio. Methods: We conducted a case-control study within the Western New York Health Cohort Study (WNYHCS) from 1996 to 2001. From January 2003 through September 2004, we completed the re-call and follow-up of 1092 cohort participants. Cases (n = 26) and controls (n = 110) were matched on age, race and recruitment period according to a 1:4 ratio. We used the unconditional logistic regression to compute crude and adjusted odds ratios (OR) and 95% confident interval (CI) of Pca in relation to 2-OHE1, 16αOHE1 and 2-OHE1 to 16α-OHE1 by tertiles of urine concentrations (stored in a biorepository for an average of 4 years). We identified age, race, education and body mass index as covariates. We also conducted a systematic review of the literature which revealed no additional studies, but we pooled the results from this study with those from a previously conducted case-control study using the DerSimonian-Laird random effects method. Results: We observed a non-significant risk reduction in the highest tertile of 2-OHE1 (OR 0.72, 95% CI 0.25-2.10). Conversely, the odds in the highest tertile of 16α-OHE1 showed a non-significant risk increase (OR 1.76 95% CI 0.62-4.98). There was a suggestion of reduced Pca risk for men in the highest tertile of 2-OHE1 to 16α-OHE1 ratio (OR 0.56, 95% CI 0.19-1.68). The pooled estimates confirmed the association between an increased Pca risk and higher urinary levels of 16α-OHE1 (third vs. first tertile: OR 1.82, 95% CI 1.09-3.05) and the protective effect of a higher 2-OHE 1 to 16α-OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31-0.90). Conclusion: Our study and the pooled results provide evidence for a differential role of the estrogen hydroxylation pathway in Pca development and encourage further study

Associations between endogenous sex hormone levels and mammographic and bone densities in premenopausal women

PURPOSE: Mammographic breast and bone mineral densities (BMD) have been associated with luteal phase hormone concentrations in premenopausal women. We assessed the associations of breast and bone densities with follicular phase hormones and sex hormone binding globulin (SHBG) in premenopausal women given that follicular phase hormones have been shown to be positively associated with premenopausal breast cancer risk. METHODS: One hundred and ninety two 40-45 year old women provided a spot urine and/or blood sample during the follicular phase. Hormone and SHBG concentrations and bone density were measured and routine mammograms were accessed and digitized to obtain breast density measures. Regression models were fit to assess the associations between hormones and SHBG and breast and bone densities. RESULTS: Positive associations were observed between percent breast density and SHBG (p trend = 0.02), as well as estradiol (p trend = 0.08), after controlling for body mass index (BMI), number of pregnancies, and breast feeding history. In addition, a statistically significant inverse association was observed between total testosterone and head BMD (p trend = 0.01), after controlling for BMI. CONCLUSIONS: Associations were observed between breast and bone densities and serum hormone concentrations during the follicular phase of the menstrual cycle

Daidzein-metabolizing phenotypes in relation to bone density and body composition among premenopausal women in the United States

BACKGROUND: Bone density has been suggested as a marker of cumulative hormone exposure. Small studies also suggest that patterns of daidzein metabolism may be related to hormone concentrations. To our knowledge, no studies in premenopausal women have compared bone density by daidzein-metabolizing phenotypes in the absence of a soy intervention. OBJECTIVE: To evaluate the relationship between daidzein-metabolizing phenotypes [equol and O-desmethylangolensin (ODMA) production] and bone density and body composition in premenopausal women in the United States. MATERIALS/METHODS: Two hundred and three women attended a clinic visit during which their bone density and body composition was measured by DXA, and 200 (99 %) provided a urine sample following a 3-day soy challenge. Samples were analyzed for isoflavones to determine daidzein-metabolizing phenotypes. RESULTS: In adjusted analyses, there were no differences in hip, spine, femoral neck, or head bone mineral density (BMD) or body composition between producers and non-producers of either equol or ODMA (p > 0.05). CONCLUSIONS: In this population of low-soy consuming premenopausal women, there were no associations between daidzein-metabolizing phenotypes and hip, spine, femoral neck, or head BMD or body composition, suggesting that these phenotypes per se do not influence premenopausal bone density or body composition

Fruit intake associated with urinary estrogen metabolites in healthy premenopausal women

Urinary concentrations of 2:16-hydroxyestrone (2:16-OHE(1)) approximate concentrations of 2-OHE(1) and 16α -OHE(1) in breast tissue. As estrogens are purported to be involved in breast cancer development, the 2:16-OHE(1) ratio can provide an indication of estrogen metabolite exposure in the breast. With prior studies observing associations between urinary estrogen metabolites and dietary intake of fruits, vegetables, and fiber ascertained from food questionnaires, we examined associations between dietary factors ascertained through 3-day food records and urinary 2:16-OHE(1) in 191 pre-menopausal healthy women. Fruit consumption was positively associated with 2:16-OHE(1) after adjustment for total energy, ethnicity, body mass index, parity, smoking history, and serum estradiol (p= 0.003). Fruit consumption was positively associated with 2- OHE(1) concentrations (p=0.006), but was not associated with 16α-OHE(1) (p=0.92). The Musaceae botanical grouping (comprised primarily of bananas) was positively associated with the 2:16-OHE(1) ratio, and Rosaceae (comprised of citrus fruits) and Musaceae botanical groupings were positively associated with 2-OHE(1) (but not 16α-OHE(1)) concentrations, after adjustment for confounders. Our data suggest that dietary fruit intake is associated with urinary 2- OHE(1) and the 2:16-OHE(1) ratio and that breast tissue exposure to estrogen metabolites may thus be influenced by diet

Fruit intake associated with urinary estrogen metabolites in healthy premenopausal women

Urinary concentrations of 2:16-hydroxyestrone (2:16-OHE(1)) approximate concentrations of 2-OHE(1) and 16α -OHE(1) in breast tissue. As estrogens are purported to be involved in breast cancer development, the 2:16-OHE(1) ratio can provide an indication of estrogen metabolite exposure in the breast. With prior studies observing associations between urinary estrogen metabolites and dietary intake of fruits, vegetables, and fiber ascertained from food questionnaires, we examined associations between dietary factors ascertained through 3-day food records and urinary 2:16-OHE(1) in 191 pre-menopausal healthy women. Fruit consumption was positively associated with 2:16-OHE(1) after adjustment for total energy, ethnicity, body mass index, parity, smoking history, and serum estradiol (p= 0.003). Fruit consumption was positively associated with 2- OHE(1) concentrations (p=0.006), but was not associated with 16α-OHE(1) (p=0.92). The Musaceae botanical grouping (comprised primarily of bananas) was positively associated with the 2:16-OHE(1) ratio, and Rosaceae (comprised of citrus fruits) and Musaceae botanical groupings were positively associated with 2-OHE(1) (but not 16α-OHE(1)) concentrations, after adjustment for confounders. Our data suggest that dietary fruit intake is associated with urinary 2- OHE(1) and the 2:16-OHE(1) ratio and that breast tissue exposure to estrogen metabolites may thus be influenced by diet

Associations between polymorphisms in glucuronidation and sulfation enzymes and sex steroid concentrations in premenopausal women in the United States

Glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGT) and sulfation, catalyzed by sulfotransferases (SULT), are pathways through which sex steroids are metabolized to less active compounds. These enzymes are highly polymorphic and genetic variants frequently result in higher or lower activity. The phenotypic effects of these polymorphisms on circulating sex steroids in premenopausal women have not yet been investigated. One hundred and seventy women ages 40-45 years had a blood sample drawn during the follicular phase of the menstrual cycle for sex steroid measures and to obtain genomic DNA. Urine was collected for 2-hydroxy (OH) estrone (E(1)) and 16α-OH E(1) measures. Generalized linear regression models were used to assess associations between sex steroids and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1. Women with the UGT1A1(TA7/TA7) genotype had 25% lower mean estradiol (E(2)) concentrations compared to the wildtype (TA6/TA6) (p = 0.02). Similar associations were observed between SULT1A1(R213/H213) and E(1) (13% lower mean E(1) concentration vs. wildtype; p-value = 0.02) and UGT2B4(E458/E458) and dehydroepiandrosterone (DHEA) (20% lower mean DHEA vs. wildtype; p-value = 0.03). The SULT1E1(A/C) and the UGT1A1(TA7)-UGT1A3(R11) haplotypes were associated with reduced estrogen concentrations. Further study of UGT and SULT polymorphisms and circulating sex steroid measures in larger populations of premenopausal women is warranted