Abstract 4634: Association between reproductive factors and urinary estrogen metabolites in premenopausal women

Abstract

Abstract Little is known about relationships among reproductive factors, individual estrogens/estrogen metabolites (EM) and patterns of estrogen metabolism. While the positive association between circulating estrogen and breast cancer is established in postmenopausal women and suggested in premenopausal women, relatively little is known about the role of estrogen metabolism. The hypothesized effects of individual EM vary, with some thought to stimulate breast proliferation and others thought to be mutagenic. These hypotheses, derived from experimental research, have been minimally explored in epidemiologic studies. We examined the associations of age at menarche, menstrual cycle length and pattern, parity, age at first birth, use of oral contraceptives (OC) and breastfeeding with luteal phase urinary EM in a sample of 603 premenopausal women within the Nurses’ Health Study II (NHSII). Data on reproductive factors were collected prospectively through biennial questionnaires. Fifteen EM were quantified using a high-performance liquid chromatography-tandem mass spectrometry method with high sensitivity, specificity and reproducibility. Creatinine-adjusted EM were evaluated individually, by metabolic pathway (e.g., 2-, 4-, and 16-hydroxylation; catechols and methylated catechols) and by pathway ratios. Geometric means and p values were calculated using multivariable generalized linear models. Significant associations were found for menstrual cycle pattern and length and age at first birth. Relative to women with regular menstrual cycles, women with irregular cycles had lower urinary levels of total EM (p=0.01), estradiol (p=0.03), 16-hydroxylation pathway EM (p<0.01) and a higher 4/16 hydroxylation ratio (p=0.02). Differences ranged from 22.1% for total EMs to 70.5% for the 4/16 hydroxylation ratio. Longer menstrual cycle length was associated with higher levels of estrone (p=0.02), estradiol (p=0.01) and 16-hydroxylation pathway EM (p=0.03). The percent difference between <26 day cycles and ≥32 day cycles ranged from 23.9% for the 16-hydroxylation pathway to 26.9% for estrone. Higher age at first birth was associated with lower 16-hydroxylation pathway EM (p=0.03) and higher 2/16-hydroxylation (p=0.02) and 4/16-hydroxylation (p=0.01) ratios. Percent difference for age at first birth ranged from 15.1% for the 16-hydroxylation pathway EM to 59.7% for the 4/16-hydroxylation ratio. Breastfeeding, OC use, parity and age at menarche were not significantly associated with urinary EM metabolic pathways. These data provide an important initial evaluation of the associations between reproductive factors important in breast cancer etiology and patterns of estrogen metabolism, as measured by the urinary luteal levels of 15 EM. In a large sample of premenopausal women, menstrual cycle length and pattern and age at first birth are significantly associated with estrogen metabolism profiles. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4634. doi:10.1158/1538-7445.AM2011-4634