Association between reproductive factors and urinary estrogens and estrogen metabolites in premenopausal women

Little is known about relationships among reproductive factors, estrogens and estrogen metabolites (jointly referred to as EM), and estrogen metabolism patterns.

In a cross-sectional analysis, we examined the associations of age at menarche, menstrual cycle length and regularity, parity, age at first and last birth, breastfeeding, and duration of and time since use of oral contraceptives with mid-luteal phase urinary EM in a sample of 603 premenopausal women, ages 33 to 51 years, within the Nurses' Health Study II (NHSII). Fifteen individual urinary EMs were measured with liquid chromatography/tandem mass spectrometry (LC/MS-MS) and analyzed both individually and in metabolic pathways.

Compared with women with extremely regular cycles, those with irregular cycles had lower levels of total EM (percent difference = 24%; P(trend) = 0.01), estradiol (23%; P(trend) = 0.02), and 16-hydroxylation pathway EM (32%; P(trend) < 0.01). Longer menstrual cycles were associated with higher levels of estrone (percent difference ≥32 vs. <26 days: 25%; P(trend) = 0.03), estradiol (24%; P(trend) = 0.01), and 16-hydroxylation pathway EM (22%; P(trend) = 0.02). Among parous women, older age at first birth was associated with lower 16-hydroxylation pathway EM (percent difference age at first birth >35 vs. ≤25 years: 20%; P(trend) = 0.02). The other reproductive factors were not statistically significantly associated with individual urinary EM or EM pathways.

These data, based on a LC/MS-MS assay with high specificity and precision, provide an initial, comprehensive evaluation of the associations between reproductive factors and estrogen metabolism patterns.