Sources of elevated serum androgens in postmenopausal women who develop breast cancer

Postmenopausal women with elevated serum androgens are at an increased risk of breast cancer. High dehydroepiandrosterone sulfate concentrations in th ese women suggest increased adrenal secretion. Both the adrenals and ovarie s could contribute to elevated concentrations of androstenedione (Delta (4) A). 11 beta -Hydroxyandrostenedione (11 beta OHA) is elevated, and the Delt a (4)A:11 beta OHA ratio is depressed when the adrenals are the primary sou rce of elevated Delta (4)A in women. Conversely, Delta (4)A:11 beta OHA is elevated when the ovaries are the primary source. We prospectively evaluate d associations of serum 11 beta OHA and Delta (4)A:11 beta OHA with breast cancer in the Columbia, Missouri Serum Bank to identify the source of eleva ted Delta (4)A related to risk. Fifty-three postmenopausal women who were n ot taking estrogens when they donated blood and were diagnosed with breast cancer up to 10 years later (median, 2.9 years) served as cases. Two contro ls, who were also postmenopausal and not taking estrogens, were matched to each case on age, date, and time of blood collection. Serum Delta (4)A conc entration was significantly (trend P = 0.02) positively associated with bre ast cancer risk. Adjusted risk ratios for women in the lowest to highest te rtiles were 1.0, 1.6, and 2.4 [95% confidence interval (CI), 0.9-6.5]. Howe ver, neither 11 beta OHA concentration nor Delta (4)A:11 beta OHA was relat ed to risk. Comparable risk ratios were 1.0, 1.2, and 1.4 (95% CI, 0.5-3.6) for 11 beta OHA and 1.0, 1.2, and 1.2 (95% CI, 0.4-3.5) for Delta (4)A:11 beta OHA, Our results suggest that neither the ovaries nor adrenals are the predominant source of elevated serum Delta (4)A in postmenopausal women wh o develop breast cancer, but rather both may contribute.