Q:Do serum levels of androgens predict cancer risk in pre/post-menopausal women? The answer to this question depends on the cohorts of patients and/or the methodologies employed. Large meta-analyses of serum androgen levels have suggested detrimental or beneficial effects in both pre- and post-menopausal women, and clinical studies evaluating only postmenopausal women taking androgens in combination with progesterone have had similarly mixed results. At this juncture, the ball is still in the air, which may be partially due to the fact that studies have not necessarily been fully able to incorporate the local intracrine environment of the breast. This is considered important, as despite the fact that serum circulating androgens are the precursors of estrogens, the eventual impact of these androgens on breast tissues will be determined by the intracrine cascade of enzymatic reactions. Because this intracrine cascade could generate very different steroid profiles in breast tissue compared with serum, the levels of steroid-metabolizing enzymes can be a pertinent confounding factor in determining the correlation between serum levels of androgens and clinical outcomes. In particular, androgens such as DHEA and testosterone can, under the appropriate intracrine environment, be converted into potent estrogens, such as estradiol, in breast cancer tissues. The main enzyme responsible for this conversion is aromatase, which utilizes testosterone as a substrate and produces estradiol as a final product.
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