Peripheral aromatization as a risk factor for breast and endometrial cancer in postmenopausal women: a review.
In menopause, estrogens are produced almost exclusively through peripheral aromatization of androgens, especially androstenedione. Obesity increases the production rate of estrogens by means of the same mechanism. In postmenopause, plasma levels of SHBG diminish significantly. Obesity even further decreases the levels of SHBG, thus increasing "free" E2 available to target tissues. The increase in circulating estrogenic activity in menopause, whether as a result of obesity or of ingestion of estrogens, implies a risk factor for endometrial and breast cancer not only because of the permissive and stimulating effects of estrogens but also due to the special circumstance that they may act on target tissues in the almost absolute absence of the "protecting effect" of progesterone. The modifications performed by obesity on the values of SHBG and circulating estrogens are reversible, since they tend to normalize with weight loss.
D000273:Adipose Tissue / Q000378:metabolism; D000728:Androgens / Q000378:metabolism; D001692:Biological Transport; D001798:Blood Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000209:etiology / Q000378:metabolism*; D004967:Estrogens / Q000096:biosynthesis; D004966:Estrogens, Conjugated (USP) / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D011485:Protein Binding; D012306:Risk; D014594:Uterine Neoplasms / Q000209:etiology / Q000378:metabolism*
D000728:Androgens; D001798:Blood Proteins; D004967:Estrogens; D004966:Estrogens, Conjugated (USP)