Obesity, hormones, and cancer.

Obesity is a physiological state associated with alterations in hormone production and metabolism. These hormonal changes may bear on the increased risk for selected neoplastic disorders. Obesity is associated with increased estrone production in young and older women as well as in men. The source of this increased estrogen appears to be extragonadal metabolism of the prehormone androstenedione, which increases 3- to 4-fold in proportion to the obesity. In severe obesity, androstenedione production itself may be increased, providing extra prehormone for conversion to estrogens. In addition, obesity appears to shift peripheral metabolism of estradiol, resulting in decreased excretion of catechol estrogens which in turn may influence target organ stimulation. Testosterone production is unchanged in obesity; however, there are decreased levels of sex hormone-binding beta-globulin leading to increased clearance rates and spuriously low levels of circulating testosterone in both obese men and obese women. Alterations in sex hormone-binding beta-globulin may further lead to changes in "free" estradiol, which may play a role in target organ stimulation. Other changes noted in obesity include: (a) increased excretion of corticoid metabolites; (b) increased secretion of insulin but decreased insulin effectiveness; (c) blunted growth hormone responses to various challenges; and (d) possibly blunted prolactin responsiveness. There are no reasons at present to suspect that these changes influence cancer risk. With weight loss, sex hormone-binding beta-globulin changes are restored toward normal as are the elevated plasma estrogens and decreased testosterone levels. BEcause weight loss and dieting per se are associated with many physiological changes, hormonal measurements during these times are difficult to interpret. Few studies to date have been performed in formerly obese patients stabilized at their new weight.