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Obesity, Androgens, Estrogens, and Cancer Risk¹

Newark Beth Israel Medical Center, New Jersey Medical School, Newark, New Jersey 07112, and V. A. Hospital, East Orange, New Jersey 07019

Obesity is associated with increased incidence of cancers arising from tissues responsive to estrogenic stimulation, including endometrium, breast, and prostate. We thus wished to explore estrogen production and its origin in obesity in an attempt to provide a possible hormonal link to explain increased cancer risk.

Studies of the hormonal milieu of obese men and women revealed several abnormalities of sex hormone production and metabolism. (a) Androstenedione production rates are elevated and serve as proehormones of both testosterone and estrogens. (b) Extragonadal aromatization of androgens to form estrogens (androstenedione to estrone and testosterone to estradiol) is elevated, resulting in (c) increased production rates of estrogens. The obese person is thus chronically exposed to hyperestrogenemia. In addition, obesity is associated with other alterations of sex hormone metabolism such as decreased levels of sex hormone-binding globulin and increased metabolic clearance rates of several hormones.

After weight loss to ideal body weight, there appears to be normalization of androgen and estrogen production rates, as well as circulating hormone levels; however, metabolic abnormalities such as increased aromatization of androgens to estrogens and accelerated metabolic clearance rates of androstenedione remain abnormal.