Controversies Surrounding Androgen Deprivation for Prostate Cancer

Stephen G. Patterson, MD, Lodovico Balducci, MD, Julio M. Pow-Sang, MD

Disclosures

Cancer Control. 2002;9(4) 

In This Article

Physiological Changes Associated With Castration

Gonadal steroids influence growth rate and body composition. Adult males of most mammalian species are heavier and have a larger skeleton, more protein, a lower amount of body fat, and a higher resting energy expenditure than female or castrated animals.[66] Castration has been observed to have cumulative detrimental effects on the musculoskeletal system, endocrine system, and cardiovascular system, as well as the more commonly considered effects on libido and potency. Testosterone is connected with the maintenance of lean body mass and body fat distribution. Reduction in serum testosterone to castrate levels frequently results in weight loss and an increase in fat gain. Animal studies have been performed examining the metabolic effects of medical castration. Studies have objectively shown castration to induce body fat, and whole body protein content has been shown to be unchanged or decreased secondary to medical castration in animals.[67,68]

An animal study performed examining the relation-ship of castration and cortical bone formation revealed that castration slowed the rate of bone formation and accelerated the rate of bone resorption.[69] Castration was found to affect the composition and the quality of cortical bone as well. The quantity of cortical bone was observed to have progressive reduction with longer time after castration. Inhibited rate of bone formation and accelerated rate of bone resorption were found to be the etiology. Compared with intact animals, castrated animals had reduced their bone mass between 12% and 29%. The reduction in bone mass after castration has also been reported by other groups.[70,71,72] It was concluded that castration produced marked osteoporosis or osteopenia of the cortical bone as a result of changed rates of both bone formation and bone resorption.[69] Observations documenting an increase in frequency of osteoporotic fractures in men receiving androgen deprivation therapy have been made[73] as well as diminished bone mineral density with increasing duration of androgen deprivation therapy.[74]

A study examining 10 men who had prostate cancer and were treated with buserelin over a 12-month period evaluated the effects of the LHRH agonist on protein and glucose metabolism. Treatment with buserelin was associated with a reduction in cortisol, an increase in triiodothyronine (T3) and free triiodothyronine (free T3), and a 17% increase in serum cholesterol. Basal energy expenditure was not changed over time. Increases in body weight, triceps skin fold, cholesterol, and fat mass were noted in the subjects.[75]

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