Androgen regulation of prostate cancer: where are we now?

Androgens play an essential role in the development and differentiation of the prostate gland; their contribution to pathological conditions, such as benign prostatic hyperplasia and prostate cancer (PC), remains unclear.

We reviewed relationships between androgens and the prostate both in physiological and pathological conditions.

A systematic search of published evidence was performed using Medline (1969 to September 2010).

Androgen-dependency of prostate growth is evident only in the hypogonadal condition, but not in the eugonadal state (the "saturation hypothesis"). There is unequivocal evidence that reducing androgen signaling to the hypogonadal range can reduce PC growth and patient symptoms. At physiological testosterone concentration there is no link between androgen levels and PC risk. In addition, different strategies of androgen deprivation (ADT) for advanced PC are only palliative and rarely cure patients. Preliminary evidence indicates that a low androgen milieu is associated with tumor aggressiveness. Transition to androgen-independence is complex and involves both selection and outgrowth of preexisting androgen resistant clones, as well as adaptative upregulation of genes that help the cancer cells to survive and grow after ADT. Because androgens are essential for the regulation of fat distribution, insulin sensitivity, and lipid and bone metabolism, recent publications have highlighted the concept that ADT may also be involved with an increase in overall, as well as cardiovascular, morbidity and mortality.

While ADT still represents a cornerstone for the palliative therapy of a small fraction of aggressive PC, a "misuse and/or abuse" of ADT should be avoided.