BENIGN PROSTATIC HYPERPLASIA - THE RESULT OF AN AGE-DEPENDENT ALTERATION OF THE ANDROGEN-ESTROGEN BALANCE

Although human benign prostatic hyperplasia (BPH) is the most common t umor in men, its etiology is still unclear. At present, it is only wid ely accepted that BPH is under the endocrine control of the testes and strongly associated with aging. Therefore, in the human prostate we d escribe the impact of aging on the activity of various androgen metabo lizing enzymes as well as on the endogenous androgen and estrogen leve ls. Moreover, the inhibition of 5 alpha-reductase by finasteride (Pros car(R)) will be reported. Among all androgen metabolizing enzymes, wit hin the human prostate 5 alpha-reduclase is the most powerful one. Mos t of the androgen metabolizing enzymes undergo a significant age-depen dent alteration. For distinct enzymes, the correlation with age is eit her negative (e.g. 5 alpha-reductase), or positive. Despite a complex pattern of age-dependent alterations, the dominance of Scr-reductase a mong all androgen metabolizing enzymes is always maintained. This is u nderlined by a strong accordance between the age-dependent Su-reductas e activity and the corresponding age-dependent endogenous DHT level. I n epithelium, both the 5 alpha-reductase activity and the DHT level de crease with age, whereas in stroma not only the 5 alpha-reductase acti vity is rather constant over the whole age range but the DHT level as well. In contrast to the relatively unaltered DHT content in the strom a of the human prostate, the estrogen content follows an age-dependent increase. On the other side, in epithelium such a positive correlatio n between the estrogen level and age is not Found. Thus, the age-depen dent decrease of the DHT accumulation in epithelium and the concomitan t increase of the estrogen accumulation in stroma will lead to a treme ndous increase with age of the estrogen/androgen ratio in the human pr ostate. This could be of pathogenetic importance for BPH development i f in fact a balanced androgen/estrogen synergism is necessary fur the integrity of the normal human prostate. Finally, it is remarkable that the inhibition of 5 alpha-reductase activity by finasteride (Proscar( R)) is significantly stronger in epithelium than in stroma. Therefore, it is conceivable that the global size-reduction of BPH under finaste ride treatment is primarily due to the regression of BPH epithelium.