Endocrine treatment of benign prostatic hypertrophy: current concepts

To summarize the endocrine approach for the treatment of BPH: much clinical data have accumulated over the past forty years. Until recently, scientists and physicians mainly concentrated on the reduction of androgens as a possible solution. We have come a long way from surgical castration, through the administration of hormones such as estrogen and progesterone, gonadotropin-releasing hormone agonists to the inhibition of an enzymatic reaction reducing testosterone to DHT--the now recognized active intracellular androgen metabolite. Recently, the role of estrogens has been emphasized with the finding that stromal hyperplasia is the main change occurring in BPH. Lately, research has been initiated to examine the clinical effect aromatase inhibitors would have in the treatment of human BPH. Since there is enough evidence that both the epithelial and stromal components of the human prostate undergo hyperplasia in BPH, and individuals vary with respect to their relative epithelial/stromal components, both structures would have to be reduced for therapy to be successful. Therefore, the combination of an antiandrogenic and antiestrogenic effect is theoretically promising. Indeed, prostates of beagles shrunken after treatment with an aromatase inhibitor, further decreased in weight after additional treatment with cyproterone acetate, an antiandrogen. We are now approaching the stage where these "antihormones" are both enzyme inhibitors with actually no side effects that preclude the use of the earlier generation's "antihormonal" hormonal drugs. Furthermore, it has recently been reported that the aromatase inhibitor, 4-hydroxy-androstenedione also inhibits human prostatic 5-alpha reductase, at least in vitro. The in vivo relevance of this finding awaits further classification. Thus, a good hormonal treatment that will be both scientifically sound, and clinically safe and effective, seems feasible in the near future. Two main factors have encouraged our interest and research into methods of inhibiting prostatic growth or reducing its obstructive symptomatology: the enormous cost of prostatic operations for outlet obstruction secondary to BPH, and the natural aging process of the population accompanied by deteriorated health precluding anesthesia and prostatic surgery. Medical treatment of BPH has to result in symptomatic improvement, elimination of residual urine, and improvement of flow to be considered successful. These are usually accomplished by surgery and results at least as good as those obtained by operation should be aimed at, if medical treatment is to replace surgery. Although indications for surgery and outcome of operations are well-defined, this is not the case when alternatives to prostatectomy are chosen.(ABSTRACT TRUNCATED AT 400 WORDS)