Wein: Campbell-Walsh Urology, 9th ed.

Copyright © 2007 Saunders, An Imprint of Elsevier

AROMATASE INHIBITORS
Rationale for Aromatase Inhibitors for Benign Prostatic Hyperplasia

The rationale for aromatase inhibition is that estrogens may be involved in the
pathogenesis of BPH. The estrogenic effect most likely mediates stromal-epithelial interactions
that regulate the proliferative activity of the prostate. Several observations support the role of
stroma in the development of BPH and the influence of estrogens on prostatic stroma. The
inductive potential of prostatic mesenchyme (stroma) is supported by the observation of Cunha
and colleagues (1980) in a mouse embryonic animal model. Coffey and Walsh (1990) reported
that estrogen treatment of castrated beagles produced a threefold to fourfold increase in the total
amount of prostatic stroma. Estrogens also greatly enhanced the ability of androgens to induce
BPH in a canine model ( Walsh and Wilson, 1976 ; DeKlerk et al, 1979 ). This synergistic effect
may be mediated by the ability of estrogens to upregulate prostatic AR content. Stromal
hyperplasia can be induced in the prostates of dogs and monkeys treated with aromatizable
androgens and prevented by aromatase inhibitors such as atamestane ( Habenicht et al, 1987 ;
Habenicht and El Etreby, 1989 ).

Review of the Literature

Atamestane is a highly selective aromatase inhibitor that lowers both serum and intraprostatic
levels of estradiol and estrone ( El Etreby et al, 1991 ). Gingell and coworkers (1995) reported a
multicenter, randomized, double-blind, placebo-controlled study comparing placebo and
400 mg of atamestane in 160 subjects with clinical BPH. Atamestane resulted in a statistically
significant decrease in serum estradiol and estrone levels and a statistically significant increase in
serum testosterone. No statistically significant group mean differences were observed for
changes in Boyarsky symptom score, PFR, or prostate volume between the atamestane and the
placebo groups. One of the explanations contributing to the failure of atamestane to achieve
clinical efficacy was the increase in testosterone. The development of atamestane for BPH was
suspended because of these negative clinical findings. The failure to demonstrate that atamestane
causes regression of established BPH or clinical improvement does not negate the influence of
estrogens in the pathogenesis of BPH.

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