Use of Inhibitors of Sex Steroid Synthesis

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5a-Reductase is an attractive target for the modulation of sex hormone synthesis. In this regard, studies have shown that treatment of animals with 4-hydroxyandrostenedione (4-OHA), a potent inhibitor of 5a-reductase activity, attenuated alterations in cytokine production after trauma-hemorrhage (Schneider et al., 2003). Other 5a-reductase inhibitors that can be used are 4-azasteroids, 6-azasteroids, and 10-azasteroids (Flores et al., 2003; Occhiato et al., 2004). Finasteride is among the first 5a-reductase inhibitors approved in the United States for the treatment of benign pro-static hyperplasia. In humans, finasteride decreases prostatic DHT levels by 70-90% and reduces prostate size (Flores et al., 2003; Occhiato et al., 2004) while testosterone tissue levels remain constant. The use of finasteride demonstrated a sustained improvement in the treatment of benign prosta-tic hyperplasia (Flores et al., 2003; Occhiato et al., 2004). Other potent and selective inhibitors of 5a-reductase, such as androstandiene-3-carboxylic, Epristeride, and estratriene carboxylic acid, have also demonstrated a high inhibitory activity (Flores et al., 2003; Occhiato et al., 2004). Epristeride has been shown to lower serum DHT levels by 50% in clinical trials (Flores et al., 2003; Occhiato et al., 2004).

Aromatase inhibitors are another class of antiestrogen medications that suppress estrogen levels in the blood by inhibiting one of the enzymes needed to produce the hormone. These drugs, which include letrozole, anastrozole, and exemestane, work best in postmenopausal women (Brodie and Njar, 2000;Arora and Potter, 2004). Furthermore, formestane and exam-estane have been shown to be effective in breast cancer patients with advanced disease (Brodie and Njar, 2000;Arora and Potter, 2004). A number of other inhibitors such as 7a-substituted androstenediones evaluated clinically are exemestane, atemestane, and 10-propagylandrostenedione (Brodie and Njar, 2000; Arora and Potter, 2004).Although both atemestane and 10-propagylandrostenedione are potent aromatase inhibitors and highly effective in lowering estrogen levels in breast cancer patients, only exemestane currently remains an available treatment option.

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