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Marked Suppression of Dihydrotestosterone in Men with Benign Prostatic Hyperplasia by Dutasteride, a Dual 5-Reductase Inhibitor

Clinical Pharmacology (R.V.C., D.J.H.) and Clinical Development (T.H.W., B.B.M., S.H.), GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709; and Department of Medicine and Endocrinology (G.R.C.), Baylor College of Medicine, Houston, Texas 77030

Address all correspondence and requests for reprints to: Richard V. Clark, M.D., Ph.D., Clinical Pharmacology–Metabolic Discovery Medicine, 17.1356H, GlaxoSmithKline Research and Development, 5 Moore Drive, P.O. Box 13398, Research Triangle Park, North Carolina 27709. E-mail: richard.v.clark{at}gsk.com.

Dihydrotestosterone (DHT) is the primary metabolite of testosterone in the prostate and skin. Testosterone is converted to DHT by 5-reductase, which exists in two isoenzyme forms (types 1 and 2). DHT is associated with development of benign prostatic hyperplasia (BPH), and reduction in its level with 5-reductase inhibitors improves the symptoms associated with BPH and reduces the risk of acute urinary retention and prostate surgery. A selective inhibitor of the type 2 isoenzyme (finasteride) has been shown to decrease serum DHT by about 70%. We hypothesized that inhibition of both isoenzymes with the dual inhibitor dutasteride would more effectively suppress serum DHT levels than selective inhibition of only the type 2 isoenzyme.

A total of 399 patients with BPH were randomized to receive once-daily dosing for 24 wk of dutasteride (0.01, 0.05, 0.5, 2.5, or 5.0 mg), 5 mg finasteride, or placebo. The mean percent decrease in DHT was 98.4 ± 1.2% with 5.0 mg dutasteride and 94.7 ± 3.3% with 0.5 mg dutasteride, significantly lower (P < 0.001) and with less variability than the 70.8 ± 18.3% suppression observed with 5 mg finasteride. Mean testosterone levels increased but remained in the normal range for all treatment groups. Dutasteride appeared to be well tolerated with an adverse event profile similar to placebo.

Abbreviations: BPH, Benign prostatic hyperplasia; DHT, dihydrotestosterone.

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