Studies in Men with Androgenic Disorders

Natural History and Anatomic Progression of Benign Prostatic Hyperplasia 

As BPH progresses, the excess tissue results in prostatic enlargement and causes urethral obstruction. This obstruction is typically associated with characteristic symptoms such as hesitancy in starting urination, diminished urine stream size and force, involuntary interruptions in stream, and a sensation of incomplete bladder emptying (Claridge, 1966). In men with BPH, the mean decrease in maximum urinary flow rate is about 0.2 ml/s/year (Ball et al, 1981). 

In patients with BPH treated with finasteride (1-100 mg/day) for 7 to 10 days prior to prostatectomy, prostatic tissue removed at surgery contained approximately 80% less DHT and 10 times more testosterone, as compared with that for placebo-treated patients (McConnell et al., 1992). In the dog, the only known animal model of spontaneous BPH, treatment with finasteride resulted in a significant reduction in prostate volume, as determined by magnetic resonance imaging (MRI), which was accompanied by a marked decrease in intraprostatic DHT levels (Cohen et al, 1991). 

Placebo-controlled urodynamic studies in men with BPH have unequivocally demonstrated that finasteride produces objective improvement in bladder oudet obstruction (Tammela and Kontturi, 1993 Kirby et al., 1992 Abrams et al., 1999 Schaffer et al., 1999). Singlecenter studies using detrusor pressure to measure outflow obstruction demonstrated that the majority of finasteride-treated patients were shifted out of the obstructed range as compared with placebo patients over a 3- to 6-month study period (Tammela and Kontturi, 1993 Kirby et al., 1992). Similar results were reported in a 1-year multicenter study in men with BPH (Abrams et al., 1999). Moreover, this study demonstrated that the magnitude of the improvement in bladder oudet obstruction and maximal urinary flow rate with finasteride over placebo increases with increasing prostate volume. Long-term (1-year), open-label follow-up evaluation for this study demonstrated further reductions in bladder oudet obstruction with chronic finasteride therapy (Schaffer etal, 1999). 

Safety was evaluated extensively in the two phase III trials. The frequency of adverse effects observed in the 12-month controlled studies 

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