PubMed · 1319540
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S Heinzl. 1992. [Target enzyme].. https://pubmed.ncbi.nlm.nih.gov/1319540/
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OBJECTIVE: To examine the long-term (4-year) safety and tolerability of dutasteride in the treatment of symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Patients who completed the double-blind phase of three dutasteride Phase III studies were eligible to enter a 2-year open-label extension, during which all patients received dutasteride 0.5 mg. Safety was assessed, including adverse-event reporting, clinical laboratory assessments, yearly physical examinations, and vital sign assessments. RESULTS: In all, 2340 patients entered the open-label phase, 1188 of whom previously received dutasteride during the double-blind phase of the study. The most common drug-related adverse events (occurring in > or = 1%) were effects on sexual function, which decreased with a longer duration of therapy. Gynaecomastia was reported in a small percentage of men throughout the 4-year study period. The incidence of individual sexual functional adverse events that led to withdrawal was < or = 1% (0.3-1.0%) during the 4-year study period. Dutasteride had no relevant effects on vital signs or clinical laboratory variables. CONCLUSION: These data show that dutasteride is well tolerated during long-term use for the treatment of symptomatic BPH.
RATIONALE: Greater incidence of anxiety and depressive disorders of women compared to men may be due in part to progesterone (P) and its neuroactive metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), acting in limbic regions, such as the amygdala. OBJECTIVE: If P's metabolism via 5alpha-reduction to 3alpha,5alpha-THP in the amygdala is critical for antianxiety and antidepressive behavior, then blocking 5alpha-reductase in the amygdala of female rats is likely to attenuate the antianxiety and antidepressive effects of high progestin levels from both endogenous and exogenous sources. METHODS: Naturally receptive female rats with high endogenous estrogen (E2) and P and ovariectomized (ovx) rats administered E2 (10 microg) and P (500 microg) subcutaneously were administered finasteride (10 microg/microl), a Type II 5alpha-reductase inhibitor, or vehicle to the amygdala. Anxiety behavior (open field, elevated plus maze, defensive freezing) and depressive behavior (Porsolt forced swim test) were assessed. RESULTS: There were similar effects of finasteride administration to the amygdala to attenuate antianxiety behavior in naturally receptive and ovx, hormone-primed rats. Finasteride administration significantly decreased central entries in the open field, decreased open arm time in the elevated plus maze, increased defensive freezing in response to footshock, and increased time spent immobile compared to vehicle. CONCLUSIONS: Thus, formation and subsequent actions of 3alpha,5alpha-THP in the amygdala may be important for antianxiety and antidepressive effects.
Prostate cancer has become the most frequently diagnosed male cancer next to non-melanotic skin cancer in the Western world. Preventive measures would therefore have important potential effects on the incidence and prevalence of this disease. A potential for effective prevention of prostate cancer is currently seen in dietary changes and perhaps in dietary supplementation with vitamins D and E or selenium. Pharmacological prevention seems a possibility with drugs acting on intraprostatic testosterone metabolism. Several large randomised trials are ongoing to clarify the potential for successful prostate cancer prevention.