D,-finasteride

Clark, R.L., Antonello, J.M., Grossman, J.T., Wise, L.D., Anderson, C., Bagdon, W.J., Prahalada, S., MacDonald, J.S. and Robertson, R.T. (1990b). External genitalia abnormalities in male rats exposed in utero to finasteride, a 5a-reductase inhibitor. Teratology 42 91-100. 

Marks, L. S., D. L. Hess, F. J. Dorey, M. Luz Macairan, P. B. Cruz Santos, and V. E. Tyler. Tissue effects of saw palmetto and finasteride use of biopsy cores for in situ quantification of pros-tatic androgens. Urology 2001 57(5) 999-1005. 

McConnell (D, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl I Med 2003 349 2387-2398. 

Spironolactone, a competitive inhibitor of aldosterone (see Chapter 15), also competes with dihydrotestosterone for the androgen receptors in target tissues. It also reduces 17a-hydroxylase activity, lowering plasma levels of testosterone and androstenedione. It is used in dosages of 50-200 mg/d in the treatment of hirsutism in women and appears to be as effective as finasteride, flutamide, or cyproterone in this condition. 

Finasteride (Propecia) is a 5K-reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone (see Chapter 40), the androgen responsible for androgenic alopecia in genetically predisposed men. Oral finasteride, 1 mg/d, promotes hair growth and prevents further hair loss in a significant proportion of men with androgenic alopecia. 

Results of recent meta-analyses and reviews suggested that saw palmetto is significantly more effective than placebo in alleviating urologic symptoms (eg, peak flow, nocturia, international prostate symptom scores) associated with mild to moderate BPH. Saw palmetto, 320 mg/d, was also shown to have comparable efficacy to 5 mg/d of finasteride (a prescription 5ot-reductase inhibitor) and 0.4 mg/d of tamsulosin (a prescription a blocker) in clinical trials lasting 6 months and 1 year, respectively. In marked contrast, a recent well-controlled, double-blind 1-year study showed no significant effect of saw palmetto on symptoms or objective measures in moderate to severe BPH. The efficacy of saw palmetto in BPH beyond 5 years has not been studied. 

De Bruyne FMJ, Jardin A, Colloi D, Resel L, Witjes WPJ, Delauche-Cavallier MC, McCarthy C, Geffriaud-Ricouard C. Sustained release alfuzosin, finasteride and the combination of both in the treatment of benign prostatic hyperplasia. Eur Urol 1998 34 169-75. 

Carraro JC, Raynaud JP, Koch G, Chisholm GD, Di Silverio F, Teillac P, Da Silva FC, Cauquil J, Chopin DK, Hamdy FC, Hanus M, Hauri D, Kalinteris A, Marencak J, Perier A, Perrin P. Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate hyperplasia a randomized international study of 1,098 patients. Prostate I996 29(4) 23 I K). 

Falsetti L, De Fusco D, Eleftheriou G, Rosina B. Treatment of hirsutism by finasteride and flutamide in women with polycystic ovary syndrome Gynaecol Endosc... 

Fruzzetti F, de Lorenzo D, Parrini D, Ricci C. Effects of finasteride, a 5 alpha-reductase inhibitor, on circulating androgens and gonadotropin secretion in hirsute women. J Clin Endocrinol Metab 1994 79(3) 831-5. 

Zimmerman RL, Fogt F, Cronin D, Lynch R. Cytologic atypia in a 53-year-old man with finasteride-induced gynecomastia. Arch Pathol Lab Med 2000 124 625-7. 

Kaplan SA, Holtgrewe HL, Bruskewitz R, Saltzman B, Mobley D, Narayan P, Lund RH, Weiner S, Wells G, Cook TJ, Meehan A, Waldstreicher J. Comparison of the efficacy and safety of finasteride in older versus younger men with benign prostatic hyperplasia. Urology 2001 57 1073-7. 

Dogol Sucar D, Botelho Sougey E, Brandao Neto J. Psychotic episode induced by potential drug interaction of sibutramine and finasteride. Rev Bras Psiquiatr 2002 24 30-3. 

Finasteride (Propecia) is a 5 -reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone, the androgen responsible for androgenic alopecia in genetically predisposed men. Oral finasteride, 1 mg/d, promotes hair growth and prevents further hair loss in a significant proportion of men with androgenic alopecia. Treatment for at least 3-6 months is necessary to see increased hair growth or prevent further hair loss. Continued treatment with finasteride is necessary to sustain benefit. Reported side effects include decreased libido, ejaculation disorders, and erectile dysfunction, which resolve in most men who remain on therapy and in all men who discontinue finasteride. 

Fig. 7. Effect of treatment with finasteride or clomiphene on expression of the 6 and 72 subunits expression and GABAergic tonic currents during pregnancy. Finasteride (25 mg/kg), clomiphene (5 mg/kg), or vehicle was administered daily from day 12 to day 18 of pregnancy, and rats were analyzed at day 19 of pregnancy for both immunohistochemistry (A—D), and electrophysiological recordings (E—H). In graphs A—D, data are expressed as percentage change relative to the...

P. O. Gisleskog, D. Hermann, M. Hammarlund-Udenaes, and M. O. Karlsson, A model for the turnover of dihydrotestosterone in the presence of the irreversible 5 alpha-reductase inhibitors Gil98745 and finasteride. Clin Pharmacol Ther 64 636-647 (1998). M. Pirmohamed and B. K. Park, in Elandbook of Drug Metabolism, T.F. Woolf (Ed.). Marcel Dekker, New York, 1999, pp. 443 76. 

K., Parlow, A.F., Miller, D.D. and Dalton, J.T. (2004) Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5a-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats new approach for benign prostate hyperplasia. Endocrinology, 145, 5420-5428. 

Canby-Hayino, E. D., Brand, T. C., Hernandez, J., and Thompson, 1. M. 2006. Chemoprevention of prostate cancer with finasteride. Expert Opin. Pharmacother. 7 849-905. 

Substances that have been associated with increases in Leydig cell tumours in mice are mainly chemicals with clear oestrogenic properties, e.g., diethylstilboestrol, methoxychlor, tri-p-anisylchloroethylene, stilboestrol, 17/3-oestradiol, oestradiol ester, tamoxifen and triphenylethylene [171-179]. Other compounds active in mice are finasteride, a 5a-reductase inhibitor that also induces Leydig cell hyperplasia, but not adenomas, in Sprague-Dawley rats [170,180] and M-nitrosodiethylamine [181]. In contrast to its effects in mice and Syrian and European hamsters [182], 17)d-oestradiol treatment of rats does not induce Leydig cell tumours and inhibits the appearance of the spontaneous tumours in the F344 strain [184]. 

Figure 23 Proposed chemical mechanism for formation of NADP-finasteride bisubstrate analog. Reprinted with permission from H. G. Bull M. Garcia-Calvo S. Andersson W. F. Baginsky H. K. Chan D. E. Ellsworth R. R. Miller R. A. Stearns R. K. Bakshi G. H. Rasmussen R. L. Tolman R. W. Myers J. W. Kozarich G. S. Harris, J. Am. Chem. Soc. 1996, 118, 2359-2365. Copyright 1996 American Chemical Society. 

Huskey, S.-E.W. Dean, D.C. Miller, R.R. Rasmusson, G.H. Chiu, S.-H.L. Identification of human cytochrome P450 isozymes responsible for the in vitro oxidative metabolism of finasteride. Drug Me-tab.Dispos., 1995, 23, 1126-1135... 

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