finasteride, Propecia
Effects of the chronic use of finasteride on testicular weight and spermatogenesis in Wistar rats.

Rhoden EL, Gobbi D, Menti E, Rhoden C, Teloken C.

Urology-Andrology Division at the Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre and Hospital Santa Casa de Misericordia de Porto Alegre, Brazil. ernanirhoden hotmail.com

OBJECTIVE: To evaluate spermatogenesis in rats chronically exposed to finasteride, as the recent use of finasteride in young men to prevent hair loss has raised concerns about chronic use and fertility. MATERIALS AND METHODS: Male Wistar rats (4 months old) were selected and divided into two groups. Group 1 (17 rats) received a finasteride suspension of 2 mg/kg/day in saline solution, 5 days/week for 10 months; group 2 (eight rats of the same age) were treated with placebo for the same period. At the end of the exposure the testes were weighed and processed for histological analysis. Spermatogenesis was evaluated as the mean number of seminiferous tubules with and without spermatozoids in their lumen, in five random fields on the same slide. Student's t-test was used to assess differences in the groups. RESULTS: In group 1, the mean (sd) weight of the testes was 1.55 (0.29) g and in group 2 1.58 (0.34) g (P>0.05). The histological analysis showed a mean of 13.35 (1.66) seminiferous tubules per field and 1.20 (3.30) tubules with no spermatozoids in group 1; in group 2 the respective values were 13.53 (1.46) and 0.06 (0.14) (P>0.05). CONCLUSION: Finasteride had no detectable effects on the quantitative and qualitative analysis of spermatogenesis in rats.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12010248&dopt=Abstract finasteride Propecia



finasteride, Propecia
Induction of apoptosis in rat ventral prostate by finasteride is associated with alteration in MAP kinase pathways and Bcl-2 related family of proteins.

Huynh H.

Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Centre of Singapore, Singapore 169610. cmrhth nccs.com.sg

Finasteride is widely used in treatment of symptomatic benign prostatic hyperplasia. Treatment of rats with finasteride caused a significant decrease in ventral prostate weight and intraprostatic dihydrotestosterone levels while intraprostatic testosterone levels were increased. Finasteride inhibited Akt-1 and MAPK expression while expression of PTEN was significantly increased only at 100 mg dose. Basal phosphorylation of c-Raf, MEK1/2, MAPK and the transcription factor Elk-1 was significantly reduced by finasteride. The rate of prostate epithelial apoptosis is equivalent to 0.1+/-0.03, 0.6+/-0.18%, 0.92+/-0.24% and 1.42+/-0.3% on treatments with 0, 1, 10 and 100 mg finasteride per kg body weight, respectively. Concomitantly, these treatments led to a 2.5-, 4.0- and 4.0-fold increase in Bad while a slight decrease in Bax was observed. Similar elevations were also observed in Bcl-xs levels which increased by 9.8-, 10- and 12-fold respectively in the finasteride treatments as compared to controls. Bcl-xL levels in ventral prostates treated with 1, 10 and 100 mg finasteride were approximately 30, 30 and 26% of control, respectively. Significant reduction in Bcl-2 expression was observed only at the dose of 100 mg/kg body weight. These findings suggest that modulation of MAP kinase and Akt expression, Bcl-xL, Bcl-xs, Bcl-2 and Bad proteins by finasteride may be, in part, responsible for the anti-proliferative and apoptotic effect of this drug seen clinically and in animal models.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12012013&dopt=Abstract finasteride Propecia



finasteride, Propecia
Potential activities of androgen metabolizing enzymes in human prostate.

Krieg M, Weisser H, Tunn S.

Institute of Clinical Chemistry, University Clinic Bergmannsheil, Bochum, Germany.

The entire androgen metabolism of the human prostate is an integral part of the DHT mediated cellular processes, which eventually give rise to the androgen responsiveness of the prostate. Therefore, the potential activities of various androgen metabolizing enzymes were studied. Moreover, the impact of aging on the androgen metabolism and the inhibition of 5 alpha-reductase by finasteride were studied. In epithelium (E) and stroma (S) of normal (NPR) and hyperplastic human prostate (BPH), for each enzyme being involved in the conversion either of testosterone via DHT, 3 alpha- and 3 beta-diol to the C19O3-triols or from testosterone to androstenedione and vice versa, the amount (Vmax) and Michaelis constant (Km) were determined by Lineweaver-Burk plots. Furthermore, Vmax/Km quotients were calculated, which served as an index for the potential enzyme activity. 17 enzymes showed a mean Vmax/Km > or = 0.10. The top four were the 5 alpha-reductases in E and S of NPR and BPH. Among those, the highest activity was found in E of NPR (1.6 +/- 0.2). Moreover, in E a significant age-dependent decrease of 5 alpha-reductase activity occurred, whereas in stroma rather constant activities were found over the whole age range. Similar age-dependent alterations were found for the cellular DHT levels. Finally, the finasteride inhibition of 5 alpha-reductase (IC50;nM) was stronger in E (35 +/- 17) than in S (126 +/- 15). In conclusion, 5 alpha-reductase is: (a) the outstanding androgen metabolizing enzyme in NPR and BPH; (b) dictating the DHT enrichment in the prostate; (c) under the impact of aging; and (d) preferentially inhibited by finasteride in E.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7542902&dopt=Abstract finasteride Propecia



finasteride, Propecia
The effects of finasteride on hematuria associated with benign prostatic hyperplasia: a preliminary report.

Puchner PJ, Miller MI.

Department of Urology, Columbia University College of Physicians and Surgeons, New York, New York, USA.

PURPOSE: The efficacy of finasteride was assessed in the treatment of gross hematuria associated with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A retrospective review was done of 18 patients who had been placed on finasteride (5 mg . daily) for the treatment of gross hematuria associated with BPH. A hematuria grading system was devised. RESULTS: Of the 12 patients with longer than 3 months of followup (mean 14) 11 improved according to the grade of hematuria after finasteride therapy. CONCLUSIONS: Finasteride is effective in treating hematuria associated with BPH. This finding is especially relevant for patients with multiple medical problems and anesthetic risks.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7563345&dopt=Abstract finasteride Propecia



finasteride, Propecia
Quantitative evaluation of glandular and stromal compartments in hyperplastic dog prostates: effect of 5-alpha reductase inhibitors.

Laroque PA, Prahalada S, Molon-Noblot S, Cohen SM, Soper K, Duprat P, Peter CP, van Zwieten MJ.

Merck Research Laboratories, Merck & Co., Riom, France.

The objective of this study was to determine the effects of 2 different 5-alpha reductase inhibitors (finasteride and MK-0434) on the glandular and stromal compartments of hyperplastic canine prostates. In this study, dogs received 1 of the 2 compounds orally, at a dose of 1 mg/kg/day for 16 weeks; control dogs received a placebo. The morphological changes in the glandular and stromal compartments in the prostate were quantitated by a point-counting method on Masson's trichrome-stained sections. Treatment with 5-alpha reductase inhibitors resulted in significant (P < or = 0.05) decreases in mean prostatic volumes, microscopic evidence of prostatic atrophy, and significant (P < or = 0.05) decreases in the absolute volumes of the prostatic glandular and stromal compartments compared to controls. In finasteride-treated dogs, the mean percent change from baseline was: epithelium, -52; lumens, -58; fibrovascular stroma, -41; and smooth muscle, -29. In MK-0434-treated dogs, the mean percent change from baseline was: epithelium, -77; lumens, -58; fibrovascular stroma, -38; and smooth muscle, -42. The effect on the glandular compartment in dogs treated with MK-0434 was slightly greater than in dogs treated with finasteride; however, the effect on the stroma was similar. These results clearly demonstrate that inhibition of 5-alpha reductase enzyme activity affects growth and maintenance of both glandular and stromal compartments of dog hyperplastic prostates. It is likely that the decrease in size of the prostate in finasteride-treated (Proscar) men is due to shrinkage of both glandular and stromal compartments.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7567690&dopt=Abstract finasteride Propecia



finasteride, Propecia
Local and systemic reduction by topical finasteride or flutamide of hamster flank organ size and enzyme activity.

Chen C, Puy LA, Simard J, Li X, Singh SM, Labrie F.

MRC Group in Molecular Endocrinology, CHUL Research Center, Quebec, Canada.

The hamster flank organ is a widely used model of the control of sebaceous gland activity by androgens and anti-androgens. Finasteride, a 5 alpha-reductase inhibitor, was administered locally on the surface of the right flank organ and right ear twice daily for 4 weeks. The treatment caused similar 12% to 30% reductions in the size of the sebaceous glands in both flank organs. Moreover, relative mRNA levels of the androgen-regulated FAR-17a gene measured by in situ hybridization as well as [3H]-thymidine incorporation and 5 alpha-reductase activity were similarly decreased in the two flank organs after topical application. The pure anti-androgen flutamide, at the same doses, exerted a more potent effect on all the same parameters, and the effect was also comparable on both the treated and untreated sides of flank organs. Finasteride and flutamide significantly decreased ventral and dorsal prostatic weights after topical application. The present data show that the topical administration of finasteride, in analogy with flutamide, causes local inhibition of sebaceous gland growth in both the costovertebral organs and ears. However, as demonstrated by the similar inhibitory effect in the contralateral untreated side and the reduced weight of the dorsal and ventral lobes of the prostate and seminal vesicles, finasteride and flutamide both exert significant systemic effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7594643&dopt=Abstract finasteride Propecia