finasteride, Propecia
Finasteride blocks the reduction in ictal activity produced by exogenous estrous cyclicity.

Frye CA, Scalise TJ, Bayon LE.

Department of Psychology, Connecticut College, New London 06320, USA.

The purpose of the present study was to examine seizure activity during reduced 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) production. Ovariectomized Long-Evans rats were stereotaxically implanted with bipolar electrodes above the perforant pathway; silastic implants filled with estradiol-17-benzoate (EB) and progesterone were inserted subcutaneously to mimic diestrus. Estrus was then induced in half of these animals by injection of EB (30 microg) and progesterone (2.5 mg), 48 and 4 h, respectively, prior to perforant pathway stimulation. Half of the estrous and diestrous rats also received a 5alpha-reductase inhibitor, finasteride (50 mg/kg), 6 h prior to perforant pathway stimulation. The estrous condition was associated with reduced number and duration of partial seizures, improved performance on a Morris water maze recovery of function test, reduced neuronal loss in the hilar region of the hippocampus, and elevated central and plasma 3alpha,5alpha-THP, compared to estrus+finasteride, diestrus+vehicle and diestrus+finasteride conditions, which did not differ from each another. These data suggest antiseizure effects of estrus may be caused, in part, by the action of 3alpha,5alpha-THP and that the precipitous decline in 3alpha,5alpha-THP may restore seizure threshold to control levels.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9630399&dopt=Abstract finasteride Propecia



finasteride, Propecia
Comparison of cyproterone acetate plus ethinyl estradiol and finasteride in the treatment of hirsutism.

Sahin Y, Bayram F, Kelestimur F, Muderris I.

Department of Obstetrics, Erciyes University, Faculty of Medicine, Kayseri, Turkey.

The aim of this study was to compare the clinical efficacy and safety of low dose cyproterone acetate-estrogen combination (Diane) and the 5 alpha-reductase inhibitor finasteride in the treatment of hirsutism. Fourty-two women with hirsutism were included in the study. Twenty-one patients treated with cyproterone acetate (CPA) 2 mg and ethinyl estradiol (E) 35 micrograms daily on days 5-25 of the menstrual cycle, 21 with finasteride 5 mg daily. Hirsutism score, hormone levels, multiscreen blood chemistry and side effects were evaluated at three-monthly intervals for 9 months. A significant decrease in hirsutism score as compared to baseline was observed after 9 months with either CPA + E (Diane) (mean +/- SE, 15.81 +/- 1.19 vs 8.38 +/- 1.21) or finasteride treatment (17.81 +/- 1.05 vs 10.86 +/- 0.91) (p < 0.0005). The reductions in hirsutism scores (mean% +/- SE) were 14.23 +/- 2.29 vs 19.77 +/- 2.22 (p < 0.05) at 3, 40.23 +/- 4.58 vs 29.49 +/- 2.69 (p < 0.02) at 6 and 50.99 +/- 4.13 vs 39.87 +/- 3.30 (p < 0.02) at 9 months in CPA + E and finasteride groups, respectively. No significant changes were observed in hormone levels during finasteride treatment. Serum free testosterone significantly decreased at the third month of treatment, and remained suppressed for the duration of treatment in CPA + E group. DHEAS levels also decreased significantly after 6 and 9 months of therapy with CPA + E. SHBG significantly increased during CPA + E treatment. We conclude that both drugs are effective and well tolerated, but CPA + E appears to be more effective than 5 alpha-reductase inhibitor finasteride in long-term treatment of hirsute women. Diane is also a cost-effective drug.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9699125&dopt=Abstract finasteride Propecia



finasteride, Propecia
[Comparative evaluation of the effectiveness and safety of combined drug therapy of patients with benign prostatic hyperplasia with finasteride and alfuzozine]

[Article in Russian]

Loran OB, Pushkar' DIu, Rasner PI.

A finasteride + alfuzozine combination was used in 3-year treatment of 138 patients with initial benign prostatic hyperplasia (BPH). The principle of the combination is in parallel administration of 5 alpha-reductase inhibitors which inhibit cell proliferation at the hormonal level and alpha-adrenoblockers affecting the smooth muscle component of prostatic stroma and detruzor blood supply. Patients participating in the study had enlanged prostate (at least 60 cm3) and pronounced symptoms (IPSS over 13 scores). Patients of two control groups received alfuzozine and finasteride monotherapy, respectively. Better micturition and relief of BPH symptoms were seen in 96% patients of the study group, 84 and 74% controls, respectively. Thus, compared to monotherapy, finasteride and alfuzozine were more effective in combination which is pathogenetically valid and perspective in BPH chemotherapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11877966&dopt=Abstract finasteride Propecia



finasteride, Propecia
Finasteride in the treatment of patients with moderate symptoms of benign prostatic hyperplasia.

Magoha GA.

Department of Surgery, College of Health Sciences, University of Nairobi.

This was a prospective study involving 27 patients with moderate symptoms of benign prostatic hyperplasia (BPH) treated continuously with 5 mg of finasteride daily for one year. There was improvement in clinical BPH symptoms in 22 patients (81.48%), increase in urinary flow rates by a mean of 2.2 mls/sec in 20 patients (74.07%) and a mean decrease in prostate volume of 20.9% in 25 patients (92.59%) comparable to the findings of the other investigators. No patient on finasteride therapy developed acute urinary retention suggesting reduced risk. The reversal in BPH progression stems from the ability of finasteride to reduce prostate volume thus relieving urinary obstruction and to decrease BPH symptoms and increase urinary flow rates. Finasteride therapy was well tolerated in this study. No adverse effect was observed except impotence in one patient (3.7%) and loss of libido in another patient (3.7%). For symptomatic relief in men with moderate obstructive symptoms of BPH, finasteride should be considered an effective alternative to watchful waiting. These findings warrant further investigations and may signal a positive change in the role of medical therapy in the future long term management of BPH.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9746993&dopt=Abstract finasteride Propecia



finasteride, Propecia
Cloning, expression and characterization of rhesus macaque types 1 and 2 5alpha-reductase: evidence for mechanism-based inhibition by finasteride.

Ellsworth KP, Azzolina BA, Cimis G, Bull HG, Harris GS.

Department of Biochemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.

The rhesus macaque types 1 and 2 5alpha-reductase (5aR1 and 5aR2) were cloned and expressed in COS cells to facilitate comparison of rhesus and human 5aRs. The deduced protein sequences of the rhesus SaRs shared 94% and 96% identity with the human type 1 and 2 isozymes, respectively. Despite a four amino acid insertion at the N-terminal region of rhesus 5aR1, the biochemical properties of rhesus and human homologs are very similar with respect to pH optimum, Km values for testosterone and progesterone, and inhibition by a variety of inhibitors. As expected, the biochemical properties of the human and rhesus 5aR2 are also very similar. The mechanism of inhibition of the rhesus 5aR1 and 5aR2 by finasteride was investigated in more detail. Finasteride displays time dependent inhibition of the rhesus 5aR1 and 5aR2 with second order rate constants of 4 x 10(3) M(-1) s(-1) and 5.2 x 10(5) M(-1)s(-1). Inhibition of rhesus 5aR2 with 3H-finasteride resulted in 3H bound to the enzyme which is not released by dialysis. Heat denaturation of the [rhesus SaR2:inhibitor] complex releases dihydrofinasteride, a breakdown product presumably related to the NADP+-adduct previously identified with the human SaRs (Bull et al., Mechanism-based inhibition of human steroid 5alpha-reductase by finasteride: Enzyme catalyzed formation of NADP-dihydrofinasteride, a potent bisubstrate analog inhibitor. J. Amer. Chem. Soc., 1996, 118, 2359-2365). Taken together, these results provide good evidence that the rhesus macaque is a suitable model to evaluate the pharmacological properties of finasteride and other 5aR inhibitors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9749833&dopt=Abstract finasteride Propecia



finasteride, Propecia
Regressive changes in finasteride-treated human hyperplastic prostates correlate with an upregulation of TGF-beta receptor expression.

Saez C, Gonzalez-Baena AC, Japon MA, Giraldez J, Segura DI, Miranda G, Rodriguez-Vallejo JM, Gonzalez-Esteban J, Torrubia F.

Department of Pathology, Hospital Universitario Virgen del Rocio, Seville, Spain. dsegura hvr.sas.cica.es

BACKGROUND: Prostatic atrophy has been documented histologically as a consequence of finasteride action on human hyperplastic prostates. An increase in apoptotic rates has also been reported in androgen-deprived hyperplastic prostates. Transforming growth factor beta (TGF-beta) signaling is implicated in apoptotic cell death. TGF-betas have been detected in normal and diseased human prostate. In the normal prostate, TGF-beta acts as a predominantly negative growth regulator. TGF-beta signaling receptors TbetaRI and TbetaRII have been shown to be negatively regulated by androgens. METHODS: We studied the histological changes in 9 selected finasteride-treated patients with benign prostatic hyperplasia (BPH), and analyzed the levels of expression and localization of TGF-beta receptor types TbetaRI and TbetaRII in these patients as compared to selected BPH controls. RESULTS: The prostatic epithelial compartment seemed to be a primary target site for finasteride action, since we observed moderate to severe glandular atrophy after 4-6 months of treatment. TGF-beta receptors were upregulated in treated cases. We assessed a twofold increase in TbetaRII mRNA levels in treated cases as compared to controls. An increase in both TbetaRI and TbetaRII at the protein level by immunostaining was observed, which also provided a helpful means for detecting glands undergoing regression. CONCLUSIONS: We conclude that finasteride may modulate the TGF-beta signaling system to promote changes leading to apoptosis of epithelial cells and prostatic glandular atrophy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9759702&dopt=Abstract finasteride Propecia