finasteride, Propecia
Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rat.

Bowman CJ, Barlow NJ, Turner KJ, Wallace DG, Foster PM.

CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709, USA.

Finasteride is a specific inhibitor of type II 5alpha-reductase, the enzyme that converts testosterone (T) to the more potent androgen receptor agonist dihydrotestosterone (DHT). In utero exposure to androgen receptor antagonists and T biosynthesis inhibitors have induced permanent effects on androgen-sensitive end points such as anogenital distance (AGD), nipple retention, and malformations of the male rat reproductive tract. The objectives of this study were to (1) characterize the dose response of finasteride-mediated alterations in androgen-dependent developmental end points, (2) determine whether prenatal exposure to finasteride permanently decreases AGD or results in nipple retention, and (3) evaluate whether AGD or nipple retention is predictive of adverse alterations in the male reproductive tract. Pregnant Crl:CD(SD)BR rats (n=5-6/group) were gavaged with either vehicle or finasteride at 0.01, 0.1, 1.0, 10, or 100 mg/kg/day on gestation days 12 to 21. All male offspring were monitored individually until necropsy on postnatal day (PND) 90. The present study design has been used previously for other antiandrogens and is sensitive to perturbations of the male rat reproductive tract. Decreases in AGD on PND 1 and increases in areolae-nipple retention on PND 13 were significantly different from controls in all finasteride-exposed male rats. Finasteride-induced changes in AGD and nipple retention were permanent in male rats exposed to finasteride at and above 0.1 mg/kg/day. On PND 90, dorsolateral and ventral prostate lobes were absent in 21 to 24% of rats exposed to 100 mg/kg/day finasteride and weighed significantly less at and above 10 mg/kg/day. In the highest dose group, 73% of animals had ectopic testes, much higher than previously reported. The most sensitive malformation other than decreased AGD and nipple retention was the dose-dependent increase in hypospadias. The lowest observed adverse effect level (LOAEL) for finasteride-induced permanent effects in this study was 0.1 mg/kg/day based on permanent changes in AGD and nipple retention. Finasteride-induced changes in AGD and retention of nipples were highly predictive of hypospadias, ectopic testes, and prostate malformations even though some animals with retained nipples or decreased AGD may not have had other reproductive tract malformations. In summary, prenatal exposure to finasteride specifically inhibited DHT-mediated development with little to no change in T-mediated development.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12773767&dopt=Abstract finasteride Propecia



finasteride, Propecia
Changes in nocturia from medical treatment of benign prostatic hyperplasia: secondary analysis of the Department of Veterans Affairs Cooperative Study Trial.

Johnson TM 2nd, Jones K, Williford WO, Kutner MH, Issa MM, Lepor H.

Birmingham/Atlanta GRECC, Atlanta VA Medical Center, 16780 Clairmont Road, Decatur, GA 30033, USA.

PURPOSE: We evaluate the efficacy of medical therapy on nocturia in men with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We performed a secondary analysis of data from the VA Cooperative Study Program Trial in which 1,229 men with BPH 45 to 80 years old were randomly assigned to receive terazosin, finasteride, combination or placebo. RESULTS: The 1,078 men who completed 12 months of the trial are included in this study. Of those men 1,040 (96.5%) had at least 1 episode of nocturia at baseline and 38 (3.5%) had less than 1 episode (baseline nocturia is an average of 2 measures). Of those 1,040 men 788 (75.8%) had 2 or more nocturia episodes. Overall, nocturia decreased from a baseline mean of 2.5 to 1.8, 2.1, 2.0 and 2.1 episodes in the terazosin, finasteride, combination and placebo groups, respectively. Of men with 2 or more episodes of nocturia 50% reduction in nocturia was seen in 39%, 25%, 32% and 22% in the terazosin, finasteride, combination and placebo groups, respectively. Changes in nocturia were correlated with changes in reported bother from nocturia (Pearson correlation 0.48), BPH impact index (0.32) and overall satisfaction with urinary symptoms (0.33). CONCLUSIONS: Terazosin and combination therapy reduced nocturia in men with BPH, yet the net advantage of terazosin over placebo was a net reduction of 0.3 nocturia episode. For a person to reach a 50% or greater reduction in nocturia, the advantage of terazosin over placebo was 17 percentage points. Changes in nocturia had a moderate impact on symptom specific quality of life measures.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12796667&dopt=Abstract finasteride Propecia



finasteride, Propecia
The expression of insulin-like growth factor 1 in follicular dermal papillae correlates with therapeutic efficacy of finasteride in androgenetic alopecia.

Tang L, Bernardo O, Bolduc C, Lui H, Madani S, Shapiro J.

Division of Dermatology, The University of British Columbia, Vancouver Hospital, Canada.

BACKGROUND: It is generally believed that dihydrotestosterone is one of the pivotal mediators of hair loss in androgenetic alopecia (AGA). Finasteride, which blocks the conversion of testosterone to dihydrotestosterone, has now become an integral part of the current treatment approaches for male AGA. Several lines of evidence support the notion that dermal papilla (DP) cells represent the androgen target within the hair follicle. The specific molecular regulators modulated by androgens within hair follicles in the balding scalp are unknown. OBJECTIVE: The purpose of this study was to identify and quantify changes in expression of specific molecular hair growth regulators in DP of men with AGA treated with finasteride and correlate these findings to clinical efficacy. METHODS: Biopsy specimens were collected from 9 male patients from both the balding area and nonbalding occipital area before and after 4 months of finasteride therapy. DP were microdissected and total RNA was extracted from an equal number of DP from each biopsy specimen. The expression of various cytokines, including insulin-like growth factor (IGF)-1, was determined by reverse transcription polymerase chain reaction. The signals were detected by autoradiography. All 9 patients were given finasteride for 1 year and evaluated for efficacy at month 12. Efficacy was graded on a 7-point scale on the basis of comparison with initial baseline photography. RESULTS: IGF-1 was up-regulated by finasteride treatment in 4 of 9 patients. Among the patients with increased IGF-1 expression, 3 of them showed moderate clinical improvement after 12 months of treatment and another patient remained unchanged. In contrast, 3 patients with decreased IGF-1 expression in the balding scalp showed clinical worsening after 12 months. The other 2 patients without noticeable change in IGF-1 expression showed either slight improvement or no change in their hair condition. CONCLUSION: In a small uncontrolled study of 9 patients with AGA, an increased expression of IGF-1 messenger RNA levels in the DP was associated with patient response to finasteride.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12894070&dopt=Abstract finasteride Propecia



finasteride, Propecia
Use of finasteride in the treatment of men with androgenetic alopecia (male pattern hair loss).

Shapiro J, Kaufman KD.

Division of Dermatology, University of British Columbia, Vancouver General Hospital, Vancouver, British Columbia, Canada.

Finasteride, a type 2-selective 5alpha-reductase inhibitor, was approved in 1997 as the first oral pharmacologic therapy for the treatment of men with androgenetic alopecia (AGA; male pattern hair loss). Originally developed for the treatment of men with benign prostatic hyperplasia (BPH) at a dose of 5 mg/day, finasteride has a well-established, excellent safety profile. Subsequent studies demonstrated that finasteride was an effective treatment for men with AGA at an optimal dose of 1 mg/day. This report summarizes the published peer-reviewed literature on the use of finasteride in the treatment of men with AGA, including the data on long-term (5 years) use of finasteride in a placebo-controlled clinical trial environment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12894990&dopt=Abstract finasteride Propecia



finasteride, Propecia
Comparison of finasteride and alpha-blockers as independent risk factors for erectile dysfunction.

Sadeghi-Nejad H, Sherman N, Lue J.

Division of Urology, Department of Surgery, UMD-New Jersey Medical School, Newark, New Jersey 07103-2714, USA.

There are insufficient data on the effects of alpha-blockers and finasteride on erectile function in men who have other risk factors for erectile dysfunction (ED). This study was conducted to compare the relative effects of these medications on ED in men who may be on other medications or have other risk factors for ED. Patients attending urology and primary care clinics were asked to complete an IRB-approved questionnaire that combined the validated Sexual Health Inventory for Men (SHIM) and a detailed medical history. A total of 123 patients completed the questionnaire. The age range was 28-88 years (mean: 68 years). Eighty-one per cent of patients had SHIM scores <21, indicating some degree of ED. The average SHIM scores in a population of patients with similar age and risk factors who had been on finasteride or alpha-blockers indicated the presence of ED but did not reveal a significant difference between the two groups. The scores were no different from an age-matched group of patients who were not on either medication, demonstrating the relatively greater importance of various other risk factors for ED. There was an inverse linear relationship between the number of ED risk factors and SHIM scores. There does not appear to be a significant difference between alpha-blockers and finasteride as independent risk factors for ED. Age and other risk factors (heart disease, diabetes, hypertension, smoking, and hypercholesterolaemia) tend to have a much stronger influence on the severity of ED as assessed by SHIM scores.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12918887&dopt=Abstract finasteride Propecia



finasteride, Propecia
Effects of androgen deprivation on chronic bacterial prostatitis in a rat model.

Seo SI, Lee SJ, Kim JC, Choi YJ, SW SW, Hwang TK, Cho YH.

Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

BACKGROUND: Many attempts have been made to improve the treatment success rate of chronic bacterial prostatitis (CBP). However, no treatment modality has achieved complete cure. The growth and development of the prostate is under direct hormonal control, and it is possible that prostatitis may be directly influenced by its hormonal milieu in a similar fashion to benign prostatic hyperplasia and prostate cancer. Therefore, the effects of androgen deprivation on the treatment of CBP were investigated in rats. METHODS: Experimental CBP was induced in one hundred, male Wistar rats by instillation of bacterial suspension (Escherichia coli Z17, O2: K1: H-) containing 1 x 10(8) CFU/ microL into the prostatic urethra. Microbiologically and histologically proven CBP was demonstrated in 62% (62 of 100) of the rats after 4 weeks of bacterial instillation. The 62 rats demonstrating CBP were randomly divided into five groups: control; castration; finasteride; estrogen; and levofloxacin groups. All drug treatments were conducted over a period of 4 weeks. RESULTS: Microbiological cultures and histological findings of the prostate and urine samples demonstrated reduced bacterial growth and improved inflammatory responses in all four experimental groups compared with the control group. The castration and estrogen groups showed coherent trends of decrease in bacterial growth and improvements in prostatic inflammation compared with the control group, but not to a statistically significant degree (P > 0.05). However, the finasteride and levofloxacin groups did show statistically significant decreases in bacterial growth and improvements in prostatic inflammation compared with the control group (P < 0.05). CONCLUSION: These results suggest that androgen deprivation is an effective modality in CBP treatment. In particular, the finasteride treatment reduced the severity of CBP in the animal model without reducing the systemic testosterone level. The combination of finasteride and levofloxacin maybe one of the effective treatment modalities for CBP.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12941127&dopt=Abstract finasteride Propecia