finasteride, Propecia
GABRA2 Alleles Moderate the Subjective Effects of Alcohol, Which are Attenuated by Finasteride.

Pierucci-Lagha A, Covault J, Feinn R, Nellissery M, Hernandez-Avila C, Oncken C, Morrow AL, Kranzler HR.

1Department of Psychiatry, Alcohol Research Center, University of Connecticut School of Medicine, Farmington, CT, USA.

GABA(A) receptors are involved in the subjective effects of alcohol. Endogenous neuroactive steroids interact with GABA(A) receptors to mediate several behavioral effects of alcohol in rodents. Based on a haplotypic association of alcohol dependence with the gene encoding the GABA(A) receptor alpha-2 subunit (GABRA2), we examined whether GABRA2 alleles are associated with the subjective response to alcohol. We also examined whether finasteride (a 5-alpha steroid reductase inhibitor), which blocks the synthesis of some neuroactive steroids, reduces the subjective response to alcohol. In all, 27 healthy social drinkers (15 males) completed a randomized, double-blind, placebo-controlled study of high-dose finasteride. After being pretreated with study drug, subjects consumed three alcoholic drinks. Subjective effects were measured repeatedly over the ascending blood alcohol curve. To examine the moderating role of genetic variation in GABRA2, a single-nucleotide polymorphism that was informative in association studies was included as a factor in the analysis. Subjects homozygous for the more common A-allele (n=7) showed more subjective effects of alcohol than did individuals with one or two copies of the alcohol dependence-associated G-allele (n=20, including two homozygotes). Among the A-allele homozygotes, there was a greater reduction in several subjective effects during the finasteride session compared to the placebo session. These findings provide preliminary evidence that the risk of alcoholism associated with GABRA2 alleles may be related to differences in the subjective response to alcohol. The effects of finasteride provide indirect evidence for a mediating role of neuroactive steroids in some of the subjective effects of alcohol.Neuropsychopharmacology advance online publication, 9 February 2005; doi:10.1038/sj.npp.1300688.

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finasteride, Propecia
[Effect of selective 5alpha-reductase inhibitor or/and testosterone undecanoate on the reproductive function of male rats]

[Article in Chinese]

Jia Y, Cue YG, Wang XD, Wang XH, Tong JS, Ma DZ, Cai RF, Di FS.

Department of Endocriology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.

OBJECTIVE: To investigate whether 5alpha-reductase inhibitor and dihydrotestosterone (DHT) play a role in spermatogenesis in male rats. METHODS: Thirty-two male rats were divided into 4 groups (Groups C, T, F and FT). Group C received plant oil injection and oral starch perfusion, Group T testosterone undecanoate (TU, 20 mg/kg) injection and oral starch perfusion, Group F plant oil injection and oral Finasteride perfusion, and Group FT TU (20 mg/kg) injection and oral Finasteride perfusion. Data on serum T and DHT, sperm count, sperm mobility and reproductive function were collected and analysed. RESULTS: (1) 5alpha-reductase inhibitor, Finasteride and TU reduced the weight of the testis and epididymis in the experiment groups compared with the negative control (Group C), but TU increased the weight of the prostate while Finasteride decreased it compared with the positive control (Group T). TU combined with Finasteride could counteract the effect of the weight increase of the prostate, but not that of the testis. (2) Finasteride, or Finasteride combined with TU, reduced the DHT but increased the testosterone level in comparison with the control group. (3) Both Finasteride and TU could inhibit epididymal sperm count and reproductive function compared with the control, but the effect was less significant in Group FT than in Group F. CONCLUSION: High dosages of 5alpha-reductase inhibitor, Finasteride, can suppress male reproductive function, but the inhibiting effect could be counteracted by administration of 5alpha-reductase inhibitor along with TU.

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finasteride, Propecia
Gleason grade remains an important prognostic predictor in men diagnosed with prostate cancer while on finasteride therapy.

Carver BS, Kattan MW, Scardino PT, Eastham JA.

Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

The controversial topic of the effect of finasteride therapy on Gleason grade, raised by the Prostate Cancer Prevention Trial, is discussed by authors from New York. They assessed a series of patients who had been treated with finasteride, and who subsequently had a radical prostatectomy, to see if this pharmaceutical agent prevented accurate Gleason grade assignment and prediction of biochemical recurrence. They found that Gleason grade remains an important prognostic predictor in men diagnosed with prostate cancer while on finasteride therapy. Authors from Amsterdam assessed the accuracy of ultrasonography-guided fine-needle aspiration cytology as a method of detecting occult lymph node metastases in patients with penile cancer, and found that it can be used as an initial investigation in such patients, with helpful clinical outcomes. OBJECTIVE To evaluate men treated with finasteride for lower urinary tract symptoms, who subsequently were diagnosed with prostate cancer and had a radical prostatectomy (RP) at our institution, to determine if finasteride therapy prevented accurate Gleason grade assignment and prediction of biochemical recurrence. PATIENTS AND METHODS Between May 1996 and July 2003, 45 men were identified who had RP and had previously been treated with finasteride for >/= 6 months before the diagnosis of prostate cancer. Clinical and pathological information was gathered from a RP database. Serum prostate-specific antigen (PSA) level, duration of finasteride therapy, biopsy Gleason grade, clinical stage, RP Gleason grade and pathological stage were reviewed. Freedom from recurrence was predicted using validated nomograms before and after RP, and compared against actuarial 5-year freedom from recurrence using the Kaplan-Meier method. RESULTS The mean duration of finasteride therapy before diagnosis was 23.6 months, the mean serum PSA (doubled to account for finasteride use) 11.02 ng/mL and mean biopsy Gleason score 6. When comparing the biopsy and RP specimen Gleason score, it was downgraded by 1 point in six men, upgraded by 1 point in eight, and upgraded by 2 points in one. The Gleason score was constant in 30 patients. The nomograms predicted freedom from recurrence in 83% and 85%, respectively; the 5-year actuarial freedom from recurrence was 86%. CONCLUSION Finasteride does not appear to compromise the assignment of Gleason grade for use in prediction tools before or after RP in men undergoing prostate biopsy or RP. The actuarial 5-year freedom from recurrence was similar to that predicted by the validated nomograms. Gleason grade remains an important prognostic predictor in men treated with finasteride and undergoing RP for clinically localized prostate cancer.

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finasteride, Propecia
Attenuating 5alpha-pregnane-3alpha-ol-20-one formation in the hippocampus of female rats increases pentylenetetrazole-induced seizures.

Rhodes ME, Frye CA.

Department of Psychology, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA.

Progesterone has antiseizure effects, which may be due to the actions of its 5alpha-reduced metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP). Whether metabolism of progesterone to 3alpha,5alpha-THP in the hippocampus is essential for its antiseizure effects was investigated. In Experiment 1, ovariectomized rats were administered subcutaneous progesterone (500mug) or vehicle (sesame oil), followed 1hour later by subcutaneous administration of an inhibitor of the 5alpha-reductase enzyme, finasteride (50mg/kg), or vehicle (90% sesame oil, 10% ethanol). Administration of progesterone increased the latency to, and decreased the number of, tonic seizures and increased hippocampal 3alpha,5alpha-THP levels, compared with vehicle. Administration of finasteride with progesterone attenuated progesterone's antiseizure effects and decreased levels of 3alpha,5alpha-THP in the hippocampus. Finasteride administration alone did not alter ictal behavior or 3alpha,5alpha-THP levels compared with vehicle. In Experiment 2, ovariectomized rats were administered subcutaneous progesterone (500mug) or vehicle (sesame oil), followed 1hour later by bilateral infusions of finasteride (10mug) or vehicle (beta-cyclodextran) into the hippocampus. Administration of finasteride to the hippocampus of progesterone-primed rats significantly increased ictal activity and decreased hippocampal 3alpha,5alpha-THP levels, compared with progesterone administration alone. These data suggest that formation of 3alpha,5alpha-THP in the hippocampus is important for progesterone's antiseizure effects.

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finasteride, Propecia
Pre-surgical finasteride therapy in patients treated endoscopically for benign prostatic hyperplasia.

Crea G, Sanfilippo G, Anastasi G, Magno C, Vizzini C, Inferrera A.

Department of Urology, University Hospital of Messina, Messina, Italy. giov.crea virgilio.it

INTRODUCTION: Transurethral resection of the prostate is considered the standard technique for patients with moderate or severe lower urinary tract symptoms related to benign prostatic hyperplasia (BPH). Pathologically BPH is characterized by an increased proliferation of stromal and acinar cells, sustained by increased vascularization (neoangiogenesis). Recent studies have also shown that finasteride reduces angiogenesis and prostatic bleeding associated with BPH. Reducing the volume as a final step in reducing neoangiogenesis could thus represent a fundamental advance in limiting intra- and postoperative bleeding in patients undergoing transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Our study included 60 patients undergoing TURP between January 2001 and January 2002. Of the patients, 30 received pretreatment with finasteride while 30 did not undergo any pretreatment (control group). In all the patients we evaluated the degree of peri-surgical bleeding, intended as a reduction in hemoglobin values in the 24 h following surgery. RESULTS AND CONCLUSIONS: In the group of patients pretreated with finasteride, blood loss, evaluated as a reduction in hemoglobin values, was minimal, and none of the patients required blood transfusion. The average hemoglobin loss in the 24 h following surgery was 0.9%. In the control group (average age 67 years), 4 patients (12%) required blood transfusion. The loss of hemoglobin was 2.36%. Finasteride, therefore, seems to play a fundamental role in the pretreatment of TURP patients, since by reducing dihydrotestosterone synthesis, it interacts with endothelial growth factors, thus reducing angiogenesis and preventing bleeding.

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finasteride, Propecia
Effects of finasteride on prostate volume and prostate-specific antigen.

Chiu KY, Yong CR.

Department of Surgery, Taichung Veterans General Hospital, Taichung, ROC. chiu3778 hotmail.com

BACKGROUND: Finasteride was introduced to treat patients with benign prostatic hyperplasia (BPH) recently, and it has shown its effects in reduction of prostate volume and decrease of prostate-specific antigen (PSA). We want to know how and how much does finasteride affect prostate volume as well as PSA and prostate-specific antigen density (PSAD), since PSA and PSAD are widely used as screening tools for early detection of prostate cancers. METHODS: Among 166 men with the diagnosis of BPH who received finasteride (5 mg/day) for 6 months, the serum PSA levels were measured. The prostate volumes before and after medication for a subgroup of 86 patients were measured by transrectal ultrasonography (TRUS). Paired t-test was used for the statistical analysis. The median percentage change in PSA of total 166 men and the median percentage changes in prostate volumes and PSAD of 86 men were also calculated. RESULTS: Among 166 men, the average serum PSA level was 2.48+/-2.02 ng/mL at baseline and 1.57+/-1.47 ng/mL at 6 months later. The median percentage change of serum PSA level was -44.26%. For 86 patients who underwent TRUS evaluation the average prostate volume changed from 39.83+/-21.10 mL to 33.62+/-20.52 mL. The median percentage change of prostatic volume was -17.80%. Also, the median percentage change in PSAD for these 86 patients after medication was -38.67%. CONCLUSIONS: Finasteride does decrease the serum PSA level and PSAD as well as prostate volume in men with BPH treated with it for 6 months. Physicians prescribing finasteride for patients with symptomatic BPH should always keep in mind its effect on PSA and PSAD levels in order not to miss potential prostate cancers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15720071&dopt=Abstract finasteride Propecia