finasteride, Propecia
Neurosteroid withdrawal model of perimenstrual catamenial epilepsy.

Reddy DS, Kim HY, Rogawski MA.

Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Rockville, Maryland 20892-1408, USA.

PURPOSE: Perimenstrual catamenial epilepsy, the increase in seizure frequency that some women with epilepsy experience near the time of menstruation, may in part be related to withdrawal of the progesterone metabolite allopregnanolone, an endogenous anticonvulsant neurosteroid that is a potent positive allosteric gamma-aminobutyric acidA (GABA(A)) receptor modulator. The objective of this study was to develop an animal model of perimenstrual catamenial epilepsy for use in evaluating drug-treatment strategies. METHODS: A state of prolonged high serum progesterone (pseudopregnancy) was induced in 26-day-old female rats by sequential injection of pregnant mares' serum gonadotropin and human chorionic gonadotropin. Neurosteroid withdrawal was induced by treatment with finasteride (100 mg/kg, i.p.), a 5alpha-reductase inhibitor that blocks the conversion of progesterone to allopregnanolone. Plasma progesterone and allopregnanolone levels were measured by gas chromatography/electron capture negative chemical ionization mass spectrometry. Seizure susceptibility was evaluated with the convulsant pentylenetetrazol (PTZ). RESULTS: Plasma allopregnanolone levels were markedly increased during pseudopregnancy (peak level, 55.1 vs. control diestrous level, 9.3 ng/mL) and were reduced by 86% 24 h after finasteride treatment (6.4 ng/mL). Progesterone levels were unaffected by finasteride. After finasteride-induced withdrawal, rats showed increased susceptibility to PTZ seizures. There was a significant increase in the number of animals exhibiting clonic seizures when challenged with subcutaneous PTZ (60 mg/kg) compared with control pseudopregnant animals not undergoing withdrawal and nonpseudopregnant diestrous females. The CD50 (50% convulsant dose) was 46 mg/kg, compared with 73 mg/kg in nonwithdrawn pseudopregnant animals and 60 mg/kg in diestrous controls. The threshold doses for induction of various seizure signs, measured by constant intravenous infusion of PTZ, were reduced by 30-35% in neurosteroid-withdrawing animals compared with control diestrous females. No change in threshold was observed in pseudopregnant rats treated from days 7 to 11 with finasteride, demonstrating that high levels of progesterone alone do not alter seizure reactivity. CONCLUSIONS: Neurosteroid withdrawal in pseudopregnant rats results in enhanced seizure susceptibility, providing an animal model of perimenstrual catamenial epilepsy that can be used for the evaluation of new therapeutic approaches.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11442149&dopt=Abstract finasteride Propecia



finasteride, Propecia
Polarographic behavior and determination of finasteride.

Amer SM.

Department of Analytical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El Eini Street, 11562 Cairo, Egypt. s_m_amer hotmail.com

The polarographic behavior of finasteride at the dropping mercury electrode (DME) was studied adopting direct current (DC(t)), alternating current (AC(t)) and differential-pulse polarography (DPP) modes. In Britton-Robinson buffer (BRb), finasteride exhibited cathodic waves over the pH range 6-12. At pH 10, a well-defined cathodic wave was obtained. The latter could be characterized as being irreversible, diffusion-controlled and partially affected by adsorption phenomenon. The number of electrons involved in the reduction process was accomplished and a proposal of the electrode reaction was presented. The current-concentration plots were rectilinear over the ranges 8-40 and 2-30 microg ml(-1) using DC(t) and DPP modes, respectively. The minimum delectability was 0.2 microg ml(-1) (5.4 x 10(-7) M), for the latter. The proposed method was successfully applied to the determination of finasteride in its commercial capsules and the results obtained were in good agreement with those given with a reference method. Copyright 2003 Editions scientifiques et medicales Elsevier SAS

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12581782&dopt=Abstract finasteride Propecia



finasteride, Propecia
Chemoprevention of prostate carcinogenesis by DFMO and/or finasteride treatment in male Wistar rats.

Esmat AY, Refaie FM, Shaheen MH, Said MM.

Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.

In the present study the chemopreventive activities of DFMO, the irreversible inhibitor of ornithine decarboxylase, and finasteride, the inhibitor of prostatic 5a-reductase, against the development of chemically induced prostate adenocarcinoma by methylnitrosourea/testosterone propionate in male Wistar rats were investigated. According to histological examination, oral administration of DFMO and finasteride, either alone or combined, for two months to MNU/TP-inoculated rats reduced the tumor incidence to 11.11%, 10% and 10%, respectively, compared to tumored controls (64.3%). DFMO and/or finasteride treatment resulted in significant reductions in the wet weight of the prostate gland and seminal vesicles and its ratio relative to the total body weight, as well as the levels of prostate total protein, DNA, RNA and DNA/RNA ratio, compared to tumored controls. However, the effect of the combined treatment was of no statistical significance compared to single DFMO or finasteride treatment, as demonstrated by the non-significant differences between the mean values of most of the studied parameters. The tumor chemopreventive activity and the prostate growth inhibitory effect of DFMO and finasteride were due to suppression of prostate polyamine synthesis. ANOVA test revealed that the relative weight of the prostate as well as blood and tissue polyamine levels could be used as significant endpoint biomarkers for DFMO and finasteride as cancer chemopreventive agents.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12597149&dopt=Abstract finasteride Propecia



finasteride, Propecia
[Benign prostatic hyperplasia: patients' perception of medical treatment and their expectations. Results of a french survey involving patients treated with finasteride]

[Article in French]

Teillac P.

Service d'Urologie, Hopital Saint-Louis, Paris, France.

Benign prostatic hyperplasia (BPH) is increasingly common in medical practice, as a result of the inevitable aging of the population. The current therapeutic strategy includes three alternatives: watchful waiting, medical treatment and invasive therapy. Finasteride is one of the pharmacological options available. Many clinical studies have demonstrated its efficacy and good safety profile in patients with BPH. The survey we report provides new insights into what has to date been a purely therapeutic approach by taking into consideration patients' expectations and their perception of finasteride treatment. Results indicate that the main preoccupation for patients with BPH is that the pharmacological treatment will reduce the risk of major urological complications and the need for surgery (treatment characteristics considered as very or extremely important by 88 and 93% of patients, respectively). Decreasing symptoms and improving quality of life take second place after these primary concerns. Patient perception of finasteride is excellent. Nearly all patients are satisfied by the efficacy of the treatment, 89% of them reporting good to extremely good improvement of symptoms, the rapid onset of relief being particularly important. The efficacy of finasteride is not hindered by any tolerability issues and is further strengthened by its ease of use. Although this novel survey includes a number of biases, it nevertheless demonstrates that treatment of BPH with finasteride is well accepted by patients and satisfies their expectations. In addition, it provides a mass of general epidemiological data on patients with BPH, as well as on current medical practice regarding this condition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12611202&dopt=Abstract finasteride Propecia



finasteride, Propecia
Inhibition of 5alpha-reductase in rat prostate reveals differential regulation of androgen-response gene expression by testosterone and dihydrotestosterone.

Dadras SS, Cai X, Abasolo I, Wang Z.

Department of Urology, Northwestern University Medical School, Chicago, IL 60611, USA.

The growth and development of some of the male sex accessory organs such as the prostate requires the conversion of testosterone to dihydrotestosterone (DHT) by 5alpha-reductase. To provide insights into the role of testosterone versus DHT in the prostate, we studied the impact of finasteride, a potent and specific inhibitor of 5alpha-reductase, on the expression of prostatic androgen-response genes in testis-intact rats and in 7-day castrated rats. Finasteride inhibition of the conversion of testosterone to DHT was confirmed by measuring serum and intraprostatic androgens. As expected, finasteride treatment caused a reduction in the wet weight of the prostate in the testis-intact rats and inhibited the testosterone-stimulated prostatic regrowth in the 7-day castrated rats. Although finasteride treatment had little or no effect on the expression of the surveyed androgen-response genes in testis-intact rats, its administration enhanced the expression of many androgen-response genes during the testosterone-stimulated regrowth of the regressed prostate in castrated rats. These observations suggest that testosterone is more potent than DHT in stimulating the expression of many androgen-response genes in the regressed prostate. The expression of androgen-response genes is mainly prostate specific and thus is likely to be associated with androgen-dependent prostatic differentiation. Therefore, testosterone is more potent than DHT in inducing differentiation and weaker in stimulating proliferation during prostate regrowth. The fact that testosterone is a strong inducer of prostatic differentiation has potential clinical implications.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11444528&dopt=Abstract finasteride Propecia



finasteride, Propecia
Effect of a novel steroid (PM-9) on the inhibition of 5alpha-reductase present in Penicillium crustosum broths.

Flores E, Cabeza M, Quiroz A, Bratoeff E, Garcia G, Ramirez E.

Department of Biological Systems, Metropolitan University-Xochimilco, Calzada Del Hueso No. 1100, 04960, Mexico, D.F., Mexico.

The conversion of testosterone (T) to 5alpha-dihydrotestosterone (DHT) has been demonstrated in Penicillium crustosum broth obtained from fermented pistachios, lemons and corn tortillas. Furthermore, the presence of 5alpha-reductase enzyme, which is responsible for this conversion, has been established by electrophoretical techniques in these cultures.5alpha-Reductase enzyme is also present in animal and human androgen-dependent tissues as well as in prostate and seminal vesicles. The increase of the conversion of T to DHT in prostate gland, has been related to some illnesses such as benign prostate hyperplasia and prostate cancer. Furthermore, treatment with 5alpha-reductase inhibitors such as finasteride reduces the prostate growth. These data have stimulated research for the synthesis of new molecules with antiandrogenic activity, whose biological effect needs to be demonstrated.The purpose of this study is to determine the inhibition pattern of 5alpha-reductase in P. crustosum by finasteride and the new steroidal compound PM-9. K(m) and V(max) values for T, were determined in the broths by Lineweaver-Burk plots using different testosterone concentrations. The inhibition pattern of finasteride and PM-9 was also determined by Lineweaver-Burk using different concentrations of T and inhibitors. Results show that finasteride and PM-9 inhibit 5alpha-reductase present in the broth in a competitive manner.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12628690&dopt=Abstract finasteride Propecia



finasteride, Propecia
Study design of the Medical Therapy of Prostatic Symptoms (MTOPS) trial.

Bautista OM, Kusek JW, Nyberg LM, McConnell JD, Bain RP, Miller G, Crawford ED, Kaplan SA, Sihelnik SA, Brawer MK, Lepor H.

George Washington University, The Biostatistics Center, Rockville, MD 20852, USA. omb biostat.bsc.gwu.edu

Alpha-blockers and 5-alpha-reductase inhibitors are medical therapies that are being used as alternatives to surgical interventions to relieve symptoms of benign prostatic hyperplasia (BPH). Taken as monotherapy, alpha-blockers and 5-alpha-reductase inhibitors have each been shown to provide relief from BPH symptoms. Treatment with finasteride over 4 years has been shown to reduce both BPH symptoms and the likelihood of acute urinary retention and the need for surgery. Direct comparison of the alpha-blocker terazosin with finasteride has been done, but only for a period of 1 year. The Medical Therapy of Prostatic Symptoms (MTOPS) trial is a multicenter, randomized, placebo-controlled, double-masked clinical trial designed to evaluate the long-term efficacy of the alpha-blocker doxazosin and the 5-alpha-reductase inhibitor finasteride, whether taken as a monotherapy or in combination, in preventing or delaying the progression of BPH. We describe in this paper the design of the MTOPS trial, the concept of BPH progression, the definition and methods of determining the primary outcome events and the proposed statistical analysis methods. A unique feature of MTOPS is the inclusion of prostate biopsies on a subgroup of randomized participants. Volunteers among randomized participants are to undergo a biopsy of the prostate at predetermined time points during the trial. Studies that will be conducted using the tissue specimens collected in MTOPS can potentially provide information at the molecular level on the natural history of BPH among medically treated and untreated men with moderate to severe symptoms of BPH.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12689743&dopt=Abstract finasteride Propecia