Changes in molecular forms of prostate‐specific antigen during treatment with finasteride
Francisco EspañaManuel Martı́nezM. RoyoA. EstellésJ.M. AlapontSilvia NavarroJ AznarJ.F. Jiménez-Cruz
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Objective To study the influence of finasteride treatment on the molecular forms of prostate‐specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH). Patients and methods Total PSA, free PSA and PSA complexed to α 1 ‐antichymotrypsin (PSA‐α 1 ACT) were measured in plasma and serum from 40 men with BPH and a total PSA of < 20 ng/mL, using in‐house and commercial immunoassays, before and during treatment with finasteride (30 men) or placebo (10 men). Results The baseline values were not significantly different between the groups, with mean ( sd ) total plasma PSA levels of 3.6 (4.3) and 4.8 (5.9) ng/mL in the finasteride and placebo groups, respectively. Finasteride, but not placebo, induced a significant reduction in total PSA, free PSA and PSA‐α 1 ACT levels in plasma and serum ( P < 0.001). However, complexed‐to‐total (c/t) and free‐to‐total (f/t) PSA ratios remained constant in both groups, both in plasma and serum, during the follow‐up. Conclusion The decrease in total PSA after finasteride treatment results from a proportional reduction in its two major molecular forms, free PSA and PSA‐α 1 ACT, which explains why the c/t and f/tPSA ratios do not change significantly despite treatment. This suggests that routine analysis of molecular forms of PSA could improve the utility of the change in total PSA associated with finasteride for the early diagnosis of prostate cancer. It also suggests that any subsequent change in both ratios, particularly an increase in c/tPSA or a decrease in f/tPSA ratio, could be considered an early sign of neoplastic degeneration rather than a therapeutic consequence.Objective To study the effect of finasteride on hematuria associated with benign prostate hyperplasia. Methods We evaluated 61 patients with intermittent hematuria who were randomized to a finasteride treated group or control group.Routine urinoscopy was carried out once a week in all the 61 patients. Results In the untreated control group hematuria recurred in 20/31 within a year but in only 7/28 in the finasteride group,which was a statistically significant difference (P0.05).Surgery was required for bleeding only in 5 controls. Conclusions Hematuria secondary benign prostatic hyperplasia may be significant if not treated.Finasteride appears to be effective in eliminating hematuria caused by benign prostate hyperplasia.
Gross hematuria
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Abstract The development and maintenance of prostate function depend on a fine balance between oestrogen and androgen levels. Finasteride inhibits 5α‐reductase, which is responsible for the conversion of testosterone into its most active form, dihydrotestosterone. Enzymes that metabolize these hormones have a highly relevant role in both the normal prostate metabolism and in the occurrence of pathological conditions. There are few studies on the impact of finasteride on male prostate development and fewer studies on the female prostate and possible intersexual differences. Therefore, we treated male and female gerbils from 7 to 14 days in postnatal life with a high dose of finasteride (500 μg/kg/day); the prostate complexes were then removed and submitted to immunohistochemistry, immunofluorescence and three‐dimensional reconstruction. In addition, hormonal serum dosages were administered. Treatment with finasteride resulted in an increased thickness of the periductal smooth musculature in the prostate of both male and female gerbils, such as well as a reduction in the thickness of developing prostate alveoli in both sexes. In addition, intersexual differences were observed as increased epithelial proliferation and decreases in the number of developing alveoli in females. Together, the data indicate that postnatal exposure to finasteride causes greater changes in the female gerbil prostate than in the male.
Dihydrotestosterone
Gerbil
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We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA) levels (14 and 17 individuals, respectively) were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs). Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b), which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b) remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.
Prostate biopsy
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To evaluate the spatial distribution of prostate cancer detected at a single positive biopsy (PBx) and a repeat PBx (rPBx).We evaluated 533 consecutive men diagnosed with prostate cancer who underwent radical prostatectomy using a clinical map document based on XML (cMDX©)-based map model of the prostate. We determined the number of cancer foci, relative tumour volume, Gleason score, zone of origin, localisation, and pathological stage after stratification according to the number of PBx sessions (PBx vs rPBx). The distribution of 3966 prostate cancer foci was analysed and visualised on heat maps. The colour gradient of the heat map was reduced to six colours representing the frequency classification of prostate cancer using an image posterisation effect. Additionally, the spatial distribution of organ-confined prostate cancer between PBx and rPBx was evaluated.Prostate cancer diagnosed on PBx was mostly localised to the apical portion and the peripheral zone of the prostate. Prostate cancer diagnosed on rPBx was more frequently found in the anterior portion and the base of the prostate. Organ-confined prostate cancer foci were mostly localised in the dorsolateral zone of the prostate in men at PBx, whereas men at rPBx had more prostate cancer foci in the anterior portion.The spatial distribution of prostate cancer with rPBx differs significantly from the spatial distribution of prostate cancer with PBx. The whole anterior portion of the prostate should be considered by rPBx.
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In their otherwise informative commentary on therapeutic advances in the treatment of benign prostatic hyperplasia, Michael Jewett and Laurence Klotz conclude that finasteride should be used routinely in men with lower urinary tract symptoms, pointing out that finasteride reduced the risk of
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Patients with benign prostatic hyperplasia (BPH) received proscar (finasteride) in daily dose 5 mg for: at least 6 months (n = 206, 20.4%), 12 months (n = 513, 50.9%), 24 months (n = 164, 16.3%), 3-4 years (n = 125, 12.4%). Because the size of the prostatic gland reduced significantly (by 22%) only after one year of proscar treatment, the duration of this treatment should be continued for at least 12 months, in some patients as long as the whole life. The duration of the treatment should be decided for each individual patient. The improvement after the proscar treatment was observed in 95% of the patients treated for benign prostatic hyperplasia.
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Applying benign prostate hyperplasia model, the effect of prosate Kangfu capsule suppressing benign prostate hyperplasia in rats and mice was observed experimentally. The results showed that prostate Kangfu capsule could significantly suppress benign prostate hyperplasia caused by testosterone propionate in rats and mice, and could reduce the bulk of prostate, decrease the wet weight of prostate, depress the level of testosterone, raise the level of estradiol in rats and suppress hyperplasia of prostate lobule. It is indicated that prostate Kangfu capsule has preventive and treating effect on benign prostate haperplasia caused by testosterone propionate.
Testosterone propionate
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Objective To evaluate the effects of finasteride tablets combined with longxuejie capsule interventions of microvessel density and vascular endothelial growth factor of the prostatic hyperplasia.Methods Sixty cases of hyperplasia of prostate patients were randomly divided into the observation group and the control group,30 cases in each group.All took TURP.before the operation,the observation group:Finasteride tablets and longxuejie capsule,oral.Control group:vitamins C tablets,oral.Results Operation blood loss,resection of the 1 g BPH blood loss of the observation group were less than that in the control group,there were significant differences(P 0.01).The number of MVD of the patients with hyperplasia of prostate of the observation group less than those in the control group,there were significant differences(P 0.01).The expression of VEGF number of the patients with hyperplasia of prostate of the observation group was less than those in the control group,there were significant differences(P 0.01).Conclusion Oral finasteride tablets and longxuejie capsule before TURP can reduce the bleeding during operation closely related it can reduce of the microvessel density and expression of VEGF of the prostate hyperplasia.
Capsule
Microvessel
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No AccessJournal of UrologyClinical Urology: Letters to the Editor1 Jul 1998RE: PROSTATE TISSUE COMPOSITION AND RESPONSE TO FINASTERIDE IN MEN WITH SYMPTOMATIC BENIGN PROSTATIC HYPERPLASIA L.S. Marks, A.W. Partin, G.J. Gormley, F.J. Dorey, E.D. Shery, J.B. Garris, E.N.P. Subong, E. Stoner, and J.B. deKemion L.S. MarksL.S. Marks More articles by this author , A.W. PartinA.W. Partin More articles by this author , G.J. GormleyG.J. Gormley More articles by this author , F.J. DoreyF.J. Dorey More articles by this author , E.D. SheryE.D. Shery More articles by this author , J.B. GarrisJ.B. Garris More articles by this author , E.N.P. SubongE.N.P. Subong More articles by this author , E. StonerE. Stoner More articles by this author , and J.B. deKemionJ.B. deKemion More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)63066-0AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "RE: PROSTATE TISSUE COMPOSITION AND RESPONSE TO FINASTERIDE IN MEN WITH SYMPTOMATIC BENIGN PROSTATIC HYPERPLASIA." The Journal of Urology, 160(1), p. 134 References 1 : Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials.. Urology1996; 48: 398. Google Scholar 2 : A randomized, placebo-controlled multicenter study of the efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia.. J. Urol.1992; 148: 1467. Abstract, Google Scholar 3 : The effect of finasteride in men with benign prostatic hyperplasia.. New Engl. J. Med.1992; 327: 1185. Google Scholar © 1998 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 160Issue 1July 1998Page: 134 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.MetricsAuthor Information L.S. Marks More articles by this author A.W. Partin More articles by this author G.J. Gormley More articles by this author F.J. Dorey More articles by this author E.D. Shery More articles by this author J.B. Garris More articles by this author E.N.P. Subong More articles by this author E. Stoner More articles by this author J.B. deKemion More articles by this author Expand All Advertisement PDF downloadLoading ...
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Abstract To determine the influence of androgen deprivation induced by the potent 5α‐reductase inhibitor finasteride on the volume of the zones of the prostate, 20 symptomatic men with established BPH were randomized to one of three groups: placebo, finasteride 1 mg, and finasteride 5 mg/day. The volume of the entire prostate gland, periurethral zone, and peripheral zone and the seminal vesicles were determined by three dimensional reconstructions of magnetic resonance contoured images of the prostate. There was no significant difference between the results achieved with 1 and 5 mg of finasteride per day; thus the results in these two groups were combined. In the placebo group there was no significant change in the volume of any structure. Following treatment for 1 year with finasteride there was a significant (P <0.02) 17% decrease in total gland size (11.5 ± 3.2 cc). Similarly, there was a significant (P <0.03) decrease in the size of the periurethral zone of the prostate (6.2 ± 3 cc). Although there was also a decrease in the size of the peripheral zone of the prostate (2.8 ± 1.2 cc) this did not reach statistical significance. There was no significant change in the volume of the seminal vesicles. These findings indicate for the first time that androgen deprivation induces a significant decrease in the size of the periurethral zone of the prostate in men with established BPH. © 1993 Wiley‐Liss, Inc.
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