The effect of finasteride on prostate-specific antigen in men with benign prostatic hyperplasia

Finasteride is a specific 5-α-reductase inhibitor that has been shown to reduce prostate size and decrease serum levels of prostate specific antigen (PSA). Among men who received finasteride (5 mg/day) for 12 months in North American clinical trials and in whom prostate cancer was not diagnosed the median percentage change in PSA was ?50% (5–95% range: ?81% to + 20%). At baseline 72% had PSA ? 4.0 ng/ml and 93% had PSA ? 10.0 ng/ml. After 12 months on finasteride, 75% had PSA ? 2.0 ng/ml and 95% had PSA ? 5.0 ng/ml. Thus, the proportion of BPH patients with PSA levels of 2.0 ng/ml and 5.0 ng/ml after 12 months of treatment was comparable to the proportion with pretreatment PSA levels of 4.0 ng/ml and 10.0 ng/ml. Among the 10 men in these trials subsequently diagnosed with prostate cancer while on long-term finasteride therapy (5 mg/day), the median percentage change in PSA was ?26% (range: ?48% to + 12%). Limited experience with finasteride in men with prostate cancer suggests that the reduction in PSA of malignant origin appears to be no greater than the percentage reduction in PSA of benign origin. These effects on PSA have not been shown to confer any therapeutic benefit. Physicians using finasteride should be aware of its effect on PSA levels. © 1993 Wiley-Liss, Inc.     

The effect of finasteride in men with benign prostatic hyperplasia

Background. Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5α-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction.Methods. In a double-blind study, we evaluated the effect of two doses offinasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period.Results. As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P <0.001), an increase of 1.6 ml per second (22 percent, P <0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P <0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups.Conclusions. The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.     

The influence of reversible androgen deprivation on serum prostate-specific antigen levels in men with benign prostatic hyperplasia

This study was designed to investigate the relationship of serum prostate-specific antigen to prostatic size and hormonal stimulation. Seven patients with benign prostatic hyperplasia were treated for six months with nafarelin acetate and then followed for an additional six months. Nafarelin acetate is a potent luteinizing-hormone-releasing hormone agonist which causes reversible testosterone deprivation resulting in involution of the prostate. During therapy and follow up, serum prostate-specific antigen correlated with: 1) serum testosterone (p less than 0.001); 2) quantity of prostatic epithelium (p less than 0.001); and 3) prostatic size (p less than 0.05). Before therapy, serum prostate-specific antigen (mean +/- SD) was 0.43 +/- 0.2 ng./ml. per gram of epithelium. This did not change significantly after six months of androgen deprivation (0.48 +/- 0.36), although the ratios of prostate-specific antigen to testosterone and to prostatic size each changed significantly. Despite testosterone levels in the castrate range at six months, five of seven patients had serum prostate-specific antigen concentrations above the female range and three of seven patients had prostatic biopsies containing columnar epithelium which stained positively for prostate-specific antigen. These results demonstrate that serum prostate-specific antigen is related to prostatic size, prostatic epithelial weight, and testosterone stimulation. However, prostatic size is not a good predictor of serum prostate-specific antigen because there is tremendous variation in the relative amount of epithelium in a prostate; in this study the ratio of prostatic size to epithelial weight varied threefold. Furthermore, although testosterone determines prostatic size and amount of prostatic epithelium, it may not totally control prostate-specific antigen production.     

Relationships between total/free prostate-specific antigen and prostate volume in Chinese men with biopsy-proven benign prostatic hyperplasia

Objective  

This study investigated relationships between total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and prostate volume (PV) in Chinese men with biopsy-proven BPH, and analyzed whether fPSA performed better than tPSA at estimating thresholds of PV.     

前列腺增生症病人待机处理期间剩余尿量测定的临床意义

目的 探讨待机处理的前列腺增生症（ＢＰＨ）病人剩余尿量变化与肾积水的关系。方法 对１６８例ＢＰＨ病人进行为期２年的ＩＰＳＳ、最大尿流率（Ｑｍａｘ）、Ｂ超剩余尿量（ＰＶＲ）检测随访、与肾积水的关系进行Ｌｏｇｉｓｔｉｃ回归分析。结果 多因素分析显示ＰＶＲ增加与肾积水的发生有关。比值比（ＯＲ值）２５．８６８,回归系数３．２５３,Ｐ＝０．０１７。手术与非手术病人比较ＩＰＳＳ（Ｐ〈０．０１）、Ｑｍａｘ（Ｐ〉     

Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia

OBJECTIVES: To assess the utility of prostate-specific antigen (PSA) as a predictor of prostate volume by characterizing the relationship between prostate volume and serum PSA in men with symptomatic benign prostatic hyperplasia (BPH) and no evidence of prostate cancer, stratified by decade of life. METHODS: Placebo-controlled multicenter trials in patients with BPH and a safety study in normal young men provided baseline measurements of serum PSA and prostate volume. The analyses included patients with a baseline prostate volume measured by either transrectal ultrasound (TRUS) or magnetic resonance imaging and baseline serum PSA. A common central laboratory was used for all but one of the individual studies; both laboratories used the Hybritech method. Patients 80 years of age or older were excluded. Patients with a baseline serum PSA greater than 10 ng/mL were excluded to reduce the likelihood of including occult prostate cancer cases. The patients in the BPH trials were screened at baseline by digital rectal examination (DRE) and serum PSA. Those with suspicious findings underwent TRUS-guided biopsy; only patients with negative biopsies are included in these analyses. RESULTS: The analyses included 4627 patients, 4448 from the BPH trials and 179 from the safety study. The men in the BPH trials were older (mean age+SE, 63.7+0.10 years) than the men in the safety study (mean age + SE, 30.8+/-0.43), had larger prostates (mean volume+/-SE, 43.7+/-0.38 mL versus 26.3+/-0.49 mL in the safety study), and had higher serum PSA values (mean+/-SE, 2.6+/-0.03 ng/mL versus 0.7+/-0.39 ng/mL in the safety study). The relationship between prostate volume and serum PSA was evaluated using only the BPH trial data. Prostate volume and serum PSA have an age-dependent log-linear relationship (ie, their logarithms are linearly related, and the parameters of the relationship depend on age). Older men tend to have a steeper rate of increase in prostate volume with increasing serum PSA (P < 0.00 for differences between slopes), and there was a slight tendency for PSA density to increase with age. Receiver operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to predict threshold prostate sizes in men with BPH. The ROC curve analyses revealed that PSA had good predictive value for assessing prostate volume, with areas under the curve ranging from 0.76 to 0.78 for various prostate volume cutoff points (30, 40, and 50 mL). Conclusions. Prostate volume is strongly related to serum PSA in men with BPH and no evidence of prostate cancer, and the relationship depends on age. Since treatment outcome or risk of long-term complications depend on baseline prostate volume, serum PSA can estimate the degree of prostate enlargement sufficiently accurately to be useful for therapeutic decision making. To achieve a specificity of 70% while maintaining a sensitivity between 65% and 70%, approximate age-specific criteria for detecting men with prostate glands exceeding 40 mL are PSA > 1.6 ng/mL, >2.0 ng/mL, and >2.3 ng/mL for men with BPH in their 50s, 60s, and 70s, respectively.     

Kinetics of postbiopsy levels of serum free prostate-specific antigen and percent free prostate-specific antigen

OBJECTIVES: We evaluated the effects of transrectal ultrasound-guided biopsy of the prostate on serum total and free prostate-specific antigen (PSA) and the free/total PSA ratio and factors affecting variations in PSA levels. METHODS: Serum total and free PSA levels and the free/total PSA ratio were determined in 48 men (mean age 66+/-7 years) before and 1 hour, 8 days, and 30 days after prostate biopsy. At least six cores were taken using a biopsy gun with an 18-gauge needle. The coefficient of variation of PSA was calculated as the postbiopsy/prebiopsy PSA ratio. Changes in PSA levels and the coefficient of variation were studied. RESULTS: Fifteen (31%) of 48 men had adenocarcinoma on biopsy. Total and free PSA values were significantly increased 1 hour and 8 days after biopsy, and both returned to baseline 30 days after biopsy. The free/total PSA ratio was significantly increased (55%) 1 hour after biopsy and significantly decreased (12%) 8 days after biopsy. Thirty days after biopsy, the median of the free/total PSA ratio (18%) was not significantly different from the prebiopsy ratio (16%). The median of the coefficient of variation of the free/total PSA ratio was 3, 0.7, and 1 at 1 hour, 8 days, and 30 days after biopsy, respectively. Age, prostate volume, number of cores, and digital rectal examination and histologic findings were not significantly associated with variation in percent free PSA. Variation in percent free PSA at day 8 was associated with prebiopsy total PSA value and the free/total PSA ratio. CONCLUSIONS: Prostate biopsy dramatically alters the percent free PSA. The free/total PSA ratio was decreased 8 days after biopsy and returned to prebiopsy levels in 75% of patients at 1 month after biopsy. Measurement of free PSA levels and the free/total PSA ratio should not be done within 4 weeks of prostate biopsy.     

Seminal plasma prostate-specific antigen level in benign prostatic hyperplasia

INTRODUCTION: We evaluated the role of the seminal plasma PSA level in the prediction of the response to alpha-blocker treatment in patients with benign prostatic hyperplasia. MATERIALS AND METHODS: 18 male patients with lower urinary tract symptoms were enrolled in the study. After their blood was sampled for PSA, ejaculates of all the subjects were obtained. Serum and seminal plasma PSA levels were calculated by Active PSA IRMA kit. Patients were given 4 mg/day doxazosin for a period of 6 weeks, following which their International Prostate Symptom Score (IPSS) evaluation was repeated. The correlation between serum PSA, seminal plasma PSA and PSA density levels and the percentage improvement in IPSS was investigated. RESULTS: The mean serum PSA level, the mean PSA density and the mean seminal PSA level of the patients were 2.7 +/- 1.2 ng/ml, 0.05 +/- 0.02 ng/ml/cm(3) and 0.7 +/- 0.39 g/l, respectively. The percentage improvement in IPSS varied from 26.9 to 53.5%. Serum PSA and serum PSA density were not useful in the prediction of the response to alpha-blocker treatment, but the seminal PSA levels correlated with the percentage improvement in the IPSS (p = 0.017). CONCLUSIONS: Seminal plasma PSA has been found to be a better predictor of the response to alpha-blocker treatment when compared to serum PSA and PSA density.     

Response of prostate volume, prostate-specific antigen, and testosterone to flutamide in men with benign prostatic hyperplasia.

Patients diagnosed as having benign prostatic hyperplasia (BPH) had determination of prostate volume (PV), prostate-specific antigen (PSA), and serum testosterone before consideration for entry into a double-blind, randomized trial of flutamide (750 mg/day for 6 months). The mean PSA level for these patients (N = 43) was 7.6 ng/ml (range: 1.0 to 45.7), and the mean PV was 76.8 cm3 (range: 24 to 198). Linear regression analysis demonstrated a strong correlation between the two (r = 0.876, P less than 0.05). Every 10 cm3 of prostate volume accounted for 1.02 ng/ml of PSA in the serum. Twenty-two patients (11 treated with flutamide, 11 with a placebo) agreed to enter the study. Prostate volume decreased by 35% and PSA by 65% (P less than 0.001) within 6 months. These changes occurred despite a 58.3% increase in serum testosterone levels (P less than 0.01). Patients treated with a placebo experienced no significant changes. Side effects were minimal, and flutamide was well tolerated. These data suggest that androgen deprivation therapy with flutamide may be an effective and safe treatment for BPH.     

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

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.     

前列腺增生症患者合并前列腺炎对血清PSA的影响

目的前列腺增生患者合并前列腺炎症对血清前列腺特异性抗原的影响。方法研究对象为在本院就诊,行经尿道前列腺电切术的前列腺增生71例患者,术前均经B超或CT、MRI诊断为前列腺增生,术后病理确诊为前列腺增生合并炎症。术前评估项目包括：年龄、前列腺体积、血清PSA、残余尿量、最大尿流率、国际前列腺症状评分（IPSS）、生活质量评分、尿中白细胞数、肌酐及术后病理诊断。纳入前列腺体积和年龄等因素的同时,分析前列腺腺周炎症、前列腺腺体炎症及基质炎症是否影响血清PSA浓度。结果前列腺体积（t=5.10）、基质炎症（χ2=10.35）、尿路感染（χ2=10.00）与血清PSA升高有关。结论血清PSA值与前列腺增生患者年龄及前列腺体积有关,前列腺炎的基质炎症与尿路感染也是前列腺增生患者血清PSA升高的危险因素。     

Evaluation of serum lipid levels in clinical benign prostatic hyperplasia patients with terazosin monotherapy

Nine clinical benign prostatic hyperplasia (BPH) patients were treated with oral terazoin monotherapy (2 mg daily) for 12 weeks. Serum lipid levels (total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, apoproteins) were estimated prior to and every 4 weeks during treatment in 5 patients. International Prostate Symptom Score (IPSS) and pressure-flow study were evaluated before and 12 weeks after treatment in 4 patients. The total cholesterol level decreased from a baseline of 210 +/- 36.6 mg/dl by 6.6% at the 12th week. This result was not significant but suggested a favorable effect of terazosin on diminishing the risk of coronary heart disease. This effect was marked especially in patients with a total cholesterol level over 200 mg/dl. On the other hand, IPSS improved in all cases. The mean change ranged from 19.5 to 10.0 and the mean peak flow rate from 9.0 to 15.7 ml/s. On Sh?ffer's nomogram, 1 patient showed improvement of obstruction and the other 3 patients were diagnosed as having week detrusor without obstruction. Clinical BPH patients with hyperlipidemia may markedly benefit from terazosin, which is a safe and useful initial treatment for BPH.     

Efficacy of terazosin in patients with benign prostatic hyperplasia.

Terazosin, a selective, long-acting alpha 1-adrenergic blocker, was evaluated in 44 men with benign prostatic hyperplasia. The dose was titrated from 2 to 20 mg nightly depending on improvement in symptoms and flow rate. All men completed at least 3 months of therapy, 26 had 6 months and 19 received 9-12 months of terazosin. There was an average increase of 2 ml/s in the peak urinary flow rate compared to baseline. This was statistically significant at the 3-month level. Residual urine decreased under treatment at each 3-month time interval. Prior to initiation of terazosin the mean was 165 ml, and it was 62, 100, and 41 ml at 3, 6 and 9 months respectively. There was a statistically significant improvement in both the obstructive and irritative symptom scores. Side effects were minimal; only 1 patient discontinued terazosin due to a hypotensive episode. Terazosin was found to be safe and effective in the dose range of 2-20 mg taken at bedtime in men with symptoms related to benign prostatic hyperplasia. The present study did not identify any baseline parameters such as initial prostate volume, peak flow rates, or obstructive or irritative symptom scores that correlated with clinical outcome.     

Prostate-specific antigen and prostate-specific antigen derivatives as predictors of benign prostatic hyperplasia progression

Benign prostatic hyperplasia (BPH) is the most common urologic affliction in aging men, leading to adverse clinical outcomes in a significant proportion of the population. Serum prostate-specific antigen (PSA) has been established as a marker for prostate cancer for the past two decades but more recently has been recognized as an equally important marker of BPH presence and progression. Over this time, the discovery and study of multiple isoforms of PSA have led to even more sensitive and specific methods to differentiate BPH from prostate cancer. Herein we review the expression, processing, and biochemistry of PSA and its derivatives and discuss the potential of these isoforms, both individually and in combination, to serve as determinants of BPH severity and progression.     

Effects of finasteride on health-related quality of life in men with symptomatic benign prostatic hyperplasia

The effects of urinary symptoms on health-related quality of life (HRQL) are important in therapeutic decision making. Few have evaluated the treatment effects on HRQL in men with benign prostatic hyperplasia (BPH), even though increased urinary symptoms are associated with greater worry, bother, and interference with living activities. We report on patient assessments of such disease-specific measures as well as general HRQL measures from two placebo-controlled clinical trials of finasteride in the treatment of symptomatic BPH. Patients treated with finasteride appeared to have greater improvement than placebo-treated patients in disease-specific measures and in patient global assessment. The treated group appeared to have a greater mean increase in sexual domain scores. As expected, general measures (health rating, life satisfaction, ladder of life) changed little. Thus, treatment with finasteride appears to reduce bother, worry, and activity interference due to symptoms but in a small percentage of men may lead to slightly reduced sexual function. © 1996 Wiley-Liss, Inc.     

The effectiveness of reducing the daily dose of finasteride in men with benign prostatic hyperplasia

Background  

Finasteride, a 5 alpha reductase inhibitor, is an established treatment for benign prostatic hyperplasia. The recommended dosage is 5 mg a day, however case reports have show effectiveness with lower doses. The objective of the current study was to determine in men with benign prostatic hyperplasia, previously treated for at least one year with finasteride 5 mg daily, if they will maintain subjective and objective improvements in urinary obstruction when treated with 2.5 mg of finasteride daily for one year.