Reduced circulating androgen bioactivity in patients with prostate cancer

BACKGROUND: Previous studies on immunoreactive androgen levels in serum have revealed equivocal associations with the risk of prostate cancer (CaP). The aim of this study was to compare serum biological androgen activity between men with newly diagnosed CaP and age-matched men with benign prostatic hyperplasia (BPH). METHODS: Caucasian men with newly diagnosed, untreated CaP (n = 101) and age-matched patients with BPH (n = 103) were investigated. Serum androgen bioactivity (ABA) levels were measured using a recently developed recombinant cell bioassay. RESULTS: In comparison to men with BPH, CaP patients with Gleason score >or=8 (n = 16) had lower serum ABA (P < 0.05), and patients with Gleason score or=8 (P = 0.07) displayed suppressed ABA levels in relation to serum testosterone. As the entire group, men with CaP (n = 101) had significantly lower serum ABA than age-matched men with BPH (n = 103): median 3.0 nM (range, 0.8-6.4 nM) versus 3.2 nM (range, 0.8-7.9 nM) testosterone equivalents, respectively (P < 0.005). By contrast, serum immunoreactive testosterone and SHBG concentrations and free androgen indices did not differ significantly between the two groups. CONCLUSIONS: Patients with CaP have lower serum ABA than controls with BPH, and men with low or high Gleason score display suppressed circulating ABA-to-testosterone ratio. These features may reflect interaction between variables such as the degree of tumor differentiation and tumor volume with androgen metabolism.     

Effect of age, castration, and testosterone replacement on the development and restoration of canine benign prostatic hyperplasia

An experiment was designed to test the effect of castration and testosterone replacement on the development of benign prostatic hyperplasia (BPH) in young and on the restoration of BPH in old beagles. Twenty beagles were divided by age into young (1.5-2.5-yr) and old (6.0-8.5-yr) groups. Each of these groups was further divided randomly into two additional groups of age-matched, intact, untreated control and castrate beagles. The latter were then treated with testosterone-filled Silastic implants designed to clamp serum testosterone at concentrations similar to those observed in adult beagles for 7 months beginning 5 months after castration. Histopathologic characterization of each prostate was completed on biopsy material obtained at the beginning and end of the experiment. Prostate weights were determined each month for 12 months via a noninvasive two-dimensional X-ray procedure. Testosterone treatment for 7 months allowed BPH to develop in young and restored BPH in old beagles. These results suggest that testosterone in the adult beagle acts permissively to allow BPH to develop in the prostate of the aging dog. Some other testicular product may be required for the continued growth of BPH in aged beagles.     

PI3K/AKT抑制剂对前列腺增生的影响及机制研究

目的:探讨磷脂酰肌醇3激酶/蛋白激酶B(PI3K/PKB或PI3K/AKT)信号通路抑制剂对前列腺增生的影响及机制。方法:选用鼠龄12周的雄性SD大鼠48只,随机分为4组:假手术对照组;BPH模型组;LY294002 50 mg组和LY294002 100 mg组,每组12只。大鼠去势后肌注丙酸睾酮10 mg/(kg.d)连续30 d建模,LY294002 50 mg组和100 mg组同时肌注LY294002 50 mg/kg和100 mg/kg,隔日1次。给药30 d后,切除各组大鼠前列腺组织,称取前列腺重量,切片观察前列腺组织细胞结构变化。免疫组化法检测K i-67、凋亡相关蛋白Bc l-2与Bax的表达情况;核酸末端原位标记法(TUNEL)检测细胞凋亡情况。结果:各组大鼠前列腺湿重(mg)和前列腺指数:假手术对照组:551±10.8,1.61±0.05;模型组:687±13.8,2.15±0.12;LY294002 50 mg组:623±23.5,1.95±0.11,与模型组相比,差异有显著性(P<0.05);LY294002 100 mg组:561±12.6,1.71±0.18,与模型组相比,差异具有极显著性(P<0.01)。凋亡相关蛋白Bax与Bc l-2的表达:假手术对照组:16.7%,16.7%;模型组:16.7%,58.3%;LY294002 50 mg组:33.3%,33.3%,与模型组相比,差异有显著性(P<0.05);LY294002 100 mg组:50.0%,25.0%,与模型组相比,差异极有显著性(P<0.01)。增殖和凋亡指数(%):假手术对照组:上皮组织14.2±6.4,6.5±1.8,间质组织7.6±2.6,2.5±0.3;模型组:上皮组织50.9±12.8,2.7±1.4,间质组织16.5±5.7,1.3±0.8;LY294002 50 mg组:上皮组织32.0±13.8,6.2±2.5,间质组织12.1±3.8,1.6±1.1;与模型组相比,差异有显著性(P<0.05);LY294002 100 mg组:上皮组织17.8±14.7,7.4±3.6,间质组织9.5±3.4,2.2±1.3;与模型组相比,差异有显著性(P<0.05)或极显著性(P<0.01)。结论:前列腺增生动物模型前列腺细胞增殖增加和凋亡的相对减少参与了BPH的发生发展过程。PI3K/AKT介导的信号通路在前列腺增生的发生发展过程中起重要作用,阻断PI3K/AKT信号通路具有抑制前列腺增生的作用。     

良性前列腺增生合并慢性前列腺炎组织中SIgA、α1-AR的表达与意义

目的:了解良性前列腺增生(BPH)合并慢性前列腺炎(CP)组织中SIgA、α1-AR的表达及意义。方法:将62例行经尿道前列腺等离子电切组织标本,根据术前前列腺按摩液(EPS)常规、经直肠前列腺B超、血清前列腺特异抗原(PSA)、国际前列腺症状评分(IPSS)、临床症状以及有无慢性骨盆疼痛综合征以及术后组织病理检查结果分为单纯BPH、BPH合并慢性前列腺炎两组。采用免疫组化、RT-PCR等实验方法研究两组前列腺组织中SIgA、α1-AR的表达。结果:62例患者中30例为BPH合并慢性前列腺炎,32例为单纯BPH,通过对患者一般资料对比和对实验结果进行统计学分析,合并慢性前列腺炎的BPH患者SIgA、α1-AR表达显著高于单纯BPH患者(0.380 8±0.144 3 vs 0.295 4±0.008 4;0.440 5±0.104 1 vs 0.383 2±0.013 6),差异有统计学意义(P<0.05)。结论:SIgA、α1-AR在BPH合并慢性前列腺炎患者中的表达上调,提示慢性前列腺炎与BPH可能有一定的内在联系,炎症反应可能是BPH的一个致病因素,与BPH的病理发展过程有关。     

Effects of Melandrium firmum methanolic extract on testosterone-induced benign prostatic hyperplasia in Wistar rats

Benign prostatic hyperplasia (BPH) is an age-related disease of unknown aetiology characterized by prostatic enlargement coincident with distinct alterations in tissue histomorphology. Instead of therapeutic agents that can cause severe side effects, plant extracts are frequently used to treat BPH. In this study, we investigated whether the Melandrium firmum methanolic extract (MFME) improves BPH, using the testosterone propionate (TP)-induced BPH rat model. Castration was performed via the scrotal route under sodium pentobarbital anaesthesia. BPH in castrated rats was generated via daily subcutaneous injections of TP (3 mg kg(-1)) dissolved in corn oil, for 4 weeks. MFME was administered daily by oral gavage at a dose of 200 mg kg(-1) for 4 weeks, along with the TP injections. The control group received injections of corn oil subcutaneously. At the scheduled termination of the experiment, all rats were killed and their prostates weighed; the relative prostate weight (prostate/body weight ratio) was calculated, and histomorphological changes in the prostate were examined. Additionally, we measured the levels of testosterone and dihydrotestosterone (DHT) in the serum and the prostate. Experimentally induced BPH led to marked decreases in the relative prostate weight and the DHT levels in the serum and the prostate. Histologically, BPH was evident in the ventral lobe of the prostate, and MFME treatment suppressed the severity of the lesions. These results indicate that MFME effectively inhibits the development of BPH induced by testosterone in a rat model. Further studies will be needed to identify the compound(s) responsibility for inducing the protective effect against BPH and determine its mechanism of action.     

Therapeutic effect of iodised serum milk protein,lycopene and their combination on benign prostatic hyperplasia induced in rats

Benign prostatic hyperplasia (BPH) is a common chronic disease in ageing men. Synthetic inhibitors of 5α-reductase commonly used in BPH treatment have limited effectiveness and may cause side effects. Evaluation of iodised serum milk protein and lycopene therapeutic effect in rat BPH model was the aim of the present study. BPH was induced in male Wistar rats by surgical castration and subsequent testosterone administrations (25 mg/kg, 7 injections). Rats with induced BPH received lycopene (5 mg/kg), iodised serum milk protein (200 µg/kg) or their combination for 1 month daily. The efficacy of the treatment was evaluated by the prostate weight, prostatic index and ventral lobe epithelium thickness. In lycopene and iodised serum milk protein-treated rats, prostate weight and prostatic index were significantly reduced compared to control group; and lycopene and iodised serum milk protein used in combination yielded an additive effect. Thus, further investigation of combined supplementation with micronutrients and plant-derived substances in BPH models may help to find new opportunities or its safe and effective treatment.     

Clearance of serum PSA after open surgery for benign prostatic hypertrophy,radical cystectomy,and radical prostatectomy

Objective: To study the clearance of serum prostate-specific antigen (PSA) after several types of prostatic tissue ablation. Methods: Serum PSA levels were measured (YANG Proscheck ultrasensitive assay) just before surgery, immediately after specimen removal, then twice weekly for 5 weeks or until it was undetectable (<0.05 ng/ml) in patients undergoing radical cystoprostatectomy for bladder cancer (n = 10), or radical prostatectomy for T1 T2 prostate cancer (n = 18) and daily for 6 days after open surgery for benign prostatic hypertrophy (BPH) (n = 10). Results: Open enucleation for BPH: the immediately postoperative PSA level was 6 times its preoperative value. It decreased following a monoexponential curve with a very short half-life of 0.55 ± 0.39 days, range (0.14–1.3), reaching a value lower than the preoperative level in all cases, except one by day 3. After radical cystoprostatectomy: the decrease of serum PSA is monoexponential with a half life of 1.92 ± 1.2 days (0.57–4.24) reaching undetectable level (<0.05 ng/ml) in all patients by day 21. After radical prostatectomy: 11/18 patients (61%) showed a one-component exponential decrease in PSA with a half-life of 2.5 ± 1.33 days (range 0.97–4.6 days), and 7/18 showed a two-component exponential decrease with a first half-life of 0.94 ± 0.8 days and a second of 7.62 ± 6.35 days); 100% of the patients reached undetectable serum PSA by day 28 in the first group compared to 14.2% of the patients with a two component exponential decrease (P < 0.01). There was no difference between these groups as far as preoperative PSA levels and specimen pathology were concerned. Conclusion: Serum clearance of PSA after extirpative prostatic surgery is closely related to the type and indication of procedure used. Radical cystoprostatectomy is probably the best model in which to study the pharmacokinetics of PSA.     

合并组织学前列腺炎的良性前列腺增生患者TURP手术对下尿路症状的影响

目的:探讨合并组织学前列腺炎的良性前列腺增生(BPH)患者行经尿道前列腺电切术(TURP)对下尿路症状的影响。方法:对2009年5月至2011年5月行TURP术后病理诊断证实为BPH的432例患者进行研究。剔除术前和术后合并有影响下尿路症状因素的病例,参照国际前列腺炎组织学分类诊断标准,分为A组:单纯BPH组(30例)、B组:合并轻度炎症组(55例)、C组:合并中度炎症组(31例)、D组:合并重度炎症组(28例)。采取国际前列腺症状评分(IPSS)评估各组术前及术后1个月的下尿路症状,将得分进行统计学分析。结果:合并组织学前列腺炎患者399例,检出率为92.4%。其中轻度炎症组269例(67.4%)、中度炎症组86例(21.6%)、重度炎症组44例(11.0%)。术前各组IPSS评分为:A组(21.43±6.09)分、B组(21.75±5.97)分、C组(27.84±4.18)分、D组(31.00±2.92)分,仅A组和B组差异无统计学意义(P=1.000),其余各组间差异均有统计学意义(P值均<0.01)。术后各组IPSS评分为:A组(5.60±2.16)分、B组(7.36±2.77)分、C组(11.55±3.39)分、D组(16.89±3.37)分,各组间差异均有统计学意义(P值均<0.01)。手术治疗后各组IPSS评分均较术前明显降低,差异有统计学意义(P值均<0.01)。合并炎症的BPH患者的病理切片中浸润的炎性细胞几乎均为淋巴细胞。结论:BPH大都合并有组织学慢性前列腺炎。合并组织学炎症的BPH患者手术前和手术后的下尿路症状严重程度要高于无炎症的BPH患者,且与炎症分级程度呈正相关。对合并中、重度炎症患者,术后仍需积极运用药物控制下尿路症状。     

3'-大豆苷元磺酸钠抗实验性小鼠良性前列腺增生的作用观察

目的:研究3'-大豆苷元磺酸钠(DSS)对实验性小鼠BPH及性激素平衡的影响。方法:40只雄性小鼠随机分为5组:正常对照组、BPH模型组、前列康组(阳性对照)、20mg/(kg.d)DSS组及40mg/(kg.d)DSS组,每组8只。皮下注射丙酸睾酮建立小鼠BPH模型。正常对照组给予橄榄油0.1ml/只,前列康组给予前列康5g/(kg.d),DSS组给予DSS20mg、40mg/(kg.d)灌胃。观察每组处理12d后小鼠前列腺湿重、前列腺指数、前列腺组织形态学变化和性激素水平。结果:DSS治疗12d后,与模型组相比,DSS组小鼠前列腺湿重及前列腺指数出现剂量依赖性的降低(P(0.05或P(0.01),光镜下见增生的腺上皮乳头减少或消失,腺体上皮细胞呈低立方或扁平状;血清T、E2含量和T/E2比值明显降低(P(0.05或P(0.01),40mg/(kg.d)DSS组的结果与前列康组相似。结论:DSS对丙酸睾酮所致小鼠BPH具有显著的拮抗作用,其作用机制在一定程度上与降低小鼠血清T、E2含量及T/E2比值有关。     

Serum concentrations of sex hormones in men with severe lower urinary tract symptoms and benign prostatic hyperplasia

OBJECTIVE: To find out the impact of age-related changes in serum concentrations of sex hormones on the development of severe lower urinary tract symptoms and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study group consisted of 61 consecutive patients subjected to prostatectomy for BPH between 2000-2001 in our clinic. Forty-five randomly assigned, age and socioeconomically matched cases without any lower urinary tract symptoms were taken as the control group. Both clinical BPH and control groups were divided to 3 age groups (namely 50-59, 60-69 and > or = 70 years) and age-related changes in serum concentrations of sex hormones were investigated. RESULTS: Prostate adenoma weight was found to be increased significantly (p = 0.02) with advancing age in clinical BPH group. There was no difference between serum concentrations of measured sex hormones between small and large prostates except for serum estradiol levels, which were found to be significantly higher in patients who had an adenoma weight of > 50 g (p = 0.047). Similar results were obtained in both clinical BPH and control groups with respect to age-related changes in serum concentrations of sex hormones. Briefly there was an age-related decrease in serum free testosterone levels and increase in serum estradiol, prolactin and gonadotropin levels. Serum free testosterone concentration was significantly higher in the control group for ages 60-69 (p = 0.015) while total testosterone was higher in BPH patients for patients older than 70 years of age (p = 0.027). No other significant change was documented between 2 groups. An age-dependent increase in serum E/freeT ratio was documented in both clinical BPH and control patients whereas serum freeT/T ratio was decreased in the BPH group with advancing age (p = 0.008). CONCLUSION: The decrease in serum free testosterone concentrations with a relative rise in serum estradiol levels with advancing age might be an important factor in the development of BPH. However it is likely that serum concentrations of sex hormones play little impact on the clinical severity of BPH.     

Aromatase inhibition in the dog. II. Effect on growth, function, and pathology of the prostate

To evaluate the role of aromatase inhibitors in the treatment of benign prostatic hyperplasia (BPH), the effects of a potent, oral, nonsteroidal aromatase inhibitor [4-(5,6,7,8-tetrahydroimidazo[1,5a]pyridin-5yl)benzonitrile; CGS-16949A, CIBA-GEIGY] on canine BPH have been studied. Twelve mature beagles with enlarged prostates were divided into two groups of similar age, prostatic size, and prostatic histology. Dogs were given either CGS-16949A at a dosage of 2.5 mg./kg./day p.o. (n = 6) or an oral placebo (n = 6) for 25 weeks. Treatment with aromatase inhibitor had no significant effect on prostatic weight nor on total DNA content when compared to controls (p greater than 0.1). Semen volume did not change with treatment, and prostatic tissue concentrations of testosterone, dihydrotestosterone (DHT), and 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol) were similar for the treated and control beagles (p greater than 0.1). Protein concentration in the ejaculate, however, was significantly greater for the dogs receiving CGS-16949A (p less than 0.01). Histologically, there was no difference in the incidence or type of BPH between the two treatment groups. Beagles treated with aromatase inhibitor, however, did have a more severe inflammatory infiltrate of the prostatic parenchyma than the control dogs (p less than 0.01). The mean serum testosterone concentration for the beagles treated with aromatase inhibitor was 10 times greater than that for the control animals (p less than 0.01). The endocrine effect of this aromatase inhibitor in the male canine is presented in the preceding paper. Taken together, these results suggest that inhibition of endogenous aromatase activity is not an effective treatment for spontaneous BPH in the intact canine.     

Total and SHBG-bound testosterone and 5 alpha-dihydrotestosterone serum concentrations in normal elderly men and patients with benign prostatic hypertrophy before and after removal of the adenoma

Serum testosterone, 5 alpha-dihydrotestosterone and their binding by sex hormone binding globulin (SHBG) were quantified in 10 patients with prostatic hypertrophy, before and after retropubic prostatectomy, and in an age-matched control group. Testosterone was significantly higher in the sera of the BPH patients. The SHBG-bound testosterone and 5 alpha-dihydrotestosterone were identical in both groups, but the fraction of testosterone and 5 alpha-dihydrotestosterone not bound to SHBG was higher in the group with BPH. Therefore patients with prostatic hypertrophy are exposed to increased androgen action. Prostatectomy did not lead to significant changes in serum testosterone, 5 alpha-dihydrotestosterone or their binding to SHBG.     

Hormonal predictors of prostate cancer

INTRODUCTION: Androgens are necessary for the development and functioning of the prostate gland. The association of serum testosterone and pituitary hormone levels with prostate cancer development is not completely understood. In this clinical study, we evaluated the role of serum testosterone, free testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in predicting prostate cancer risk in patients who had transrectal ultrasonography-guided prostate biopsy with the suspicion of prostate cancer. MATERIAL AND METHODS: A total of 211 patients who were selected to undergo prostatic biopsy due to abnormal digital rectal examination and/or a serum prostate-specific antigen (PSA) level >2.5 ng/ml were included in the study. The patient characteristics of total PSA, free/total PSA ratio, serum total testosterone, free testosterone, free/total testosterone ratio, FSH and LH levels were compared according to the pathological diagnosis. RESULTS: The mean age was 63.91 years (range 44-83) and the mean PSA level was 9.23 ng/ml (range 0.13-50.41) in the whole group. Of 211 patients, 69 (32.7%) were positive for prostate cancer. The patients who were positive for prostate cancer had statistically lower levels of serum total testosterone compared with the patients who were diagnosed as having benign prostatic hyperplasia (BPH; 405 vs. 450.5 ng/dl, respectively; p = 0.013). The serum FSH level was significantly higher in men with prostatic cancer than in men with BPH (7.56 vs. 6.06 mIU/ml, respectively; p = 0.029). No significant differences between men with prostatic cancer and those with BPH were found for serum LH levels. When normal ranges for serum free and total testosterone levels were defined as 9 pg/ml and 300 ng/dl, respectively, patients who had low free testosterone and total testosterone levels had significantly higher cancer detection rates than patients with high serum androgen levels: 40.8% (40/98) versus 25.6% (29/113) (p = 0.021), and 48.6% (18/37) versus 29.3% (51/174), respectively (p = 0.023). After logistic regression analysis, none of the hormones showed a significant difference in predicting the risk of prostate cancer in patients undergoing prostate biopsy with suspicion of the disease. CONCLUSION: Our data suggest that patients diagnosed with prostate cancer have low levels of serum testosterone and high levels of serum FSH compared with the patients with BPH. No support was found for the theory that high levels of testosterone increase prostate cancer risk. Further studies are needed to clarify the relationship between hormones and prostate cancer etiology.     

良性前列腺增生病人血清IGF-1、IGFBP-3水平分析

目的 :检测良性前列腺增生 (BPH)病人血清胰岛素生长因子 Ⅰ(IGF 1 )及其结合蛋白 3 (IGFBP 3)的水平 ,探讨IGF 1、IGFBP 3对揭示BPH病因及治疗方面的价值。　方法 :采用免疫放射分析法 (IRMA)测定 64例BPH病人血清中IGF 1、IGFBP 3水平 ,并以 30例健康男性作对照。BPH病人按照其前列腺总体积 (PV)的大小分为 3组 :A组PV≤ 30ml,1 8例 ;B组　PV 31～ 50ml,2 4例 ;C组　PV≥ 50ml,2 2例。　结果 :BPH组血清IGF 1、IGFBP 3含量与对照组比较 ,差异均无显著性。BPH组中 ,C组与A组比较 ,IGF 1、IGFBP 3水平均显著升高 (P<0 .0 5) ,C组与B组比较 ,IGF 1水平显著增高 (P =0 .0 0 3) ,IGFBP 3水平无统计学差异。IGF 1、IGFBP 3的水平随PV的增加而升高 ,均呈正相关 (r =0 .58,r =0 .48)。　结论 :IGF 1、IGFBP 3水平的高低与前列腺增生的程度有关 ,对BPH病因的揭示及BPH的非手术治疗均有一定的临床价值     

Growth of an androgen-sensitive human prostate cancer cell line,LNCaP, in nude mice

This study was undertaken to establish an androgen-sensitive model of human prostatic carcinoma in nude mice. The androgen-sensitive prostatic carcinoma cell line, LNCaP, was suspended in reconstituted basement membrane (Matrigel) and injected subcutaneously into nude mice. The LNCaP cell line was chosen for the study, because the cell line is androgen-sensitive and secretes prostate specific antigen (PSA) into culture media. Following injection of 1 × 10⁶ LNCaP cells with 0.25 ml of Matrigel, 88. of mice exhibited palpable tumor burdens after 12 weeks of observation. In addition, significant levels of PSA were observed in the serum of LNCaP-bearing mice. Bilateral orchiectomy of mice resulted in tumor regression and stabilization of serum PSA levels, compared to testis-intact controls. A significant correlation of PSA to tumor volume and weight was observed. The castrate level of testosterone was confirmed by radioimmunoassay and was similar to testosterone levels in female nude mice. Matrigel allows for a conducive environment to propagate LNCaP cells in nude mice. Furthermore, the growth can be manipulated by castration, leading to involution of tumor and stabilization of serum PSA level. This in vivo model of hormone-sensitive human prostate cancer cell line will serve as a model for the study of prostate tumor biology and treatment. © 1993 Wiley-Liss, Inc.     

Genetic and hormonal control of bone volume,architecture, and remodeling in XXY mice

Klinefelter syndrome is the most common chromosomal aneuploidy in men (XXY karyotype, 1 in 600 live births) and results in testicular (infertility and androgen deficiency) and nontesticular (cognitive impairment and osteoporosis) deficits. The extent to which skeletal changes are due to testosterone deficiency or arise directly from gene overdosage cannot be determined easily in humans. To answer this, we generated XXY mice through a four‐generation breeding scheme. Eight intact XXY and 9 XY littermate controls and 8 castrated XXY mice and 8 castrated XY littermate controls were euthanized at 1 year of age. Castration occurred 6 months prior to killing. A third group of 9 XXY and 11 XY littermates were castrated and simultaneously implanted with a 1‐cm Silastic testosterone capsule 8 weeks prior to sacrifice. Tibias were harvested from all three groups and examined by micro–computed tomography and histomorphometry. Blood testosterone concentration was assayed by radioimmunoassay. Compared with intact XY controls, intact androgen‐deficient XXY mice had lower bone volume (6.8% ± 1.2% versus8.8% ± 1.7%, mean ± SD, p = .01) and thinner trabeculae (50 ± 4 µm versus 57 ± 5 µm, p = .007). Trabecular separation (270 ± 20 µm versus 270 ± 20 µm) or osteoclast number relative to bone surface (2.4 ± 1.0/mm² versus 2.7 ± 1.5/mm²) did not differ significantly. Testosterone‐replaced XXY mice continued to show lower bone volume (5.5% ± 2.4% versus 8.1% ± 3.5%, p = .026). They also exhibited greater trabecular separation (380 ± 69 µm versus 324 ± 62 µm, p = .040) but equivalent blood testosterone concentrations (6.3 ± 1.8 ng/mL versus 8.2 ± 4.2 ng/mL, p = .28) compared with testosterone‐replaced XY littermates. In contrast, castration alone drastically decreased bone volume (p < .001), trabecular thickness (p = .05), and trabecular separation (p < .01) to such a great extent that differences between XXY and XY mice were undetectable. In conclusion, XXY mice replicate many features of human Klinefelter syndrome and therefore are a useful model for studying bone. Testosterone deficiency does not explain the bone phenotype because testosterone‐replaced XXY mice show reduced bone volume despite similar blood testosterone levels. © 2010 American Society for Bone and Mineral Research.     

复方玄驹胶囊联合溴隐亭治疗高泌乳素血症导致的勃起功能障碍的疗效观察

目的:观察复方玄驹胶囊联合溴隐亭治疗高泌乳素血症导致的勃起功能障碍的疗效。方法:46例高泌乳素血症导致勃起功能障碍患者,随机平均分为治疗组和对照组,治疗组同时口服复方玄驹胶囊(3粒,3次/d)和溴隐亭进行治疗,对照组单用溴隐亭进行治疗,治疗至病情稳定后观察勃起功能、血清泌乳素水平、血清睾酮水平变化并对疗效进行评估。结果:治疗组、对照组经治疗12周后国际勃起功能指数(IIEF-5)分别为(13.7±3.5)、(16.4±3.7),两组病例经治疗12周后勃起功能较治疗前均明显改善(P<0.05),治疗组病例勃起功能较对照组改善更显著(P<0.05),治疗组、对照组病例治疗后血清泌乳素水平分别为(156.07±26.31)mIU/L、(164.73±28.58)mIU/L,较治疗前均有显著下降(P<0.05),两组间治疗后血清泌乳素水平无显著差异(P>0.05),治疗组、对照组病例治疗后血清睾酮水平分别为(15.34±5.27)nmol/L、(12.02±2.36)nmol/L,较治疗前均有升高(P<0.05),治疗组血清睾酮水平较对照组显著升高(P<0.05),治疗组、对照组治疗后勃起功能改善有效率分别为86.96%(20/23)、65.22%(15/23),治疗组明显高于对照组(P<0.05)。结论:复方玄驹胶囊联合溴隐亭能有效治疗男性高泌乳素血症导致的勃起功能障碍,联合用药较单用溴隐亭疗效更为显著。     

Ⅳ型前列腺炎炎症分级和范围与前列腺特异性抗原之间的关系

目的:探讨Ⅳ型前列腺炎炎症组织病理学分级和范围与前列腺特异性抗原(PSA)的关系。方法:对120例临床可疑前列腺癌患者采用B超引导下经会阴前列腺穿刺病理活检,排除前列腺癌及不合并炎症的前列腺增生病例,仅BPH合并前列腺炎病例入选,采用NIH-Ⅳ型前列腺炎组织病理学分类方法对每例患者标本按炎症位置、范围和分级3方面分3级比较,评价炎症与血清PSA的关系。结果:120例患者中BPH合并前列腺炎症46例。①组织病理学炎症范围分级,1级35例,2级7例,3级4例,tPSA分别为(8.46±4.09)μg/L、(15.26±5.26)μg/L和(21.05±7.58)μg/L,fPSA分别为(1.75±0.93)μg/L、(2.54±0.72)μg/L和(3.19±1.13)μg/L,PSAD分别为0.15±0.11、0.26±0.07和0.42±0.19。三级之间比较tPSA(P=0.001)、fPSA(P=0.008)和PSAD(P<0.001)差异均具有显著性。②组织病理学炎症分级,1级32例,2级10例,3级4例。tPSA分别为(8.37±4.07)μg/L、(13.30±5.69)μg/L和(21.05±7.58)μg/L。fPSA分别为(1.76±0.93)μg/L、(3.27±2.21)μg/L和(3.19±1.13)μg/L。PSAD分别为0.14±0.11、0.25±0.06和0.42±0.19。三级之间比较tPSA(P=0.002)、fPSA(P=0.024)和PSAD(P<0.001)差异均有显著性。③组织病理学炎症位置分级,1级19例,2级17例,3级10例,三级之间tPSA、fPSA、%fPSA差异均无显著性(P>0.05)。④组织病理学炎症范围与tPSA(r=0.6,P<0.001)、fPSA(r=0.5,P=0.001)和PSAD(r=0.6,P<0.001)呈显著正相关关系。组织病理学炎症分级与tPSA(r=0.5,P<0.001)、fPSA(r=0.4,P=0.008)和PSAD(r=0.7,P<0.001)呈显著正相关关系,与%fPSA呈显著负相关关系(r=-0.4,P=0.013)。结论:无症状前列腺炎症患者组织病理学炎症的分级和范围与血PSA显著相关,病理医生应对前列腺穿刺标本进行炎症描述,其对高分级前列腺炎症患者可避免反复活检。     

BPH合并前列腺炎患者IPSS与IL-8、COX-2水平相关性研究

目的:观察良性前列腺增生(BPH)合并前列腺炎患者国际前列腺症状评分(IPSS)与前列腺按摩液(EPS)和前列腺组织中炎症因子白介素-8(IL-8)、环氧化酶-2(COX-2)水平的相关性。方法:将80例拟行经尿道前列腺电切术(TURP)BPH患者,根据术后病理学诊断分为单纯性增生组(30例)和增生伴炎症组(50例),两组均于术前行IPSS评分、EPS中IL-8、COX-2含量测定,术后前列腺组织中IL-8、COX-2的水平测定,进行统计学分析。结果:增生伴炎症组EPS中IL-8和COX-2水平显著高于单纯性增生组[IL-8:(15.31±1.22)ng/ml vs(5.89±0.91)ng/ml,COX-2:(371.09±14.99)ng/ml vs(156.96±29.47)ng/ml,P均<0.01],前列腺组织中两组IL-8和COX-2水平差异也显著(0.15±0.00 vs 0.05±0.02,0.13±0.01 vs 0.07±0.01,P均<0.01),IPSS两组差异也有显著性[(25.60±5.03)分vs(18.47±4.97)分,P<0.01];单纯增生组中IPSS与EPS和组织中IL-8及COX-2的表达呈中度相关(r=0.712、0.699、0.623、0.731,P均<0.05);增生伴炎症组中IPSS与IL-8、COX-2的表达呈高度相关(r=0.819、0.879、0.798、0.855,P均<0.05)。结论:EPS中IL-8、COX-2水平能间接反映前列腺组织中IL-8、COX-2水平,通过检测患者EPS中IL-8、COX-2水平并结合临床症状可以初步判定BPH患者是否合并前列腺组织学炎症。     

Effect of the dual 5α‐reductase inhibitor,dutasteride, on serum testosterone and body mass index in men with benign prostatic hyperplasia

Study Type – Therapy (RCT)
Level of Evidence 1b

OBJECTIVE

To investigate the effects of dutasteride on serum testosterone level and body mass index (BMI) in men who received medical therapy for benign prostatic hyperplasia (BPH).

PATIENTS AND METHODS

In all, 120 patients with BPH were randomized to three treatment groups: tamsulosin 0.2 mg/day (α‐blocker group), dutasteride 0.5 mg/day (dutasteride group), or tamsulosin 0.2 mg plus dutasteride 0.5 mg/day (combination group) for 1 year. For all patients the BMI and serum testosterone levels were checked at baseline and after 1 year of treatment.

RESULTS

Among the evaluable 107 patients, the dutasteride (33) and combination groups (37) had significantly greater increases in serum testosterone level (16.3% and 15%, respectively) than the α‐blocker group (37; 0.3%) after 1 year of treatment (both P < 0.001). When analysed by baseline serum testosterone tertile, the increases in serum testosterone level among the dutasteride and combination group were greatest in the lowest tertile. For BMI, the dutasteride and combination group had mean decreases of 0.17 and 0.20 kg/m², respectively, at 1 year, whereas the α‐blocker group had a mean increase of 0.04 kg/m². The decreases in BMI for the dutasteride and combination group were statistically significant only in the lowest tertile (P = 0.048 and 0.010, respectively).

CONCLUSION

Our results show that dutasteride treatment in men with BPH led to a significant increase in serum testosterone level and a significant decrease in BMI among those with relatively lower baseline serum testosterone levels.