Peripheral hormone levels in controls and patients with prostatic cancer or benign prostatic hyperplasia: results from the Dutch-Japanese case-control study.

The possible relationship between changes in peripheral hormone levels and the occurrence of prostatic pathology was studied in a case-control study, involving estimation of various plasma hormones in 368 Dutch and 258 Japanese men, who were grouped as controls and patients with benign prostatic hyperplasia, focal prostatic carcinoma, or clinically evident prostatic carcinoma. Results of a number of previous, smaller studies concerning interrelationships between hormone levels in elderly men were confirmed within the Dutch and Japanese groups. Plasma levels of testosterone and estradiol were significantly lower in the Japanese men, when compared with those in Dutch men. Probably as a result of this difference in testosterone levels, the ratio between serum levels of testosterone and sex hormone-binding globulin (SHBG) was decreased in the Japanese men, while the ratio between the concentrations of dihydrotestosterone and testosterone was increased. These differences were also found when results from Japanese subgroups (controls and patients with prostate pathology) were compared with those from the Dutch subgroups. There were no significant differences in plasma androgen levels between Japanese or Dutch prostate cancer cases and their respective control subgroups. These findings do not support a correlation between the lower plasma testosterone levels and a lower incidence of prostate cancer in the Japanese men. Furthermore, no significant differences were found between salivary levels of testosterone or the ratio between testosterone and SHBG in the various Dutch subgroups. In Japanese benign prostatic hyperplasia patients, the testosterone to SHBG ratio was significantly increased. In conclusion, the results of this retrospective, cross-sectional study do not indicate that hormonal levels play a primary role in the origin or promotion of prostatic abnormalities. The finding of a lower plasma testosterone in the Japanese men, however, remains suggestive, warranting a more extensive prospective study.     

Zinc and cadmium concentrations in indigenous blacks with normal, hypertrophic, and malignant prostate

In order to determine the role of cadmium and zinc in the very low incidence (10/100,000) of cancer of the prostate, in African blacks which contrasts with the very high incidence (100/100,000) in American blacks, the authors measured the serum and prostatic concentrations of these trace metals in healthy Nigerian men and those with benign prostatic hypertrophy (BPH) and prostatic cancer using atomic absorption spectrophotometric study. The mean plasma zinc concentration of healthy men was 14.9 mumol/l +/- 0.5 SEM, whereas those with BPH and malignant glands were 16.5 mumol/l +/- 0.6 SEM and 11 mumol/l +/- 0.7 SEM, respectively. The mean serum cadmium concentrations were 15.2 mumol/l +/- 0.6 SEM, 15.5 mumol/l +/- 0.7 SEM, and 24.2 +/- 0.9 SEM for normal, BPH, and cancer subjects, respectively. The mean prostatic tissue zinc concentration in normal gland was 12.1 mumol/g +/- 0.8 SEM, BPH 17.9 mumol/g +/- 0.6 SEM, and cancer gland 2.9 mumol/g +/- 0.4 SEM. The mean prostatic tissue cadmium concentration for normal BPH and malignant glands were 3.8 mumol/g +/- 0.6 SEM, 14.6 mumol/g +/- 0.37 SEM. The serum and prostatic tissue values of these trace metals in our controls, BPH, and cancer subjects compare with those from populations with higher prostatic cancer rates. This suggests that these metals do not primarily play any significant role in the reported low incidence rate of prostatic cancer in our community. Furthermore, in control subjects and those with BPH, cadmium/zinc ratio, whether evaluated for serum or prostatic tissue was one or less. In patients with cancer, however, this ratio was always greater than one. The possible clinical use of this ratio to diagnose cancer of the prostate gland and to follow-up such patients needs to be further evaluated through more studies.     

Estimation of prostatic growth using serial prostate-specific antigen measurements in men with and without prostate disease.

Prostate growth curves were estimated from serial prostate-specific antigen (PSA) measurements on frozen sera in three groups of men: (a) 16 men with no prostatic disease by urological history and examination; (b) 20 men with a histological diagnosis of benign prostatic hyperplasia (BPH) who had undergone simple prostatectomy; and (c) 18 men with a histological diagnosis of prostate cancer. The median number of repeated PSA measurements over an 8- to 26-yr period prior to histological diagnosis or exclusion of prostate disease was eight and 11 for noncancer and cancer subjects, respectively. Predicted rates of change in PSA (PSA velocity) were linear and curvilinear for control and BPH subjects, respectively. Subjects with cancer demonstrated both a linear and an exponential phase of PSA velocity. Based on time to double PSA, we estimated the epithelial doubling time for men without prostate disease to range from 54 +/- 13 yr at age 40 to 84 +/- 13 yr at age 70. For men with BPH, doubling times ranged from 2 +/- 13 yr at age 40 to 17 +/- 5 yr at age 85. Subjects with local/regional and advanced/metastatic cancer had similar PSA doubling times of 2.4 +/- 0.6 yr and 1.8 +/- 0.2 yr, respectively. These data are consistent with what is known about prostatic growth with age in men without prostate disease and BPH, and the kinetics of prostate cancer growth. Estimates of prostatic growth rate from changes in PSA may be useful clinically in management of men with prostate disease.     

Epidermal growth factor receptors in human prostate cancer: correlation with histological differentiation of the tumour

The presence of specific and high affinity epidermal growth factor receptors (EGF-R) has been demonstrated in human prostate cancer (CaP). Scatchard analysis of the binding data revealed a linear plot consistent with a single class of binding sites with a mean dissociation constant (Kd) +/- s.d. = 1.6 +/- 0.4 nmol 1-1. Additionally the binding was specific for EGF since no other competitor than EGF was able to displace the binding of the labelled ligand from its receptor. Comparison of the concentrations of EGF-R in tissues from 19 patients with CaP with those measured in a group of 18 patients with benign prostatic hyperplasia (BPH) reveal that the expression of EGF-R was significantly higher in BPH (mean +/- s.d. = 125 +/- 7 fmol mg protein-1) than in CaP (52 +/- 11 fmol mg protein-1; P less than 0.01). Furthermore, in CaP the expression of EGF-R varied according to the histological grade of the cancer: well differentiated tumours demonstrated more receptors (84 +/- 13 fmol mg protein-1) than poorly differentiated tumours (22 +/- 5 fmol mg protein-1; P less than 0.01). Clearly the depletion in the expression of EGF receptors in CaP is a function of the histological grade of the cancer and as such EGF receptors could be used as a biochemical marker for tumour differentiation.     

血清cPSA对前列腺癌诊断价值的研究

 目的　探讨血清中结合前列腺特异性抗原 (c PSA)在前列腺癌 (PCa)诊断中的临床价值。方法　用磁微粒子免疫化学发光法测定 72例良性前列腺增生 (BPH)患者和 38例PCa患者c PSA、t PSA ,并计算c PSA/t PSA比值。结果　c PSA及c PSA/t PSA比值可有效地区分BPH和PCa(P <0 .0 0 5 ) ,尤其是在诊断灰值区 (t PSA为 4～ 1 0ng/ml)时效果更显著。在以t PSA≤1 0 .0ng/ml和c PSA/t PSA≥0 .72为筛选界值联合对PCa进行筛选时 ,临床概率敏感度为 93.8%。结论　c PSA的引入及c PSA/t PSA比值的应用 ,对PCa的诊断具有重要临床意义 ,尤其是在前列腺特异性抗原的诊断灰值区。     

Obesity and sex steroids during gonadotropin-releasing hormone agonist treatment for prostate cancer.

PURPOSE: To evaluate effects of obesity on sex steroid levels during treatment with a gonadotropin-releasing hormone agonist in men with prostate cancer. EXPERIMENTAL DESIGN: Forty-nine hormone-na?ve men with recurrent or locally advanced prostate cancer were included in the analyses. All subjects were treated with leuprolide 3-month depot for 48 weeks. Serum levels of estradiol, sex hormone-binding globulin, total testosterone, and free testosterone were assessed at baseline, 24 weeks, and 48 weeks. Subjects were categorized by body mass index (BMI) and percent body fat. RESULTS: Pretreatment serum sex hormone-binding globulin and total testosterone levels were significantly lower in overweight and obese men than in men with normal BMI. In the overall study population, mean serum testosterone concentrations decreased from 372 +/- 18 ng/dL at baseline to 13 +/- 1 ng/dL at week 48 (P < 0.001). Free testosterone decreased from 6.75 +/- 0.33 ng/dL at baseline to 0.21 +/- 0.02 ng/dL at week 48 (P < 0.001). During treatment with leuprolide, obese men had significantly higher total and free testosterone levels than men with normal BMI. Compared with normal men, total and free testosterone levels during treatment were 1.8-fold and 2.3-fold higher in obese men. Similar results were observed when subjects were categorized by body fat. CONCLUSIONS: Despite lower pretreatment serum testosterone levels, obese men have higher total and free testosterone levels during leuprolide treatment than men with normal BMI. These differences may contribute to the association between obesity and increased prostate cancer mortality.     

Skp2和P27kip1在前列腺癌组织中的表达与临床病理特征的相关性研究

背景及目的:F-box蛋白Skp2参与细胞周期抑制蛋白P27kip1泛素化降解,研究发现Skp2在乳腺癌、胃癌、前列腺癌等多种恶性肿瘤中表达增加.本研究旨在探讨Skp2和P27kip1在前列腺癌组织中的表达及与前列腺癌各项临床病理特征的关系,并探讨两者的相关性.方法:用免疫组化EnVisionTM方法检测Skp2和P27 kip1蛋白在41例前列腺癌和20例良性前列腺增生组织中的表达情况.结果:在前列腺癌中的Skp2蛋白阳性率[(8.52±2.40)%]显著高于良性前列腺增生[(0.21±0.15)%](P＜0.001).Skp2蛋白表达与前列腺癌术前血清前列腺特异性抗原(PSA)水平(r=0.360,P=0.021)、局部浸润(r=0.570,P＜0.001)、肿瘤分期(r=0.531,P＜0.001)、病理分级(r=0.514,P=0.001)呈正相关.在前列腺癌中的P27kip1蛋白阳性率[(70.71±4.25)%]显著低于良性前列腺增生[(97.21±2.10)%](P＜0.001).P27kip1蛋白表达与前列腺癌术前PSA水平(r=-0.399,P=0.010)、局部浸润(r=-0.329,P=0.036)、肿瘤分期(r=-0.453,P=0.003)、病理分级(r=-0.290,P=0.046)呈负相关.前列腺癌中P27kip1蛋白与Skp2表达呈负相关(r=-0.572,P＜0.001).结论:前列腺癌中Skp2蛋白表达与靶蛋白P27 kip1蛋白降解有关,提示Skp2蛋白可能与前列腺癌的发生发展有关.     

Impact of age, benign prostatic hyperplasia, and cancer on prostate-specific antigen level

BACKGROUND: The distribution of prostate-specific antigen (PSA) values for men with or without prostate carcinoma are confounded because of verification bias. Correcting for verification bias, the means and variances of PSA values were estimated in specific clinical scenarios. METHODS: Existing receiver operating characteristic (ROC) curves, adjusted for the presence of verification bias in a screening population, were used to estimate the mean and variance of PSA values for men with or without prostate carcinoma, stratified by age and the presence or absence of benign prostatic hyperplasia. Men with a suspicious digital rectal exam (nodular) were excluded from analysis. RESULTS: Among men with cancer and the absence of benign prostatic hyperplasia, mean PSA values were 2.05 ng/mL and 2.66 ng/mL for younger (<60 yr) and older (> or =60 yrs) men, respectively. These estimates were 2.56 ng/mL and 3.90 ng/mL in the presence of benign prostatic hyperplasia for younger and older men, respectively. For men without prostate carcinoma, these values were 0.78 ng/mL and 1.23 ng/mL for younger and older men, respectively, among those without benign prostatic hyperplasia, and 0.97 ng/mL and 1.75 ng/mL for younger and older men, respectively, among those with benign prostatic hyperplasia. CONCLUSIONS: Accurate estimates of the mean and variance of PSA values for men with or without cancer may provide PSA thresholds for biopsy that are specific for age and prostate size as assessed by digital rectal exam. Therefore, the current threshold of 4.0 ng/mL should not be applied indiscriminately.     

Serum and urinary prostatic inhibin-like peptide in benign prostatic hyperplasia and carcinoma of prostate

The levels of immunoreactive prostatic inhibin-like peptide (PIP), having follicle-stimulating hormone suppressing properties, were estimated in the sera and urine samples of patients with benign prostatic hyperplasia (BPH) and prostatic carcinoma (PC) as compared to age-matched controls. Significantly elevated serum PIP levels in BPH (107.8 +/- 19 ng/ml) and PC (88.7 +/- 9 ng/ml) patients were observed as compared to those in control men (10.2 +/- 1 ng/ml). Unlike serum, in urine high levels of PIP in BPH (294 +/- 49 micrograms/24 h) and extremely low levels in PC (23.6 +/- 5 micrograms/24 h) patients were seen as compared to control values (137.6 +/- 10 micrograms/24 h). Furthermore, striking differences were observed between the urinary PIP levels of BPH and PC patients. The results of the present investigation thus indicate the possible use of urinary PIP as a biological marker for prostate cancer.     

Serum testosterone and sex hormone-binding globulin concentrations and the risk of prostate carcinoma: a longitudinal study.

BACKGROUND: It has been hypothesized that high androgen levels are determinants of prostate carcinoma. METHODS: Serum concentrations of testosterone, sex hormone-binding globulin (SHBG), and androstenedione were analyzed to determine their role as predictors of prostate carcinoma in a longitudinal, population-based, nested case-control study. The serum concentrations of testosterone, SHBG, and androstenedione were determined from serum samples collected by the Finnish Mobile Clinic Health Examination Survey between 1968-1972 and stored at -20 degrees C. During a follow-up period of 24 years, a total of 166 prostate carcinoma cases occurred among men who originally were cancer free. Two controls (matched for age and municipality) were chosen. RESULTS: There was no association between serum testosterone, SHBG, or androstenedione concentrations and the occurrence of subsequent prostate carcinoma in the total study population or in subgroups determined based on age or body mass index. The association was not strengthened by simultaneous adjustment for the hormonal variables. CONCLUSIONS: The results of the current study do not appear to corroborate the hypothesis that serum testosterone, SHBG, or androstenedione are determinants of the subsequent occurrence of prostate carcinoma.     

Urinary pyridinoline and deoxypyridinoline in prostate carcinoma patients with bone metastasis.

Bone metastases from prostate carcinoma are predominantly osteoblastic. Recently, urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) have been employed as indicators of bone resorption. In this study, we evaluated urinary Pyr and Dpyr levels in 19 prostate carcinoma patients, of whom 12 had bone metastasis and seven had not, and 11 age-matched control subjects. There was a significant difference in Pyr levels between the control group and the patients with metastasis (mean +/- s.d., 19.5 +/- 7.2 vs 73.3 +/- 67.1 nmol mmol-1 creatinine, P < 0.05). The mean level of Dpyr in the patients with metastasis (10.8 +/- 8.0 nmol mmol-1 creatinine) was significantly higher than that in the control group (3.1 +/- 2.1 nmol mmol-1 creatinine, P < 0.01), and also higher than that in the patients without metastasis (3.5 +/- 1.9 nmol mmol-1 creatinine, P < 0.05). There was no significant difference in Pyr and Dpyr levels between the control group and the patients without metastasis. These results suggest that bone resorption is also accelerated in prostate carcinoma patients with bone metastasis.     

Differences in the leucine aminopeptidase activity in extracts from human prostatic carcinoma and benign prostatic hyperplasia.

Extracts of tissue showed that prostatic carcinomas contain less leucine aminopeptidase activity than benign prostatic hyperplasia. This is true when activity is expressed as specific activity (P = 0.0033), specific activity/% epithelium (P = 0.0007), activity/wet weight of tissue (P = 0.0028), or activity/wet weight of tissue/% epithelium (P = 0.0005). Almost all histochemically demonstrable activity is located in the epithelium. Enzymatic activities in extracts and in histochemical preparations showed similar differences between carcinoma and benign prostatic hyperplasia and were related (R = -0.38, P = 0.0400) to Gleason's grades. The transurethrally resected prostate cancers studied contained no well-differentiated tumors and a high proportion of poorly differentiated tumors. Histochemical activity is absent in most prostatic carcinomas and decreased in others. This observation is particularly interesting in view of the growing knowledge of tumor suppressor genes.     

Serum pituitary and sex steroid hormone levels in the etiology of prostatic cancer--a population-based case-control study.

The hypothesis that serum concentrations of pituitary hormones, sex steroid hormones, or sex hormone-binding globulin (SHBG) affect the occurrence of prostatic cancer was tested in a consecutive sample of 93 patients with newly diagnosed, untreated cancer and in 98 population controls of similar ages without the disease. Cases did not differ significantly from controls regarding serum levels of luteinising hormone (LH) or follicle stimulating hormone (FSH). Remarkably close agreement was found for mean values of total testosterone (15.8 nmol l-1 in cases and 16.0 in controls), and free testosterone (0.295 and 0.293 nmol l-1, respectively), with corresponding odds ratios for the highest vs lowest tertile of 1.0 (95% confidence interval 0.5-1.9) for testosterone and 1.2 (95% confidence interval 0.6-2.4) for free testosterone. Similar close agreement between cases and controls was found for serum concentrations of estradiol, androstenedione and SHBG, although the mean estradiol level was non-significantly (P = 0.30) lower among cases. Changes secondary to the disease were unlikely to have affected the results materially, since only LH and FSH were associated with stage of disease and this relationship was weak. Our findings suggest that further analyses of serum hormone levels at the time of diagnosis are unlikely to improve our understanding of the etiology of prostatic cancer.     

Serum steroid binding proteins and the bioavailability of estradiol in relation to breast diseases

Serum concentrations of sex hormone binding globulin (SHBG), corticosteroid binding globulin (CBG), and albumin were found to be normal in women with breast cancer (Ca), with benign breast disease (BBD), or with a family history of breast cancer (FHCa). Comparisons between serum steroid binding capacities and immunoassayable SHBG and CBG concentrations did not reveal abnormal forms of either protein. The serum distribution of estradiol (E2) was also determined, and women with Ca were found to have a significantly (P less than .025) higher mean percentage of non-protein-bound E2 than matched controls, but the difference was very small. In general, women with Ca also had proportionately more (P less than .05) albumin-bound E2 and less (P less than .05) SHBG-bound E2 in their sera than the controls, but the serum distributions of E2 in the BBD and FHCa subjects were the same as in controls. The dissociation rates of 5 alpha-dihydrotestosterone and E2 from SHBG in serum appear to increase with time in frozen serum samples, and this factor may effect measurements of the distribution of these steroids in serum.     

Latent prostatic carcinomas found at autopsy in men over 90 years old.

Step-sections of 29 whole prostate glands obtained at autopsy from elderly men aged 90 years or over have been investigated. Latent prostatic carcinomas were found in 17 cases (58.6%), all in the peripheral region. The majority of these latent prostatic carcinomas in very old individuals were considered to correspond to stage A1 tumors since, in 75% of cases, the diameter was less than 1 cm. Benign nodular hyperplasia and atypical hyperplasia were also observed in 26 (89.7%) and 14 cases (48.3%), respectively. There was a clear correlation between the appearance of atypical hyperplasia and the presence of latent prostatic carcinoma.     

p40检测在前列腺良恶性病变鉴别诊断中的价值

目的 探讨p40（△Np63）与p504s联合检测在前列腺良恶性病变鉴别诊断中的价值,并与p63表达进行对比.方法 应用免疫组织化学MaxVision法检测92例前列腺增生、67例前列腺癌组织中p40、p63、p504s的表达.结果 p40、p63在前列腺增生组织中的阳性率分别为95.7％（88/92）、87.0％（80/92）（x2=4.381,P＜ 0.05）,其中p63较p40更多见断续表达及弱表达;p40、p63在前列腺癌组织中均未见表达,但p63在癌细胞内出现胞质异常着色占17.9 ％（12/67）;联合检测p40和p504s诊断前列腺增生及前列腺癌的特异度均高达100％.结论 p40对前列腺基底细胞具有更高的敏感性,联合检测p40和p504s对鉴别前列腺良恶性病变具有很高的实用价值.     

Physical characteristics and factors related to sexual development and behaviour and the risk for prostatic cancer.

A case-control study of prostatic cancer was carried out to examine the association between selected physical characteristics and factors related to sexual development and behaviour and the risk for this disease. In consideration of an endocrinologic mechanism for these putative risk factors, the association between selected factors and serum hormone level in a comparison group, free of prostate cancer, was also examined. One-hundred cases and 113 controls were included for study. An elevated risk for prostatic cancer was found for those currently married (odds ratio (OR) = 4.0), those who had been married once (OR = 2.8), and those who were currently practising a religion (OR = 2.0). Compared to subjects with one child, those with more than one child and those with no children were more common among cases than controls. Prostatic cancer risk was associated with large body size and, in particular, with greater weight (p < 0.01). Early age at attainment of adult height was also associated with prostatic cancer risk (p < 0.01). Only moderate associations were found between increased frequency of sexual intercourse and prostatic cancer risk. The levels of testosterone (T), dihydrotestosterone, salivary testosterone and T/SHBG (sex hormone binding globulin) did not vary with age. Older men had higher oestradiol levels. Further, little association between hormone levels and risk factors was found, except for married subjects having increased serum androgens (p < 0.05) and heavy subjects having decreased serum androgens (not significant).     

Target validation of cytochrome P450 CYP1B1 in prostate carcinoma with protein expression in associated hyperplastic and premalignant tissue

PURPOSE: To investigate the localization and distribution of cytochrome P450 CYP1B1 protein expression in patients diagnosed with prostate carcinoma compared to those with bladder carcinoma. To validate CYP1B1 as a molecular target for the development of selective cancer therapeutics for use in combination with radiation. METHODS AND MATERIALS: Prostatectomy specimens (n = 33) of moderate Gleason grade (3 + 3 and 3 + 4) were analyzed immunohistochemically for CYP1B1 protein expression using a specific monoclonal antibody for the enzyme. The intensity of CYP1B1 staining was assessed both semiquantitatively using visual scoring and quantitatively by spectral imaging microscopy using reference spectra and compared with bladder carcinoma (n = 22). RESULTS: CYP1B1 protein expression was present in 75% of prostate carcinomas (n = 27) compared to 100% of bladder carcinomas (n = 22). In both cases, CYP1B1 protein expression was heterogeneous and localized in the cytoplasm of the tumor cells but absent from the surrounding stromal tissue. CYP1B1 was also detected in premalignant prostatic intraepithelial neoplasia (n = 2, 100%), as well as noncancerous tissues, including benign prostatic hyperplasia (n = 27, 82%), metaplastic prostatic urothelium (n = 8, 100%), and hyperplastic prostatic urothelium (n = 14, 100%). Higher CYP1B1 protein expression in bladder vs. prostate carcinoma was confirmed by their corresponding average normalized absorbances (+/- standard deviation), measured as 1.40 +/- 0.44 and 0.55 +/- 0.09, respectively. Overall CYP1B1 staining intensity in prostate carcinoma was similar to that in prostatic intraepithelial neoplasia, benign prostatic hyperplasia, and hyper-/metaplastic urothelial tissue. No CYP1B1 was detected in normal prostate tissue. CONCLUSIONS: CYP1B1 is overexpressed in prostate carcinoma at a high frequency and is also detectable in the associated premalignant and hyperplastic tissue, implicating a possible link with malignant progression and CYP1B1 as a suitable target for therapy. Spectral imaging microscopy has highlighted differences in CYP1B1 protein expression between different cancers.     

Serum alpha-L-fucosidase. A useful marker in the diagnosis of hepatocellular carcinoma.

BACKGROUND AND METHODS. The value of serum alpha-L-fucosidase activity in the diagnosis of hepatocellular carcinoma (HCC) was investigated by determining the enzyme activity levels in 21 patients with HCC, 76 patients with cirrhosis, 22 patients with other malignant neoplasms, and 23 healthy subjects. RESULTS. The serum alpha-L-fucosidase activity level in patients with HCC (575.76 +/- 212.86 nmol/ml/h) was significantly higher than that found in patients with cirrhosis (274.55 +/- 138.97 nmol/ml/h; P less than 0.001) or other neoplasms (257.91 +/- 128.12 nmol/ml/h; P less than 0.001) and in controls (221.23 +/- 114.45 nmol/ml/h; P less than 0.001). No significant differences were found between controls and patients with cirrhosis and between controls and patients with other malignant neoplasms. When 443 nmol/ml/h is taken as the cutoff value (mean value of controls plus 2 standard deviations), alpha-L-fucosidase sensitivity and specificity were 76% and 90.9%, respectively. CONCLUSIONS. These results suggest that alpha-L-fucosidase is a useful marker for detecting HCC, in conjunction with alpha-fetoprotein and ultrasonography.     

Hormonal profile of diabetic men and the potential link to prostate cancer

OBJECTIVE: Previous studies suggest men with diabetes may be at reduced risk for prostate cancer as compared to men without diabetes. To investigate potential biological mechanisms, hormonal profiles of diabetic men and non-diabetic controls were compared. METHODS: In the Health Professionals Follow-Up Study, plasma levels of C-peptide, testosterone, sex-hormone binding globulin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 were determined in 171 diabetic men and 3,001 non-diabetic controls. Multiple linear regression analysis was conducted and least square means were calculated for hormones of interest. RESULTS: Plasma levels of several hormones either /=15 years after diagnosis with diabetes were examined. As time since diabetes diagnosis increased, plasma levels of C-peptide and IGFBP-3 significantly decreased (p for trend: C-peptide =.05, IGFBP-3 =.03). While testosterone and SHBG levels both significantly increased with increasing time since diabetes diagnosis (p for trend: testosterone =.02, SHBG =.002), the ratio of testosterone to SHBG decreased, suggesting a reduction in bioavailable testosterone. Plasma IGF-1 levels were lower in diabetics than non-diabetics, but no significant time trend was noted. CONCLUSION: This study of hormonal profiles of diabetic versus non-diabetic men identified changes in diabetic men that may be consistent with reduced prostate cancer risk.