Age-specific reference levels of serum prostate-specific antigen and prostate volume in healthy Arab men

OBJECTIVE; To determine age-specific reference ranges for serum prostate-specific antigen (PSA) concentration and prostate volumes in a population of healthy Arab men. SUBJECTS AND METHODS: Blood samples were taken from 396 healthy Arab men (from Kuwait and Oman) aged 15-79 years and from across the social spectrum. Men aged >40 years had a digital rectal examination and transrectal ultrasonography of the prostate to determine prostate volume. The serum PSA level was measured using commercial kits, and age-specific ranges for PSA levels and prostate volume determined. RESULTS: The serum PSA ranges (ng/mL) for each age range in Arab men were: 40-49 years, 0-0.9; 60-69, 0-2.7; 70-79, 0-5.5 ng/mL; the respective prostate volumes were 8-22, 9-30 and 10-33 mL. The serum PSA level and prostate volume correlated with age (P < 0.001). Arab men had lower serum PSA levels and prostate volumes than those reported for Caucasians, but similar to those reported for Asians (Japanese and Chinese). CONCLUSION: These results indicate that Arab men have lower PSA levels and prostate volumes than Caucasians. The levels are slightly lower than those reported in the Japanese and, as in the Japanese, low PSA levels and small prostate volumes might be related to the low incidence of clinical prostate cancer in Arab men.     

健康男性的胰岛素抵抗指数、肥胖、血清PSA水平间的关系

本研究旨在确定血清PSA水平低于4ngmL^-1的健康男性的胰岛素抵抗指数、肥胖和血清前列腺特异性抗原（PSA）水平之间的关系。调查对象为韩国水力原子力株式会社的11827名健康男性职员,在2003年1月到2008年12月间接受了体检,体检项目包括空腹血糖水平、空腹胰岛素水平和血清PSA水平。用稳态模式评估法（HOMA;[空腹血糖水平×空腹胰岛素水平]／22．5）和定量胰岛素敏感性检验指数（QUICKI;1／[10g（空腹胰岛素水平）＋log（空腹血糖水平）]）测定胰岛素抵抗指数。协方差分析（ANOVA）和Duncan’s多重比较试验显示,随着用HOMA和OuICKI测定的胰岛素抵抗指数四分位的上升,年龄标化体重指数（BMI）也显著增加（P〈0．001）。多变量线性回归分析表明,相对于血清PSA水平,年龄、BMI、以及用HOMA或QUICKI测得的胰岛素抵抗指数都是显著的独立变量（P〈0．001）。本研究说明胰岛素抵抗指数和BMI都是血清PSA水平的独立变量,在健康男性体内,两者都与血清PSA水平呈负相关,两者之间呈正相关。     

Relationship between serum prostate-specific antigen and prostate volume in Korean men with benign prostatic hyperplasia: a multicentre study

OBJECTIVES: To evaluate the relationship between prostate specific antigen (PSA) and prostate volume (PV) in Korean men, as PV is a key predictor of both disease progression and response to medical therapy in patients with benign prostatic hyperplasia (BPH), and PSA has been suggested as a proxy marker to estimate the total PV, mainly in Caucasians. PATIENTS AND METHODS: From 1999 to 2004, men aged 50-79 years with lower urinary tract symptoms (LUTS) and BPH were enrolled into this multicentre study. The analyses included 5716 patients presenting to 11 medical centres with LUTS (International Prostate Symptom Score >8, peak urinary flow rate <15 mL/s); they had a mean age of 64.3 years, mean baseline PV of 36.9 mL, and mean baseline PSA level of 2.2 ng/mL. Men with a baseline PSA of >10 ng/mL were excluded, to reduce the likelihood of including occult prostate cancer. A biopsy was taken in those with suspicious findings on a digital rectal examination or serum PSA level of >4 ng/mL, to exclude prostate cancer. Receiver operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to predict threshold PV in men with BPH. RESULTS: The PV and serum PSA level had an age-dependent log-linear relationship, the strength of which increased with age. The ROC curve analysis showed that PSA had good predictive value for various prostate volume thresholds (30, 40 and 50 mL). CONCLUSIONS: The PSA-PV relationship in Korean men is similar to that in Caucasians, but Korean men have a slightly lower PSA level and a smaller PV than Caucasians. The approximate age-specific criteria for detecting Korean men with a PV of >40 mL were a PSA level of >1.3 ng/mL, >1.7 ng/mL and >2.0 ng/mL for men with BPH in their sixth, seventh and eighth decade, respectively.     

Association between serum prostate-specific antigen level, liver function tests and lipid profile in healthy men

OBJECTIVE

To assess the association between serum prostate‐specific antigen (PSA) level and age, liver function tests (LFTs) including alkaline phosphatase (ALP), total bilirubin (TB), lipid profile (total cholesterol, TC, triglycerides, TG, high‐density lipoprotein, HDL) and fasting blood sugar (FBS), and to determine the significant factors for predicting the serum PSA level in men with a low risk of having prostate cancer.

SUBJECTS AND METHODS

In all, 38 157 healthy male employees of the Korea Electric Power Corporation (KEPCO) who were aged <60 years and had serum PSA levels of <4 ng/mL and serum creatinine levels of <1.4 mg/dL were enrolled between January 2002 and December 2006. Body weight and height were measured, and levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), ALP, TB, FBS, TC, TG, and HDL, and serum PSA were measured.

RESULTS

The mean (sd ) age of the study population was 44.4 (7.90) years and the mean PSA level 0.89 (0.51) ng/mL. In a univariate analysis there were significant interrelations between serum PSA level and age, BMI, AST, ALT, ALP, TB, HDL and FBS (P < 0.05). The multiple logistic regression analyses using four percentiles (10th, 25th, 75th, 90th percentile) of serum PSA level showed trends that being older was associated with serum PSA level, and that BMI, ALT, HDL and FBS were negatively correlated with serum PSA level.

CONCLUSIONS

These results suggest that serum PSA level was significantly influenced by age, BMI, ALT, HDL and FBS. Further studies are needed to confirm our results and to explain the underlying mechanisms.     

Polymorphisms in the prostate-specific antigen gene promoter do not predict serum prostate-specific antigen levels in African-American men

A major problem with the use of serum prostate-specific antigen (PSA) in predicting prostate cancer risk is the considerable variability of such measurements. Cramer et al. identified a set of single-nucleotide polymorphisms (SNPs) in the upstream regulatory region of the PSA gene that were each associated with increased promoter activity and serum PSA, further suggesting that genotyping these SNPs could be useful in improving the predictive value of PSA screening. In order to replicate this finding, DNA samples from 475 African-American men were genotyped for the same SNPs and no association was observed with either serum PSA level or prostate cancer diagnosis.     

Ethnic differences in the age-related distribution of serum prostate-specific antigen values: a study in a healthy Korean male population

Objectives. To further improve the use of prostate-specific antigen (PSA) as a screening test for prostate cancer in Asian countries, we sought to establish the normal distribution of serum PSA values in Korean men, because, until recently, studies conducted to establish normal serum PSA values have involved few Asian populations.Methods. Between May 1995 and June 1997, 5805 healthy Korean men 30 to 79 years old who visited our hospital for a routine health checkup were entered into a prospective study of early screening for prostate cancer. All men underwent detailed clinical examinations, including a digital rectal examination and serum PSA determination. All men who were more than 50 years old with abnormal digital rectal examination findings and/or an elevated serum PSA level (greater than 4.0 ng/mL) also underwent transrectal ultrasound-guided sextant biopsy. Four were found to have cancer and were excluded from the analysis.Results. The median serum PSA concentration (5th to 95th percentile range) was 0.8 ng/mL (0.2 to 1.8) for patients 30 to 39 years old (n = 1382); 0.8 ng/mL (0.2 to 2.0) for patients 40 to 49 years old (n = 1776); 0.9 ng/mL (0.2 to 2.4) for those 50 to 59 years old (n = 1775); 1.0 ng/mL (0.2 to 3.9) for men 60 to 69 years old (n = 746); and 1.3 ng/mL (0.5 to 6.3) for patients 70 to 79 years old (n = 122). The serum PSA concentration correlated with age (P <0.001), with an increase by approximately 1.2% annually, although the statistical correlation was weak (r = 0.16). Almost no change occurred in the median serum PSA value in patients 50 years old or younger; a gradual increase was observed in patients older than 50. In those 50 years old or older, the median and 95th percentile serum PSA values for Korean men were lower than those for white men.Conclusions. Contrary to earlier observations that the serum PSA level strongly correlates with age, the influence of age on serum PSA was found to be weaker in this study. Moreover, the results also demonstrated that the distribution of the serum PSA level differs along ethnic lines. The cutoff value for serum PSA in mass screening for prostate cancer should be adjusted in nonwhite races.     

Effect of constipation on serum total prostate-specific antigen levels in men

Objectives: Many factors affecting serum prostate‐specific antigen (PSA) levels have been described. The aim of this study was to examine the effect of constipation on serum PSA levels in men. Methods: Serum total PSA values were measured in 136 constipated patients before and after treatment for constipation. Moreover, they were compared with 45 control patients. Results: Serum total PSA values in the constipated patients before treatment were significantly higher than those in the control group (2.29 ± 1.29 ng/mL vs 1.28 ± 0.86 ng/mL, P < 0.0001). After the treatment of constipation, serum total PSA values in the constipated patients were still higher than those in the control group, but this difference was not statistically significant (P = 0.0871). After the treatment of constipation, prostate biopsy rates were 6.6% and 2.2% in the study and control group, respectively (P = 0.2769). No prostate cancer was found in both groups. Conclusions: Constipation increases serum PSA levels in men. The presence of constipation must be considered in patients whose PSA is examined, especially in those with PSA levels that are borderline high or in the range of 2–10 ng/mL. Constipated patients must be first treated and then re‐evaluated.     

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.     

Body mass index and serum lipid profile influence serum prostate-specific antigen in Chinese men younger than 50 years of age

This study is to assess the potential factors that could affect the serum prostate-specific antigen (PSA) level in healthy younger men. We evaluated the associations of age, body mass index (BMI) and serum lipid profile with serum PSA level in 6774 Chinese men (aged 20-49 years) who received a routine health examination. Eligible men were classified into 10-year age groups. BMI was categorized as underweight (<18.5), normal (18.5-22.9), overweight (23.0-24.9), obese (25.0-29.9) and very obese (>30) according to the redefined World Health Organization (WHO) criteria for the Asia-Pacific region. PSA levels were compared among groups as well. In multiple linear regression analysis, PSA was positively correlated with age (P<0.0001). Negative correlations existed between PSA and BMI (P<0.0001) and triglyceride level (P=0.01). No relationship could be found between PSA and serum cholesterol (P=0.711) or high-density lipoprotein (HDL; P =0.665). In addition, we found that serum PSA levels increased with age and decreased with BMI. Our study demonstrates that age, BMI and triglyceride levels influence the PSA level in men <50 years of age.     

Daily variability of serum prostate-specific antigen in men over 50 years of age

In order to investigate the variability ofserum prostate-specific antigen(PSA) levels a total of 44 men 50 years or older with normal digital rectalexamination were enrolled. Blood samples were obtained three times withina day, and, immediately before and 72 hours after hospitalisation.Alterations in serum PSA value during the day and after hospitalisation,which might affect clinical decision, occurred in 15%of the cases withborderline PSA values. The results indicate that there may be significantchanges in serum PSA levels within a day and after hospitalisation.     

Beyond prostate-specific antigen: alternate serum markers

There is a need to improve existing methods for early diagnosis of prostate cancer (CaP) and to identify men at risk for developing aggressive disease. In an effort to replace and/or supplement prostate-specific antigen many serum analytes have been examined, but with little supportive data for clinical use. Recently, technological advances in molecular assays have improved investigational outcomes and have led to the discovery of a number of prospective markers with high specificity. Further promise for providing more accurate CaP diagnosis and prognosis lies in proteomic array profiling and DNA methylation assays. This review illustrates the current benefits and limitations of potentially useful CaP serum markers that have considerable existing data and touches upon other future markers as well as the field of proteomics.