Is serum PSA a predictor of male hypogonadism? Testing the hypothesis

ABSTRACT Objective: Male hypogonadism (MH) is common among infertile men. Besides testosterone, limited MH biomarkers are available, while researchers have suggested the use of prostate-specific antigen (PSA) to help diagnose MH. Hence, we sought to evaluate the potential use of PSA to predict MH among relatively young men with infertility in Nigeria. Materials and methods: The study included 707 male partners (35-44 years) in infertile couples seeking infertility evaluation at a third-level care center in Nigeria. MH was diagnosed using standard guidelines. Receiver operating characteristic (ROC) and regression analyses explored the potential of serum free PSA (fPSA) and total PSA (tPSA) in predicting MH and MH-related clinical features. Results: In all, 29.7% of the patients had MH (MH+ve). The MH+ve group had lower mean values of fPSA and tPSA than the group without MH (MH-ve). The best fPSA threshold of < 0.25 μg/L compared with the best tPSA threshold of < 0.74 μg/L had higher accuracy (area under the curve [AUC] 0.908 versus 0.866, respectively), sensitivity (87% versus 83%, respectively), and specificity (42% versus 37%, respectively) for MH diagnosis. After adjustment for confounders, fPSA level ≤ 0.25 μg/L was more likely to predict MH-related decreased libido (odds ratio [OR] 2.728, p<0.001) and erectile dysfunction (OR 3.925, p<0.001) compared with tPSA ≤ 0.74 μg/L in the MH+ve group. Conclusion: For MH diagnosis, fPSA and tPSA had good sensitivity but very poor specificity, although fPSA had better potential for MH diagnosis and association with MH-related clinical features than tPSA. Hence, fPSA could complement other biomarkers for MH diagnosis in men 35-44 years, although we recommend further studies to confirm these findings.

Evaluation of Serum Prostate Specific Antigens in Breast Cancer.

Serum Prostate Specific Antigen (PSA) is an established tumor marker for prostate cancer but its “specificity” for prostatic diseases was challenged after its extra prostatic sources and its presence in female serum was detected. Various studies showed the association of Total PSA (TPSA) and Free PSA (FPSA) with breast cancer in females. The present study was conducted to evaluate the status of TPSA and FPSA as a tumor marker in breast cancer patients. 54 breast cancer cases with 36 fibroadenoma patients along with 40 controls were selected for the study. Their blood samples were analyzed for estimation of serum Testosterone, TPSA and FPSA along with routine biochemical parameters. 34 breast cancer with 20 fibroadenoma cases were reevaluated for TPSA and FPSA 6 months after tumor removal by surgery. Our observations revealed high TPSA in the patient group compared to controls and raised FPSA specifically in breast cancer cases. FPSA was also found to be the predominant molecular form in breast cancer cases. A significant positive association was documented between serum Testosterone and PSA level in the study group. Both the parameters registered a significant decline after surgery. On statistical analysis TPSA and FPSA were found to possess high specificity for breast cancer cases but were deficient in the desired sensitivity to be considered as an ideal tumor marker.

Utilidad del APE libre en el diagnóstico de cáncer de próstata / Use of free PSA ratio in the diagnosis of prostate cancer

El Cáncer de próstata (CaP) constituye una importante causa de muerte en nuestro país. La razón Antígeno Prostático Específico libre/ Antígeno Prostático Específico total (APE-L/T) es una de las medidas descritas para mejorar la pesquisa de la enfermedad. MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo analítico en el Hospital Naval de Viña del Mar entre enero 2007 a diciembre 2011 que incluyó 588 pacientes con biopsias prostáticas que presentaban APE- T entre 2-10 ng/ml. Se evaluó la edad al diagnóstico, el valor de APE-T y la razón APE-L/T en relación al resultado histológico de las biopsias. Se realizaron curvas de rendimiento diagnóstico (ROC) para APE- T y para la razón APE-L/T. Se calculó sensibilidad y especificidad para diferentes puntos de corte para la razón APE-L/T. RESULTADOS: 33 por ciento de las biopsias fueron positivas para CaP. Los valores de la razón APE-L/T fueron significativamente más bajos en pacientes con CaP (p<0.001), alcanzando un área bajo la curva ROC 0,615. El mejor punto de corte para la razón APE-L/T fue de 15 por ciento con una sensibilidad de 60 por ciento y una especificidad de 58 por ciento. Para la razón APE-L/T > 25 por ciento la sensibilidad es 20 por ciento y la especificidad 91 por ciento. En cambio, el APE-T no mostró diferencias estadísticamente significativas (p=0,1) con un AUC 0,55. CONCLUSIONES: El APE-T por sí solo no parece tener capacidad discriminante para detectar CaP cuando los valores se encuentran entre 2-10 ng/ml. La razón APE-L/T tiene una utilidad limitada frente al paciente para decidir efectuar o no una biopsia de próstata.

Prostate cancer (PCa) is one of the major causes of death in our country. The Free/Total Prostate specific antigen ratio (f/t PSA) is one of the measurements that have been used to improve the diagnosis of this disease. MATERIAL AND METHODS: A retrospective analytic study in the Almirante Nef Hospital in Viña del Mar between January 2007 and December 2011 was made, which included 588 patients with prostate biopsies that had tPSA between 2-10 ng/ml. The age at diagnosis was evaluated and the value of tPSA and the f/t PSA ratio were compared with the histological results of the biopsies. Curves were performed for the diagnostic yield (ROC) for tPSA and the f/t PSA ratio. The sensitivity and specificity for different cut-off points for the f/t PSA ratio in the diagnosis of PCa were also calculated. RESULTS: 33 percent of the biopsies were positive for PCa. The f/t PSA ratio values were significantly lower in patients with CaP (p<0.001), reaching an area under the curve of 0,615. The best cutoff for f/t PSA ratio was 15 percent with 60 percent sensitivity and 58 percent specificity. For f/t PSA ratio > 25 percent sensitivity was 20 percent and specificity was 91 percent. PSA showed no statistically significant differences (p = 0.1) with AUC: 0.55. CONCLUSIONS: tPSA alone does not seem to have discriminatory power to detect PCa in patients when values are between 2-10 ng/ml. The f/t PSA ratio has a limited utility to decide to perform a prostate biopsy or not.

Analysis of age-specific prostate specific antigen and related parameters in 22 055 elderly men / 中华泌尿外科杂志

[Abstract] Objective To define the age-specific normal reference values of prostate specific antigen (PSA) and related parameters in Chinese middle-aged and elderly men.Methods From April 2007 to November 2011,serum PSAs of over 22 055 men aged more than 40 years old in our medical examination center were statistically analyzed.The men was divided into five groups by a 10-year-old interval.Total PSA (tPSA),free PSA (fPSA) and prostate ultrasound results were recorded.The free-total PSA ratio (f/t),PSA density (PSAD) and PSA velocity (PSAV) were calculated.By convention,the 95th percentile (P95)was used as the upper limit value,and the 5th percentile (P5) as the lower limit value.Results The tPSAs were positively correlated with age (r=0.349,P＜0.001).f/t was negatively correlated with age (r=-0.154,P＜0.01).Although f/t was significantly different (P＜0.001) among each age group,P5 of all groups were 0.18.PSAD was significantly different (P＜0.001) between men over and under 70 years,with P95 as 0.09 and 0.15,respectively.PSAD had a positive correlation with age (r =0.263,P＜0.01).The significant difference of PSAV raised between men over and under 60 years,with P95 as 0.21 and 0.58,respectively.PSAV was positively correlated with age (r=0.130,P＜0.01).Conclusions PSA,PSAD and PSAV are positively correlated with age,while f/t is negatively correlated with age.The normal range of f/tis 0.18-1.00 for Chinese men over 40 years old.PSAD's normal ranges are ＜0.09 and ＜0.15 in Chinese men over and under 70 years,respectively.The normal range of PSAV are ＜0.21 and ＜0.58 for Chinese men over and under 60 years,respectively.

Evaluation of Architect Total PSA Chemiluminescence Immunoassay for Diagnosing Prostate Cancer / 대한진단검사의학회지

BACKGROUND: Serum prostate specific antigen (PSA) is used as a marker for early diagnosis, monitoring of therapy, and detection of recurrence of the prostatic tumor or benign prostatic hyperplasia (BPH). In Korea, over 15 instruments have been used for measuring PSA. In this study, chemiluminescence microparticle immunoassay Architect total PSA (Abbott Lab., Abbott Park, IL, USA) was evaluated for analytical performance and diagnostic usefulness as a marker for prostate cancer. METHODS: The within-run and between-run precision, lower detection limits, correlation with AxSYM total PSA (Abbott Lab., Abbott Park, IL, USA) and clinical investigation were evaluated. Three level control serums (0.5, 4.0, and 23.0 ng/mL) were used for a precision test. The linearity was evaluated using a patient serum sample with a PSA concentration of 100 ng/mL. Functional and analytical sensitivities were tested using a patient serum sample with a PSA concentration of less than 0.1 ng/ mL and saline. A correlation study with AxSYM total PSA was done with 42 serum samples. Clinical evaluation was done with 230 patients of whom 17 had prostate cancer. RESULTS: The total PSA showed a good precision result with less than 5 % of CV and showed linearity to 100 ng/mL. The functional sensitivity was 0.025 ng/mL and analytical sensitivity 0.001 ng/mL. The correlation evaluation showed Y (Architect)=1.0575X(AxSYM)+0.1895, r=0.9960. A Cut-off value of 8.35 ng/mL showed 88.2% sensitivity, 80.3% specificity as a diagnostic marker for prostate cancer. CONCLUSIONS: Architect total PSA showed an acceptable analytical performance with its high sensitivity and could be a useful marker for early detection and recurrence of prostate cancer.

Significance of Serum Concentration of Free and Total Prostate Specific Antigen in Benign Prostatic Hyperplasia and Prostate Cancer / 대한비뇨기과학회지

PURPOSE: This study was performed to investigate whether the free to total PSA ratio(F/T PSA ratio) offers a better discriminant for the detection of patient with prostatic cancer(CaP) and those with benign prostatic hyperplasia(BPH) than serum total PSA alone. MATERIALS AND METHODS: From September 1996 to February 1999, free and total PSA levels were measured on frozen sera samples of 154 men with BPH and 46 with CaP using immunoradiometric assay. RESULTS: In all subjects, the mean total PSA was significantly higher in CaP group(72.59+/-66.58ng/ml) than BPH group(3.12+/-4.10ng/ml). The mean PSAD was significantly higher in CaP group(1.64+/-1.86) than BPH group(0.08+/-0.01). The mean F/T PSA ratio was significantly lower in CaP group(0.19+/-0.07) than BPH group(0.30+/-0.13). Among 41 subjects whose total PSA were between 4-20ng/ml, the mean PSAD was significantly higher in CaP group(0.37+/-0.16) than BPH group(0.17+/-0.07), but the mean F/T PSA ratio was not significantly different between CaP(0.19+/-0.10) and BPH group(0.25+/-0.13). By comparing the sensitivity and specificity of total PSA alone, PSAD and F/T PSA ratio on receiver operating characteristic(ROC) curve in all subjects and subjects with total PSA between 4-20ng/ml, F/T PSA ratio had no superiority than total PSA alone and PSAD for. discrimination between CaP and BPH. CONCLUSIONS: We suggest that the F/T PSA ratio is not superior to total PSA alone and PSAD in the detection of prostatic cancer, and further evaluation of the usefulness of F/T PSA ratio should be required.

The Effect of Age, Prostate volume and Total PSA on Percent free PSA in Men with Benign Prostatic Disease / 대한비뇨기과학회지

PURPOSE: We assessed the influence of age and prostate volume on the serum total PSA and percent free PSA level, and total PSA on the percent free PSA level in men with benign prostatic disease except clinically detectable prostatic cancer. MATERIALS AND METHODS: Sera were obtained from 250 men with total PSA level of 0 to 20 ng/ml who were clinically negative for cancer. Total and free PSA levels were measured using ELSA-PSA2 and FPSA-RIACT immunoradiometry assay. Prostate volume was determined by transrectal ultrasound. RESULTS: Age and prostate volume correlated significantly with Total PSA levels (r=0.204 and 0.482, p<0.05) and free PSA levels (r=0.246 and 0.539, p<0.05) but not with percent free PSA(r=0.057 and -0.039, p=0.188 and 0.541). Total PSA levels correlated significantly with free PSA(r=0.853, p<0.05) and percent free PSA(r=-0.398, p<0.05). CONCLUSIONS: Among men with total PSA levels of 0 to 20 ng/ml and do not have clinically detectable prostatic cancer, total PSA and free PSA increases with increasing age and prostate volume. And percent free PSA decreases with increasing total PSA but it was not influenced by age and prostate volume.

The Value of Free/Total Prostate Specific Antigen Ratio in the Diagnosis of Prostate Cancer / 대한비뇨기과학회지

PURPOSE: We investigated the value of the free to total PSA ratio of intermediate serum PSA levels(4-20ng/m1) in the detection of prostate cancer. MATERIALS AND METHODS: Free PSA, total PSA levels and free to total PSA ratio(F/T ratio) were measured on sera samples of 103 men with symptomatic BPH and 20 men with prostate cancer, who were proved by biopsy, by using ELSA-PSA2 and FPSA-RIACT. And we used transrectal ultrasound determined prostate volume to calculated PSA density(PSAD). RESULTS: In all patients, mean PSAD was significantly greater for patients with cancer(2.07+/- 1.65) versus BPH(0.120.12). The F/T ratio was significantly lower for cancer(0.12+/-0.04) compared with BPH(0.32+/-0.20). At a time, when serum PSA between 4 and 20ng/m1 was considered in 8 patients with cancer and 38 patients with BPH, mean total serum PSA was significantly greater for patients with cancer(12.02+/- 3.54ng/m1) versus BPH(7.21 +/-3.68ng/m1). Mean PSAD was significantly greater for patients with cancer(0.36+/- 0.12) versus BPH(0.20+/-0.12) and the F/T ratio was significantly lower for cancer(0.14+/-0.03) compared with BPH(0.25+/-0.12). Use of the Ff ratio of 0.15 resulted in the highest sensitivity(75%) and specificity(89.5%) and the F/T ratio was superior to total PSA when compared with receiver operating characteristic curve . CONCLUSIONS: The F/T ratio give a significant improvement over total PSA value in the diagnosis of prostate cancer in patients with intermediate PSA levels. But, to assess accurately usefullness of F/T ratio in early prostate cancer detection, further studies are needed and consensual threshold value is necessary.

Age Specific Free PSA to Total PSA Ratio in Normal Korean Men / 대한비뇨기과학회지

Prostate specific antigen (PSA) is known as the most sensitive marker for detecting prostate carcinoma (CaP). Nevertheless, PSA testing lacks sufficient sensitivity and specificity to be considered the perfect tumor marker for the detection of early prostate cancer. PSA exists in the serum in several molecular forms; free PSA and complexed PSA (PSA complexed to alpha-1-antichymotrypsin or a-2-macrogloburin or inter-alpha -trypsin inhibitor). It has been suggested that analysis of level of free to total PSA ratio improves specificily of PSA assays in the early detection of prostate carcinoma. We measured free PSA and total PSA of 367 healthy men aged from 30 to 79 years old using radioimmunoassay (PSA-RIACT and FPSA-RIACT kit) in order to know the normal range of PSA, free PSA and free PSA to total PSA ratio. The mean free to total PSA ratio in normal Korean men is 0.31+/-0.14 and there is no correlation with patient age.