Study
PLCO
(Learn more about this study)
Project ID
2008-0044
Initial CDAS Request Approval
Oct 22, 2008
Title
Effect of circulating androgens and sex hormones on serum PSA levels in the PLCO study
Summary
Introduction: Prostate specific antigen (PSA) levels in men with prostate cancer (CaP) are known to decrease in response to treatment with therapies that decrease circulating androgen levels. However, the relationship between circulating androgens and serum PSA in men without CaP has not been clearly established. We used data from a subset of men in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial to examine these relationships. Methods: From 1993 through 2001, PLCO investigators randomized 38,349 men aged 55-74 to be offered annual PSA and DRE screening. Investigators conducted a nested case control study of sex hormones and prostate cancer risk. We determined serum levels of testosterone, androstenedione, testosterone and sex-hormone binding globulin (SHBG) in addition to PSA at baseline. The current study analyzes 949 Caucasian men who were selected as controls. We stratified hormone levels into quartiles. We also examined the age, body mass index (BMI), family history of prostate cancer and history of an enlarged prostate as factors which might influence PSA levels. Multivariate linear regression was used to evaluate determinants of serum PSA. Results: The mean age of the cohort was 64.8 years; median serum PSA was 1.67 ng/mL. Of the characteristics of the cohort examined, increasing age (p=0.01) and history of an enlarged prostate (p<0.01) showed a positive correlation with serum PSA levels. BMI showed a trend toward an inverse relationship with PSA (p=0.14); family history did not correlate with PSA. Testosterone levels showed a positive correlation with PSA levels (p=0.02, Table). Likewise, androstenedione (p=0.03) showed a positive correlation with PSA levels. SHBG level showed a negative correlation with PSA (p<0.01, Table). BMI trended toward an inverse relationship with PSA. Conclusions: In a screened population of men without prostate cancer, PSA correlates positively with serum testosterone and androstenedione levels and inversely with SHBG levels in a multivariate model controlling for other cohort characteristics. Among cohort characteristics, only age and history of an enlarged prostate correlated with PSA levels. The relationship between age, BMI, sex hormone levels and PSA is complex and requires further study.
Aims
Specific Aim#1: To determine the relationship between serum testosterone and serum PSA in a screening population of men. Circulating androgens are known to be a growth factor for prostate cancer and withdrawal of androgens has a profound effect on prostate cancer growth and subsequently decreases PSA levels. However, less is know about the effect of circulationg androgens on PSA levels in men without prostate cancer or with localized prostate cancers. Specific Aim#2: To determine the association of other serum sex hormones with serum PSA levels Testosterone is not the only circulating androgen. We propose to examine the effect of other related circulating sex hormones on PSA levels.
Collaborators
Amanda Black
Jerome Mabie (IMS)
Lawrence Ragard (Westat)
Robert Greenlee (Marshfield Clinic)
Tom Hickey (Westat)
Gerald Andriole (Washington University)
Robert Grubb (Washington University)
Grant Izmirlian (IMS)
Paul Pinsky
Tom Riley (IMS)
