We report a nested case-control study of serum
biomarkers of
5 alpha-reductase activity and the incidence of
prostate cancer. From a cohort of more than 125,000 members of the Kaiser Permanente Medical Care Program who underwent multiphasic health examinations during 1964-1971, we selected 106 incident
prostate cancer cases. A control was pair matched to each case on age, date of serum sampling, and clinic location. Serum levels of total
testosterone, free
testosterone,
androsterone glucuronide, and 5 alpha-androstane-3 alpha,17 beta androstanediol
glucuronide (
3 alpha-diol G) were measured on the stored samples and scored as quartiles. Potential confounders included alcohol, smoking, and body mass index. The adjusted odds ratios and 95% confidence intervals for a one quartile score increase were 1.00 (0.75-1.34) for total
testosterone, 1.14 (0.86-1.50) for free
testosterone, 1.13 (0.84-1.53) for
androsterone glucuronide, and 1.16 (0.86-1.56) for
3 alpha-diol G. A limitation of this study is that there are two different
5 alpha-reductase isoenzymes, only one of which is expressed in high levels within the prostate, yet both of which may affect serum
biomarkers. Since the two
isoenzymes are encoded on different chromosomes, variation in one would act as an independent source of measurement error in any analysis of serum
biomarker effects of the other. Consequently, the odds ratios may be underestimated and the study, although negative, cannot exclude the previously hypothesized possibility that a positive relationship between intraprostatic
5 alpha-reductase activity and
prostate cancer may exist. A clinical trial to test this hypothesis is under way.