Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies

Abstract

Background: Sex hormones in serum have been hypothesized to influence the risk of prostate cancer. We performed a collaborative analysis of the existing worldwide epidemiologic data to examine these associations in a uniform manner and to provide more precise estimates of risks.

Methods: Data on serum concentrations of sex hormones from 18 prospective studies that included 3886 men with incident prostate cancer and 6438 control subjects were pooled by the Endogenous Hormones and Prostate Cancer Collaborative Group. Relative risks (RRs) of prostate cancer by fifths of serum hormone concentration were estimated by use of conditional logistic regression with stratification by study, age at recruitment, and year of recruitment. All statistical tests were two-sided.

Results: No associations were found between the risk of prostate cancer and serum concentrations of testosterone, calculated free testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, androstenedione, androstanediol glucuronide, estradiol, or calculated free estradiol. The serum concentration of sex hormone-binding globulin was modestly inversely associated with prostate cancer risk (RR in the highest vs lowest fifth = 0.86, 95% confidence interval = 0.75 to 0.98; P(trend) = .01). There was no statistical evidence of heterogeneity among studies, and adjustment for potential confounders made little difference to the risk estimates.

Conclusions: In this collaborative analysis of the worldwide data on endogenous hormones and prostate cancer risk, serum concentrations of sex hormones were not associated with the risk of prostate cancer.

Fig. 1

Associations between risk of prostate cancer and increasing fifths of hormone concentrations. The position of each square indicates the magnitude of the relative risk, and the area of the square is proportional to the amount of statistical information available (inverse of the variance of the logarithm of the relative risk). The length of the horizontal line through the square indicates the 95% confidence interval. The chi-square 1 degree of freedom statistic for linear trend is calculated by replacing the categorical variables with a continuous variable scored as 0, 0.25, 0.5, 0.75, and 1. The P value was two-sided for statistical significance of the chi-square linear trend statistic. RR = relative risk; CI = confidence interval; DHT = dihydrotestosterone; DHEA-S = dehydroepiandrosterone sulfate; SHBG = sex hormone–binding globulin.

Fig. 2

Association between risk of prostate cancer and sex hormone concentrations according to stage of disease (A) and grade of disease (B). The relative risk is the estimate of the linear trend for each sex hormone obtained by replacing the categorical variables representing the fifths with a continuous variable scored as 0, 0.25, 0.5, 0.75, and 1. The position of each square indicates the magnitude of the relative risk, and the area of the square is proportional to the amount of statistical information available (inverse of the variance of the logarithm of the relative risk). The length of the horizontal line through the square indicates the 95% confidence interval. The chi-square statistic for heterogeneity ( ${\mathrm{\chi }}_1^2$ het) is to assess whether the relative risk estimates for each characteristic are different from each other. The P value was two-sided for statistical significance of the chi-square heterogeneity statistic. RR = relative risk; CI = confidence interval; DHT = dihydrotestosterone; Adiol-G = androstanediol glucuronide; DHEA-S = dehydroepiandrosterone sulfate; SHBG = sex hormone–binding globulin.

Fig. 3

Association between risk of prostate cancer and sex hormone concentrations according to time interval between blood collection and diagnosis (A) and year of diagnosis (B). The relative risk is the estimate of the linear trend for each sex hormone obtained by replacing the categorical variables representing the fifths with a continuous variable scored as 0, 0.25, 0.5, 0.75, and 1. The position of each square indicates the magnitude of the relative risk, and the area of the square is proportional to the amount of statistical information available (inverse of the variance of the logarithm of the relative risk). The length of the horizontal line through the square indicates the 95% confidence interval. The chi-square statistic for heterogeneity ( ${\mathrm{\chi }}_2^2$ het) is to assess whether the relative risk estimates for each characteristic are different from each other. The P value was two-sided for statistical significance of the chi-square heterogeneity statistic. RR = relative risk; CI = confidence interval; DHT = dihydrotestosterone; Adiol-G = androstanediol glucuronide; DHEA-S = dehydroepiandrosterone sulfate; SHBG = sex hormone–binding globulin.

Fig. 4

Association between risk of prostate cancer and sex hormone concentrations according to age at diagnosis (A) and prostate-specific antigen level at recruitment (B). The relative risk is the estimate of the linear trend for each sex hormone obtained by replacing the categorical variables representing the fifths with a continuous variable scored as 0, 0.25, 0.5, 0.75, and 1. The position of each square indicates the magnitude of the relative risk, and the area of the square is proportional to the amount of statistical information available (inverse of the variance of the logarithm of the relative risk). The length of the horizontal line through the square indicates the 95% confidence interval. The chi-square statistic for heterogeneity ( ${\mathrm{\chi }}_2^2$ and ${\mathrm{\chi }}_1^2$ het) is to assess whether the relative risk estimates for each characteristic are different from each other. The P value was two-sided for statistical significance of the chi-square heterogeneity statistic. RR = relative risk; CI = confidence interval; DHT = dihydrotestosterone; Adiol-G = androstanediol glucuronide; DHEA-S = dehydroepiandrosterone sulfate; SHBG = sex hormone–binding globulin.