Objective: To assess whether sex hormone levels are associated with subsequent development of prostate cancer. Methods: A case-cohort study was conducted within the ongoing Osteoporotic Fractures in Men cohort study of community-dwelling men <65 years old recruited at 6 US clinical sites. After a mean follow-up of 4.7 years, all men with incident-confirmed prostate cancer and a random sample of the full cohort (subcohort) were selected for analysis: after excluding men with a history of prostate cancer and those who reported androgen or antiandrogen therapy at baseline, the resulting analytic sample comprised 275 cases and 1652 noncases with complete sex hormone measurements. Serum testosterone, estradiol, estrone, and sex hormonebinding globulin were assayed at baseline (prediagnosis) by gas chromatography combined with mass spectrometry. Associations between incident prostate cancer and each sex hormone were evaluated using Cox proportional hazards regression models adjusted for age, race, study site, body mass index, and person-time. Results: In the subcohort, the mean age was 73 years. Higher serum estrone was strongly related to an increased risk of prostate cancer: compared with men in the lower quartile, the risk of prostate cancer among those in the highest 3 quartiles (>24.9 pg/dL) was nearly 4-fold higher (adjusted heart rate = 3.93, CI: 1.61-9.57). Other sex hormones were not associated with the risk of prostate cancer. Conclusions: In this cohort of older men, higher estrone levels were strongly associated with an increased risk of incident prostate cancer. This association between estrone and prostate cancer risk needs to be clarified by further study.
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