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Hormone levels not associated with lower prostate cancer risk among older men with diabetes
Among men aged at least 70 years, type 2 diabetes appeared associated with a 35% reduction in risk for prostate cancer after consideration of standard risk factors, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
The longitudinal analysis of more than 3,000 men also showed that men with a history of diabetes had an altered hormone profile compared with men without diabetes, including lower androgen levels and higher insulin-like growth factor I levels, but the observed association was not explained by these differences.
“Prostate cancer is an androgen-dependent cancer, and previous authors have hypothesized that lower [testosterone] in patients with type 2 diabetes may account for decreased prostate cancer risk seen in these patients,” Yi X. Chan, MBBS, of the University of Western Australia School of Medicine in Perth, Australia, and colleagues wrote. “A high frequency of hypogonadotropic hypogonadism has been reported in men with type 2 diabetes. This is in keeping with lower androgen levels observed in men with diabetes in this cohort. Despite this, the role of androgens in the development of prostate cancer is still unclear.”
Chan and colleagues analyzed data from 3,149 older men (mean age, 77 years) participating in the Perth-based Health in Men Study. Men provided fasting blood samples to assess sex hormones, IGF-I levels, glucose and advanced glycation end (AGE) products as potential mediators of the association between diabetes and prostate cancer over a mean follow-up of 12 years.
Within the cohort, 450 men had diabetes at baseline and 315 men were diagnosed with prostate cancer during follow-up. In a subset of 2,440 men with fasting insulin and glucose data, 253 men were diagnosed with prostate cancer, according to researchers.
Compared with men without diabetes, men with diabetes had a higher BMI (mean, 27.5 kg/m² vs. 26.5 kg/m²; P < .001), lower testosterone (mean, 11.4 nmol/L vs. 13.4 nmol/L; P < .001), lower dihydrotestosterone (mean, 1.21 nmol/L vs. 1.47 nmol/L; P < .001) and lower sex hormone binding globulin (mean, 38.2 nmol/L vs. 43.3 nmol/L; P < .001).
Researchers found that diabetes was associated with a lower prostate cancer risk after adjusting for conventional risk factors (standardized HR = 0.63; 95% CI, 0.43-0.92). The association persisted after adjusting for testosterone, dihydrotestosterone, estradiol and sex hormone binding globulin. Adjusting the model for IGF-I or its binding proteins 1 and 3, or for glucose, also did not alter the association, according to researchers. The AGE compound carboxymethyllysine (CML) was not associated with risk for prostate cancer, and additional correction for CML in the fully-adjusted model did not alter the inverse association of diabetes and prostate cancer risk, according to the researchers.
“Prostate cancer is an age-related cancer,” the researchers wrote. “Since our population consisted of older men and diabetes is associated with increased mortality, it is possible that our results may be affected by competing risks or biased toward men who have favorable biologic or lifestyle factors. Whilst the competing risk [for] death was taken into account in this study, residual bias may still be present.”
The researchers noted that the findings do not suggest a role for insulin resistance in mediating the observed association; however, confirmation is necessary in larger studies.
“Further research into potential mediators of decreased prostate cancer risk in men with diabetes is required, and ongoing studies are required to assess if statistical methods in which competing risks are conventionally handled may account for bias in results of current epidemiological studies,” the researchers wrote. – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.