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Insulin-like growth factor-I (IGF-I) and testosterone may be related to prostate cancer risk. Acromegaly is associated with clinically high IGF-I concentrations. Klinefelter's syndrome, testicular hypofunction and hypopituitarism are associated with clinically low testosterone concentrations. We aimed to investigate whether diagnosis with these conditions was associated with subsequent prostate cancer diagnosis and mortality. We used linked English national Hospital Episode Statistics and mortality data from 1999 to 2017 to construct and follow-up cohorts of men aged ≥35 years diagnosed with i) acromegaly (n=2,495) and ii) hypogonadal-associated diseases (n=18,763): Klinefelter's syndrome (n=1,992), testicular hypofunction (n=8,086) and hypopituitarism (n=10,331). We estimated adjusted hazard ratios (HRs) and confidence intervals (CIs) for prostate cancer diagnosis and death using Cox regression in comparison with an unexposed reference cohort of 4.3 million men, who were admitted to hospital for a range of minor surgeries and conditions (n observed cases =130,000, n prostate cancer deaths=30,000). For men diagnosed with acromegaly, HR for prostate cancer diagnosis was 1.33 (95% CI 1.09-1.63; P=0.005; n observed cases=96), HR for prostate cancer death was 1.44 (95% CI 0.92-2.26; P=0.11; n deaths=19). Diagnosis with Klinefelter's syndrome was associated with a lower prostate cancer risk (HR=0.58, 95% CI 0.37-0.91; P=0.02; n observed cases=19) and hypopituitarism was associated with a reduction in prostate cancer death (HR=0.57, 95% CI 0.42-0.79; P=0.001; n deaths=23). These results support the hypothesised roles of IGF-I and testosterone in prostate cancer development and/or progression. These findings are important because they provide insight into prostate cancer etiology. This article is protected by copyright. All rights reserved.

Original publication




Journal article


Int J Cancer

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Epidemiology, IGF-I, hormones, prostate cancer, record-linkage, testosterone