Hormone-related diseases and prostate cancer: an English national record linkage study


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Eleanor Watts1,Timothy Key1,Ruth Travis1,Aurora Perez-Cornago1,Raphael Goldacre1,Naomi Allen1
1University of Oxford, Oxford, UK



There is evidence that circulating insulin-like growth factor (IGF-I) and testosterone concentrations are related to prostate cancer risk. Acromegaly is associated with clinically high IGF-I concentrations, while Klinefelter’s syndrome, testicular hypofunction and hypopituitarism are associated with clinically low testosterone concentrations. We aimed to investigate whether diagnoses with these conditions are associated with subsequent prostate cancer diagnosis and mortality.


Linked English national Hospital Episode Statistics and mortality data from 1999 to 2017 were used 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 subsequent 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 wide range of relatively minor surgeries and conditions, among whom there were nearly 130,000 observed prostate cancer diagnoses and 30,000 prostate cancer deaths.


For men diagnosed with acromegaly, the subsequent HR for prostate cancer was 1.33 (95% CI 1.09-1.63; P=0.005; n observed cases=96) and the 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 reduced risk of prostate cancer death (HR=0.57, 95% CI 0.42-0.79; P=0.001; n deaths=23).


Our results support the hypothesised role of IGF-I and testosterone in prostate cancer development and/or progression. These findings are important because they provide insight into prostate cancer etiology.