Hormone‐related diseases and prostate cancer: An English national record linkage study

Abstract

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) hypogonadalassociated 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 = 0.53, 95% CI 0.35-0.79; p = 0.002; 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 aetiology.Additional Supporting Information may be found in the online version of this article.

Somatotropic‐Testicular Axis: A crosstalk between GH/IGF‐I and gonadal hormones during development, transition, and adult age

“…Slight increase in PSA levels and International Prostate Symptom Scores (IPSS) are also reported in these patients, although prostatic symptoms are often absent 67,69 . Moreover, as results from a large population study, prostatic cancer (PCa) incidence is increased both in healthy individuals with IGF‐I levels in the upper reference range 70,71 and in acromegalic patients 72 . However, a recent meta‐analysis of 23 studies in acromegaly reveals some potential sources of bias in the association between acromegaly and PCa: for example, cancer incidence was more pronounced in smaller and single‐center studies (selection bias) and the enlarged PV in acromegaly may lead to more frequent US examination (diagnostic workup bias) 73 …”

“…67,69 Moreover, as results from a large population study, prostatic cancer (PCa) incidence is increased both in healthy individuals with IGF-I levels in the upper reference range 70,71 and in acromegalic patients. 72 However, a recent meta-analysis of 23 studies in acromegaly reveals some potential sources of bias in the association between acromegaly and PCa: for example, cancer incidence was more pronounced in smaller and single-center studies (selection bias) and the enlarged PV in acromegaly may lead to more frequent US examination (diagnostic workup bias). 73 In GHD patients, replacement therapy restores prostate size to normal, with no increase in prostate abnormalities or PSA levels; an even greater increase in PV is observed in hypogonadal patients also receiving concurrent testosterone replacement therapy.…”

Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank

“…1 However, its well-established risk factors age, ethnicity family history and other genetic factors are not modifiable. 2,3 There is evidence that higher circulating insulinlike growth factor-I (IGF-I) concentrations are related to higher overall prostate cancer risk, 4,5 and obesity has been associated with a higher risk of aggressive disease. 6 Moreover, men with low free testosterone concentrations may have a lower risk of overall prostate cancer.…”

Using Evidence to End Homelessness

“…Data linkage presents important opportunities and progress on this front is encouraging. In 2018, the Scottish Government linked homelessness and health datasets for the first time at a national level to explore the relationship between homelessness and health, revealing that at least 8 per cent of the Scottish population had experienced homelessness at some point in their lives (Waugh et al, 2018).…”

“…The growing engagement of health-related disciplines is helping enormously in this rebalancing endeavour (see also Marshall and Bibby, this volume). For example, the strong association between poor health and homelessness was emphatically underlined by the findings of a recent administrative data linkage study in Scotland (Waugh et al, 2018). This revealed that a sizeable minority of the whole of Scotland's population (at least 8 per cent) had been assessed as homeless or threatened with homelessness by local authorities between 2001 and 2016.…”