Prediagnostic androgen level not linked to prostate cancer outcome

Low prediagnostic levels of circulating sex hormones are not associated with more aggressive disease in patients with prostate cancer (PCa), say US researchers.

In an analysis of two large, prospective cohorts of patients with PCa, Lorelei Mucci (Harvard School of Public Health, Boston, Massachusetts) and colleagues found no overall association between prediagnostic circulating sex hormone levels and lethal PCa or total mortality.

Using data obtained from the Health Professionals Follow-up Study and the Physicians' Health Study, the team identified 963 cases of men who had been diagnosed with PCa at a mean age of 69.1 years. The men had been assessed for circulating androgen levels before PCa diagnosis, at a mean age of 64.7 years.

Overall, 421 of the men died over a mean follow-up period of 12.9 years after diagnosis and 134 of the deaths were due to PCa. For the analysis, the team grouped these 134 men together with 14 men who were still alive but had bone or organ metastases, to create a lethal PCa group.

As reported in European Urology, Cox proportional hazard modelling showed no association between lethal PCa or total mortality and levels of testosterone, sex hormone binding globulin (SHBG), SHBG-adjusted total testosterone, free dihydrotestosterone, androstanediol glucoronide, or estradiol, after adjustment for age at diagnosis, body mass index, physical activity, smoking status, Gleason score, and tumor, nodule, metastasis (TNM) stage.

In subset analyses stratified by Gleason score, TNM stage, age, and interval between blood sampling and diagnosis, still no such association was observed.

Several studies have previously shown an association between lower pretreatment testosterone levels and increased cancer-specific mortality in men with PCa, says the team. The researchers say their findings suggest that this reflects reverse causality, with low pretreatment levels being a consequence of PCa rather than aggressive PCa being a result of the hormonal milieu in which it develops.

"Indeed, several studies have suggested that PCa may result in suppression of circulating total testosterone and free testosterone, noting an increase in these hormones following radical prostatectomy," they write.

"Although likely not etiologic, pretreatment hormone levels may nonetheless have clinical utility in risk stratification and prognostication, and further prospective studies are needed to investigate this area," concludes the team.

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