Prostate CancerAndrogen-Deprivation Therapy and the Risk of Stroke in Patients With Prostate Cancer
Introduction
Androgen-deprivation therapy (ADT) has been the mainstay of treatment for advanced prostate cancer since first described by Huggins and Hodges in 1941 [1]. However, ADT is not an innocuous therapy. Beyond the quality-of-life side effects, the suppression of testosterone levels has been associated with several adverse effects often called the androgen-deprivation syndrome. This hypogonadal condition is characterised by metabolic changes such as dyslipidemia [2], [3], [4], insulin resistance [5], and modification of body composition towards an increase of fat mass [4], [6]. All these metabolic changes put patients at an increased risk of cerebrovascular events, such as ischaemic strokes and transient ischaemic attacks (TIAs). Evidence for these potential adverse events is limited and conflicting, with just three studies published on the subject [7], [8], [9].
Given the increasing use of ADT, particularly in men with earlier stage disease [10], it is imperative to adequately assess the cerebrovascular risks associated with this therapy. Thus the objective of this large population-based study was to determine whether different types of ADT increase the risk of stroke and TIA in patients newly diagnosed with prostate cancer.
Section snippets
Data source
This study was conducted using the General Practice Research Database (GPRD), a large primary care database from the United Kingdom [11]. The geographic distribution of the practices participating in the GPRD has been shown to be representative of the UK population, and age and sex distributions of patients in the GPRD are similar to those reported by the National Population Census [12]. Participating general practitioners have been trained to record medical information including demographic
Results
The cohort consisted of 22 310 patients newly diagnosed with prostate cancer (Fig. 1). The mean (standard deviation [SD]) age at cohort entry was 72.3 (3.9) yr, and the mean duration of follow-up was 3.9 (3.0) yr. At cohort entry, the median prostate-specific antigen (PSA) was 15.2 ng/ml. Overall, 15 375 (68.9%) of the cohort received ADT at some point during follow-up, of which 12 758 (83.0%) received it within 6 mo of diagnosis.
A total of 938 patients experienced a first-ever stroke/TIA
Discussion
The results of this large population-based study indicate that different types of ADTs may increase the risk of stroke/TIA in patients with prostate cancer. Increased risks were observed with all ADTs, with the highest in patients who underwent bilateral orchiectomy. No increased risk was observed for those on combined androgen blockade, but this analysis may have been limited by the few cases exposed. For patients on GnRH agonists, the risk was observed early in the treatment but then declined
Conclusions
This study provides additional evidence that ADT may increase the risk of stroke/TIA. Although ADT remains the mainstay of treatment for advanced disease, it is increasingly being prescribed to men with earlier stage disease [10]. As such, treating physicians and patients should be aware of this potential risk when considering this therapy.
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