Androgen-Deprivation Therapy and the Risk of Stroke in Patients With Prostate Cancer

doi:10.1016/j.eururo.2011.08.041

European Urology

Volume 60, Issue 6, December 2011, Pages 1244-1250

https://doi.org/10.1016/j.eururo.2011.08.041 Get rights and content

Abstract

Background

Some evidence indicates that androgen-deprivation therapy (ADT) increases the risk of diabetes and cardiovascular disease. To date, few studies have investigated whether this therapy also increases the risk of cerebrovascular events.

Objective

To determine whether different types of ADT increase the risk of stroke/transient ischaemic attacks (TIAs) in patients with prostate cancer.

Design, setting, and participants

We conducted a population-based cohort study using a nested case-control analysis within the United Kingdom's General Practice Research Database population. The cohort included all patients at least 40 yr of age newly diagnosed with prostate cancer between January 1, 1988, and December 31, 2008, and followed until December 31, 2009. Cases consisted of those who experienced a first-ever stroke/TIA during follow-up. Up to 10 controls were matched to each case on age, year of cohort entry, and duration of follow-up.

Measurements

Adjusted rate ratios (RRs) of stroke/TIA associated with the use of different ADTs (gonadotropin-releasing hormone [GnRH] agonists, oral antiandrogens, combined androgen blockade, bilateral orchiectomy, and others) were estimated using conditional logistic regression.

Results and limitations

The cohort included 22 310 patients with prostate cancer, followed for a mean of 3.9 yr, where 938 patients experienced a first-ever stroke/TIA (rate: 10.7 per 1000/yr). Compared with nonusers of ADT, current users of GnRH agonists (adjusted RR: 1.18; 95% confidence interval [CI], 1.00–1.39), oral antiandrogens (adjusted RR: 1.47; 95% CI, 1.08–2.01), and those who underwent bilateral orchiectomy (adjusted RR: 1.77; 95% CI, 1.25–2.39) were at an increased risk of stroke/TIA. No statistically significant increased risks were observed for patients on combined androgen blockade and other ADTs, but the small numbers do not rule out a possible association.

Conclusions

The results of this large population-based study provide additional evidence that different forms of ADT may increase the risk of stroke/TIA.

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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Prostate CancerAndrogen-Deprivation Therapy and the Risk of Stroke in Patients With Prostate Cancer

Abstract

Background

Objective

Design, setting, and participants

Measurements

Results and limitations

Conclusions

Introduction

Section snippets

Data source

Results

Discussion

Conclusions

Urology

Urology

Lancet

Lancet

Urology

Urol Oncol

The effect of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate

Cancer Res

Lipoprotein profile in men with prostate cancer undergoing androgen deprivation therapy

Int J Impot Res

Metabolic syndrome in men with prostate cancer undergoing long-term androgen-deprivation therapy

J Clin Oncol

Changes in body composition during androgen deprivation therapy for prostate cancer

J Clin Endocrinol Metab

Impact of androgen deprivation therapy on cardiovascular disease and diabetes

J Clin Oncol

Prostate Cancer
Androgen-Deprivation Therapy and the Risk of Stroke in Patients With Prostate Cancer