GnRH ANAGONISTS AND CARDIOVASCULAR RISK

In a study of Swedish men with prostate cancer reported in the Journal of Clinical Oncology, O’Farrell et al found that use of gonadotropin-releasing hormone (GnRH) agonists and orchiectomy were associated with a significantly increased risk of incident cardiovascular disease. In patients with prior cardiovascular disease, risk for a cardiovascular event within 6 months of starting androgen-deprivation therapy was significantly increased with GnRH agonist use, antiandrogen use, and orchiectomy.

Study Details

The study involved data from Swedish national health-care registers on 41,362 men with prostate cancer on androgen-deprivation therapy and an age-matched cohort of 187,785 men without prostate cancer. From 2006 to 2012, 10,656 men were on antiandrogens, 26,959 were on GnRH agonists, and 3,747 underwent orchiectomy.  

Increased Risk

Compared with the prostate cancer–free cohort, incident cardiovascular disease risk was significantly increased in men using GnRH agonists (hazard ratio [HR] = 1.21, 95% confidence interval [CI] = 1.18–1.25) and men who had undergone orchiectomy (HR = 1.16, 95% CI = 1.08–1.25), whereas men using antiandrogens had a decreased risk (HR = 0.87, 95% CI = 0.82–0.91). Cardiovascular disease risk was highest during the first 6 months of androgen-deprivation therapy in men with at least two cardiovascular events before therapy; HRs were 1.91 (95% CI = 1.66–2.20) in those on GnRH agonists, 1.60 (95% CI = 1.24–2.06) in those on antiandrogens, and 1.79 (95% CI = 1.16–2.76) in those with orchiectomy vs the comparison cohort.

The investigators concluded: “Our results support that there should be a solid indication for [androgen-deprivation therapy] in men with [prostate cancer] so that benefit outweighs potential harm; this is of particular importance among men with a recent history of [cardiovascular disease].”

Sean O’Farrell, BSc, MRes, of King’s College London, is the corresponding author of the Journal of Clinical Oncology article.

The study was supported by the Swedish Research Council, Stockholm Cancer Society, Cancer Research-United Kingdom, Swedish Council for Working Life and Social Research, Västerbotten County Council, Guy’s and St Thomas’ National Health Service Foundation Trust, and King’s College London’s Comprehensive Biomedical Research Centre.

Jan Adolfsson, MD, PhD, Pär Stattin, MD, PhD, and Mieke Van Hemelrijck, PhD, reported consulting or advisory roles with Ferring.