Androgen deprivation therapy is associated with diabetes: Evidence from meta‐analysis

Abstract

Aims/IntroductionThere is still no obvious evidence proving that androgen deprivation therapy (ADT) would increase the risk of diabetes. To determine if ADT is associated with diabetes in men with prostate cancer, we carried out the present study.Materials and MethodsWe systematically searched Medline, Embase and the Cochrane Library Central Register through 2014. Studies comparing ADT vs control aimed at treating prostate cancer reporting diabetes as outcome were included. Data were extracted independently by two reviewers. This meta‐analysis was reported based on the Preferred Reporting Items for Systematic reviews and Meta‐Analyses checklist. Observational studies were evaluated through the Meta‐analysis Of Observational Studies in Epidemiology checklist.ResultsEight studies were identified with 65,695 ADT users and 91,893 non‐ADT users. The pooled incidence of diabetes was 39% higher in ADT groups. A significant association was observed in the overall analysis (risk ratio [RR] 1.39, 95% confidence interval [CI] 1.27–1.53; P < 0.001). In subgroup analyses, diabetes was found to be significantly associated with gonadotropin‐releasing hormone (GnRH) alone (RR 1.45, 95% CI 1.36–1.54; P < 0.001), GnRH plus oral antiandrogen (RR 1.40, 95% CI 1.01–1.93; P = 0.04) and orchiectomy (RR 1.34, 95% CI 1.20–1.50; P < 0.001), but not with antiandrogen alone (RR 1.33, 95% CI 0.75–2.36; P = 0.33). Diabetes was strongly related to long duration of ADT (RR 1.43, 95% CI 1.22–1.68; P < 0.001), and was slightly associated with short duration of ADT (RR 1.29, 95% CI 1.12–1.49; P = 0.0004).Conclusions ADT, especially long duration (>6 months) of this treatment, GnRH alone, GnRH plus antiandrogen and orchiectomy can increase the incidence of diabetes.

Role of androgens in energy metabolism affecting on body composition, metabolic syndrome, type 2 diabetes, cardiovascular disease, and longevity: lessons from a meta-analysis and rodent studies

“…However, other SRMA studies found 10-38% and 17% increases in the incidence of CV disease and CV death, respectively [64,65], and a 12% increase in the risk for stroke [66]. SRMAs have also found that androgen deprivation therapy altered body composition by increasing body fat and decreasing lean body mass [67], increased the risk of diabetes by 36-39% [68,69], and increased the risk for MetS by 75% [69]. These results provide a consensus that androgen deprivation increases the risk of T2DM, MetS, and CV disease.…”

Incidence of the adverse effects of androgen deprivation therapy for prostate cancer: a systematic literature review

“…for meta-analysis from four cohort and four cross sectional studies. Incidence of diabetes amongst men receiving ADT (GnRH agonists, combined androgen blockade or orchiectomy) was 10.9% (27). The risk of diabetes was 39% higher for these men than for men not receiving ADT or men on watchful waiting or active surveillance (RR 1.39; 95%CI 1.27-1.53, P<0.001) (27).…”

“…Incidence of diabetes amongst men receiving ADT (GnRH agonists, combined androgen blockade or orchiectomy) was 10.9% (27). The risk of diabetes was 39% higher for these men than for men not receiving ADT or men on watchful waiting or active surveillance (RR 1.39; 95%CI 1.27-1.53, P<0.001) (27). Sub group analyses for ADT type and duration showed that GnRHa, combined androgen blockade and orchiectomy are significantly associated with risk of diabetes, and longer duration of ADT with elevated risk (27).…”

“…The Bosco et al(8) review mentioned above reported a RR of 1.36 (95% CI 1.17, 1.58) for men receiving ADT. Wang et al(27), pooled data 18-34 months HR 1.48 (1.17, 1.97; <P 0.001) ≥35 months HR 1.80 (1.45, 2.24; <P 0.001)…”

Considerations for the use of gonadotropin‐releasing hormone agonists and antagonists in patients with prostate cancer

“…ADT has been linked to decreased insulin sensitivity, 43 diabetes 44,45 and alterations in body composition. In fact, in 2010, the FDA issued a safety warning on the labels of GnRH agonists regarding an increased risk of diabetes (due to the development of insulin resistance or altered insulin sensitivity), obesity and other metabolic changes.…”