Association between duration and type of androgen deprivation therapy and risk of diabetes in men with prostate cancer

Abstract

Androgen deprivation therapy (ADT) for prostate cancer (PCa) increases risk of type 2 diabetes (T2DM); however the association between types and duration of ADT has not been fully elucidated. We examined how type and duration of ADT affects risk of T2DM. Using data from Prostate Cancer database Sweden (PCBaSe) we investigated risk of T2DM in a cohort of 34,031 men with PCa on ADT; i.e., anti‐androgens (AA), orchiectomy, or gonadotropin‐releasing hormone (GnRH) agonists compared to an age‐matched, PCa‐free comparison cohort (n = 167,205) using multivariate Cox proportional hazard regression. T2DM was defined as a newly filled prescription for metformin, sulphonylurea, or insulin in the Prescribed Drug Register. A total of 21,874 men with PCa received GnRH agonists, 9,143 AA and 3,014 underwent orchiectomy. Risk of T2DM was increased in men in the GnRH agonists/orchiectomy group during the first 3 years of ADT [i.e., 1 − 1.5 years HR: 1.61 (95%CI: 1.36 − 1.91)], compared to PCa‐free men. The risk decreased thereafter (e.g., 3 − 4 years HR: 1.17 (95% CI: 0.98 − 1.40)). Conversely, no increased risk was seen in men on AA (HR: 0.74 (95%CI: 0.65 − 0.84). The incidence of T2DM per 1,000 person‐years was 10 for PCa‐free men, 8 for men on AA, and 13 for men on GnRH agonists/orchiectomy. Duration of ADT has a significant impact on risk of T2DM. With the peak after three years of treatment, our data indicates that men on ADT, even for a limited period of time, such as adjuvant to radiotherapy, are at increased risk of T2DM.

Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer

“…Our findings regarding changes in CCI, particularly the increase in CVD, diabetes and stroke, are consistent with evidence from several large population-based studies, which points to increased risk of serious adverse effects for GnRH agonists compared with AA. Reported AEs include coronary vascular disease (CVD) [9][10][11][12] , diabetes and other metabolic syndrome components 9,16,21 , thromboembolic events 14 , and osteoporosis and bone fractures 7 . Recent meta-analyses also show higher risk of CVD morbidity and CVD mortality for GnRH agonists than AA 8,22 .…”

“…GnRH agonists are also associated with metabolic adverse effects including bone loss with increased risk of fractures [5][6][7] , cardiovascular disease [8][9][10][11][12] , stroke 10,11,13 , thrombolytic events 14 , type 2 diabetes 9,15,16 and dementia 17 . For AA, the most frequently reported adverse events are breast pain and gynaecomastia 18 .…”

A systematic review of the literature exploring the interplay between prostate cancer and type two diabetes mellitus

“…All seven studies were cohort studies. Five were from North American cohorts [ 7 , 52 – 54 , 58 ], one European [ 59 ] and one Asian [ 60 ]. The studies combined include 97,893 men on ADT and 287,312 not on ADT.…”

“…The magnitude of this risk varies from a 16% increase reported by Alibhai et al . [ 52 ] to 61% [ 58 , 59 ]. The one outlier is the study by Teoh et al .…”

Prostate Cancer Radiation Therapy and Risk of Thromboembolic Events

“…For the present study we selected 46,826 men free of PCa. This comparison with a non-PCa cohort has been successfully applied previously in Prostate Cancer data Base Sweden when investigating the risk of TED, cardiovascular disease, or diabetes after ADT or surgery (2,3,(12)(13)(14). Radiation therapy data were obtained from the NPCR, as well as from RetroRadioTherapy, a separate retrospective data collection at radiation units in Sweden.…”