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

Int J Cancer. 2016 Dec 15;139(12):2698-2704. doi: 10.1002/ijc.30403. Epub 2016 Sep 19.

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.

Keywords: androgen deprivation therapy; prostate cancer; type two diabetes.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / adverse effects*
  • Androgen Antagonists / therapeutic use
  • Antineoplastic Agents, Hormonal / adverse effects*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Biomarkers, Tumor
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / etiology*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Orchiectomy / adverse effects*
  • Proportional Hazards Models
  • Prostatic Neoplasms / complications*
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / therapy
  • Registries
  • Risk
  • Sweden / epidemiology

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor