title: 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.
authors.affiliation: Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London. Danielle.Crawley@kcl.ac.uk.
authors.forename: Danielle
authors.initials: D
authors.lastname: Crawley
authors.affiliation: Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London.
authors.forename: Hans
authors.initials: H
authors.lastname: Garmo
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust and King's College London's Comprehensive, Biomedical Research Centre, London.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rudman
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.|Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Pär
authors.initials: P
authors.lastname: Stattin
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.|Department of Biobank Research, Umeå University, Umeå, Sweden.|Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Christel
authors.initials: C
authors.lastname: Häggström
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Zethelius
authors.affiliation: Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London.
authors.forename: Lars
authors.initials: L
authors.lastname: Holmberg
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Adolfsson
authors.affiliation: Division of Cancer Studies, Cancer Epidemiology Group, King's College London, London.
authors.forename: Mieke
authors.initials: M
authors.lastname: Van Hemelrijck
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000209:etiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009919:Orchiectomy / Q000009:adverse effects*; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D012042:Registries; D012306:Risk; D013548:Sweden / Q000453:epidemiology
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor
keywords: androgen deprivation therapy; prostate cancer; type two diabetes