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IMPORTANCE Men with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Meanwhile, gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer (PCa) are associated with increased risk of CVD. OBJECTIVE To evaluate the association between GnRH agonist use, PCa diagnosis per se, and CVD risk in men with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS This nationwide population-based cohort study identified men with type 2 diabetes by use of data in the Prostate Cancer Data Base Sweden version 4.1 and the Swedish National Diabetes Register, with longitudinal data from 2006 to 2016. These data were used to create 2 cohorts, 1 including men with and without PCa and the other including men with PCa who received and did not receive GnRH agonists. Data analysis was conducted from January 2006 to December 2016. EXPOSURES Treatment with GnRH agonists and PCa diagnosis were the primary exposures. MAIN OUTCOMES AND MEASURES Primary outcome was a 10% increase in predicted 5-year CVD risk score. Secondary outcome was worsening hypertension as defined by the European Society of Hypertension Guidelines. Cox proportional hazards regression models were used to analyze the association. RESULTS The PCa exposure cohort included 5714 men (median [IQR] age, 72.0 [11.0]), and the non-PCa cohort included 28 445 men without PCa (median [IQR] age, 72.0 [11.0]). The GnRH agonist-exposure cohort included 692 men with PCa who received a GnRH agonist, compared with 3460 men with PCa who did not receive a GnRH agonist. Men with PCa receiving GnRH agonists had an increased estimated 5-year CVD risk score compared with men without PCa (hazard ratio [HR], 1.25; 95% CI, 1.16-1.36) and compared with men with PCa not receiving GnRH agonists (HR, 1.53; 95% CI, 1.35-1.74). Men receiving GnRH agonists had decreased blood pressure compared with men without PCa (HR, 0.70; 95% CI, 0.61-0.80) and compared with men with PCa not receiving GnRH agonists (HR, 0.68; 95% CI, 0.56-0.

PURPOSE Pathways involving sex hormones and insulin-like growth factors (IGFs) have been proposed to explain, in part, the lower risk of prostate cancer among men with diabetes. To gain insights into potential biological mechanisms we explored differences in serum concentrations of sex hormones and IGFs across the trajectory from normoglycemia to prediabetes to poorly controlled diabetes. METHODS Using cross-sectional data from the National Health and Nutrition Examination Survey III we examined differences in levels of circulating sex hormones, sex hormone-binding globulin (SHBG), IGF-1, and IFG-binding protein 3 (IGFBP-3), according to diabetes status: no diabetes [n = 648], prediabetes [n = 578], undiagnosed diabetes [n = 106], well-controlled diabetes [n = 42], and poorly controlled diabetes [n = 56]. Adjusted geometric mean concentrations were derived using multivariable linear regression, adjusted for age, race, and other lifestyle factors. RESULTS Total testosterone concentrations were lower among prediabetics (4.89 ng/mL, 95% confidence interval (CI) 4.95-5.21) than men without prediabetes/diabetes (5.29 ng/mL, 95% CI 5.06-5.53) but did not reduce further across diabetes groups. Concentrations of estradiol, estimated free testosterone, SHGB, IGF-1, and IGFBP-3 did not differ. While the ratio of IGF-1 to IGFBP-3 was lower among men with prediabetics and undiagnosed diabetes than men without prediabetes/diabetes, there was no trend across groups. A positive trend for the ratio of estradiol-to-testosterone levels was observed across groups (p trend = 0.045). CONCLUSION Our findings do not provide clear support for either an androgen driven or IGF-driven pathway for the inverse association between diabetes and prostate cancer risk.

Background Gonadotropin Releasing Hormones agonists (GnRH), which are first line treatment for metastatic prostate cancer (PCa), increase risk of type 2 diabetes mellitus (T2DM). This study aims to quantify the association of use of GnRH with diabetes control in PCa men with T2DM. Methods Nationwide population-based cohort study in the Swedish National Diabetes Register and Prostate Cancer data Base Sweden 4.1, on the association between GnRH and diabetes control in T2DM men with PCa by comparing T2DM men with PCa vs. without PCa, as well as comparing T2DM men with PCa on or not on GnRH. The primary exposure was use of GnRH. Worsening diabetes control was the primary outcome, defined as: 1) HbA1c rose to 58 mmol/mol or higher; 2) HbA1c increase by 10 mmol/mol or more; 3) Start of antidiabetic drugs or switch to insulin. We also combined all above definitions. Cox proportional hazards regression was used to analyze the association. Results There were 5714 T2DM men with PCa of whom 692 were on GnRH and 28,445 PCa-free men with T2DM with similar baseline characteristics. Diabetes control was worse in men with GnRH vs. PCa-free men (HR: 1.24, 95% CI: 1.13-1.34) as well as compared with PCa men without GnRH (HR:1.58, 95% CI: 1.39-1.80), when we defined the worsening control of diabetes by combining all definitions above. Conclusion Use of GnRH in T2DM men with PCa was associated with worse glycemic control. The findings highlight the need to closely monitor diabetes control in men with T2DM and PCa starting GnRH.

Existing literature examining warfarin's association with prostate cancer (PCa) risk provides conflicting results, while the association with direct oral anticoagulants (DOACs) has not yet been studied. We investigated the association of warfarin and DOAC use on PCa risk among men within the population-based Prostate Cancer database Sweden (PCBaSe), using a case-control design. The study population included PCa cases diagnosed 2014-2016 and five age-matched PCa-free controls. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for PCa associated with warfarin and DOAC use, adjusted for marital status, education level, other drug use, and comorbidities. Among 31,591 cases and 156,802 controls, there were 18,522 (9.8%) warfarin and 4,455 (2.4%) DOAC users. Warfarin ever-use was associated with reduced risk of PCa overall (OR 0.92 95% CI 0.88-0.96) as were both past and current use. DOAC use was not associated with PCa risk. For some warfarin exposures, decreased risk was observed for unfavorable PCa (high risk/locally advanced/distant metastatic) but not with favorable PCa (low/intermediate risk). Increased risk of favorable PCa was observed for men whose initial warfarin exposure occurred in the 12 month period before diagnosis (OR 1.39; 95% CI 1.13-1.70). Our findings are consistent with previous publications reporting decreased PCa risk with warfarin exposure. Increased risk of favorable PCa suggests detection bias due to increased prostate specific antigen testing when starting on warfarin. Decreased overall PCa risk could reflect bias due to reduced biopsy rates among long-term warfarin users.

Objectives Both prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are increasingly prevalent conditions, which frequently coexist in men. Here, we set out to specifically examine the impact of a PCa diagnosis and its treatment on T2DM treatment. Setting This study uses observational data from Prostate Cancer database Sweden Traject. Participants The study was undertaken in a cohort of 16778 men with T2DM, of whom 962 were diagnosed with PCa during mean follow-up of 2.5 years. Primary and secondary outcome measures We investigated the association between PCa diagnosis and escalation in T2DM treatment in this cohort. A treatment escalation was defined as a new or change in anti-T2DM prescription, as recorded in the prescribed drug register (ie, change from diet to meforrnin or sulphonylurea or insulin). We also investigated how PCa diagnosis was associated with two treatment escalations. Multivariate Cox proportional hazards regression with age as a time scale was used while adjusting for educational level and initial T2DM treatment. Results We found no association between PCa diagnosis and risk of a single treatment escalation (HR 0.99, 95% Cl 0.87 to 1.13). However, PCa diagnosis was associated with an increased risk of receiving two consecutive T2DM treatment escalations (HR 1.75, 95% CI 1.38 to 2.22). This increase was strongest for men on gonadotropin-releasing hormone (GnRH) agonists (HR 3.08, 95% Cl 2.14 to 4.40). The corresponding HR for men with PCa not on hormonal treatment was 1.40 (95% CI 1.03 to 1.92) and for men with PCa on antiandrogens 0.91 (95% Cl 0.29 to 2.82). Conclusions Men with T2DM who are diagnosed with PCa, particularly those treated with GnRH agonists, were more likely to have two consecutive escalations in T2DM treatment. This suggests a need for closer monitoring of men with both PCa and T2DM, as coexistence of PCa and its subsequent treatments could potentially worsen T2DM control.

Prostate cancer (PCa) and type two diabetes mellitus (T2DM) are both increasing prevalent conditions and often occur concurrently. However, the relationship between the two is more complex than just two prevalent conditions co-existing. This review systematically explores the literature around the interplay between the two conditions. It covers the impact of pre-existing T2DM on PCa incidence, grade and stage, as well as exploring the impact of T2DM on PCa outcomes and mortality and the interaction between T2DM and PCa treatments.