Table 3.
Studies regarding the cardio-vascular effects of the androgen deprivation therapy.
| First Author [Reference] |
Year | Study Type | Pts Enrolled | Type of ADT/No pts | Treatment in the Control Group/No pts | Median Age | Follow-Up | Results |
|---|---|---|---|---|---|---|---|---|
| Studies Showing an Additional Cardio-Vascular Risk in Patients on ADT | ||||||||
| Keating [53] |
2006 | Observational SEER program 11 population-based cancer registries | 73,193 | GnRH agonists 25,570 |
No therapy/orchiectomy 47,623 |
74.2 ± 5.8 | 4.5 years | Increased risk of DM, CAD, MI, SCD, in the GnRH agonist group versus non therapy group Increased risk of DM in orchiectomy group versus non therapy group |
| D’Amico [54] |
2007 | Randomized study | 1372 | GnRH agonist + flutamide + RT | RT | 70.88 | 3–8 months | Fatal MI occurs earlier in men older than 65 years who received 6 months of ADT than in those without ADT and in men younger than 65 years. No significant difference (p = 0.97) was observed in the time to fatal MIs in men age 65 years or older who received 6 to 8 months of ADT compared with 3 months of ADT |
| Tsai [55] |
2007 | Observational study |
4881 | 3262 pts on radical prostatectomy + ADT in 1051 pts | RT 1630 pts | 63 | 3.8 years | The use of ADT appears to be associated with an increased risk of death from cardiovascular causes in patients undergoing radical prostatectomy for localized prostate cancer |
| O’Farrell [52] |
2015 | Retrospective study | 229,147 | 41,362 pts on GnRH agonist ± non steroidian antiandrogen | 187,785 cancer free pts | 75 | 6 years | CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy |
| Alibhai [56] |
2009 | Cohort study | 116769 | 46,995 on ADT | No ADT 69,774 | 75 ± 6.3 | 6.47 years | ADT use for at least 6 months in older men is associated with an increased risk of diabetes and fragility fracture but not MI or sudden cardiac death. |
| Studies Showing No Additional Cardio-Vascular Risk in Patients on ADT | ||||||||
| Nanda [57] |
2009 | Retrospective study | 5077 | 1521 pts on GnRH agonist+ non steroidian antiandrogen | 3556 RT | 69.5 | 2 years | ADT is significantly associated with an increased risk of all-cause mortality among men with a history of CAD-induced HF or MI but not among men with no comorbidity or a single CAD risk factor. |
| Bolla [58] |
2009 | Randomized study | 970 | 487 pts on RT + 2.5 years GnRH agonists | 483 pts on RT + 6 months GnRH agonists | 69 | 6.4 | There was no significant difference in the cumulative incidence of fatal cardiac events at 5 years: 4.0% in the short-term group and 3.0% in the long-term group |
| Punnen [59] |
2011 | Retrospective study of CaPSURE registry | 7248 | ADT (1086 pts) ADT + local therapy (485 pts) |
Local therapy (5170 pts), watchful waiting/active surveillance (506 pts) |
>65 | 47.6–57 months | A propensity-matching algorithm in a subset of 1391 patients was unable to find a significant difference in cardiovascular mortality between those who did or did not receive ADT. |
| Efstathiou [60] | 1987–1992 | randomized | 945 | RT + goserelin (477) |
RT (468) | 70 | 9 years | GnRH agonists do not seem to increase cardiovascular mortality in men with locally advanced prostate cancer |
| Studies That Compared Different Type of ADT Regarding Their Cardiotoxicity | ||||||||
| Liang [61] | 2009–2017 | Meta analysis | 5 studies | ADT 63,258 |
Non ADT 209,403 |
69–75 | Abiraterone and enzalutamide increased risk of AMI, CAD, in contrast, this association is not detected in SCD. | |
| Shore [62] |
2017–2018 | Randomized phase III trial (HERO) | 930 pts | 622 pts relugolix | 308 pts leuprolide | 71 | 1 year | Relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events |
| Moreira [63] |
2011–2014 | Meta-analysis | 4 studies/5183 pts | Abiraterone-prednisone/prednisone 1333/936 |
Enzalutamid/placebo 1672/1244 |
46–95 | 5 years | Abiraterone was associated with cardiovascular adverse effects; enzalutamide was associated with fatigue |
| Margel [64] |
2019 | Phase II randomized study included patients with pre-existing cardio-vascular disease; primary endpoint endothelial dysfunction | 80 pts | GnRH antagonist/41 pts | Gn agonist/39 pts | 71–72 | 1 year | 20% randomized to GnRH agonist experienced a major cardiovascular and cerebrovascular event compared to 3% of those on GnRH antagonist |
| Zhang [65] |
2000–2020 | Analysis of FDA Adverse Event Reporting System (FAERS} | 6231 hormone monotherapy | 1793 combined therapy | ≥18 years | 20 years | GnRH antagonists were associated with fewer cardiovascular adverse events than GnRH agonists as monotherapy and combination therapy, especially in men ≥ 60 years | |
SEER = Surveillance Epidemiology and End Results, ADT = androgen deprivation therapy RT = radiotherapy GnRHagonist = gonadotrophin releasing hormone receptor agonist CAD = coronary artery disease MI = myocardial infarction; HF = heart failure CVD = cardiovascular disease DM = diabetes mellitus; SCD = sudden cardiac death.