Cardiovascular Disease With Androgen Deprivation: The (forgotten) Role of Testosterone
Authors: Jeanny B. Aragon-Ching
Journal: Journal of Clinical Oncology (2009)

Alibhai et al 1 presented significant data regarding cardiovascular and diabetic morbidity results in men 66 years of age or older undergoing androgen deprivation therapy (ADT), in which they found an increased risk of diabetes and fragility fracture but not acute myocardial infarction (MI) or sudden cardiac death.This report is consistent with that of some studies, such as the nonstatistically significant risk of cardiovascular mortality in men with localized prostate cancer undergoing ADT in Radiation Therapy Oncology Group (RTOG) 92-02, 2 RTOG 86-10, 3 and RTOG 85-31, 4 but contrary to other studies which have reported that ADT as short as 3 months could impact men older than 65 years with increased fatal cardiovascular events. 5,6The effects of ADT on cardiovascular disease and risk factors are not new, yet time and again, we see conflicting results regarding this basic question.While the differences may be explained by the retrospective nature or the differences in population number, as suggested by the authors, this study did not take into consideration one of the basic observations regarding baseline cardiovascular risk in older men, that is, lower testosterone levels with increasing age.Of the contemporary causes of death among all American men age 65 or older, heart disease is still the leading cause with an incidence of about 30.5%, compared with cancer, at 25.4%. 7While there are certainly controllable risk factors, such as hypertension, diabetes, smoking, which Alibhai et al's study controlled for in their analysis, certain unknown risk factors come into play that could result in increased risk of sudden cardiac death.In Alibhai et al's study, which comprises of the most patients compared with other studies that have evaluated cardiovascular risk in those undergoing ADT, no increased risk of sudden cardiac death or MI was concluded.One of the data which could be useful, though not available, is the testosterone data.Hypogonadism has been recognized to increase in prevalence with increased age.The incidence is approximately 20% for men older than 60, 30% in men older than 70, and up to 50% in men older than 80 years. 8Hypogonadism has been associated with increased cardiovascular risk.In a study by Khaw et al, 9 men with testosterone levels of at least 19.6 nmol/L had a 41% lower risk of dying in 10 years compared with men who had testosterone levels of 12.5 nmol/L or less and for every 6-nmol/L increase in endogenous testosterone, the risk of death decreased 14%.While ADT certainly suppresses further the degree of hypogonadism, studies on testosterone kinetics after 6 months of ADT would lead to testosterone recovery at a median of 15.4 weeks. 10However, in this study, no data was specifically available regarding the specific number of patients who underwent specific duration of ADT therapy.While categorization of fewer than 3 months, 3 to 6 months, 6 to 24 months, and longer than 24 months does prove useful and simplifies analysis, these duration stratification can have variable effect on testosterone recovery.In addition, we have previously shown that factors such as age older than 67 years, for instance, take even a longer time to