Prostate cancer ADT linked to worsening metabolic profile

Chinese patients receiving androgen deprivation therapy (ADT) for prostate cancer are exposed to increased risk of new-onset diabetes mellitus (DM),hyperlipidaemia and hypertension (HTN), as well as a higher likelihood of step-up pharmacotherapy for these pre-existing conditions, according to a prospective multicentre cohort study by the Chinese University of Hong Kong (CUHK) and Tuen Mun Hospital.

“Evidence supports an association between ADT and cardiometabolic diseases in prostate cancer patients in Caucasian [populations] … whereas in Asian populations, the evidence is contradictory,” noted the researchers. “Prospective data on the metabolic effects of ADT in Asian patients, especially Chinese, are also lacking.” [Int Urol Nephrol 2022;doi:10.1007/s11255-022-03151-2]

In the study, data were prospectively collected from two cohorts of newly diagnosed prostate cancer patients in Hong Kong, including the READT (Real-life Experience of ADT in Asia) database (ie, ADT treatment group; n=151; mean age, 77.55 years; mode of ADT: luteinizing hormone-releasing hormone [LHRH] agonist, 69.3 percent; LHRH antagonist, 20.9 percent; bilateral orchidectomy, 9.8 percent) and HK-Cap (Hong Kong Prostate Cancer Study Group) database (ie, control group; n=447; mean age, 68.82 years). The primary outcomes were new diagnosis of an array of cardiometabolic diseases, such as DM, HTN and hyperlipidaemia, developed within 2 years of ADT use.

ADT was found to significantly increase the risk of developing any metabolic illnesses of concern (23.8 percent vs 13.0 percent; p=0.001) and new-onset DM (16.6 percent vs 4.4 percent; p<0.001) vs control. “Its association with new-onset cardiometabolic problems is also valid, after adjusting for possible confounding factors, including age, and other pre-existing metabolic illnesses as well as statin use,” pointed out the researchers.

In addition, more patients in the ADT vs control group needed to step up pharmaceutical control of these pre-existing metabolic illnesses. Compared with the control group, a significantly higher number of ADT-treated patients required initiation of new medications (52.3 percent vs 24.4 percent; p<0.001), including antihypertensives (37.8 percent vs 12.5 percent; p<0.001), statins (23.7 percent vs 12.8 percent; p=0.023), oral hypoglycaemic agents (12.6 percent vs 4.9 percent; p=0.001), and insulin (4.0 percent vs 0.05 percent; p=0.001).

According to the researchers, ADT may contribute to the development of new-onset metabolic diseases through several mechanisms. “When testosterone is lowered, patients experience hypogonadism, with decrease in lean body mass and increase in body fat in the central and subcutaneous compartments. This could happen as early as 3 months after [ADT] treatment. This effect is shown not to be limited to old men,” they explained. “Together with the detrimental effects of inducing insulin resistance, and increasing triglycerides and low-density lipoprotein [LDL] levels, ADT use has been proven to bring negative metabolic changes.”

Although secondary outcomes of occurrence of ischaemic heart disease (1.5 percent vs 1.0 percent; p=0.640) and new cerebral vascular accidents (4.4 percent vs 1.5 percent; p=0.082) were more frequent in the ADT vs placebo group, the between-group difference did not reach statistical significance during the study period. “Understandably, such events generally take a longer duration to develop upon initiating ADT, and adequate event rates may take up to 5–10 years to materialize,” they continued.

“The present study demonstrated the negative effect of ADT on control of metabolic diseases in Chinese population … This highlights physicians’ role in monitoring metabolic profiles in at-risk men offered ADT,” they suggested.