**8. ADT and lipid alterations**

Hyperlipidemia is a known risk factor for cardiovascular disease. Recent epidemiological research suggests that low serum TST levels in men are associated with an adverse lipid

predisposing them to cardiovascular disease. Lifestyle changes or suitable interventions to

Epidemiological studies have shown that low TST levels predict the development of insulin resistance and type 2 diabetes (103, 104, 105). Studies have also confirmed a direct relationship between serum TST and insulin sensitivity (106). These findings are further supported by interventional studies showing an improvement in insulin sensitivity with

There is some evidence, that the onset of insulin resistance can be detectable after 3 months of ADT (108, 109). 3-month prospective study using combined androgen blockade with leuprolide and bicalutamide showed a 43% increase in fat mass and a 26% increase in insulin levels from baseline, again indicating development of insulin resistance with increasing adiposity (110). Although there was no significant change in fasting glucose levels, a statistically significant increase in glycosylated hemoglobin was seen (though this increase was within the normal range from 5.46–5.62%). These observations suggest that insulin resistance develops within a few months of initiating ADT; however, this

Observational study of a population-based cohort found that men undergoing ADT with GnRH agonists had a higher risk of incident diabetes (11%), coronary artery disease (25%), myocardial infarction, and sudden death (111). Interestingly, orchiectomy was associated only with a higher risk of diabetes. In some men, this risk was evident within 4 months of starting ADT. These findings suggest that although both medical and surgical modalities of ADT result in increased metabolic burden, GnRH analogs are also

After 12 months of ADT, serum fasting glucose increased significantly (112), suggesting that men with PCa who are receiving long-term ADT are at risk for developing insulin resistance and hyperglycemia, thus leading to their increased risk of cardiovascular disease (113). A retrospective study which enrolled 396 patients with a median follow-up of 60.1 months, 36 (11.3%) patients developed new- onset diabetes mellitus (NODM). In 77 patients with pre-existing diabetes, there was an increase of >/=10% in serum HbA1c or fasting glucose levels in 15 (19.5%) and 22 (28.6%), respectively. On multivariate analysis, a BMI of >/=30 kg/m(2) was associated with an increased risk of developing NODM

In conclusion, patients receiving ADT for PCa with or with no history of diabetes should have routine surveillance of glycaemic control, with appropriate preventive and treatment

Hyperlipidemia is a known risk factor for cardiovascular disease. Recent epidemiological research suggests that low serum TST levels in men are associated with an adverse lipid

minimize the effect of ADT on body composition need to be investigated.

compensatory hyperinsulinemia prevents the development of diabetes.

**7. ADT and insulin resistance** 

**7.1 Early metabolic changes** 

**7.2 Late metabolic changes** 

associated with cardiovascular events.

(odds ratio 4.65, P = 0.031) (114).

**8. ADT and lipid alterations** 

measures.

TST replacement in hypogonadal obese men (107).

profile, especially elevated total cholesterol, LDL cholesterol, and triglycerides (115). Furthermore, interventional studies have shown that TST replacement in hypogonadal men results in an improvement in lipid profile (116).

During long-term ADT, triglycerides rise by approximately 26% and total cholesterol approximately 10%. (117, 118, 119) In addition, high-density lipoprotein (HDL) rises approximately 8% to 11%. The net effect of these changes on cardiovascular risks is unknown. Significant changes can be observed within the first 3 months of treatment, with more modest subsequent change (110).
