Emerging cardiometabolic complications of androgen deprivation therapy

Figures & data

Table I.  Studies documenting changes in body composition with androgen-deprivation therapy.

Study	Aim(s)	Patient population	Study design	Length of study	Conclusions/comments
Galvão et al. [52]	To assess the effects of ADT on whole-body and regional muscle, fat and bone mass in men with PCa without metastatic bone disease	72 patients with PCa (aged 44–88 yrs) receiving intermittent ADT	Prospective	36 weeks	Overall lean body mass decreased by 2.4% (p < 0.001); upper limb by 5.6% (p < 0.001) and lower limb by 3.7% (p < 0.001).
					Overall fat mass increased by 13.8% (p < 0.001) with accumulation mostly localised to the extremities (upper limb 20.7%, p < 0.001 and lower limb 18.7%, p < 0.001). Truncal fat increased by 12% (p < 0.001)
Smith et al. [18]	To evaluate the treatment effects of GnRH agonist on body composition in asymptomatic men with non-metastatic PCa.	32 subjects with locally advanced, lymph-node positive or recurrent PCa.	Prospective	48 weeks	Compared to baseline, after 48 weeks of leuprolide treatment, weight increased by 2.4% ± 0.8% (p = 0.005), fat mass increased by 9.4% ± 1.7% (p < 0.001) and lean mass decreased by 2.7% ± 0.5% (p < 0.001).
					Subcutaneous abdominal fat increased by 11% ± 3.4% (p = 0.003) while intraabdominal fat did not change significantly (p = 0.94).
Smith [17]	To study the effects of androgen deprivation therapy on body composition in men with non metastatic PCa.	79 men with Stage M0 PCa.	Prospective	12 months	Weight increased by 1.8% ± 0.5% (p < 0.001), fat mass increased by 11% ± 1.7% (p < 0.001) and lean mass decreased by 3.8% ± 0.6% (p < 0.001).
Basaria et al. [19]	To determine the effect of ADT on body composition and muscle strength.	Three groups:	Cross-sectional	Cross-sectional	Cross-sectional analysis revealed that ADT group had higher overall % fat mass compared to the non-ADT and control group (32.2% ± 5.4% vs. 26.2% ± 6.0% and 22.4% ± 4.1%, respectively, p ≤ 0.0001). Truncal and extremity fat mass also highest in the ADT group.
		(1) 20 men with PCa undergoing ADT for at least 12 months (ADT group)			Upper body muscle strength was lowest in the ADT group compared to non-ADT and control group (47.6 ± 15.6 kg vs. 79.6 ± 35.3 and 61.1 ± 21.4, respectively, p = 0.001).
		2) 18 age-matched men with non metastatic PCa not on ADT (non-ADT group)			Quality of life (QOL) was lowest in men in the ADT group. Men in the ADT group had significant physical limitation (p = 0.006), role limitation (p = 0.02) and decreased health perception (p = 0.004).
		3) 20 age-matched healthy men (control group)

Table II.  Studies documenting metabolic and cardiovascular perturbations with ADT.

Study	Aim(s)	Patient population	Study design	Length of study	Conclusions/Comments
Dockery et al. [61]	To assess metabolic and vascular effects of ADT in men with PCa.	16 men with PCa were given ADT-while a control group of 15 age-matched healthy men were followed for a period of 3 months.	Prospective	3 months	In the ADT group, fasting insulin levels were increased after 3 months from 6.89 ± 4.84 to 11.34 ± 8.16 (p = 0.02). No changes were observed in fasting glucose.
					Decreased arterial compliance was noted in the ADT group compared to the control group (p = 0.03).
Smith et al. [30]	To characterize the short-term effects of GnRH agonist on insulin sensitivity.	25 men with PCa followed for 3 months.	Prospective	3 months	Whole body insulin sensitivity index decreased by 12.9% ± 7.6% (p = 0.02) after 3 months of ADT.Fasting plasma insulin levels increased by 25.9% ± 9.3% (p = 0.04)
					Fat mass increased by 4.3% ± 1.3% (p = 0.002) and lean mass decreased by 1.4% ± 0.5% (p = 0.006).
Smith et al. [31]	To determine the effects of ADT on body composition, metabolic parameters and arterial stiffness.	22 men (mean age 67 ± 8 year) with newly diagnosed PCa who were started on ADT and observed for a period of 3 months.	Prospective	6 months	No changes in lipid profiles or serum glucose levels. Median serum fasting insulin rose from 11.8 mU/l to 19.3 mU/l in 3 months (p = 0.02).
					ADT also resulted in increased central arterial pressure and higher pulse wave velocity.
Basaria et al. [32]	To evaluate the long-term effects of ADT on glucose and insulin metabolism	Three study groups:	Cross-sectional	Cross-sectional	Men in the ADT group had higher fasting insulin levels compared with the non-ADT and control group. (45.0 ± 7.25 μU/ml vs. 24.0 ± 7.24 μU/ml, p = 0.05 & 19.0 ± 7.39 μU/ml, p = 0.02 respectively).
		(1) 18 men with PCa on ADT for at least 12 months (ADT group)			HOMA IR index was highest in ADT treated men (17 ± 2.78), compared to non-ADT (6.0 ± 2.77, p < 0.01) and control group (5.0 ± 2.83, p = 0.01). Fasting glucose levels were 131 ± 7.43 mg/dl, 103 ± 7.42 mg/dl, (p = 0.01) and 99 ± 7.58 mg/dl (p < 0.01) in the ADT, non-ADT and control groups, respectively.
		(2) 17 age-matched men with non metastatic PCa and not on ADT (non-ADT group)
		(3) 18 age-matched healthy men (control group)
Braga-Basaria et al. [40,51]	To evaluate the prevalence of metabolic syndrome in men undergoing ADT.	Three study groups:	Cross-sectional	Cross-sectional	55% of men in the ADT group met criteria for metabolic syndrome, compared with 22% and 20% of men in the non-ADT and control groups, respectively (Overall p = 0.03).
		(1) 20 men with PCa undergoing ADT for at least 12 months (ADT group)
		(2) 18 age-matched men with PCa not on ADT (non-ADT group)
		(3) 20 age-matched healthy controls (Control group)

Figure 1.  Metabolic parameters in men undergoing long-term ADT compared with non-ADT and healthy controls (adapted from Ref. [32]).

Figure 2.  Association between duration of ADT and severity of metabolic abnormalities (adapted from Ref. [32]).

Figure 3.  Prevalence of metabolic syndrome in ADT group compared with non-ADT and control groups (adapted from Ref. [51]).

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