Long-term effects of intermittent androgen suppression therapy on lean and fat mass: a 33-month prospective study

To examine changes to whole body and regional lean mass (LM) and fat mass (FM) over 33 months of intermittent androgen suppression therapy (IAST).

Phase II cohort study of 72 prostate cancer patients without metastatic bone disease. Patients received flutamide 250 mg tid and leuprolide 22.5 mg three monthly depot for the 9-month initial treatment phase (iTREAT), at which point patients ceased therapy providing PSA <4 ng ml(-1) with continued monitoring for further 2 years (POST). AST was recommenced when PSA exceeded pretreatment level or ≥ 20 ng ml(-1). Body composition was assessed using dual energy X-ray absorptiometry at baseline, completion of treatment phase, and 1 and 2 years post treatment phase (months 21 and 33).

LM decreased by 1.3 kg and FM increased by 2.3 kg (P<0.001) following iTREAT. During the POST period, there were no further adverse effects on LM or FM, but also no recovery to pretreatment levels. Patients who failed to recover testosterone by month 33 experienced a significant increase in FM compared with those who recovered eugonadal levels of testosterone (10 nmol ml(-1); P = 0.019). Change in testosterone was moderately correlated to changes in % FM (r = -0.314, P<0.028) and LM (r = 0.300, P<0.036) during POST phase. Waist circumference progressively increased over time and by 2 years, POST had not recovered to baseline levels.

Loss of LM and gain in FM during the 9-month iTREAT was not reversed during 2-year POST, although further deterioration was not observed. Subgroup analysis identified those recovering testosterone showed some body composition improvements. These findings suggest potential benefits of IAST, where testosterone levels are able to recover, to reduce the ongoing adverse effects on body composition, such as the acceleration of sarcopenia and risks associated with metabolic disease.