Long-term Effects of Intermittent Androgen Suppression on Testosterone Recovery and Bone Mineral Density: Results of a 33-month Observational Study
Faculty of Computing, Health and Science
School of Exercise, Biomedical and Health Science / Centre for Exercise and Sports Science Research
To investigate changes in bone mineral density (BMD) and osteoporosis, over 3 years of intermittent androgen-suppression therapy (IAST). This was a Phase II individual cohort study of 72 patients with prostate cancer without metastatic bone disease, enrolled between 1999 and 2002. Patients had 9 months flutamide (250 mg, three times daily) and leuprolide (22.5 mg, 3-monthly depot) after which, patients ceased therapy providing that their PSA levels were <4 ng>/mL. AST re-commenced when the PSA level exceeded the pretreatment level or was >20 ng/mL. BMD for hip and spine was the primary endpoint; assessed at baseline; completion of initial treatment period; and at 1 and 2 years after initial treatment (POST period). Osteoporosis increased from 7% at baseline to 10% at 3 years. The BMD declined after 9 months treatment, at −1.9% and −3.3% at hip and spine, respectively (P < 0.001). Subsequent BMD decline in the POST period was attenuated; at 1 years and 2 years later, hip −0.6% (not significant), and −0.8% (P < 0.014), and spine +1.0% and +0.2% (not significant). The BMD change in those remaining ‘off’ therapy for 2 years (n = 20) was strongly associated with the level of testosterone recovery; a peak testosterone level of <5 nmol/L associated with a greater then normal physiological loss. Testosterone recovery was less likely in older men. The attenuation of spine and hip BMD decline after 3-year IAST compared with those reported for continuous AST appears to be due to testosterone driven BMD recovery in the POST period. Failure of testosterone recovery was associated with worse final BMD. By reducing the potential risk for adverse bone complications, intermittent therapy may become an important consideration when the therapeutic ratio is narrow.