Long-term effects of androgen deprivation therapy in prostate cancer patients


Adrian S. Dobs, MD, MHS, Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 1830 E.Monument Street, Suite-328, Baltimore, MD 21287, USA. Tel.: + 410 955 2130; Fax: + 410 955 8172; E-mail: adobs@welch.jhu.edu


background Prostate cancer (PCa) is one of the most common cancers in men and has an increasing incidence. In 1999, 37 000 men died from PCa in the USA. Androgen deprivation therapy (ADT) with GnRH agonists is frequently employed in the treatment of recurrent and metastatic PCa by inducing medical castration, rendering these men hypogonadal. Because hypogonadism in men is associated with a wide range of complications, we attempted to determine the effects of long-term ADT in men with PCa.

methods We conducted a cross-sectional study at a tertiary care centre to determine the effect of ADT on lean body mass (LBM), muscle strength, bone mineral density (BMD), sexual function, and quality of life (QOL) in men with PCa. Three groups of men were enrolled: (1) 20 men with PCa who were undergoing medical castration with GnRH agonists for at least 12 months prior to the onset of the study (ADT group); (2) 18 age-matched men with nonmetastatic PCa who were post prostatectomy and/or radiotherapy but had not yet undergone ADT (non-ADT group); and (3) 20 age-matched normal men who were healthy and ambulatory (control group).

results Men on ADT had castrate levels of serum total testosterone (P < 0·0001), free testosterone (P < 0·0001) and oestradiol (P < 0·0001), which were significantly lower than in the other groups. Total body (P = 0·03) and lumbar spine (P < 0·0001) BMD was significantly lower in patients on ADT compared to other groups and was associated with higher levels of urinary N-telopeptide (P = 0·02). The ADT group had higher fat mass compared to the other groups (P = 0·0001) and significantly reduced upper body strength (P = 0·001) when compared to non-ADT patients. The ADT group had lower overall scores on Watt's Sexual Function Questionnaire compared to other groups (P = 0·0001), in particular a decrease in desire, arousal and frequency of spontaneous early morning erections. The ADT group also had lower overall QOL scores, resulting in significant limitation of physical function (P = 0·001), role limitation (P = 0·02) and perception of physical health (P = 0·004).

conclusions This study suggests that osteoporosis, unfavourable body composition, sexual dysfunction and reduced quality of life are seen in patients receiving androgen deprivation therapy for at least 12 months. Longitudinal studies in this patient population will shed further light on the timing of the development and the extent of these complications. Meanwhile, this information will assist both physicians and patients with prostate cancer to make informed decisions regarding androgen deprivation therapy.