Cognitive and mood changes in men undergoing intermittent combined androgen blockade for non-metastatic prostate cancer

Abstract

Purpose: Men with prostate-specific antigen (PSA)-only relapse of prostate cancer after primary therapy are generally fully functional and asymptomatic with a life expectancy of up to 10 or more years. Androgen deprivation therapy (ADT) is a common treatment option. This study examined mood and cognitive changes in otherwise healthy men with prostate cancer prior to, during and after ADT.

Experimental design: Twenty hormone naïve, eugonadal prostate cancer patients without evidence of metastases and with a rising PSA were treated with intermittent ADT consisting of 9 months of complete androgen blockade (CAB) achieved with combined leuprolide and flutamide followed by an 'off treatment' period. Cognitive function tests and mood measures were administered at baseline, after 3 and 9 months of ADT and after 3 months of no treatment. Twenty healthy control patients without prostate cancer range matched for age and education were tested at the same time intervals.

Results: ADT patients evidenced a significant decline in spatial reasoning, spatial abilities and working memory during treatment compared with baseline. No changes were noted for measures of verbal or spatial memory, selective attention or language. Significant changes in self-rated mood such as increased depression, tension, anxiety, fatigue and irritability were evident during treatment compared with baseline for ADT patients. No significant changes in either cognitive tests or mood measures were noted for the healthy control group.

Conclusions: These findings, suggest that 9 months of combined androgen blockade may result in some adverse changes in cognition and mood. However, many but not all of these changes can return to baseline after cessation of ADT.

Figure 1

Study procedure outline. For all the following figures: Red solid line is the ADT group and blue dashed line is the controls at baseline before treatment, during treatment and off treatment at the 12 month assessment. Error bars represent standard deviation.

Figure 2

Mean serum Testosterone (left) and Estradiol (right) levels. ADT group demonstrated a significant decline in testosterone and estradiol levels during treatment. Controls demonstrated a significant increase in estradiol levels at month 3 compared to baseline. There was a group by time interaction effect (p<.05) for both Testosterone and estradiol.