Effects of Androgen Deprivation Therapy on Pain Perception, Quality of Life, and Depression in Men With Prostate Cancer

Abstract

Context: Previous animal and human research suggests that testosterone has antinociceptive properties. Castration in male rodents increases pain perception which is reversed by testosterone replacement. Pain perception also improves in hypogonadal men with testosterone therapy. However, it remains unclear whether androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with an increase in pain perception.

Objectives: To evaluate the effects of ADT on pain perception, depression and quality of life (QOL) in men with PCa.

Methods: Thirty-seven men with PCa about to undergo ADT with leuprolide acetate (ADT group) were followed prospectively for six months to evaluate changes in clinical and experimental pain. Forty men who had previously undergone prostatectomy for localized PCa and were in remission served as controls (non-ADT group). All participants were eugonadal at study entry. Primary outcomes were changes in clinical pain (assessed with Brief Pain Inventory questionnaire) and experimental pain (assessed with quantitative sensory testing). Secondary outcomes included evaluation of depression, anxiety levels, and quality of life.

Results: Serum testosterone levels significantly decreased in the ADT group but remained unchanged in the non-ADT group. There were no significant changes in pain thresholds, ratings, or other responses to quantitative sensory tests over the 6-month course of the study. Clinical pain did not differ between the two groups, and no changes from baseline were observed in either group. Men undergoing ADT did experience worsening of depression (0.93; 95% CI = 0.04-1.82; P = 0.042) and QOL related to physical role limitation (-18.28; 95% CI = -30.18 to -6.37; P = 0.003).

Conclusion: ADT in men with PCa is associated with worsening of depression scores and QOL but is not associated with changes in clinical pain or pain sensitivity.

Keywords: GnRH agonists; Prostate cancer; depression; pain perception; pain tolerance; quality of life; quantitative sensory testing; testosterone.

Figure 1

Changes in serum total testosterone levels in both groups. Data displayed as means; error bars are 95% CI.

Figure 2

Changes in (A) total BPI, (B) BPI severity and (C) BPI interference scores during the study. Data displayed as means; error bars are 95% CI.

Figure 3

Changes in (A) initial rating of pain, (B) prolonged pressure pain at 30 seconds, (C) prolonged pressure pain at 60 seconds, (D) mechanical pain temporal summation, (E) pain score with first stimulus, (F) pain score with tenth stimulus, (G) mechanical pain temporal summation in the distraction trial, (H) pain score with first stimulus in the distraction trial, (I) pain score with tenth stimulus in the distraction trial; (J) cold pain tolerance, and (L) CPM index in each group. Data displayed as means; error bars are 95% CI. CPM, conditioned pain modulation.

Figure 4

Changes in (A) composite scores of pain catastrophizing, and (B) helplessness, (C) magnification and (D) rumination subdomain scores in each group. Data displayed as means; error bars are 95% CI.

Figure 5

Changes in C-reactive protein concentrations in each group during the course of the study. Data displayed as means; error bars are 95% CI.

Figure 6

Changes in (A) depression scores on PHQ-9 questionnaire, (B) physical functioning domain on SF-36 questionnaire, (C) physical role limitations domain on SF-36, and (D) emotional well-being on SF-36 in each group. Data displayed as means; error bars are 95% CI.

Figure 7

Changes in (A) STAI-state and (B) STAI-trait scores in each group. Data displayed as means; error bars are 95% CI.