CP/CPPS: Data show evidence of HPA-axis abnormality

September 1, 2007

Similar to patients with other chronic pain conditions, men with chronic prostatitis/chronic pelvic pain syndrome have evidence of a hypothalamic-pituitary-adrenal-axis abnormality.

In this study funded by the National Institute of Diabetes and Digestive and Kidney Diseases, Dr. Anderson and his team assessed HPA-axis endocrine abnormalities by measuring salivary cortisol levels on 2 consecutive days in 33 men (mean age, 43 years) with CP/CPPS and 18 healthy controls. The men with CP/CPPS had had symptoms for at least 3 months (mean pain duration, 81 months), NIH Chronic Prostatitis Symptom Index (NIH-CPSI) scores of at least 15, and pain scores higher than 0.

All participants collected nine saliva samples each day-on awakening, 15 minutes later, 30 minutes later, 1 hour later, 3 hours later, and then 3 more samples at 3-hour intervals. Measurements were by luminescent immunoassay. Cortisol levels in individuals were utterly consistent from one day to the next, but significant differences between the two groups emerged.

The normal pattern of cortisol is a rise in the morning by 50% to 60% within 30 minutes of awakening and a gradual decrease throughout the day to an evening low. But the Stanford researchers found that men with CP/CPPS had much steeper slope elevation of their morning levels-a mean increase of 85%-than did their healthy counterparts (mean increase, 57%).

"These guys are waking up in the morning ready to go," Dr. Anderson observed.

This phenomenon has been seen in other conditions with chronic pain, including chronic back pain, fibromyalgia, and breast cancer, Dr. Anderson noted.

The psychometric tests taken by the men dispelled one notion that has been attached to these men: that they have a type A personality. While no difference between the groups in type A behavior was identified, the men with CP/CPPS had significantly higher levels of stress, anxiety, depression, somatization, obsessive-compulsive behavior, interpersonal sensitivity, hostility, phobic activity, social alienation, paranoid ideation, and psychoticism than their healthy counterparts did (p<.001). The CP/CPPS patients' psychometric test scores did not correlate with the duration of their symptoms or with their NIH-CPSI scores.

Dr. Anderson pointed out that this study couldn't show whether these traits were a result of the stress of chronic pain or whether the men were already predisposed to them. He will continue his research to uncover what the connections between the personality traits and the HPA-axis abnormalities might be by looking at serum cortisol levels in response to stress and possibly by testing to see whether treatment affects cortisol levels or proinflammatory cytokines. However, it is understood that stress triggers a cascade of physiologic events involving activation of the HPA-axis and the autonomic nervous system. Chronic activation of the physiologic stress is thought to induce glucocorticoid resistance, alter immunity, and promote release of proinflammatory cytokines and prostaglandins that may contribute to myalgia.

How to treat that disordered system has no easy answer. Evidence of endocrine disruption hasn't led to endocrine answers.

"[These patients] have been given steroids in the past," Dr. Anderson said. "That doesn't work."

He believes that CP/CPPS may have a neurologic and neuromuscular basis. Neuromuscular trigger points may be irritated and stimulated in some fashion, perhaps by an inflammatory process. That hypothesis is the basis of Dr. Anderson's therapy for men with refractory CP/CPPS, which uses a combination of cognitive behavioral therapy and physiotherapy. Dr. Anderson thinks that trying to further modify cerebral function with therapies such as hypnosis can be beneficial.

In his practice, Dr. Anderson's team tries to ease patients off medications and to treat them instead with cognitive behavioral-physiotherapy. But Dr. Anderson cautioned that this approach isn't necessarily first-line therapy.