There are multiple approaches to the management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); and lately the data suggesting the ability of acupuncture treatment to decrease pain, positively impact quality of life and potentially modulate inflammation has suggested it as a potential therapeutic option for men with CP/CPPS. We conducted this study to determine whether acupuncture is really an effective therapeutic modality for CP/CPPS in terms of >50% decrease in total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score from baseline compared with sham.
One hundred patients with CP/CPPS (category III B) in an outpatient urology clinic were randomized to receive acupuncture at either seven acupoints bilaterally or sham points adjacent to these points. NIH-CPSI was completed by each patient before and 6, 8, 16, 24 weeks after the treatment. Mean values of total CPSI score and subscores after the treatment and on follow-up following the treatment were compared.
Of the acupuncture participants, 92% were NIH-CPSI responders (>50% decrease in total NIH-CPSI score from baseline) compared with 48% of sham participants, 8 weeks after the end of the therapy. Both groups experienced significant decrease in CPSI subscores throughout the whole follow-up period; however, the decline remained significantly greater in the active acupuncture group as compared with the sham group.
Our results show that the use of acupuncture in treatment of men with CP/CPPS symptoms resulted in a significant decrease in total NIH-CPSI scores.
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common problem for men with a prevalence of 2–10% worldwide.1 Currently, there are multiple approaches to the management of CP/CPPS depending on the classification of the related symptoms. Conventional therapies include antibiotics, alpha-blockers, anti-inflammatory agents and other medical agents, none of which has proven to be totally effective.2, 3, 4 TURP and open prostatectomy have been advocated for CP/CPPS on the basis of a few anecdotal experiences, but there are absolutely no reliable data or experiences to substantiate a treatment effect. A recent case series employing transurethral microwave thermotherapy and transurethral needle ablation suggested a therapeutic minimally invasive therapy.5, 6
Recently, a multi-modal treatment approach and the use of complementary and alternative medicine strategies such as acupuncture and phytotherapy have also been suggested as potential treatment options for CP/CPPS.7, 8 Data suggesting the ability of acupuncture treatment to decrease pain, positively impact quality of life (QoL) and potentially modulate inflammation has suggested it as a potential therapeutic option for men with CP/CPPS. The precise mechanisms of action of acupuncture are not completely clear, but include gate control of pain pathways, increased endogenous opioid release and altered sympathetic tone.9, 10, 11, 12, 13 Although a number of published studies tested the utility of acupuncture treatment for CP/CPPS, in a previous noncontrolled study we presented that acupuncture improved pain, voiding symptoms and QoL.14 We now report a randomized, blind comparison of acupuncture with sham acupuncture for CP/CPPS.
Materials and methods
After approval from local ethics committee of our hospital, the study was performed. Patients approaching our outpatient clinic with lower urinary tract symptoms suggestive of prostatitis were evaluated for bacterial infection by Meares–Steamey criteria. Those patients who were found to be negative for leucocyte and culture (ureaplasma, mycoplasma and chylamidia) were evaluated according to the National Institutes of Health (NIH) consensus criteria.15 The patients with CP/CPPS (NIH category IIIB) had a history of disease refractory to standard conventional therapy including antibiotics, alpha-blockers and anti-inflammatory agents, and had symptoms of pain or discomfort in the pelvic region for at least 3 of the previous 6 months. Exclusion criteria included: acute prostatitis or bacterial prostatitis, BPH, prostate cancer, urinary tract infection within 1 year, pathology at urinary system ultrasonography including bladder and urethral stones, and any traditional or alternative medical therapy within past 6 weeks. Localized skin infections concerning the acupoints, bleeding diathesis and use of anticoagulation, as well as severe chronic or uncontrolled co-morbid disease were also criteria of exclusion for application of acupuncture. Patients over 50 years of age were also excluded to minimize the confounding role of BPH-related symptoms.
Male patients 20–50 years of age, who expressed a willingness to participate, were enrolled for the study after informed consent was obtained, and were randomized to acupuncture or sham acupuncture group using a computer-generated, random block design.
The therapy protocol included a total of seven acupuncture points bilaterally (BL-33, BL-34, BL-54, CV-1, CV-4, SP-6 and SP-9) (Table 1, Figure 1). These acupoints were selected according to the theory of neuroanatomy and myofascial pain syndromes and depending on the literature and textbooks on this aspect.16, 17, 18, 19 All acupuncture points were prepared with 70% alcohol pads with participants lying prone or at lithotomy position regarding the manipulation of acupoints selected. Acupuncture and sham acupuncture procedures were performed by three experienced acupuncturists. Acupuncture was performed using two disposable stainless steel needles (0.3 mm diameter, 60 mm length, Suzhou, Jiangsu, China) that were inserted to a depth of maximum 2.5–3 cm. We placed the needle 0.5–1 cm deep only for spots in the perineum. The sensation of ache or heaviness in the area surrounding the inserted needle (known as de qi) was always achieved. Punctures in the sham group were performed 1 cm left of each selected acupoint, with the same type of needles, of the same duration and frequency. Overall treatment lasted for 20 minutes in both groups and half of this period covered by needle stimulation through rotation.
The procedure was repeated every week for a period 6 weeks without other treatment modalities. The NIH Chronic Prostatitis Symptom Index (NIH-CPSI), comprised of a total of nine items, was completed by each patient before and after the treatment and on 6th, 8th, 16th and 24th week following the treatment (Figure 2). Participants used self-administered questionnaires. Another researcher independently observed and recorded all procedures to ensure that interaction between the acupuncturists and patients was limited to needle placement and withdrawal. The patients were asked to report any adverse effects as well on each session of treatment and control.
Primary endpoint was a 50% decrease in NIH-CPSI total score from baseline to week 8. Secondary outcomes included: complete resolution, NIH-CPSI total score and subscales at weeks 6, 8, 16 and 24. Combined, the primary and secondary endpoints addressed all recommended outcome domains for chronic pain trials.4, 14, 19
Setting significance at 0.05 with 80% power, 49 participants were required, assuming response in 57% of acupuncture and 35% of sham participants with 15% dropouts. The data were analyzed by using Number Cruncher Statistical System 2007 (NCSS, Logan, UT, USA). Descriptive statistical methods (mean±s.d.) and repeated measures by analysis of variance were performed, subgroup comparisons were done by Newman–Keuls multiple comparison test and independent t-test was used to compare the two groups.
One hundred patients enrolled for this study, between the ages of 22 and 49 years, were randomized; 50 to acupuncture and 50 to sham acupuncture groups. Ninety-one patients completed treatment and all posttreatment visits (Figure 3). Mean age of the acupuncture group was 32.1±7.2 years, and the mean duration of symptoms of the disease was 9.6±3.5 months (ranging between 6 and 15 months). Mean age of the sham group was 32.8±7.0 years, and the mean duration of symptoms of the disease was 9.5±2.3 months (ranging between 6 and 16 months). Both groups were similar at baseline. Regarding ethnicity, all of the participants were Turkish. Each patient underwent six sessions of acupuncture treatments and was followed up for 24 weeks.
After 6 weeks, NIH-CPSI total scores decreased from baseline in both groups (P<0.001), but the decrease after 24th week of treatment was more prominent in acupuncture group (P<0.001) (Figure 4). After 8 weeks, 92% of acupuncture participants were NIH-CPSI responders compared with 48% of sham participants (P<0.001). The response rate of acupuncture patients at the end of follow-up was 74%, whereas it was only 30% for the sham group (Figure 5). After 8 weeks, 24 patients (48%) experienced complete resolution compared with 18 (36%) sham participants. Both groups experienced significant reduction in CPSI subscores of pain, urinary and QoL throughout the whole follow-up period; however, the decline on 24th week remained significantly greater in the active acupuncture group as compared with sham group (P<0.001) (Table 2).
No adverse event was recorded in any patient throughout the survey that was related to acupuncture or sham treatment.
In this study, acupuncture proved clinically effective in CP/CPPS patients as compared with sham acupuncture. Almost a 92% positive response was achieved in the acupuncture group, whereas only ~48% of sham participants revealed more than a 50% decrease in total NIH-CPSI score from baseline at the completion of therapy. At the end of 24 weeks of treatment, success in the acupuncture group was 74%, whereas it was only 30% in the sham group.
Acupuncture is one of the oldest standardized neuromodulatory therapies available. The method of acupuncture treatment involves the insertion of fine, single-use, sterile needles in acupoints according to a system of channels and meridians. The needles are stimulated by manual manipulation, electrical stimulation or heat. The general theory of acupuncture is based on the premise that there are patterns of energy flow (Qi) through the body that are essential for health. Disruptions of this flow are believed to be responsible for disease. Acupuncture may correct imbalances of flow at identifiable points close to the skin.9
Many uncontrolled studies have suggested that acupuncture therapy provide benefit for men who have symptoms of CP/CPPS.12, 17, 18, 19, 20, 21 Chen and Nickel19 reported that acupuncture improved pain, voiding symptoms and QoL in 12 men with CP/CPPS and a significant decrease in total NIH-CPSI pain, urinary and QoL scores (P<0.05) after 6 weeks of treatment and for an average of 33 weeks of follow-up.21
Capodice et al.22 investigated whether standardized 6-week full-body and auricular acupuncture helped lower urinary tract symptoms experienced by 10 men with CP/CPPS IIIA or IIIB for >6 months, refractory to at least one conventional therapy. This study reported a significant decrease in NIH-CPSI total, pain, urinary and QoL scores after 6 weeks of follow-up.
Our previous non-controlled study of 97 men with treatment-refractory CP/CPPS demonstrated significant amelioration of CP-related symptoms with acupuncture treatment. A significant improvement in the average CPSI total score, as well as the separate domains of pain, urinary and QoL scores, was observed at the end of treatment. More than 92% of patients turned out to be NIH-CPSI responders at 12 weeks.14 Not having a control group was the most important limitation of our previous study.
This trial follows controlled acupuncture trial recommendations.23 Posadzki et al. in CP/CPPS patients on acupuncture treatment in a randomized controlled study have evaluated the methodological using the Jadad score in their review.24. Several acupuncture trials have employed various control arms. Only one study of Lee et al. found scores above 3. Lee et al.25 reported the first randomized, blinded comparison of acupuncture with sham acupuncture for CP/CPPS.
In this study, we selected 7 acupoints bilaterally which are deemed as points to restore qi and considered effective for voiding dysfunction together with dysuria and lower abdominal pain (CV1, CV4, SP6 and SP9). CV-1, CV-4 and SP-6 has immune enhancing and urinary retention preventive effect. SP-6 and SP-9 has reduced dysuria symptoms. We combined BL-33, BL-34 and BL-54 to these acupoints, which are located in the third and fourth posterior sacral foramen, in order to benefit from the stimulation of segments of sacral nerve.26, 27, 28 In fact, these segmental approaches would generally be found to produce a more intense analgesic response because of direct inhibition at the spinal cord level.17, 18 When we increase the number of acupuncture points, we can further improve the success of treatment, create an additive effect and we thought we could also provide long-lasting effects. This may be the explanation of the higher success rate of our study when compared with the study conducted for CP/CPPS by Lee et al.25 In their randomized sham-controlled study, using only four acupoints and no needle stimulation, they showed long-term responses 24 weeks after acupuncture treatment in 32% of acupuncture group and in only 13% of sham acupuncture recipients, which was far low when compared with our results.
Another study by Lee and Lee29 showed that electroacupuncture relieved pain; they determined the responders’ percentage showing a ≥25% decrease in total NIH-CPSI score as ~75% in the electroacupuncture group in contrast to 16.7% of sham electroacupuncture. They also showed that the prostaglandin E2 levels in urine samples after electroacupuncture decreased, indicating the anti-inflammatory properties of acupuncture.
The unique feature of this study was the use of a sham control. Use of a validated sham control minimizes the possibility that responses observed in the active group were just due to attention or to the ritual of receiving acupuncture. In addition, lack of observed significant differences in measures of blinding further decreases the likelihood that differences found between groups were due to placebo-related phenomena. In the literature there are studies aimed at different practices about sham acupuncture. Sham acupuncture can be done as pining wrong location, far and irrelevant spots or can be done as giving pressure by needle into the skin without incurring. We chose to use the points 1 cm laterally that are not defined as meridian points.30, 31
This study had several strengths. Acupuncture as treatment modality has been extensively investigated especially in Asian countries. To our knowledge, there is no another study in Turkish population. The evaluation and inclusion and exclusion criteria adhered to the consensus recommendations.15 We had an adequate sample size and excellent follow-up. Interventions were developed following literature review and expert consultation, subsequently administered by trained practitioners. Side effects were not observed in our study. This lack of side effects might have been influenced by the positive perception of the patients.
Acupuncture therapy seems to have independent therapeutic effects superior to sham acupuncture, particularly in pain relief, for men complaining of CP/CPPS symptoms. There is sufficient evidence of acupuncture’s value to expand its use into conventional medicine in this aspect and to encourage further studies of its physiology and clinical value. Acupuncture’s efficiency as a treatment modality has been accepted by the World Health Organization, too. The treatment process with acupuncture and its efficacy at short term after treatment are well known. Long-term effects about treatment need more studies. In addition, we believe that short and long term is evaluated with factors that affect the patient’s health.