Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pelvic or perineal pain or painful voiding, in addition to LUTS including urgency, frequency, hesitancy, and poor interrupted flow. Since CP/CPPS has a significant negative impact on the patient’s quality of life (QOL), the desire for treatment is high and effective treatment is required in clinical practice. Phytotherapy using cernitin pollen extract (cernitin), which is one of the traditional treatment options for CP/CPPS, is considered to be safe and effective for the relief from pelvic pain. PDE5 inhibitor such as tadalafil, which has multiple actions, including suppression of inflammation by the downregulation of Rho-kinase activity, is reported to be effective for CP/CPPS.
It is of clinical interest to determine whether these old and new drugs, cernitin and tadalafil, respectively, can improve chronic pain or discomfort of the pelvic or perineal in patients with CP/CPPS. To the best of our knowledge, no randomized controlled studies have compared the improvement in chronic prostatitis symptoms in patients treated with one of these medications. Therefore, the aim of the present study was to compare the efficacy of treatment with cernitin or tadalafil on not only LUTS, but also pelvic pain or discomfort, in patients with persistent CP/CPPS.

This was a single-center, open label, and randomized controlled trial. The study included men who had persistent chronic prostatitis symptoms such as perineal and/or pelvic discomfort and/or pain after α1-blocker monotherapy for 12 weeks or more. The inclusion criteria were as follows: age ≥ 45 years; National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) pain sub-score ≥ 4; total International Prostate Symptom Score (IPSS) ≥ 8; and prostate volume ≥ 20 mL. .
A total of 100 patients with refractory CP/CPPS despite α1-blocker monotherapy were randomized to receive add-on therapy with cernitin (4 capsules/day) or tadalafil (5 mg/day) for 12 weeks. At week 12, changes from baseline in the patients’ CP/CPPS, LUTS, and voiding function, as assessed using NIH-CPSI, IPSS, and uroflowmetry, respectively, were compared between the groups. The primary endpoint was defined as the change from baseline to week 12 in the NIH-CPSI total score and NIH-CPSI pain sub-score. Additionally, we evaluated the change in NIH-CPSI urinary sub-score, NIH-CPSI QOL sub-score, IPSS, and voiding parameters on UFM as secondary endpoints.

The final analysis included 42 and 45 patients in the cernitin and tadalafil groups, respectively. Although the NIH-CPSI total, NIH-CPSI pain sub-score, and NIH-CPSI quality of life (QOL) sub-score significantly improved in both groups, the cernitin (vs. tadalafil) group showed significantly greater improvements in the NIH-CPSI total score (-6.8 vs. -4.6, p = 0.02) and NIH-CPSI pain sub-score (-4.1 vs. -1.5, p < 0.001) (Figure. 1). Half (50%) of the patients in the cernitin group showed a reduction greater than 50% in their NIH-CPSI pain sub-score; in the tadalafil group, only four patients (8.9%) showed ≥ 50% improvement (p < 0.001). In contrast, the improvement in LUTS, including the NIH-CPSI urinary sub-score and IPSS storage sub-score, was significantly superior in the tadalafil group.

These findings may provide clinicians with an evidence-based strategy in selecting a medical treatment for the subgroup of patients with persistent chronic prostatitis despite α1-blocker monotherapy, who are frequently encountered in clinical practice. The detailed mechanisms underlying the significantly greater efficacy of cernitin than that of tadalafil in the improvement in chronic pelvic pain remains incompletely understood, but we can offer a plausible hypothesis. Although few studies have focused on the association between the inflammatory suppression of prostate tissue and the alleviation of pelvic pain, the suppression of chronic prostatic inflammation may contribute to the improvement of chronic pelvic pain and discomfort. When comparing the beneficial effects of the two drugs on prostate inflammation, cernitin might suppress inflammation more effectively in prostate tissue than tadalafil.

This comparative study showed that both cernitin and tadalafil significantly improved chronic pelvic pain and QOL in patients with refractory CP/CPPS (NIH category IIIA) despite α1-blocker monotherapy. The add-on of cernitin was more effective than tadalafil for pelvic pain and discomfort, which are pathognomonic symptoms in CP/CPPS, although the improvement of LUTS such as storage symptoms was significantly superior for the add-on treatment with tadalafil.