Reviewed: Gravas S, Samarinas M, Zacharouli K, et al. The effect of hexanic extract of Serenoa repens on prostatic inflammation: results from a randomized biopsy study. World J Urol. March 2019;37(3):539-544. doi: 10.1007/s00345-018-2409-1.

Many men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) have chronic prostatic inflammation. Saw palmetto (Serenoa repens, Arecaceae) extract, which has demonstrated anti-inflammatory, antiandrogenic, and antiproliferative effects in vitro and in vivo, is one of the most commonly used plant extracts for the management of male LUTS, according to the authors of this study. Human clinical trials have investigated the effects of a hexanic extract of saw palmetto (HESr)* on male LUTS, but clinical studies investigating its effects on prostatic inflammation are scarce. The authors conducted a randomized, controlled study to evaluate the effects of HESr in patients diagnosed with prostatic inflammation. No standardization information about the HESr was provided.

The study was conducted at the University Hospital in Larissa, Greece. Of the 110 enrolled men with prostatic inflammation, which was confirmed by transrectal ultrasound-guided biopsy, 13 were excluded from the final analysis because they developed prostate cancer during the study. All patients had undergone biopsy because of an elevated prostate-specific antigen (PSA) level, a positive digital rectal examination (DRE), or both. The patients were randomly assigned to receive 320 mg of HESr daily for six months (n = 49) or no therapy (control group, n = 48). The patients underwent a second biopsy at the end of the study.

The primary endpoint was the change in inflammation from baseline to study end, which was assessed by total Irani’s score (a prostatic inflammation scoring system) and immunohistochemical staining. The extent of inflammation was graded from 0 to 3 based on the degree of invasion of inflammatory cells in prostatic tissue. The aggressiveness of inflammation was graded from 0 to 3 based on the degree of contact or disruption of prostatic glandular epithelium by inflammatory cells.

Secondary endpoints were changes in prostatic inflammation assessed by immunohistochemical staining for the following antibodies specific for inflammatory cells: CD3, CD4, CD8, CD20, and CD163. The expression of each antibody in prostate tissue was graded from 0 to 3.

At baseline, the mean inflammation grading score for the HESr group was 1.55; this score significantly decreased to 0.79 after the six-month treatment period (P = 0.001). The mean aggressiveness grading score decreased from 1.55 to 0.87 during the study (P = 0.001). In the control group, the mean inflammation grading score decreased from 1.44 to 1.23 (P = 0.09), and the mean aggressiveness grading score decreased from 1.09 to 0.89 (P = 0.74) from baseline to the end of the study.

The total Irani’s score mean decreased significantly in the HESr group (P = 0.001) and slightly but not significantly in the control group (P = 0.52) during the study. A significantly greater decrease in inflammation grading scores (P = 0.001), aggressiveness grading scores (P = 0.009), and total Irani’s score (P = 0.001) was found in the HESr group compared with the control group. The inflammation score was increased in 25% of patients (12 out 48) in the control group while only 6.1% (3 out of 49) of the HESr patients had a higher Irani’s score at the second biopsy.

Immunohistochemical staining revealed a significant decrease in the production of CD3, CD4, and CD8 (marker proteins for T-leukocytes), CD20 (for B-leukocytes), and CD163 (for macrophages) antibodies in the HESr group at the second biopsy compared with the baseline biopsy results (P < 0.001 for all). No significant changes were reported in the control group. The changes in reduction of cells involved in the inflammatory response were significantly greater in the HESr group after six months compared with the control group (P < 0.001 for CD3, CD8, CD20, and CD163; and P = 0.002 for CD4).

According to the authors, “These results suggest that inflammation seems to progress over time and confirm the anti-inflammatory properties of HESr.” The results are limited by the fact that only patients with elevated serum PSA levels or a positive DRE, or both, were eligible for a prostate biopsy, and only those with confirmed inflammation on baseline biopsy were included in the study. The study was also limited by the lack of a placebo control. The authors suggest that a larger trial should investigate if and how the improvements in prostatic inflammation reported here can be translated into clinical practice and if patients with greater decreases in prostatic inflammation experience LUTS relief.

The authors concluded that “HESr seems to reduce prostatic inflammation in terms of histological and immunohistochemical parameters in patients who underwent two biopsies due to elevated PSA and/or suspicious DRE.”