Combination Therapy With Curcumin Plus Tamsulosin and Finasteride in the Treatment of Men With Benign Prostatic Hyperplasia

A Single Center, Randomized Control Study

Jing Qiao; Yu Gan; Yuchen Gong; Qingtian Song; Bo Zhang; Bingsheng Li; Feng Ru; Yang Li; Yao He

Disclosures

Transl Androl Urol. 2021;10(8):3432-3439. 

In This Article

Discussion

BPH is a common diagnosis in older men. However, the pathogenesis of BPH is far from being completely understood. In recent years, growing evidence has become available to show that BPH is associated with chronic inflammation.[1,2] Besides, it has been proven that obesity is correlated with the LUTS of BPH and ED.[17,18] Treatments of BPH include medications and surgery. Surgical treatments are indicated for patients who fail to respond or respond poorly to drug therapy, including TURP, holmium laser resection of the prostate (HoLEP), prostate laser vaporization, etc. However, surgery is traumatic and has many complications, such as bleeding, urethral stricture, retrograde ejaculation, and urinary incontinence.[19,20] The standard medical treatments for BPH are alpha-blockers and 5-alpha reductase inhibitors, both of which lack direct anti-inflammatory effects and may have potential adverse effects on sexual function and erection.[3,4]

Curcumin is the main bioactive component of turmeric. Curcumin has a long history of being used as a spice in diet, and also its use as traditional medicine can be traced to more than 2,000 years ago in India and China.[9] Previous experimental studies have demonstrated that curcumin possesses anti-inflammatory, antioxidant, anti-cancer, anti-fibrosis, lipid-modifying, and antiarthritic properties.[12] In addition, curcumin has been reported to effectively inhibit the occurrence and development of BPH in male Wistar rats and reduce the expression of TGF-1, an inflammatory cytokine, in prostate tissues.[21] A prospective clinical comparative study showed that compared with finasteride alone, the additional use of curcumin was superior in improving patients' IPSS and QoL scores and controlling urinary tract infection.[11] However, the effect of curcumin on sexual function in BPH patients was not investigated in the former study.

The findings of our prospective trial indicate that the IIEF-5 score decreased from baseline in the BSM (tamsulosin and finasteride) group after 6-month standard medical treatment. The adverse effect of finasteride may be the main cause.[22] Interestingly, the IIEF-5 score increased moderately from baseline in the curcumin + BSM group. Moreover, there was a statistically significant improvement of the IIEF-5 score in the curcumin + BSM group compared with that in the BSM group, indicating that curcumin may have a protective and promoting effect on sexual function. It has been proven that curcumin can enhance erectile function in a rat model of type-2 diabetes by increasing the expression of heme oxygenase-1 and decreasing the expression of NF-κβ-activating proteins.[23] Furthermore, Abdel Aziz et al.[24] previously reported that curcumin combined with tadalafil showed obvious superiority in improving erectile function compared to tadalafil alone in a diabetic model of ED. These animal experimental results were consistent with the findings from the current clinical study.

The IPSS questionnaire has been applied to evaluate the severity of LUTS and disease progression in BPH patients. The IPSS is comprised of seven items. The IPSS-S score mainly describes urinary storage symptoms, including frequency, urgency, and nocturia, making patients' lives difficult and affecting patients' daily work and social life. The IPSS-V score mainly describes urination obstruction symptoms, including incomplete emptying, intermittency, weak stream, and straining to void, which can also be very painful for patients. In this study, although there were significant improvements in PV, Qmax, IPSS-total, IPSS-V, IPSS-S, and QoL scores from baseline after treatment in both groups, the IPSS-S and QoL scores showed a better and significantly increased improvement in the curcumin + BSM group when compared with the BSM group. These results support the hypothesis that the IPSS-S score is mainly affected by prostatitis and that curcumin has a significant anti-inflammatory effect on prostatitis.[25–27]

PPF consists of highly active adipocytes, which can secrete many growth factors, chemokines, and inflammation-modifying molecules as paracrine cells, and it may play a predominant role in the occurrence and progression of prostate diseases.[13] Preliminary studies by our group have shown that PPFT was significantly associated with PV, LUTS, and severity of ED in BPH patients, and PPFT could better identify high-risk patients with clinical progression of BPH.[14] Besides, we found that the lipo-factor leptin was able to aggravate BPH by down-regulating BMP and activin membrane-bound inhibitor homolog (Xenopus laevis) (BAMBI) to activate the TGF-β/EMT signaling pathway in a rat model of testosterone BPH.[28] In addition, Jazayeri-Tehrani et al.[15] stated that nano-curcumin could significantly reduce WC, blood sugar, and serum lipid levels in patients with non-alcoholic fatty liver disease (NAFLD), without significant reduction in body weight and BMI. However, another study on NAFLD showed that curcumin could significantly reduce body weight and BMI.[16] Moreover, curcumin has been shown to significantly decrease serum leptin levels and increase serum adiponectin levels in NAFLD patients.[29] However, no studies have been carried out to explore the effect of curcumin on PPF in BPH patients.

To the best of our knowledge, this is the first study evaluating the effects of curcumin combined with BSM treatment on BMI, body weight, and PPF in BPH patients. In the present study, no statistically significant differences were observed in BMI, WC, and PPFT in the BSM group compared with baseline, while significant differences were observed in WC and PPFT in the curcumin + BSM group without a significant difference in BMI. The present study suggests a significant benefit of curcumin in improving abdominal fat distribution and reducing PPF in BPH patients. Consistent with the findings of our previous studies, curcumin may indirectly affect disease progression in BPH patients by affecting the secretion of adipocytokines in PPF, a hypothesis that needs to be tested by further in vitro studies.

Overall, the treatment of curcumin was well-tolerated. In our study, curcumin combined with BSM treatment for 6 months significantly improved PPFT, erectile function, and urinary retention symptoms and QoL scores. Thus pharmacological treatment of BPH involved anti-inflammatory treatment such as curcumin may provide a better treatment option for BPH patients. The current study has several limitations. First, this prospective study was designed as a single-center study with a relatively small number of patients enrolled and limited clinical data. Second, a follow-up period of 6 months is relatively short when studying a chronic disease. Ideally, a comprehensive evaluation would include assessments at multiple time points throughout the follow-up procedure. Third, a standard dosage of curcumin was used, and future studies should assess different dosages. Fourth, this study was not a randomized controlled trial to study the pharmacokinetic gradients to determine the optimal dose; such trials should be carried out in the future. Furthermore, although this study was designed to explore the effect of curcumin combined with BSM on PPF, serum lipids, leptin, and adiponectin, other adipocytes were not included in this study due to cost consideration.

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