Complementary therapies in the control of male lower urinary tract symptoms: A systematic review

Abstract Objective: to evaluate diverse scientific evidence on the effectiveness of complementary therapies in the control of lower urinary tract symptoms in the adult and aged male population. Method: a systematic review developed according to the PRISMA checklist. The search was performed in the CINAHL, Embase, LILACS, PEDro, PubMed, Web of Science and Google Scholar databases. Results: a total of 585 records were identified and 12 clinical trials were selected that met the inclusion criteria. The outcomes considered by the studies for analyzing effectiveness of the complementary therapies were validated questionnaires to assess the severity of the lower urinary tract symptoms (sensation of incomplete bladder emptying, frequent urination, intermittent flow, weak flow, pain or difficulty urinating, nocturia and urgency) and urodynamics parameters. The studies analyzed the complementary phytotherapy (n=8) and electroacupuncture (n=4) therapies. Six studies related to phytotherapy showed statistical significance. Electroacupuncture showed a significant improvement in the symptoms in two studies. Conclusion: pytotherapy was effective to control the simptoms related to frequency, urgency, nocturia, incomplete emptying, intermittence, weak flow and effort to initiate urination. To confirm the effectiveness of electroacupuncture, research studies with well-designed methodologies will also be necessary to resolve the divergences between the studies of this review.


Selection criteria
The PICO strategy was used to establish the guiding question, in which the letter P refers to the population or

Sample definition and period
By reading the titles and abstracts, studies with samples consisting of mixed populations, children and animals were excluded, as well as original research studies whose design was not clinical trial; publications such as reviews, letters, editorials, protocols and case reports; and records that did not have an online summary available.

Data collection
The web version of EndNoteBasic ® was used to groupe the searches and exclude the duplicates.
Subsequently, all the references underwent a manual screening to extract key information from the studies Selection of the studies was carried out by two researchers, PhD students in Nursing (P1 and P2), independently and in two phases. In the first phase, from the reading of titles and abstracts, those studies potentially eligible for systematic review were identified, considering the inclusion and exclusion criteria defined.
In the second phase, the studies selected were read in full and those that did not meet the inclusion criteria were excluded. The selection divergences between both researchers (P1 and P2) were discussed and, when there was no consensus, they were evaluated by a third researcher, PhD in Nursing (P3), who decided on the inclusion or exclusion of the studies.

Data analysis
The quality evaluation of the studies selected questions with four answer options (yes, no, uncertain or not applied) (18) .
In relation to the categorization of the methodological quality of the clinical trials from the instrument applied, studies that had 70% or more "yes" answers were classified as with low risk of bias, with 50% to 69% of "yes" as with moderate risk, and with 49% or fewer "yes" answers as with high risk.
The risk of bias assessment was performed independently by two researchers (P1 and P2). A third researcher (P3) was considered for evaluating possible divergences.

Results
A total of 585 records were identified in the searches conducted in the databases, among which 96 duplicates were removed. After reading titles and abstracts, 478 records were excluded in the first phase and 11 articles were selected for full reading. In addition to these, the search using other methods resulted in the selection of three articles, and another four articles were selected from the reference lists.
Considering the inclusion and exclusion criteria established, of the 18 articles selected and read in full during the second phase, six were excluded. The final sample consisted of 12 studies that met the selection criteria. The process for identification, inclusion and exclusion of the studies is described in Figure 2.    (20) to 357 participants (31) . The mean age of the participants was 60.7 years old (±5.6). The follow-up time varied from two to 18 months for the phytotherapy clinical trials (±5.1) and from one to three months for electroacupuncture (±4.7).
Four phytotherapy studies evaluated the effectiveness of Saw palmetto (S. palmetto) for controlling LUTS. This herbal medication was compared to placebo at daily doses of 320 mg (19,(21)(22)26) , 640 mg (22) and 960 mg (22) . The 320 mg daily dose, fractionated twice a day, significantly improved (p < 0.001) the I-PSS score after 24 weeks of treatment (26) and showed a mean reduction of 4.4 (±5.9) points in the intervention group, with a significant difference (p = 0.038) when compared to the placebo after six months (19) .
This same dose also reduced 0.68 (±0.35) points in the mean AUASI score of the intervention group, but without a statistically significant difference with the placebo group (95% CI: -0.93 to 1.01) (21) . Higher daily doses of 640 mg and 960 mg reduced 2.20 points (95% CI: -3.04 to -0.36 points) in the mean AUASI score, but an improvement was also observed in the placebo group (22) . None of the evaluated doses of S. palmetto improved the Qmax, PURV and prostate volume urodynamics parameters (19,(21)(22)26) .
In addition, two phytotherapy studies evaluated the effectiveness of using cranberry in LUTS controls (27)(28) .
This herbal medication was compared to placebo at daily doses of 250 mg (28) , 500 mg (28) and 1,500 mg (27) . At the highest dose of 1,500 mg, fractionated in three times a day, there was a significant reduction (p < 0.050) in the I-PSS score of the intervention group, as well as an improvement of the urodynamic parameters, Qmax, Qave and PURV, in 70% of the participants of this group (27) .
In the study that evaluated the 500 mg and 250 mg Regarding the studies that evaluated the effectiveness of electroacupuncture, three included acupuncture points (AcPts) belonging to the bladder meridian (20,25,29) . Point B32, which belongs to this meridian, was the most used AcPt (20,29) . It is noteworthy that, when compared to the conventional medication (Oxybutynin 5 mg) and the placebo tablet, 5 to 10 Hz electrostimulation at the highest tolerated intensity of AcPt B32, promoted LUTS control with a significant improvement of the I-PSS score (p <
Other AcPts of the bladder meridian were B10 and B40 (20) , B21 and B23 (29) and B33 (25) . AcPt B33 was the only one that presented a 3. Another electroacupuncture study evaluated the effectiveness of the AcPts belonging to the different spleen-pancreas (BP6), stomach (E36) and conception vessel (CV3 and CV4) meridians (30) . When stimulated with 3 Hz and intensity of 2 to 2.5 mA, the points of these meridians showed a significant improvement in the Qmax (p = 0.030), Qave (p = 0.026) and bladder emptying volume urodynamics parameters (p = 0.038), when compared to placebo electroacupuncture (30) . However, there was no reduction in the I-PSS score (30) .
The studies included in this review were submitted to methodological quality analysis, based on the Joanna Briggs Institute (JBI) Critical Appraisal Tool -Checklist for randomized clinical trials (18) . In this evaluation, six studies were classified as withlow risk of bias, five of which were on phytotherapy (19,(21)(22)(23)(24) and another one on electroacupuncture (25) .
Three studies were classified as with moderate risk of bias, one on phytotherapy (28) and the other two on Rev. Latino-Am. Enfermagem 2022;30:e3543.
For the analysis of the effectiveness of the CTs, one of the methods adopted considered the subjective evaluation of LUTS. Thus, self-administered and internationally validated questionnaires (31)(32) were used to classify and standardize the recording of LUTS, being an important tool to determine the severity of this involvement (31)(32)(33)(34) .
The following stand out among the questionnaires for LUTS evaluation: AUASI questionnaires of the American Urological Association committee (31) and the I-PSS questionnaire (32) , which refers to an adaptation of AUASI with inclusion of an item that evaluates quality of life by classifying the impact of the discomfort caused by the LUTS on a scale from zero to six (33) . The two instruments assess LUTS severity based on seven questions related to the following: sensation of incomplete bladder emptying, frequent urination, intermittent flow, weak flow, pain or difficulty while urinating, nocturia and urgency (32) . The frequency of each symptom is attributed a score from zero to five, whose sum determines the severity (mild: 0-7 points, moderate: 8-19 points or severe: 20-35 points) (31)(32) .
Another method for LUTS evaluation presented by the studies was based on the urodynamic study. This is an objective test to evaluate the function of the lower urinary tract considered as the gold standard in the clinical practice electroacupuncture (20,30) . The studies were classified as with moderate risk of bias because they did not describe the losses that occurred during the follow-up or the blinding of the research team responsible for analyzing the outcomes (20,28,30) . In the phytotherapy study (28) , the method used to blind the researchers who applied the intervention was not informed. In the electroacupuncture studies, failures were observed in the description of the participants' allocation process (20) , in addition to the absence of double-blinding (20,30) .
High risk of bias was identified in three studies, two on phytotherapy (26)(27) and another one on electroacupuncture (29) . As items of methodological weaknesses we have the incomplete description of the randomization method, the differences between the groups at the beginning of the study, and non-description of the blinding and of the sample losses during followup (26)(27)29) . The results of the risk assessment in the studies included are presented in Figure 4.
context (35) . Among the urodynamic study parameters considered by the studies, the peak rate of urinary flow (Qmax), prostate volume and post-urination residual volume (PURV) predominated. It is emphasized that only one study did not consider the effectiveness of the intervention applied from the urodynamic evaluation (20) .
As for effectiveness of the CTs, nine studies pointed them as an effective alternative for LUTS control in the male population (19,(23)(24)(25)(26)(27)(28)(29)(30) . Phytotherapy stands out, pointed out as one of the most used CTs by the general population (16,36) . Phytotherapy is based on the use of medicinal plants for the treatment of certain symptoms, being a practice widely recognized and disseminated by the World Health Organization (37) . The following herbal medications were analyzed in this review: S. palmetto (19,(21)(22)26) , G. lucidum (23)(24) and cranberry (27)(28) .
Among the four studies that evaluated the effectiveness of S. palmetto (19,(21)(22)26) , half (19,26) concluded that this herbal medication at a dosage of 320 mg a day was effective in controlling LUTS in men. Both studies indicated a statistically significant reduction in the I-PSS scores in the intervention group when compared to the placebo group (19,26) . One of them (26) showed that S. palmetto was also able to improve Qmax, corroborating other studies that also point to an improvement in Qmax, in addition to a reduction in nocturia (12,38) .
S. palmetto, scientific name Serenoa repens, is a herbal medication of the palm family that, due to its anti-inflammatory and anti-androgenic properties, has been commonly used for LUTS control, especially those associated with BPH (39)(40) . Despite diverse evidence favorable to its use, its applicability and effectiveness in the clinical practice are still questioned (15) . In part, the significant variability in the components' concentration and bioavailability, depending on the laboratory responsible for the production of the extract, may justify the difficulty defining its effectiveness (41) . In addition, the absence of standardization of the concentrations makes it difficult to establish comparisons between the clinical trials (42) .
In relation to two studies that did not verify the effectiveness of the S. palmetto herbal medication effective, variables such as the type of extract (21) and the dosage administered (22) can justify the results obtained.
There is more than one type of S. palmetto extract, and the forms of ethanolic and hexane extraction present greater clinical effectiveness of the compound (42) . In this context, it is emphasized that one of the studies (21) adopted the carbon dioxide extract, whose effectiveness is lower (42) . None of the other studies specified the type of S. palmetto extract evaluated (19,22,26) .
Regarding dosage of the S. palmetto herbal medication, one of the studies included (22) concluded that S. palmetto was not superior to placebo. This clinical trial (22) evaluated the effectiveness of S. palmetto at staggered doses of 320 mg, 640 mg and 960 mg a day, that is, it considered the double and triple of the dose used in the other studies (19,21,26) . Thus, considering the discrepancy between the dosages established, a number of precautions are suggested for the interpretation of the results and the relevance of future studies.
G. lucidum, the herbal medication of choice in another two studies of this review (23)(24) , consists of a type of mushroom that is well-known in Asian countries, with triterpenes and polysaccharides as its outstanding bioactive components (43)(44) . Although the mechanisms that justify its antitumor, antioxidant and antibacterial effects are not completely elucidated (44) , the satisfactory results presented by the studies included (23)(24) are noteworthy, in which there was a significant improvement in the I-PSS scores in the intervention group. Thus, the diverse evidence (23)(24) suggests effectiveness of G. lucidum at a dosage of 6 mg a day for LUTS control in men.
This review also includes two studies (27-28) that analyzed cranberry, scientific name Vaccinium spp., a fruit widely consumed in North American countries to control lower urinary tract infections (45) . The cranberry powder analyzed in both studies was provided by the same laboratory, which favors comparison of the results.
At dosages of 250 mg (28) and 1,500 mg a day (27) , this herbal medication significantly reduced the I-PSS score in the intervention group (27)(28) . However, considering the urodynamic evaluation, more effective results were better at higher dosages, for example, 1,500 mg a day (27) . It is suggested that the sialic acid found in cranberry extract has anti-inflammatory and analgesic effects, especially by the ability to decrease adhesion of microorganisms in the bladder wall (45) .
Electroacupuncture was another CT evaluated in four clinical trials of this review (20,25,(29)(30) . The therapeutic effects of acupuncture are obtained from activation of the energy flow or Qi, through the insertion of needles in certain AcPts with the objective of restoring homeostatic balance (46) .
In this context, electroacupuncture represents an acupuncture variation in which an electric current is applied to the needles seeking to accentuate and enhance the therapeutic effects (47) . The flow of electric current through a biological conductive medium triggers physiological effects, involving electrochemical, electrophysical and electrothermal phenomena. Stimulatory frequency stands out among the most relevant and studied physical parameters in electroacupuncture, especially its relationship with the release of endogenous opioids in analgesic and anti-inflammatory processes (48) .
Due to the blinding difficulty of the clinical studies in this area (47) , it is believed that this fact may justify the uniblind design of the four studies that evaluated the effect of this therapy (20,25,(29)(30) .
As for the AcPts used in electroacupuncture, the majority included at least one point referring to the bladder meridian (20,25,29) , with emphasis on AcPt B32 (Ciliao) (20,29) . Recent studies have identified significant results for the treatment of BPH symptoms in men (49) and overactive bladder (OB) symptoms in rats based on AcPt B32 stimulation (50) . It is known that AcPt B32 is one of the four points located in the four sacral foramina, being considered the most important because it has broad indications (voiding dysfunctions, dysmenorrhea, low back pain and sciatica and infertility) and is one of the points that produces the greatest tonifying effect of the Kidney and Essence (51) .

Only one study included in this review chose to
use AcPts from other meridians that do not match the bladder's (30) , namely: spleen-pancreas (BP6 -Sanyinjiao),

stomach (E36 -Zusanli) and conception vessels (CV3 -
Zhongji; CV4 -Guanyuan). A study conducted in rats with overactive bladders evidenced that point B33 (Zhongliao) presented a superior effect to points BP6 (Sanyinjiao) and B40 (Weizhong) with regard to the increase in the interval between the contractions (52) . Therefore, it is suggested that this fact may justify the predominance of protocols that adopt AcPts associated with the bladder meridian when compared to the others.
Regarding the heterogeneity of the inclusion criteria established by the studies, among the phytotherapy clinical trials, three considered I-PSS or AUASI scores above eight for inclusion of the participants (19,21,28) , two defined a maximum score of 19 in the I-PSS score (24,26) , one defined a maximum limit of 24 points in the AUASI score (22) , and another study considered a minimum score of five in the I-PSS score (23) . Only one study (27) did not consider the score in the LUTS assessment questionnaires to define the sample.
In addition, two phytotherapy clinical trials used the AUASI and I-PSS scores to define the BPH diagnosis among their participants (21,26) and the majority only considered the participation of men without prostate surgical history (19,(21)(22)(23)(24)28) . This heterogeneity to define the LUTS underlying cause and severity can influence Three studies considered men with I-PSS scores above eight points (20,25,30) and one study did not consider any score for sample definition (29) . In relation to the underlying cause for the LUTS, two studies included men with BPH in their samples, one study defined the diagnosis based on the I-PSS score (25) , and another made the diagnosis from a transrectal ultrasound exam (30) . In addition to that, one of the electroacupuncture studies included men who have already undergone transurethral resection of the prostate (29) , while another study (30) had a sample with only men with no prostate surgical history. As for the perspectives of including these therapies in Nursing care, it is known that the Nursing Interventions Classification (NIC) includes the "phytotherapy" (2420) and "cutaneous stimulation" (1340) interventions (53) .
Nurses are prominent professionals in the implementation and use of several CTs, as the principles of their training are similar to the paradigms of the medical rationalities that involve Integrative Medicine. However, the number of these professionals who work with these therapies or who have the knowledge to prescribe and refer users to this type of care is still reduced. There is a movement, albeit incipient, of nurses who seek specialization courses in this area, which contributes to the dissemination of these therapies to the community, with the consequent improvement of Nursing care (54) .  In general, it is known that CTs are minimally invasive, which implies a lower risk of sequelae when compared to surgical procedures, in addition to having few reports of adverse events, unlike medications.