Use of radiofrequency for the treatment of urinary incontinence in women: a systematic review

INTRODUCTION Urinary incontinence (UI) is defined as involuntary loss of urine1, affecting 25–45% of women, depending on the population2. Its classification is based on the pathophysiology and clinical condition of the patient, with the most common being urgency (UUI), stress (SUI), and mixed (IUM). The SUI is characterized by the involuntary loss of urine due to a cough or physical exertion3. The etiology is multifactorial, which may be related to inadequate support and/or weakening of the pelvic floor muscles (PFM), deficiency in the closing mechanism of the urethral meatus, and reduction of collagen synthesis in the pelvic structures4,5. The dysfunction has social and psychological impacts, especially on the well-being of the individual. The main risk factors are age, obesity, menopause, pregnancy, parity, and type of delivery2. The treatment varies and depends on the classification of incontinence, the patients’ perception of symptoms, and their daily life habits6. According to the literature7,8, surgical techniques, drug therapy, and conservative treatments, such as PFM exercises and electrical stimulation, have been shown to improve UI symptoms. Currently, the search for alternatives and safe treatment methods with high cure rates are the targets of research to avoid surgical interventions. Radiofrequency (RF) therapy has been studied as a possible therapeutic modality for SUI, in addition to its increasing clinical use as a non-surgical and non-pharmacological treatment9. RF is a minimally invasive procedure involving the application of alternating current that creates electrical fields and generates heat by conversion only in the treatment area. Its frequency can vary from 30 kHz to 300 MHz, and the energy emission mode depends on the number of electrodes, which can be monopolar, bipolar, tripolar, or multipolar10. RF can be used to treat SUI and MUI as it promotes submucosal collagen denaturation in the bladder neck and throughout the lower urinary tract, causing tissue retraction in these structures. Therefore, urinary symptoms are expected to be minimized as they are related to the pathophysiology of these types of incontinence8. The search for treatment options that are quick to apply, less invasive, safe, and with fewer adverse effects has been growing rapidly, and this therapeutic modality is a good treatment option. Thus, this review highlights the effectiveness and complications of RF therapy for the treatment of UI in women.


INTRODUCTION
Urinary incontinence (UI) is defined as involuntary loss of urine 1 , affecting 25-45% of women, depending on the population 2 . Its classification is based on the pathophysiology and clinical condition of the patient, with the most common being urgency (UUI), stress (SUI), and mixed (IUM).
The SUI is characterized by the involuntary loss of urine due to a cough or physical exertion 3 . The etiology is multifactorial, which may be related to inadequate support and/or weakening of the pelvic floor muscles (PFM), deficiency in the closing mechanism of the urethral meatus, and reduction of collagen synthesis in the pelvic structures 4,5 . The dysfunction has social and psychological impacts, especially on the well-being of the individual. The main risk factors are age, obesity, menopause, pregnancy, parity, and type of delivery 2 .
The treatment varies and depends on the classification of incontinence, the patients' perception of symptoms, and their daily life habits 6 . According to the literature 7,8 , surgical techniques, drug therapy, and conservative treatments, such as PFM exercises and electrical stimulation, have been shown to improve UI symptoms. Currently, the search for alternatives and safe treatment methods with high cure rates are the targets of research to avoid surgical interventions. Radiofrequency (RF) therapy has been studied as a possible therapeutic modality for SUI, in addition to its increasing clinical use as a non-surgical and non-pharmacological treatment 9 .
RF is a minimally invasive procedure involving the application of alternating current that creates electrical fields and generates heat by conversion only in the treatment area. Its frequency can vary from 30 kHz to 300 MHz, and the energy emission mode depends on the number of electrodes, which can be monopolar, bipolar, tripolar, or multipolar 10 . RF can be used to treat SUI and MUI as it promotes submucosal collagen denaturation in the bladder neck and throughout the lower urinary tract, causing tissue retraction in these structures. Therefore, urinary symptoms are expected to be minimized as they are related to the pathophysiology of these types of incontinence 8 .
The search for treatment options that are quick to apply, less invasive, safe, and with fewer adverse effects has been growing rapidly, and this therapeutic modality is a good treatment option. Thus, this review highlights the effectiveness and complications of RF therapy for the treatment of UI in women.

METHODS
This systematic review was conducted from June 2020 to May 2021 by searching articles on the Web of Science, Lilacs, Scielo, PubMed, Cochrane, Pedro, Embase, Science Direct, CINAHL, and Scopus platforms. The following descriptors were used by combination: ["Woman" OR "Women"] AND ["Urinary Incontinence" OR "Urge urinary incontinence" OR "Stress Urinary incontinence"] AND ["Radiofrequency" OR "Radio Waves" OR "Pulsed Radiofrequency Treatment" OR "Radiofrequency Ablation" OR "Radiofrequency Therapy"].
The study population was composed of women with UI using any type of RF as an intervention, and there may be divergences between the studies related to cost and time of application. Regarding the comparison of treatments, there were no limitations, and the various treatments included no treatment, placebo, vaginal estrogen, or pelvic floor muscle training (TMAP).
The main outcome was the volume of urinary loss measured using the Pad test. Secondary outcomes were urinary loss measured by voiding diary and impact of UI on quality of life, which were assessed using validated International Continence Society questionnaires. Non-urinary variables, such as alterations related to the vaginal epithelium, vaginal dryness, and sexual function were also considered as secondary outcomes. The systematic review was conducted by two authors to select and evaluate the studies and by another to analyze the differences. The kappa test was performed to analyze the inter-rater agreement.
The following were included: clinical trials regardless of randomization and blinding and prospective studies conducted between 2016 and 2021, without language limitations. The exclusion criteria were as follows: studies with less than 3 months of intervention/follow-up; gray literature; animal and cytological studies; articles whose main objective was to evaluate the use of other types of energy for the treatment of UI; and articles aimed at rejuvenating vaginal, fecal incontinence, vaginal atrophy, and other urinary tract diseases.
The PARSIFAL platform was used to verify duplicate studies and the Mixed Methods Appraisal Tool (MMAT) in the 2011 version to assess the methodological quality of the articles.

RESULTS
A total of 279 articles were identified, of which 70 were duplicates and 181 were excluded after consideration by title and abstract. Six studies (n=247 women) were selected for final analysis ( Figure 1). The inter-rater kappa test showed an agreement of 76% (κ=0.76; p<0.001).

Radiofrequency procedure
The studies diverged regarding the devices, parameters, temperature, form of application, and number of sessions. It was observed that the monopolar RF 11,12 and non-ablative 13,14 RF were the most used. Two studies 11,12 used the Viveve system protocol (220 pulses of 90 J/cm² in the vaginal introitus). An article 13 used Spectra G2 Tonederm ® , which applies a high frequency of 0.5 MHz. In the study using the Votiva device 15 , the parameters were adjusted according to the conditions of the volunteers. An article 14 used the ThermiVa device without specifying the parameters. Another 16 configured the device at 45 W and 4 MHz to supply power to 64 microneedles, 0.2 mm in length, allocated in an area of 8 mm × 8 mm. Of the studies that specified the temperature, it ranged between 39-45°C [13][14][15] .
Two studies 11,12 divided the treatment area into quadrants of the vaginal opening, with each quadrant having five consecutive pulse passages. One study applied RF to the external urethral meatus 13 , two 14,15 applied in the vaginal canal and labia majora, and one 17 in the urethral meatus and vaginal wall.
Regarding treatment sessions, two studies 11,12 used one session for group I and two for group II, with an interval of 6 weeks; one study 13 described a weekly application for 5 weeks; one study 15 did not specify; and two others 14,16 performed treatment every 30 days for three months. All studies performed follow-ups, ranging from 1 to 12 months [11][12][13][14][15][16] . These and other detailed information from the articles are shown in Table 1.

Primary outcomes
The volume of urinary loss was analyzed using the Pad test as the primary outcome [11][12][13]16 . Allan et al. 11 showed in their 6-month study that the leakage volumes of the absorbent weight were similar between the randomized groups at the final assessment. The authors reported that 69% of the overall sample achieved a >50% improvement in pad weight. In the second study 12 , with a 12-month follow-up, there was a difference between the randomized groups in relation to the weight loss of the pad, which was >50%. The group that received the two interventions showed a 54% improvement. In the group that received only one intervention, the evolution rate was 50%.
The study by Lordelo et al. 13 evaluated the individual evolution of each patient with a 1-h Pad test for three months. It was observed that 70% of the patients had a reduction in UI, 20% did not complain of additional loss, and 30% showed worsening of the additional loss.  In contrast, another study 16 found that the 1-h Pad test had a mean significant decrease of 7.22 g after treatment in all groups (p<0.001) but no differences between them (p=0.987). However, the authors did not justify why the results were similar.
In their first study, Allan et al. 11 reported an 80% decrease in leakage episodes in both groups according to the 7-day voiding diary. A sustained improvement was observed for 6 months in relation to the subjective measures, based on the UDI-6, IIQ-7, and ICIQ-UI-SF questionnaires, compared to the initial assessment. In a second study 12 , 64% of randomized subjects reported fewer episodes of leakage compared to that at the baseline. They also showed a decrease in UI symptoms and an improvement in quality of life through the UDI-6 and ICIQ-UI-SF questionnaires.
Regarding the use of questionnaires, Slong et al. 16 observed that there was a significant improvement between the groups in the evaluation of the ICIQ-UI-SF, highlighting a better result in the RF group with TMAP, which evolved from 13.6±3.8-8.2±5.2.
In Caruth's study 15 , there was an improvement in the impact of UI (62.7%) and quality of life (64.6%) in the 2-month evaluation using the IIQ-7 and ICIQ-UI-SF. Leibaschoff et al. 14 observed a significant difference between the control (17.3±0.78) and active (11.4±0.66) groups in relation to the ICIQ-UI-SF. The UDI-6 also showed an improvement between groups (33.7±12.5 versus 16.2±6.0).
The so-called non-urinary outcomes considered the effects of RF in relation to changes related to the vaginal epithelium, vaginal dryness, and sexual function. However, not all studies evaluated these parameters, but those that covered these variables used the vaginal health index (VHI) 14,16 and ICIQ Vaginal Symptoms Questionnaire (ICIQ-VS) 15,16 . Some studies included the impact of pelvic organ prolapse and the impact of anorectal and urinary symptoms on patients' quality of life, using the Pelvic Floor Impact Questionnaire (PFIQ-7) 15 .
To assess vaginal and sexual symptoms and quality of life, Leibaschoff et al. 14 showed differences between the control group and the active group. There was a significant improvement in the active treatment group, from 11.5±0.67-19.3±2.01, relative to VHI.
An author 15 observed an improvement of 50.6% for vaginal symptoms, 72.1% for sexual issues, and 61.2% for pelvic floor impact on reassessment after 2 months of intervention in the ICIQ-VS and PFIQ-7 assessments. Other authors 16 also found improvement in the ICIQ-VS after treatment in all groups, with the greatest improvement in the RF group (-9), followed by the RF+TMAP (-4.4) and TMAP groups (-3.4). The same authors also found improvement in vaginal moisture, fluid volume, vaginal pH, and elasticity only in the RF and RF+TMAP groups but with no difference between them. It was also observed that the epithelial integrity improved in all groups and vaginal dryness improved in the RF group. In terms of VHI, the RF+TMAP (+3.2) and RF (+2.9) groups were superior to the TMAP group (+0.5). Regarding flaccidity, there was no significant difference between the groups.

Adverse effects
No serious or unexpected adverse effects were observed [11][12][13][14][15][16] . Lordelo et al. 13 reported the presence of burning soon after the menstrual period in one patient; however, the physical examination did not show any change. Slongo et al. 16 described that a participant in the RF group had mild vaginal burns with spontaneous improvement and mild dyspareunia after three months.

DISCUSSION
UI is a public health problem, with varied treatments. Of these, surgical treatment is an option, which may be associated with complications and recurrences 17 . Other therapies can be recommended according to the nature and intensity of the UI, such as TMAP, which is a conservative treatment option 18 . The growing search for safe, non-invasive, and effective alternatives has become increasingly popular, emphasized review studies like this. RF therapy has been widely used to treat dermatological and gynecological conditions. The microablative fractional-type RF, which is used to improve skin, vaginal, and vulvar mucosal trophism 19 , results in promising responses in neocollagenesis and neoelastinogenesis 20,21 , consequently leading to clinical improvement. Thus, it is observed that this therapy provides a less invasive treatment for women with SUI and MUI [11][12][13][14][15][16] .
The importance of objective data evaluations is known, and thus, more accurate and coherent results can be obtained with the research. However, only four studies used the 1-h pad test to measure urine volume. Regarding secondary outcomes, two studies 13,16 evaluated PFM through digital palpation quantified by the modified Oxford scale. Another study 14 performed the cytological analysis through a biopsy. Other studies 11,12,15 performed the evaluation using questionnaires.
Importantly, the main objective of this review was to evaluate the application of RF in relation to urine loss and not factors related to intimate esthetics and sexuality. All studies addressed patients diagnosed with SUI, and only one 17 included MUI in the sample.
Only two 12,16 studies showed a longer period of intervention. It is believed that a short period of intervention may not be able to assess the expected changes in neocollagenesis and neoelastinogenesis 20,21 and thus may not provide reliable results. Regarding sampling, most studies 11-15 recruited a small number of volunteers, and only one had more than 100 patients in the sample 16 .
This review had some limitations. The studies that were included had low strength, lack of blinding, short post-intervention follow-up, and lack of clear description of randomization. Despite these limitations, it was observed that RF is an alternative therapy, proving to be effective and safe for the issues evaluated, which, according to the studies, is an alternative for the conservative management of patients with SUI.

CONCLUSIONS
The studies included in this review showed significant results of RF to resolve or minimize the complaints of women with SUI; however, according to the MMAT, the methodological quality of the studies was low. Therefore, more randomized, controlled, and blinded clinical trials are needed to provide safe therapy.