We found an improvement in genitourinary signs and symptoms in this pilot study that used non-ablative RF in postmenopausal women with GSM. The application of RF was considered safe because only one adverse effect in one patient was found up to three months after treatment. To our knowledge, this is the first study to assess genitourinary symptoms and sexual function of the GSM associated with cytological analysis, and patient satisfaction after using non-drug and non-ablative treatment with intracavitary monopolar RF.
Vaginal dryness was the main symptom reported by patients in this study and showed an important improvement when assessed both by self-report and by VHI. Based on the histological changes evidenced in previous studies, the process of neocolagenesis and neoelastogenesis that occurs after the exposure of controlled RF thermal energy in the vaginal tissue restores most vaginal functions such as secretion, absorption, elasticity, lubrication, and tissue consistency, which are decreased in GSM 9,15,16. This hypothesis is supported by previous knowledge that this high-frequency current induces collisions and movements between atoms and molecules, resulting in energy transfer to the tissue in the form of heat and a consequent controlled increase in temperature, promoting an increase in the arterial circulation, and vasodilation, improving tissue oxygenation17.
VD can generate or contribute to SAPain just as abstinence from intimate relationships is involved in the decline of lubrication, often forming a cycle. Vaginal trophism is fundamental for a comfortable sexual relationship, which depends on the lubrication promoted by vasodilation of the lamina propria and the vaginal epithelium (18,19). We observed in this study that a patient who did not have dyspareunia in the pre-treatment started to report this symptom in the third month. An assumption is that the increase in the frequency of sexual activity may favor the appearance of this symptom. To confirm this hypothesis, we must include the investigation of sexual frequency before and after treatment. We are developing a randomized clinical trial where this variable has been included and, therefore, soon we may have this information. The increase in sensory perception by neurogenesis can occur after using RF (16), which can lead to a greater perception of the vagina and, therefore, some patients may start to report these symptoms. However, further morphometric investigations for neuronal analysis are necessary.
Other studies have also found positive results in dyspareunia. Alinsod (2015) studied RF with controlled temperature (TTCRF) with intra and extra vaginal application in six menopausal women and 10 in the peri-menopausal period with dyspareunia symptoms, demonstrating the safety and beneficial effects of the treatment (20). A randomized clinical trial with 20 postmenopausal women applied three sessions of intra and extra vaginal TTCRF (ThermiVa) once a month with reduced RV and dyspareunia (21).
RF has also been widely used to improve collagen levels. Its diathermic effects cause the denaturation of collagen. As the temperature rises, some of the cross-links are broken, causing the structure of the triple helix to unwind. Thus, there is a consequent activation of fibroblasts, with subsequent neocolagenesis, neoelastogenesis, and tissue remodeling (22). Coad et al. (2013) evaluated the histological effect of non-ablative RF on the vaginal introitus of sheep before, after seven, thirty, and ninety days. There was a significant increase in the activation of the submucosa fibroblasts and an increase in collagen when to the control group (23). In our study, we used NRS to grade vaginal laxity and all patients improved this complaint. Three patients who did not have the complaint initially, reported mild intensity in the reassessments, which can also be justified by the increase in sensory perception after treatment. Assessing the symptoms of GSM is challenging, due to its subjective nature. The development of a specific score with a cut-off point for the quantification of these symptoms and clinical improvement may be of great relevance to better evaluate these patients and verify the treatment effect.
Previous studies have obtained positive results with the use of monopolar RF with cryogenic surface cooling in pre-menopausal women with a history of at least one vaginal delivery and complaints of vulvovaginal atrophy/symptoms of GSM or vaginal laxity (22,24). Alinsod (2015) used the TTCRF in 23 pre-menopausal women with VL, with improvement on a seven-point scale, called the vaginal laxity questionnaire (VLQ) (25). Krychman et al. (2017) carried out a multicenter study with 189 premenopausal women complaining of VL during sexual intercourse with significant improvements in self-report and sexual function by FSFI (24).
Symptoms such as itching, burning, and pain are also common complaints in GSM. Hypoestrogenia is a reduced number of epithelial layers and vessels, thinning of smooth muscles (26), and an increase in nociceptive sensory afferents (27), leading to these symptoms. Also, the increase in tissue friction caused by the decrease in trophism and hydration causes greater mucosal fragility, contributing even more to the condition (18,28). In this study, there was an important improvement in these symptoms. This clinical improvement can be supported by the thermal effect of RF, which deeply affects the tissue layers. As a consequence of local peripheral vasodilation and increased blood flow, there is an improvement in trophism, oxygenation, cellular metabolism, and lubrication (10,29). High-frequency thermal therapy seems to act through the effects of analgesia, but the mechanisms by which RF controls pain are still unclear, seeming to involve the transduction of C fiber signals (30).
The analysis of vaginal cytology through the Vaginal Maturation Index (VMI) and the measurement of pH are well-used measures to establish diagnostic parameters of GSM (31,32) but have not yet been analyzed in RF research in GSM. Brizzolara et al. (1999) carried out a study in 70 postmenopausal women determining a specific vaginal pH range that correlates with high levels of parabasal cells in the VMI, defined as at least 20%, and found a correlation between these two objective measures (33). We also found in this study that pH values ≥ 6.0 were compatible with a greater number of parabasal cells (≥ 20%). On the other hand, these results showed that there is no pattern of clinical/objective findings with the symptoms reported by the patients. VMI and pH, unlike NRS, remained similar in most patients (six − 54.6% and seven − 63.3%, respectively) in the first month after treatment. In the third month after treatment, most patients (six − 54.6%) had an improvement in VMI and four (36.4%) had an improvement in pH. Vaginal cytology, in part, has been inconsistent with clinical findings (31). A smaller-scale and more sensitive tape is recommended to detect minor variations.
GSM can have adverse effects on sexual function and general well-being. FSFI is an instrument used worldwide to assess sexual function. In this study, it had improved in most of the sample (81.8%) in the first month and the third month (72.7%). We also evaluated the patients in our study with the QS-F. It is a questionnaire specifically developed for the Brazilian population (34).
In terms of the total score, we observed an increase in the QS-F in most of the participants.
The promising results stimulated our group to carry out an RCT of RF in the treatment of signs and symptoms of GSM that is in progress. This type of study is encouraged by the European Society of Sexual Medicine (35). Using the non-ablative RF technique, Lordelo et al. (2016) carried out a randomized clinical trial with 43 women dissatisfied with the appearance of their genitalia. They applied RF to the external genitalia, with an improvement in sexual function by 3.51 points in the group treated in the evaluation by FSFI (11).
RF has been considered one of the most innovative non-surgical modalities to treat urinary incontinence (UI) and VL (36). In addition to modifying the trophism of the vaginal canal, it also targets the urethral mucosa and seems to improve not only the symptoms of GSM but also those of UI. In our study, 66.7% and 83.8% improved urinary symptoms, one and three months after treatment, respectively. Lalji & Lozanova (2017) in a pilot study carried out three treatment sessions with monopolar RF, intra, and extra cavitary, in 27 women with stress urinary incontinence (SUI). They found that 96.3% decreased the frequency of urinary loss by at least one level, 59.3% reported a decrease in the amount of loss (37). Another study with 10 patients with SUI showed improvement in the pad test one month after treatment with monopolar non-ablative RF in the urethral meatus (38). Despite different outcome measures and application forms, radiofrequency therapy appears to be a good alternative for the treatment of SUI. Histological studies have observed a reduction in collagen in the walls of the urethra in the event of loss of urethral support and/or internal sphincter dysfunction (39), which supports the use of RF in this dysfunction.
Treatment satisfaction was assessed in this study by the five-point Likert Scale, with most patients reporting satisfaction with treatment. This was reinforced by the decrease in the symptoms recorded in that research. On the other hand, we observed that, although most of the outcome measures have improved, the indication of patient satisfaction was greater, showing that the degrees of satisfaction do not always correspond to the results. Thus, satisfaction is not only linked to the therapeutic result but possibly also to the level of expectations of the people involved. It is important to consider the Hawthorne effect, which says that when individuals believe they are experiencing a form of treatment, they are more likely to respond and be satisfied with therapeutic responses (40). In this sense, we also justified to carry out a randomized clinical trial to better assess this issue.
Although part of the patients continued to show improvement in their symptoms in the third month, some symptoms were accentuated in that period. Studying the frequency of reapplication after the end of treatment to maintain clinical improvement is essential in future studies.