The efficacy and safety of a combined multipolar radiofrequency with pulsed electromagnetic field technology for the treatment of vaginal laxity: a double-blinded, randomized, sham-controlled trial

Vaginal introital laxity is a common consequences of pregnancy, vaginal childbirth, and connective tissue changing due to aging [1, 2]. However, this condition is frequently underreported due to embarrassment and lack of recognition [3, 4]. Vaginal laxity (VL) may result in loss of physical and sexual sensation during intercourse leading to a negative impact on female sexual function, self-image, and quality of life [5‐8].

Many treatment modalities for VL exist ranging from Kegel exercises and electrical stimulation to promote perineal muscle strength, pharmacological therapy to surgical and non-surgical procedures [9‐13]. Surgical options can be performed to improve vaginal introitus tightness but are associated with pain, significant risks, and post-operative downtime [11, 12]. The use of non-invasive, energy-based devices including radiofrequency (RF) and lasers as a non-surgical option for treatment of vaginal laxity (VL), vulvovaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM), orgasmic dysfunction, and stress urinary incontinence (SUI) has recently gained popularity. Both laser and RF treatments induce neocollagenesis, neoelastogenesis, and neovascularization in the submucosa which may contribute to improved tightness of the vaginal canal and may also improve sensitivity of vulvovaginal tissues. The mechanism is believed to be secondary to activation of heat shock proteins and triggering of the inflammatory and proliferative cascade [13‐16].

Unlike lasers, which involve selective photothermolysis of specific chromophores causing ablation and thermal coagulation of tissue, RF produces an electromagnetic wave that generates heat through tissue impedance in the vaginal tissue without disruption of the epidermal-dermal barrier. Based on their number of electrodes, non-invasive RF devices can be categorized as monopolar, bipolar, tripolar, quadripolar, and multipolar (with or without cooling systems) [13‐16]. In the same device, RF can be combined with pulsed electromagnetic fields (PEMF) which has been used for non-ablative skin tightening, facial rejuvenation, and treatment of cellulite and striae [17‐20]. PEMFs are induced by short pulses of electrical current that penetrates into the tissue and results in non-thermal stimulation of molecular and cellular activities. PEMF increases collagen production by dermal fibroblasts, stimulates growth factor synthesis, and angiogenesis, leading to its wound-healing effects [18, 21, 22].

The primary objective of this study was to evaluate the efficacy and safety of a combined multipolar RF with PEMF device for the treatment of VL. The secondary objective was to determine the treatment satisfaction, pelvic floor muscle strength, and sexual function in both groups.

All of the 32 enrolled female subjects completed the study protocol and were included in the safety and efficacy analysis. Baseline characteristics are shown in Table 1.

Therapeutic options for vaginal laxity range from conservative pelvic floor muscle (Kegel) exercises and topical and systemic hormone replacement to non-invasive energy-based devices and surgical procedures [9‐11]. Three non-surgical energy-based therapies have been developed for vulvovaginal rejuvenation: fractional CO2 laser, erbium:YAG laser, and RF. Each modality utilizes different mechanisms to penetrate and stimulate the vulvovaginal tissue. Non-ablative RF and microablative fractional laser treatments have recently gained popularity because of the minimal downtime, decreased risks, and side effects compared with invasive surgical modalities; however, well-designed, randomized controlled studies to confirm the safety and efficacy of these devices are lacking [13‐16]. Currently, no device has been Food and Drug Administration (FDA) or European Medicines Agency (EMA) approved for the indication of treatment of VL or other genitourinary indications [29].

Radiofrequency are electromagnetic waves that generate heat upon meeting tissue impedance causing thermal injury of the tissue which activates micro-remodeling through heat shock protein cascades to stimulate connective tissue restoration with subsequent tissue tightening. RF devices have therapeutic applications in various aesthetic indications including facial rejuvenation, skin tightening, body contouring, cellulite, and non-invasive fat removal [24, 31‐33]. Recently, RF has been used for vaginal rejuvenation; vaginal tightening; and in many other female genitourinary complaints such as stress urinary incontinence, genitourinary syndrome of menopause, and female sexual dysfunction [12‐16, 23, 24, 30]. The principle of non-ablative RF treatment to improve VL is to induce heat in the vaginal wall to temperatures of 40 to 45 °C leading to fibroblast stimulation, collagen contraction, neocollagenesis, elastogenesis, vascularization, and growth factor production which play a role in restoring vaginal elasticity and increasing the moisture of vaginal mucosa. [13‐16, 24]

This study is the first randomized, sham-controlled study to evaluate the efficacy and safety of a combination multipolar RF + PEMF therapy for the treatment of VL. Following 3 treatments results showed statistically significant improvements of self-reported vaginal laxity (VLQ), contraction pressure of the pelvic floor muscle, and overall sexual function (FSFI) with mild adverse effects. To the best of our knowledge, this is the second randomized, sham-controlled trial evaluating the effectiveness of RF treatment of VL in premenopausal women.

Significant improvements in the mean VLQ scores were achieved after RF + PEMF therapy compared to baseline (percentage improvement of 128% and 134% at 4- and 12-weeks post-treatments respectively) which were significantly greater than sham scores at both visits. Fifty percent of subjects in the active group reported no laxity (VLQ score > 4) at the second follow-up compared to 12% in the sham group, although this did not reach statistical significance between groups. Nonetheless, all subjects that still reported laxity post-active treatments showed at least some degree of VLQ improvement over baseline, whereas 8 subjects (50%) in the sham group showed no improvement. These results are similar to the findings in a previous sham-controlled study evaluating a surface-cooled monopolar RF device for VL in premenopausal women. Six months after one RF session, 43.5% of subjects reported no laxity compared to 19.6% receiving sham [24].

The study outcomes obtained by objective perineometer and Brink assessments of voluntary pelvic muscle contractions verified the patients’ self VLQ assessments. Maximum and mean contraction pressure of pelvic floor muscle contractions at both follow-up visits were significantly better in the active group compared to sham, and improvements over baseline were also significantly increased only in the active arm. Digital palpation Brink score assessment has been shown to correlate with perineometer measurements of pelvic floor muscle strength [27, 34]. Perineometer measurements in this study also confirmed the Brink assessments performed by a blinded nurse in which the active group achieved a 25% reduction in the number of weak score range and almost 20% increase in the very strong score range over baseline at 12 weeks post-treatment, while the sham group demonstrated no change in the percentage of subjects with weak scores after treatment and only slight 6.25% improvement in the strong scores.

Although this study was not designed to assess the effects of the device to treat female sexual dysfunction, it is probable that the improvement of VL and new nerve formation resulting from combination of RF heat and PEMF could positively impact subjects’ sexual function. Score results for the combined FSFI domains showed significantly greater FSFI improvements after RF + PEMF compared to the sham group. However, there was also a smaller, but statistically significant, FSFI improvement from baseline that occurred in the sham group, which could be attributed to a possible placebo effect. Placebos have been shown to improve outcomes, and placebo effects have been established in studies investigating treatment for female sexual dysfunction [35‐38]. Previously, the sham effect has been noted in RF treatment on sexual function in women with VL, arising as a short-lasting effect which was unexpectedly high at 30% and 33% at 1 and 3 months post-intervention, respectively [24]. This emphasizes the strengths of this study which included a comparative sham group to substantiate that treatment outcomes are attributed to the active RF + PEMF intervention rather than to biases related to patients’ or investigators’ expectations of therapy. Despite the significant improvement of FSFI scores over baseline in this study, further studies enrolling women with VL and a baseline FSFI total score ≤ 26.5 indicating sexual dysfunction are potentially needed to establish the impact of RF + PEMF on sexual function.

The positive results from this study established in the active group over sham therapy support the proposed mechanism of action and safety profile of combined RF with PEMF delivery to the vaginal tissue. The RF induces the generation of bulk heat to 40–45 °C without tissue damage enhancing the structural integrity of mucosal squamous epithelial, while tightening the connective tissue in lamina propria and stimulating fibroblasts to produce new collagens and elastic fibers as was histologically confirmed in this study. To our knowledge, this study is the second to confirm the histologic changes in human vaginal tissue after RF treatment. The previous histology study performed in five females with VL who underwent pre- and post-treatment biopsies of the labia majora and vaginal canal 60 days after 3 transcutaneous temperature-controlled RF (TTCRF) treatments at 4-week intervals demonstrated post-TTCRF neocollagenesis, neoelastogenesis, and neoangiogenesis and was the first to report TTCRF-related neurogenesis [39]. Additionally, the nonrandomized vaginal TTCRF treatments resulted in significant improvements in vulvovaginal laxity, atrophic vaginitis, and sexual satisfaction. The authors proposed that improvements in orgasmic function and sexual satisfaction could be explained by the theory of thermal neurogenesis, in which repeated heat stimulation may induce neurite outgrowth [40].

PEMF also helps in increasing collagen synthesis by altering nitric oxide (NO) metabolism, which can induce an anti-inflammatory response via increased lymph and blood flow. NO also regulates cyclic guanosine monophosphate (cGMP) production which stimulate the release of relevant growth factors including fibroblast growth factor-2 (FGF-2), tumor necrosis factor alpha (TNFα) for collagen synthesis, vascular endothelial growth factor (VEGF) for angiogenesis, and transforming growth factor beta (TGF-β) for tissue remodeling [18, 21, 22, 31]. These underlying architectural modifications may improve the underlying structures including the vaginal canal and the circumferential of clitoral complex, hence enhancing genital arousal and potentially improved sexual function as observed in the FSFI score improvement in this study. In addition, the improvement in our patients’ sexual satisfaction might be explained by the aforementioned temperature-controlled repeated thermal stimulation from RF which has been shown to promote restoration of the nervous system and induce the new nerve formation [39, 40]. Additionally, a study of the regulation of neuritogenesis by a pulsed electromagnetic field suggests that PEMF stimulation independently induced neuronal repair [41]. Thus, simultaneous treatment with combination RF + PEMF in this device may have synergistic effects not only on tissue remodeling, neocollagenesis, and angiogenesis but also on neurite formation which may further benefit in female sexual function. Interestingly, a clinical study on the effects of repetitive, cumulative exposure to low-frequency PEMF in treatment of neuropathic pain was shown to quantitatively increase nerve fiber density and reduce itching but not pain which correlates to the adverse effects reported in this study in which the active group receiving PEMF had significantly less vaginal itching than the sham [42]. PEMF therapy has been used to manage postsurgical pain and edema, chronic wounds, and neuropathic pain. Therefore, it is possible that combination RF + PEMF may cause less pain and side effects than other RF devices. In this study, RF + PEMF treatment associated pain was minimal (VAS pain scores 0.50 out of 10). In comparison with a study utilizing a low energy monopolar RF device for VL treatment, the mean pain score was 1.5, and side effects included post-procedure vaginal leukorrhea and lower abdominal pain none of which were reported in this study [23]. Adverse effects in another study using monopolar RF therapy with cryogen surface cooling for treatment of VL were reported in 32.5% of 117 subjects, and the most common was vaginal discharge. Additionally, one treated subject experienced treatment pain that warranted discontinuation of the procedure [24].

The difference of this multipolar device over the monopolar devices is in how the electric current passes from the device through the tissue between the electrodes, with monopolar systems penetrating most deeply causing the possibility of hot-spot formation and more pain or adverse effects [31, 32]. This RF + PEMF device also allows for greater ease of use for the treatment provider since the internal vaginal applicator is maintained in stationary positioning during the 15-min treatment time. This is in contrast with the monopolar handpiece designs such as the cryogen-cooled RF [12, 23, 24] and the transcutaneous temperature-controlled RF device [43] that require introital rotations or sweeping movements passed over the multiple treatment zones while avoiding the urethral area with longer treatment durations of approximately 30 min.

The strengths of this randomized, clinical study included the double-blinded design in which both subjects and investigators were blinded of the interventions performed by therapists not involved in any other parts of the study and the inclusion of the sham arm to eliminate the potential placebo response after procedures [37, 38]. However, the small number of subjects and relatively short follow-up period (12 weeks) were the key limitations to this study. Given the ongoing effects of natural aging and other potential contributing factors (further childbearing, etc.), subsequent tissue changes could occur outside the time period analyzed in the study. It is warranted to have a longer follow-up period to fully assess the longevity of these results.

This is the first randomized, sham-controlled, double-blinded clinical study using combined multipolar radiofrequency and pulsed electromagnetic energies for vaginal tightening in females experiencing vaginal laxity after vaginal deliveries. Three treatments with this device demonstrated significant objective and subjective improvements of VL with positive histological changes. Treatments were well tolerated with a favorable safety profile during the 18-week study period.