Short-term safety and preliminary patient-reported outcomes of bipolar radiofrequency therapy for mild-to-moderate erectile dysfunction: a prospective single-arm pilot study

Introduction

Erectile dysfunction (ED) is defined as the persistent inability to attain or maintain an erection sufficient for satisfactory sexual performance. It is a common condition that increases in prevalence with age and has a substantial impact on quality of life for patients and their partners. ED is multifactorial and may result from vasculogenic, neurogenic, endocrinologic, metabolic, psychogenic, medication-related, or postsurgical causes. Among organic etiologies, vasculogenic ED is the most prevalent and is closely linked to endothelial dysfunction, impaired arterial inflow, veno-occlusive dysfunction, and structural alterations within the corpora cavernosa (1,2).

Normal erection depends on coordinated smooth muscle relaxation, adequate arterial inflow, sinusoidal expansion, and effective venous occlusion. Chronic hypoxia and vascular injury have been associated with loss of cavernosal smooth muscle, increased collagen deposition, and corporal fibrosis, changes that may impair tissue compliance and contribute to persistent ED. Current guideline-supported therapies, including phosphodiesterase type 5 inhibitors (PDE5i), intracavernosal therapy, vacuum erection devices, and penile prostheses, remain effective for symptom management in appropriately selected patients; however, these treatments are not generally regarded as restorative therapies directed at reversing the underlying structural abnormalities of the corpora cavernosa (1,2).

This therapeutic gap has generated interest in noninvasive, energy-based approaches for ED. Low-intensity shockwave therapy (LiSWT) is the most widely studied modality in this category. It is thought to exert biologic effects through mechanotransduction and microtrauma-mediated signaling, but published protocols remain heterogeneous and the quality of evidence is variable, which has limited uniform guideline adoption (3). Bipolar radiofrequency (RF), by contrast, delivers controlled thermal energy rather than acoustic or mechanical energy, and may influence tissue architecture and local vascular responses through heat-based biophysical mechanisms. In non-urologic applications, RF devices have been used in dermatology, aesthetic medicine, and vaginal tissue applications because of their controlled thermal effects on collagen architecture and soft-tissue remodeling. Experimental studies have associated RF exposure with collagen contraction, neocollagenesis, neoangiogenesis, and increased fibroblast growth factor 2 expression in skin tissue, while clinical studies have evaluated RF-based therapy for vaginal laxity and genitourinary syndrome of menopause (4,5).

However, the biologic effects of bipolar RF on penile tissue remain insufficiently characterized, and mechanistic claims regarding vascular or collagen remodeling in clinical ED populations should therefore be considered hypothesis-generating rather than established. Early clinical studies of RF-based treatment for ED have suggested feasibility and short-term tolerability, but the evidence base remains limited and requires further controlled evaluation (6).

Accordingly, the present study was designed as a prospective single-arm pilot study to evaluate the short-term safety, feasibility, and preliminary patient-reported outcomes of six weekly sessions of bipolar RF therapy in men with mild-to-moderate organic ED. We present this article in accordance with the TREND reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0313/rc).

Methods

We conducted a prospective, single-arm, open-label pilot study evaluating a handheld bipolar RF device (Forma applicator, InMode MD Ltd.) in men with mild-to-moderate organic ED. The study was prospectively registered on ClinicalTrials.gov (No. NCT06299332). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Sterling Institutional Review Board (IRB No. 11000-RJValenzuela), registered with the U.S. Office for Human Research Protections (No. IRB00001790), and informed consent was obtained from all individual participants.

Participants were recruited through site-based clinical screening and referral at Washington Heights Urology and LC Medical Aesthetics, two outpatient urology clinics in New York, NY. Screening and recruitment occurred from September 8, 2023 to March 6, 2024; baseline enrollment visits were completed by March 12, 2024, and follow-up for the present analysis was completed by July 23, 2024. Eligible participants were men aged 40 to 80 years with mild-to-moderate organic ED who met prespecified clinical and laboratory eligibility criteria, including PDE5i responsiveness, an International Index of Erectile Function erectile function domain (IIEF-EF) score of 11 to 25, and an Erection Hardness Score (EHS) of at least 1. Participants were required to abstain from ED medications and device-based therapies during the study period and to undergo protocol-specified PDE5i washout before follow-up assessments. Full inclusion and exclusion criteria are shown in Table 1.

Organic ED was determined through routine pre-enrollment clinical evaluation by the treating urologist, including medical and sexual history, laboratory eligibility criteria, validated questionnaire-based assessment, PDE5 inhibitor responsiveness, and penile duplex Doppler ultrasonography when clinically indicated as part of standard office workup. Duplex findings supported clinical ED phenotype classification but were not collected as protocol-specified endpoints. Participants with a primarily psychogenic presentation were excluded based on clinical assessment.

Participants underwent six weekly RF treatment sessions, each lasting approximately 15 minutes, using the Forma applicator (Figure 1). Treatment was delivered to the penile shaft and crura with a target skin temperature of approximately 42.0–42.5 ℃. Recorded session-level parameters included treatment area, energy level, cut-off temperature, treatment duration, and procedural comments. Across recorded sessions, the energy level ranged from 25 to 30. Pulse frequency was determined by the device platform and was not recorded as a separate session-level variable. Treatments were administered in the outpatient clinic setting by trained study personnel according to the study protocol. Study-related treatment sessions and follow-up assessments were provided at no cost to participants.

Figure 1 Forma bipolar radiofrequency device. Representative image of the treatment device used for bipolar radiofrequency therapy. The inset provides a close-up view of the Forma applicator (InMode MD Ltd.).

The primary outcome was change in erectile function from baseline to 1 and 3 months, assessed using the erectile function domain of the International Index of Erectile Function (IIEF-EF). The full IIEF questionnaire was administered at study visits; however, in accordance with the prespecified study objective, the primary endpoint analysis was limited to the erectile function domain (IIEF-EF). Secondary outcomes included Erection Hardness Score (EHS), the Global Assessment Questionnaire (GAQ), the Sexual Encounter Profile (SEP), and procedural discomfort measured using the Numeric Pain Rating Scale (NPRS). Although longer-term follow-up time points were listed in the registry, the present analysis was limited to outcomes through 3 months. As a pilot study, a formal sample size calculation was not performed; target enrollment was based on feasibility and study capacity.

Safety and tolerability were assessed throughout treatment and follow-up by review of study documentation and directed questioning regarding local and systemic symptoms, including pain, erythema, edema, burns, bruising, sensory changes, urinary symptoms, and worsening erectile symptoms. Procedural discomfort was recorded after treatment sessions using a 0–10 NPRS. Adverse events, treatment discontinuations, and any events considered possibly related to treatment were recorded throughout the study period.

Statistical analysis

Given the pilot design, small sample size, and repeated-measures structure, analyses were considered exploratory. Descriptive statistics were used to summarize baseline characteristics, patient-reported outcomes, and tolerability. Changes across baseline, 1 month, and 3 months were assessed in the complete-case cohort using the Friedman test. When appropriate, post hoc pairwise comparisons were performed with Wilcoxon signed-rank tests with Holm correction for multiple testing. GAQ responses, SEP responses, and procedural discomfort ratings were summarized descriptively. All statistical analyses were performed using R version 4.5.3 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Nineteen participants were enrolled. Eighteen contributed at least one post-baseline IIEF-EF assessment, and 17 contributed complete baseline, 1-month, and 3-month IIEF-EF and EHS data for the repeated-measures analyses. Two participants did not complete follow-up as planned. These withdrawals were attributed primarily to the time commitment associated with treatment sessions and follow-up visits and were not related to treatment-emergent adverse events.

Baseline characteristics of the complete-case cohort are summarized in Table 2. Mean age was 58.4±9.1 years, mean testosterone was 441.1±129.1 ng/dL, and mean hemoglobin A1C was 5.75%±0.60%. Mean baseline IIEF-EF was 16.4±4.9, consistent with mild-to-moderate ED. Baseline characteristics of the two participants who withdrew appeared generally similar to those of participants retained in follow-up, although no formal comparison was performed given the very small number of withdrawals.

No treatment-emergent adverse events or serious adverse events were documented during the study period. Across all recorded treatment sessions in treated participants (n=19), procedural discomfort was minimal, with a mean NPRS score of 0.18±0.73, a median of 0.0, and a maximum recorded value of 4. The median value of 0.0 reflects the skewed distribution of scores, as 14 of 19 participants (73.7%) reported no discomfort across all recorded sessions, whereas 5 (26.3%) reported any discomfort; all recorded scores were mild (0–4/10). These findings are summarized in Table 3.

Among participants with complete repeated assessments (n=17), mean IIEF-EF increased from 16.4±4.9 at baseline to 22.6±3.1 at 1 month and 23.7±3.1 at 3 months (Table 4). The overall change across visits was significant on Friedman testing (χ²[2] =30.58, P<0.001). Pairwise Wilcoxon signed-rank testing with Holm adjustment showed significant improvements from baseline to 1 month (adjusted P<0.001) and from baseline to 3 months (adjusted P<0.001). The comparison between 1 and 3 months also remained significant (adjusted P=0.03), suggesting additional improvement between these follow-up time points within the complete-case cohort.

Median EHS improved from 2.0 (IQR, 2.0–3.0) at baseline to 3.0 (IQR, 3.0–4.0) at 1 month and 3.0 (IQR, 3.0–4.0) at 3 months. The overall change across visits was significant (Friedman χ²[2] =23.41, P<0.001). Pairwise Wilcoxon testing with Holm adjustment showed significant improvements from baseline to 1 month (adjusted P=0.003) and from baseline to 3 months (adjusted P=0.003), whereas the difference between 1 and 3 months was not significant (adjusted P=0.32).

Subjective improvement on the GAQ was also high. At 1 month, all participants with available follow-up data reported improvement in erectile function and sexual activity [18/18 (100.0%) for both items]. At 3 months, 16 of 17 participants (94.1%) reported improvement in erectile function and 16 of 17 (94.1%) reported improvement in sexual activity (Table 4).

For SEP Question 2, the proportion of participants reporting successful penetration increased from 2/19 (10.5%) at baseline to 5/18 (27.8%) at 1 month and 13/17 (76.5%) at 3 months. For SEP Question 3, the proportion reporting erections lasting long enough for successful intercourse increased from 2/19 (10.5%) at baseline to 1/18 (5.6%) at 1 month and 12/17 (70.6%) at 3 months (Table 4). These findings should be interpreted as exploratory given the pilot design and the small number of participants with complete repeated SEP assessments.

Discussion

In this prospective single-arm pilot study, bipolar RF therapy was feasible and well tolerated in men with mild-to-moderate organic ED, with favorable short-term changes observed across multiple patient-reported outcome measures. IIEF-EF improved at 1 month and again at 3 months, while EHS, GAQ, and SEP outcomes showed a similar directional pattern. Importantly, no treatment-emergent adverse events or serious adverse events were documented, and procedural discomfort was low. However, the uniformly positive GAQ responses at 1 month should be interpreted with particular caution, as global improvement measures in open-label, single-arm ED studies may be susceptible to placebo effects, expectation effects, and response bias. Therefore, these findings support the short-term safety and practicality of this approach in a pilot setting, but they cannot be causally attributed to bipolar RF therapy and should be interpreted as preliminary and hypothesis-generating rather than confirmatory evidence of efficacy.

The biologic rationale for RF therapy in ED remains plausible but incompletely defined. Organic ED, particularly vasculogenic ED, has been linked to endothelial dysfunction, cavernosal hypoxia, smooth muscle loss, and progressive fibrosis, all of which may impair corporal compliance and erection quality (1). In other fields, RF-based treatments have been associated with thermal effects on collagen architecture and tissue remodeling pathways, which has led to interest in whether a similar strategy could have restorative relevance in selected men with ED (4). At the same time, the present study did not include vascular imaging, histologic assessment, or other objective biologic endpoints. Accordingly, the observed short-term improvements in patient-reported outcomes should not be interpreted as direct evidence of vascular or collagen remodeling.

This distinction is especially important when comparing RF with other energy-based approaches, particularly LiSWT. LiSWT is the most widely studied restorative-energy modality in ED, with randomized trials and meta-analyses reporting improvements in erectile function scores, particularly among men with vasculogenic ED and mild-to-moderate baseline dysfunction. However, published protocols remain heterogeneous with respect to energy density, number of pulses, treatment sites, session frequency, and total treatment duration, and effects on hardness, sexual encounter outcomes, and objective vascular parameters have been less consistent across studies (7,8). Current guidelines therefore remain cautious, with LiSWT generally framed as investigational or appropriate only for selected patients after counseling regarding uncertainty of benefit (1). RF differs mechanistically in that it delivers controlled thermal energy rather than acoustic or mechanical energy (7). For that reason, direct comparisons across modalities should be made cautiously. The present results may be viewed as consistent with a broader interest in noninvasive energy-based therapies for ED, but they do not establish equivalence, superiority, or a shared mechanism relative to LiSWT or other emerging modalities.

The present findings should also be interpreted in the context of the limited clinical literature on RF for ED. A prior pilot cohort study of RF therapy similarly suggested short-term tolerability and improvement in erectile function measures, while a sham-controlled trial of 448-kHz RF reported between-group differences after treatment (6,9,10). Taken together, these early reports support further controlled evaluation of RF-based therapy in ED. However, the current evidence base remains small, methodologically heterogeneous, and insufficient to support definitive clinical conclusions. The current study therefore adds incremental pilot data rather than providing confirmatory evidence.

Several limitations should be acknowledged. The study was small, single-arm, and open-label, without a sham or control group; therefore, placebo effects, expectation effects, regression to the mean, and natural fluctuation in sexual performance cannot be excluded. Participants underwent clinical screening to support an organic ED phenotype, and those with a primarily psychogenic presentation were excluded. However, ED phenotype was not centrally adjudicated, and penile duplex parameters were not analyzed as protocol-specified endpoints; therefore, mixed psychogenic contributions may still have influenced patient-reported outcomes. The protocol also required PDE5 inhibitor responsiveness at baseline, washout before follow-up assessments, and abstinence from ED medications during the study period, but residual confounding related to medication exposure or adherence remains possible. The modest sample size and two withdrawals related to study burden may also limit generalizability. Longer-term follow-up beyond 3 months was not available, limiting conclusions regarding durability.

Despite these limitations, the study incorporated several methodological features that support interpretation of the findings, including prospective registration, predefined eligibility criteria, use of validated patient-reported outcome instruments, and systematic capture of short-term safety and tolerability data. In addition, the low discomfort profile and absence of treatment-related adverse events suggest that this approach is acceptable enough to justify more rigorous evaluation. Future studies should use randomized, sham-controlled designs with larger samples, longer follow-up, and objective vascular or structural endpoints to clarify whether bipolar RF therapy produces durable clinical benefit and whether any biologic remodeling effect can be demonstrated.

Conclusions

In this prospective single-arm pilot study, bipolar RF therapy was feasible and well tolerated in men with mild-to-moderate organic ED, with favorable short-term improvements observed in patient-reported erectile function outcomes. No treatment-related adverse events were documented, and procedural discomfort was low. Given the small sample size, open-label design, and absence of a control group, these findings should be considered preliminary and hypothesis-generating rather than confirmatory. Larger sham-controlled studies with longer follow-up and objective physiologic endpoints are needed to further define the durability, tolerability, and clinical relevance of this approach.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the TREND reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0313/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0313/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0313/prf

Funding: This work was supported by InMode MD Ltd.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0313/coif). R.J.V. and L.C. report that InMode MD Ltd. provided support for the present study, including temporary provision of radiofrequency equipment/materials and support related to protocol and IRB preparation/administration. They also report financial support/payment from InMode MD Ltd. to the investigator and study site. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Sterling Institutional Review Board (IRB No. 11000-RJValenzuela), registered with the U.S. Office for Human Research Protections (No. IRB00001790), and informed consent was obtained from all individual participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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