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Radiofrequency energy in the treatment of erectile dysfunction – a novel cohort pilot study on safety, applicability, and short-term efficacy

Authors:

Abstract

Collagen is an essential component of the structures involved in the erectile mechanism and as such, impaired collagen may hinder it. Because Radiofrequency (RF) energy has been shown to renew and restore spatial structural arrangement of collagen fibers, treatment of ED with RF could lead to anatomical and physiological changes at the penile tissue level and could lead to improvement in the erectile mechanism. We conducted this study to assess the effect of RF treatment on erection quality. We evaluated the safety, applicability, and efficacy of a self-applied, handheld, low-intensity radiofrequency device (Vertica®) in men with moderate and mild-to-moderate organic ED. The treatment protocol consisted of 12 treatments (twice a week during the 1st month, and once a week during the 2nd month), each participant treated himself individually. Treatment outcomes were evaluated using the International Index of Erectile Function (IIEF-15), Erection Hardness Scale (EHS), Erectile Dysfunction Index of Treatment Satisfaction (EDITS), Benefit, Satisfaction & Willingness to continue (BSW), Quality of Erection Questionnaire (QEQ), Sexual Quality of Life (SQOL) questionnaires and specific questions addressing side-effects and ease of use. Twenty-eight out of 32 men (mean age 59.5.7 ± 9.8, range: 41-78y) completed a one-month follow-up after treatment. Mean IIEF-15 (43.7. ±7.8 vs 60.9 ± 10.8, p < 0.01), IIEF-Erection Function domain (IIEF-EF) (16.8 ± 3.1 vs. 24.4 ± 4.4, p < 0.001), and EHS scores (2.2 ± 0.8 vs. 3.2 ± 0.5, p = 0.01) were all significantly improved. Fifty percent of patients achieved normal EF parameters (IIEF-EF score ≥ 25). High mean scores were achieved in the EDITS (76.8 ± 20.3), BSW (4.83 ± 1.1), QEQ (73.4 ± 23.8), and SQOL (67 ± 29.4) questionnaires. No side effects were reported and participants rated the device as very comfortable, simple, and easy to operate.
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Radiofrequency energy in the treatment of erectile
dysfunction a novel cohort pilot study on safety,
applicability, and short-term ecacy
Ilan Gruenwald ( i_gruenwald@rambam.health.gov.il )
rambam https://orcid.org/0000-0003-0330-2859
Boaz Appel
Arik Shechter
Rambam Healthcare Campus https://orcid.org/0000-0001-8270-8069
Alexander Greestein
Article
Keywords: Radiofrequency, erectile dysfunction, treatment, home-use
Posted Date: February 6th, 2023
DOI: https://doi.org/10.21203/rs.3.rs-2531066/v1
License: This work is licensed under a Creative Commons Attribution 4.0 International License.
Read Full License
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Abstract
Collagen is an essential component of the structures involved in the erectile mechanism and as such,
impaired collagen may hinder it. Because Radiofrequency (RF) energy has been shown to renew and
restore spatial structural arrangement of collagen bers, treatment of ED with RF could lead to
anatomical and physiological changes at the penile tissue level and could lead to improvement in the
erectile mechanism. We conducted this study to assess the effect of RF treatment on erection quality. We
evaluated the safety, applicability, and ecacy of a self-applied, handheld, low-intensity radiofrequency
device (Vertica®) in men with moderate and mild-to-moderate organic ED. The treatment protocol
consisted of 12 treatments (twice a week during the 1st month, and once a week during the 2nd month),
each participant treated himself individually. Treatment outcomes were evaluated using the International
Index of Erectile Function (IIEF-15), Erection Hardness Scale (EHS), Erectile Dysfunction Index of
Treatment Satisfaction (EDITS), Benet, Satisfaction & Willingness to continue (BSW), Quality of Erection
Questionnaire (QEQ), Sexual Quality of Life (SQOL) questionnaires and specic questions addressing
side-effects and ease of use. Twenty-eight out of 32 men (mean age 59.5.7 ± 9.8, range: 41-78y)
completed a one-month follow-up after treatment. Mean IIEF-15 (43.7. ±7.8 vs 60.9 ± 10.8, p < 0.01), IIEF-
Erection Function domain (IIEF-EF) (16.8 ± 3.1 vs. 24.4 ± 4.4, p < 0.001), and EHS scores (2.2 ± 0.8 vs. 3.2 
± 0.5, p = 0.01) were all signicantly improved. Fifty percent of patients achieved normal EF parameters
(IIEF-EF score  25). High mean scores were achieved in the EDITS (76.8 ± 20.3), BSW (4.83 ± 1.1), QEQ
(73.4 ± 23.8), and SQOL (67 ± 29.4) questionnaires. No side effects were reported and participants rated
the device as very comfortable, simple, and easy to operate.
Introduction
Erectile dysfunction (ED) is dened as the consistent or recurrent inability to attain and/or maintain a
penile erection sucient for sexual satisfaction[1]. The worldwide prevalence of ED is estimated to be up
to about 80% in adults, and increases with age [2].
The quest for an ED treatment modality that would provide a rehabilitative or curative impact for ED and
would put an end to coupling the treatment to sexual activity is still ongoing. Most contemporary
treatments (e.g., oral medications, intracorporal injections, or use of a vacuum-constriction device) require
timing treatment before any expected sexual activity, negatively affecting the spontaneity of any sexual
activity and leading to a less satisfying relationship [3].
In the recent years, applying external energy to the penis emerged as a new concept of treatment to
improve erection quality. Such treatment is not applied prior to sexual activity, and therefore eliminates
the need to time and schedule ahead the use of medications before sexual activity and intercourse,
consequently restoring spontaneity to sex life. Low-Intensity Shockwave Therapy (LI-ESWT) which results
in micro-anatomical and physiological changes at the level of the cavernosal tissue is one form of such
treatment modality [4]. Radiofrequency (RF) energy has been shown to renew collagen and to restore their
spatial structural arrangement in various tissue bers due to its heating effect [5]. Collagen layers are
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present abundantly in the tunica albuginea (TA), and in the corpora cavernosa. We hypothesise that
applying RF to penile tissues may trigger remodeling of the collagen in those tissues that are involved in
the erectile mechanism. In addition, hyperthermia may promote upregulation of nitric oxide synthase
involved in the erectile mechanism.[6] These mechanisms triggered by RF may act synergistically to
improve the quality of erection. We conducted our study to evaluate the safety, applicability, and ecacy
of a self-applied RF handheld device for the treatment of ED.
Methods
Study population:
Men 40–85 years old with mild or mild-to-moderate organic ED (IIEF-EF scores between11-20) with an ED
duration of 6 months and a stable relationship for at least three months comprised the study population.
The diagnosis of organic ED was based on a medical and sexual history. The study protocol was
reviewed and approved by the local institutional review board and each participant gave his written
informed consent to participate in this study.
Patients using phosphodiesterase type 5 inhibitors (PDE5i) treatment were not excluded and were
instructed to adhere to their routine pattern of treatment during the whole study period. Excluded were
men with any penile dermatologic disease or lesion, micropenis, history of penile carcinoma, penile
piercing, penile prosthesis, Peyronie’s disease, documented urethral stricture, sensory disorders, and any
known allergy to aqueous gel.
Device: The Vertica® (Ohhmed, Israel), is a computerized hand-held device that generates pulses of RF
energy delivered at a frequency of 1Mhz. into the penis via 3 couples of electrodes, creating an internal
thermal heating effect. (Photo 1). The temperature in the corpora cavernosa and the surrounding TA
reaches 41–43ºC. The level of energy is fully controlled by the patient, increasing, or decreasing it via the
+ and - buttons on the control panel of the device (Photo 2) according to the heat sensation on the penis.
The Vertica® (Ohhmed, Tiberius, Israel) consists of two parts. One is a handheld ring into which the penis
is placed. The ring component contains a circle of electrodes that deliver the RF energy in a
predetermined digitally revolving order to the corpora cavernosa, encompassing the penis without
covering the urethra or the neurovascular bundle area, as the electrodes in the these areas (12 and six
o'clock) are inactive and do not deliver RF energy, The second part is a pad that contains 3 electrodes that
are used for RF energy delivery and is placed at the perineal area, covering the crural region of the penis
while sparing the urethral area (Photo 3).
As a safety measure, all the electrodes have a built-in thermistor that is set to immediately stop the
energy discharge whenever the skin temperature level on the skin reaches 40ºC. As an additional safety
measure in order to deliver the RF energy, the patient is required to press the "treatment" button
continuously for operating the device, thus in any situation in which the patient feels any discomfort, he
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can immediately shut the energy delivery off by simply removing the nger from the "treatment" button
(Photo 2).
Protocol:
The study was conducted between 2018–2019. Patients attending the neuro-urology unit complaining of
ED were recruited. None of them received incentives of any form. The device was supplied by the
manufacturer (Ohhmed, Tiberius, Israel). All men received a short explanation on the operation of the
device. After applying an aqua gel on the penile shaft, the penis is placed into the electrode ring of the
handheld piece and the perineal electrode pad is placed at the perineal area. During the treatment
session, to cover the whole penile pendulous part, the patient slowly slides the Vertica® from the base of
the penis, along the shaft to the distal part (the corona sulcus line), applying the preferred intensity of RF
by self-controlling the heat level at the penis. Each treatment session starts with the lowest intensity level
and the patient then gradually increases it until he reaches his individually comfortable heat intensity.
Each participant treated himself individually with the Vertica® device at the Neuro-Urology unit, Rambam
Medical Center, initially under the guidance of the investigator until complete adequate operation by the
patient was achieved. This took no more than 2 sessions. Treatment protocol was based on the dermal
treatment protocols. The patient was then left alone in a private room for continuing self-treatment. The
treatment protocol consisted of 12 treatments (twice a week during the 1st month, and once a week
during the 2nd month). Each treatment session duration at the clinic was 30 minutes,15 minutes with the
ring part, and additional 15 minutes with both the ring and pad.
Baseline status and outcomes were evaluated before treatment and one month after completion of all 12
treatment sessions, using IIEF-15, IIEF-EF, Erection Hardness Scale (EHS). For evaluation of their status
post treatment, Erectile Dysfunction Index of Treatment Satisfaction (EDITS), Satisfaction Willingness to
continue (BSW), Quality of Erection Questionnaire (QEQ) and Sexual Quality of Life (SQOL)
questionnaires. All questionnaires used in the study were professionally translated to Hebrew. These
questionnaires are accepted and used by the urological community clinical and research tools in Israel.
As outcome measure of success we used the strict criteria for minimal clinical signicant improvement of
quality of erections, dened by the MCID (Minimal Clinical Important Difference) of the IIEF-EF [7]
Specic questions addressing safety and side-effects (pain, fever, burning, discomfort, urinary disorders)
and ease of use were handed each session. The International Prostate Symptom Score (IPSS) was used
to evaluate any possible deleterious effect on micturition. Patients on PDE5i treatment were constantly
and actively followed up for conrming their use of PDE5i during the whole study duration, and all the
evaluations at baseline and at follow-up reected the patients' erectile function while using the
medication.
In addition, the rst 10 participants underwent a penile Flow Mediated Dilatation (FMD) study. This is a
modied plethysmography measure at the penile level, done in the accid state. The technique includes a
rapid cessation of a 3–5 minutes’ ischemic period (achieved by using a designated strain gauge). This
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technique aims to assess arterial elasticity representing penile endothelial function and was performed at
baseline and 1 month after the last (12th) treatment [8] [9].
Statistical analysis:
For analysis of sample size for an 80% power with a 5% level of signicance, we used a sample size
calculator for comparing paired differences in IIEF-EF for mean score changes of 4.0 ± 4.0 resulting in a
need for 10 participants. Calculating the sample size assessment for our 28 participants, a power of 95%
was reached.
Descriptive statistics in terms of mean, standard deviation, median and percentage were calculated to all
parameters in the study. Wilcoxon Signed Ranks Test was used to test the differences between IIEF − 15
for IIEF-EF at baseline vs. one-month after ending treatment.
Repeated measure model was demonstrated to test the changes of IIEF-EF at baseline vs. one-month
after ending treatment when controlling for combined treatment, age < 60, age  60 and for ED duration
at 3 categories: <12 months, 18–24 months and > 30 months.
SPSS version 28 was used for all statistical analysis. The statistical signicance level was set as p <
0.05.
Results
Thirty-two men were recruited. Four of the 32 participants were withdrawn from results analysis due to
protocol violation, not due to side effects related to the treatment: one due to separation from his steady
partner, one due to COVID-19 restrictions, one due to evaluation of a new incidental pathologic nding in
the lungs, and one due to unexpected personal issues necessitating traveling abroad.
Twenty-eight out of 32 men with ED (mean age 59.5 ± 9.8, range: 41-78y), completed the entire treatment
protocol and one-month follow-up. Their average ED duration was 41.4 ± 30.6: range 6 to 120 months.
Overall, a statistically signicant improvement was demonstrated in the IIEF-15 (43.7 ± 7.8 vs 60.9 ± 10.8,
p < 0.01), IIEF-EF (16.8 ± 3.1 vs. 24.4 ± 4.4, p < 0.01). (Table1). Fourteen out of twenty-eight (50%) reached
normal EF parameters (IIEF-EF score 25). only 3 patients did not meet the MCID criteria and were
considered failures.
EHS scores (2.2 ± 0.8 vs. 3.2 ± 0.5, p < 0.001) when comparing baseline parameters to one month after
ending treatment. 25/28 improved their erections according to the IIEF-EF MCID criteria. (Table1). At
baseline, 13 (46.4%) reported an EHS of 3, 8 (28.5%) reported an EHS 2 and 7 (25%) reported EHS 1.
Following treatment,19 (67.8%) reported an EHS of 3, 7 (25%) reported EHS score of 4 and 2 patients
reported and EHS 2 (7.1%). None of the patients reported an EHS of 1, (Graph 1).
Sexual desire domain was the only domain of the IIEF-15 that did not improve signicantly (7.59 ± 1.46
vs. 8.08 ± 1.29; p = 0.23) (Table1).
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Since 8/28 patients were using PDE5is, we compared IIEF-EF scores according to use (n = 8) and non-use
(n = 20) of PDE5Is. Mean IIEF-EF scores increased signicantly in both groups, (fom 17.45 ± 2.64 to 25.1 
± 4.54, p < 0.001), and from (16.29 ± 3.40 to 24.0 ± 4.47 p = 0.005)) respectively, without a statistically
signicant difference between the two groups (p = 0.13) (Graph 2).
When analyzing IIEF-EF scores of the participants according to age groups, the young (< 60) and old (
60) age group. IIEF-EF scores improved signicantly in both age groups (16.47 ± 2.99 to 24.4 ± 5.35; p < 
0.001) and (18.0 ± 2.48 vs. 25.33 ± 3.17, p < 0.001.) respectively, Without a statistically signicant
difference between the two age groups (P = 0.69).
When analyzing IIEF-EF scores of the participants according to ED duration;<12 months, 13–24 months
and > 25 months, a statistically signicant improvement was demonstrated in all three ED duration
groups (18.8 ± 2.38 vs 27.2 ± 3.83, p < 0.004, 17.8 ± 2.95 vs 26.4 ± 4.21, p = 0.015, and 15.9 ± 2.77 vs
23.42 ± 4.96, p < 0.001), respectively without a statistically signicant difference between the three ED
duration groups. (p = 0.84).
High scores were achieved in the EDITS (76.8 ± 20.3), BSW (4.83 ± 1.1), QEQ (73.4 ± 23.8) and SQOL (67 ± 
29.4), questionnaires (Table1).
Quantied endothelial function improved signicantly in all 3 FMD parameters; baseline ow, max ow
and area under the curve (blood volume) by 53%, 124% and 125%, respectively (Table1).
No signicant deleterious effect of the treatment on lower urinary tract symptoms was demonstrated by
the IPSS questionnaire (9.40 ± 7.48 vs. 8.49 ± 6.8, p = 0.6).
Twelve participants reported re-appearance or improved morning erections, without being directly asked
about it. No side effects such as pain, fever, burning sensation, local pressure, discomfort and dysuria
were reported, nor any dropouts due to side effects occurred. Participants rated the device as very
comfortable and easy to operate.
Discussion
In this proof-of-concept study, we were able to conrm that RF treatment for ED is effective, safe and
easily applicable. We demonstrated statistically signicant improvement in all IIEF-15 domains, except
for the sexual desire domain. The improvement in erectile function was prominently emphasized by the
EHS scores, as at baseline only 46.4% reported an EHS score of 3 (penis is hard enough for penetration
but not completely hard) while following treatment 67.8% reported an EHS score 3 and an additional 25%
an EHS score of 4 (Penis is completely hard and fully rigid) while none reported an EHS score of 1 (Graph.
1).
Our interest in applying RF as external physical energy to the penis for the treatment of ED evolved from
the documented benecial results of LI-ESWT applied to the penis for ED treatment [4][10]. RF, which is
routinely used in medicine, is a type of electric current between two electrodes.[11] When applied at low
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frequencies, it causes interactions between charged molecules and ions and creates heat within the
tissue. The heat causes collagen bers to undergo structural changes, resulting in the remolding of new
collagen and elastin bers[12] [13]. This type of low-intensity RF is currently used in the dermatology eld
to improve skin laxity and treat cellulite and wrinkles[14] These treatments are based on several
laboratory research studies showing a statistically signicant increase in collagen types I and III,
consisting of newly synthesized collagen found in the histology of the human skin following RF
treatment .[15]. Zelickson et al, using a bovine tendon histological and ultrastructural model of an RF
application, documented dermal remodeling with new collagen regeneration[16]. In addition,
rearrangements of collagen tissue were found in vaginal wall biopsies before and after RF application in
postmenopausal women who were treated for stress urinary incontinence [17].
The rationale for improving erection quality by altering collagen characteristics is based on the fact that
during erection, the increase in intracavernosal pressure depends, among others, on the integrity and
function of the bro-elastic components (collagen and elastin) within the sinusoids and within the TA[18].
Collagen types I and III are mainly present in the TA, interlaced with elastin bers, and involved in the
compression of the emissary veins. In addition, the corpora cavernosa contains an evident amount of
collagen type IV[19]
Collagen IV is the major structural scaffold of the intracavernosal pillars which have an important role in
maintaining the cylindrical shape, strength, and rigidity of the penis during erection, and they also
signicantly contribute to the regulation of the intracorporal pressure during erection [20][21] Collagen
type IV also constitutes the scaffold of the basal membranes in the corpora cavernosa tissue, providing
more exibility and support to the vessels[22]. It is important to note that in recent years the basal
membrane area has also been recognized as an important regulator of cell behavior, probably serving as
an extracellular microenvironment sensor for endothelial cells[23]. At the penile level, the basal membrane
may play a role in tissue and organ morphogenesis and angiogenesis. Collagen type IV is ideally suited
for the incorporation of laminins, molecules that interact with receptors and regulate multiple cellular
activities and signaling pathways [22]. Therefore, our assumption is that remodeling these components in
both corpora and TA by application of low-intensity RF may improve and restore erectile quality.
Remodeling collagen by applying RF energy is a biological process that lasts approximately three months
[23]. We documented favorable results as early as 4 weeks, which merit further discussion. However,
similar early results were also reported following treatment of ED by other external energy sources such
as LISWT[24]. According to Ciampa et al., the peak expression of the neovascularization response
following LI-ESWT occurs as early as 4 weeks after treatment, which may be related to the nitric oxide
(NO) mechanism.[25] Cavernosal NO activity may be enhanced by the direct effect of the higher
temperature leading to vasodilation and increased blood ow, consequently leading to increases in penile
PO2. High oxygen tension arterial levels promote the activation eNOs and nNOs (mediators involved in
the erectile mechanism)[25, 26, 27].
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Activation of these enzymes by increased temperature was demonstrated in several laboratory studies;
Ilangovan et al. demonstrated that eNOs is induced in cultured endothelial cells when exposed to mild
heat (42oC), and concluded that induced heat may upregulate NO synthase in cardiac cells [6]. Harris et
al, in a Bovine aortic endothelial cells model, reported that incubation of cells for 1 h at 42oC was
associated with increased eNOs activity, agonist-stimulated NO release, and a decreased vasoconstrictor
response [27]. The penile hemodynamic changes in our study were veried objectively by penile FMD in
all three measured parameters. Furthermore, our FMD results after RF treatment are in concert with data
presented by Mamede et al using Duplex ultrasound and showing that RF energy improves hemodynamic
parameters [28].
We expect to achieve a sustained effect of ED improvement similar to the reported dermal RF protocols
[16], which is explained by vascular changes leading to physiological variations. The adventitial tissue
that surrounds the penile arterioles responds to arterial "injury" by activating its resident progenitor cells
and induces the process of collagenesis and angiogenesis [29–31]. The repeated heat caused by RF to
the penis applied during the protocol we used, may induce the same “injury” effect and promote the
remodeling of vascular cavernosal body components. In addition, Korshunov et al reported that the local
heat dissipated by RF energy triggers endothelial cell interaction with medial and adventitial cells and
may contribute to vascular remodeling[32]
Another possible mechanism for the early RF effects is the fact that heating by RF is volumetric, and a
reverse thermal gradient is created, causing small amounts of transudate to accumulate in the
extracellular matrix. A mild perivascular inltrate after RF treatment has already been documented [33]
[16]. This natural inammatory process could by itself trigger angiogenesis and collagenesis, but we can
assume that some of the uid remains in the extracellular matrix. Following repeated exposures to RF
treatment, accumulation of extracellular uid contributes to better compression of the draining venules
against the TA inner wall during the following events of increased intracorporal pressure, clinically
expressed as improved erections.
We used questionnaires for outcome assessments because some data such as severity and frequency of
sexual function is better assessed in real life settings using patient reported outcomes (PROs), avoiding
elaborated laboratory-based diagnostic testing [34]. Therefore, evaluation was done primarily based on
PROs, leaving out nocturnal penile tumescence test, omitting a PDE5i washout period and allowing the
participants to continue their routine sexual activity pattern. IIEF-15 served only in the initial evaluation of
the patients as an additional tool for exclusion/inclusion of the patients. Nevertheless, due to the
innovative nature of our study, and to have a better understanding of the underlying hemodynamic
changes induced by RF treatment, we decided to apply the FMD test in a cohort of ten participants before
and one month after completion of all RF sessions.
To the best of our knowledge, this is the rst study in the English literature in which a benecial effect of
RF on ED was proven by using the contemporary ED evaluation protocols. However, our study served
merely as a proof-of-concept trial. The small number of patients, lack of a sham-controlled group and
Page 9/18
short-term follow-up are its main limitations. Because collagen type III is present in the brous plaques of
Peyronie's Disease as well as in the normal tunical tissue, a link between RF therapy and Peyronie's merits
further research.[32]
Further randomized sham-controlled studies are essential to verify our preliminary results. In order to
dene the ideal treatment protocol and the most favorable levels of energy for optimal results.
Conclusions
To our knowledge, this is the rst clinical trial on RF treatment for ED published in the english literature. In
this pilot study we evaluated a RF energy-based treatment for ED. Its innovation lies in the pioneering use
of RF energy for treatment of ED, by employing an innovative handheld, individually operated device
specically designed for home-use. We demonstrated the applicability, safety, and short-term ecacy of
this novel self-use device in improving ED. Our preliminary results are promising but still call for
multicenter, long-term, randomized and sham-controlled studies to better dene its ecacy and to explore
the characteristics of the patient who will benet most from it.
Declarations
Ilan Gruenwald: designed the protocol, participated in executing the study protocol data extraction and
evaluation, reviewing and editing the manuscript.
Boaz Appel: designed the protocol, participated in executing the study protocol data extraction and
evaluation, reviewing and editing the manuscript.
Arik Shechter: designed the protocol, participated in executing the study protocol data extraction and
evaluation, reviewing and editing the manuscript.
Alexander Greenstein: designed the protocol, participated in executing the study protocol data extraction
and evaluation, reviewing and editing the manuscript.
This study was funded by Ohhmed. Tiberius, Israel. The sponsor was not involved in the preparation of
the study protocol, data acquisition and analysis nor in the construction of the manuscript or its
conclusions.
References
1. McCabe MP, Sharlip ID, Atalla E, Balon R, Fisher AD, Laumann E, et al. Denitions of Sexual
Dysfunctions in Women and Men: A Consensus Statement From the Fourth International
Consultation on Sexual Medicine 2015. J Sex Med 2016;13:135–43.
https://doi.org/10.1016/j.jsxm.2015.12.019.
Page 10/18
2. Kessler A, Sollie S, Challacombe B, Briggs K, Van Hemelrijck M. The global prevalence of erectile
dysfunction: a review. BJU Int 2019;124:587–99. https://doi.org/10.1111/bju.14813.
3. Debasis B, Ann SP, Bhimaro FS, Sonia M. Erectile Dysfunction: A Review on Prevalence, Perceptions,
Diagnosis and Management in India. J Assoc Physicians India 2020:57–61.
https://pubmed.ncbi.nlm.nih.gov/33187038/ (accessed June 8, 2021).
4. Gruenwald I, Spector A, Shultz T, Lischinsky D, Kimmel E. The beginning of a new era: treatment of
erectile dysfunction by use of physical energies as an alternative to pharmaceuticals. Int J Impot Res
2019;31:155–61. https://doi.org/10.1038/s41443-019-0142-y.
5. Meyer PF, de Oliveira P, Silva FKBA, da Costa ACS, Pereira CRA, Casenave S, et al. Radiofrequency
treatment induces broblast growth factor 2 expression and subsequently promotes neocollagenesis
and neoangiogenesis in the skin tissue. Lasers Med Sci 2017;32:1727–36.
https://doi.org/10.1007/s10103-017-2238-2.
. Ilangovan G, Osinbowale S, Bratasz A, Bonar M, Cardounel AJ, Zweier JL, et al. Heat shock regulates
the respiration of cardiac H9c2 cells through upregulation of nitric oxide synthase. Am J Physiol -
Cell Physiol 2004;287. https://doi.org/10.1152/ajpcell.00103.2004.
7. Rosen RC, Allen KR, Ni X, Araujo AB. Minimal clinically important differences in the erectile function
domain of the international index of erectile function scale. Eur Urol 2011;60:1010–6.
https://doi.org/10.1016/j.eururo.2011.07.053.
. Vardi Y, Dayan L, Apple B, Gruenwald I, Ofer Y, Jacob G. Penile and Systemic Endothelial Function in
Men with and without Erectile Dysfunction. Eur Urol 2009;55:979–85.
https://doi.org/10.1016/j.eururo.2008.07.041.
9. Dayan L, Greunwald I, Vardi Y, Jacob G. A new clinical method for the assessment of penile
endothelial function using the ow mediated dilation with plethysmography technique. J Urol
2005;173:1268–72. https://doi.org/10.1097/01.JU.0000152290.71948.BF.
10. Capogrosso P, Frey A, Jensen CFS, Rastrelli G, Russo GI, Torremade J, et al. Low-Intensity Shock
Wave Therapy in Sexual Medicine—Clinical Recommendations from the European Society of Sexual
Medicine (ESSM). J Sex Med 2019;16:1490–505. https://doi.org/10.1016/j.jsxm.2019.07.016.
11. Bonjorno AR, Gomes TB, Pereira MC, de Carvalho CM, Gabardo MCL, Kaizer MR, et al.
Radiofrequency therapy in esthetic dermatology: A review of clinical evidences. J Cosmet Dermatol
2020;19. https://doi.org/10.1111/jocd.13206.
12. El-Domyati M, El-Ammawi TS, Medhat W, Moawad O, Brennan D, Mahoney MG, et al. Radiofrequency
facial rejuvenation: evidence-based effect. J Am Acad Dermatol 2011;64:524–35.
https://doi.org/10.1016/J.JAAD.2010.06.045.
13. Beasley KL, Weiss RA. Radiofrequency in cosmetic dermatology. Dermatol Clin 2014;32:79–90.
https://doi.org/10.1016/J.DET.2013.09.010.
14. Lolis MS, Goldberg DJ. Radiofrequency in cosmetic dermatology: A review. Dermatologic Surg
2012;38:1765–76. https://doi.org/10.1111/j.1524-4725.2012.02547.x.
Page 11/18
15. de Araújo AR, Soares VPC, da Silva FS, Moreira T da S. Radiofrequency for the treatment of skin
laxity: mith or truth. An Bras Dermatol 2015;90:707–21. https://doi.org/10.1590/ABD1806-
4841.20153605.
1. Zelickson BD, Kist D, Bernstein E, Brown DB, Ksenzenko S, Burns J, et al. Histological and
Ultrastructural Evaluation of the Effects of a Radiofrequency-Based Nonablative Dermal Remodeling
Device: A Pilot Study. Arch Dermatol 2004;140:204–9. https://doi.org/10.1001/archderm.140.2.204.
17. Leibaschoff G, Izasa PG, Cardona JL, Miklos JR, Moore RD. Transcutaneous Temperature Controlled
Radiofrequency (TTCRF) for the Treatment of Menopausal Vaginal/Genitourinary Symptoms. Surg
Technol Int 2016;29:149–59.
1. Dean RC, Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin
North Am 2005;32:379–95. https://doi.org/10.1016/j.ucl.2005.08.007.
19. Raviv-R Kiss-J Vanegas GP, Petein Danguy-C Schulman E Wespes MA, Raviv P Vanegas GJ,
Schulman Wespes CE, Kiss Danguy RA, Petein M. Objective measurement of the different collagen
types in the corpus cavernosum of potent and impotent men: an immunohistochemical staining with
computerized-image analysis. vol.15. 1997.
20. Luangkhot R, Rutchik S, Agarwal V, Puglia K, Bhargava G, Melman A. Collagen alterations in the
corpus cavernosum of men with sexual dysfunction. J Urol 1992;148:467–71.
https://doi.org/10.1016/S0022-5347(17)36630-2.
21. Goldstein Amb, Meehan JP, Morrow JW, Buckley PA, Rogers FA. The brous skeleton of the corpora
cavernosa and its probable function in the mechanism of erection. Br J Urol 1985;57:574–8.
https://doi.org/10.1111/J.1464-410X.1985.TB05869.X.
22. Pozzi A, Yurchenco PD, Iozzo R V. The nature and biology of basement membranes. Matrix Biol
2017;57–58:1–11. https://doi.org/10.1016/J.MATBIO.2016.12.009.
23. Longo C, Galimberti M, De Pace B, Pellacani G, Bencini PL. Laser skin rejuvenation: epidermal
changes and collagen remodeling evaluated by in vivo confocal microscopy. Lasers Med Sci
2013;28:769–76. https://doi.org/10.1007/S10103-012-1145-9.
24. Vardi Y, Appel B, Jacob G, Massarwi O, Gruenwald I. Can low-intensity extracorporeal shockwave
therapy improve erectile function? A 6-month follow-up pilot study in patients with organic erectile
dysfunction. Eur Urol 2010;58:243–8. https://doi.org/10.1016/J.EURURO.2010.04.004.
25. Ciampa AR, De Prati AC, Amelio E, Cavalieri E, Persichini T, Colasanti M, et al. Nitric oxide mediates
anti-inammatory action of extracorporeal shock waves. FEBS Lett 2005;579:6839–45.
https://doi.org/10.1016/J.FEBSLET.2005.11.023.
2. Kim N, Vardi Y, Padma-Nathan H, Daley J, Goldstein I, De Tejada IS. Oxygen tension regulates the
nitric oxide pathway. Physiological role in penile erection. J Clin Invest 1993;91:437–42.
https://doi.org/10.1172/JCI116220.
27. Harris M, Blackstone M, Ju H, Venema V, Venema R. Heat-induced increases in endothelial NO
synthase expression and activity and endothelial NO release. Am J Physiol Heart Circ Physiol
2003;285. https://doi.org/10.1152/AJPHEART.00726.2002.
Page 12/18
2. Mamede c, Quibervile a S p. Non-ablative radiofrequency improves hemodynamic parameters in
patients with erectile dysfunction: preliminary data., MELBOURNE: n.d.
29. de Araújo AR, Soares VPC, da Silva FS, Moreira T da S. Radiofrequency for the treatment of skin
laxity: mith or truth. An Bras Dermatol 2015;90:707–21. https://doi.org/10.1590/ABD1806-
4841.20153605.
30. Majesky MW, Dong XR, Hoglund V, Daum G, Mahoney WM. The adventitia: A progenitor cell niche for
the vessel wall. Cells Tissues Organs 2011;195:73–81. https://doi.org/10.1159/000331413.
31. Majesky MW, Dong XR, Hoglund V, Mahoney WM, Daum G. The adventitia: a dynamic interface
containing resident progenitor cells. Arterioscler Thromb Vasc Biol 2011;31:1530–9.
https://doi.org/10.1161/ATVBAHA.110.221549.
32. Korshunov VA, Schwartz SM, Berk BC. Vascular remodeling: Hemodynamic and biochemical
mechanisms underlying Glagov’s phenomenon. Arterioscler Thromb Vasc Biol 2007;27:1722–8.
https://doi.org/10.1161/ATVBAHA.106.129254.
33. Lolis MS, Goldberg DJ. Radiofrequency in cosmetic dermatology: a review. Dermatol Surg
2012;38:1765–76. https://doi.org/10.1111/J.1524-4725.2012.02547.X.
34. Deshpande P, Sudeepthi Bl, Rajan S, Abdul Nazir C. Patient-reported outcomes: A new era in clinical
research. Perspect Clin Res 2011;2:137. https://doi.org/10.4103/2229-3485.86879.
Tables
Table 1 is available in the Supplementary Files section.
Figures
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Figure 1
Erection Hardness Scores according to visits
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Figure 2
IIEF-EF scores in the PDE5i's treated and non-treated groups
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Figure 3
Vertica® front view
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Figure 4
Vertica® rear view
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Figure 5
Vertica® User panel
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Figure 6
Vertica®: Ring and Pad
Supplementary Files
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Introduction: Definitions of sexual dysfunctions in women and men are critical in facilitating research and enabling clinicians to communicate accurately. Aims: To present the new set of definitions of all forms of sexual dysfunction in women and men adopted by the Fourth International Consultation on Sexual Medicine (ICSM) held in 2015. Methods: Classification systems, including the International Classification of Diseases, 10th Edition and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and systems that focus on only specific types of sexual dysfunctions (eg, the International Society for Sexual Medicine definition for premature ejaculation) were reviewed. Main Outcome Measures: Evidence-based definitions were retained, gaps in definitions were identified, and outdated definitions were updated or discarded. Where evidence was insufficient or absent, expert opinion was used. Some definitions were self-evident and termed clinical principles. Results: The evidence to support the various classification systems was carefully evaluated. A more comprehensive analysis of this evidence can be found in two other articles in this journal that consider the incidence and prevalence and the risk factors for sexual dysfunction in men and women. These data were used to shape the definitions for sexual dysfunction that have been recommended by the 2015 ICSM. Conclusion: The definitions that have been adopted are those that are most strongly supported by the literature at this time or are considered clinical principles or consensus of experts' opinions. As more research and clinical studies are conducted, there likely will be modifications of at least some definitions.
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The demand for noninvasive methods of facial and body rejuvenation has experienced exponential growth over the last decade. There is a particular interest in safe and effective ways to decrease skin laxity and smooth irregular body contours and texture without downtime. These noninvasive treatments are being sought after because less time for recovery means less time lost from work and social endeavors. Radiofrequency (RF) treatments are traditionally titrated to be nonablative and are optimal for those wishing to avoid recovery time. Not only is there minimal recovery but also a high level of safety with aesthetic RF treatments.
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Background: Fine lines and rhytides are clinically evident signs of photodamage. Traditionally, ablative and nonablative lasers have been used for nonsurgical facial rejuvenation, but their side effects and downtime have limited their use. Objective: Radiofrequency (RF) is novel nonablative technology originally used to target photodamage. It differs from lasers in that it uses an electric current rather than a light source. It is frequently used in dermatology to treat skin laxity, rhytides, acne vulgaris and scarring, and cellulite. The goal of this review is to summarize the various types of RF devices and their uses and to determine the evidence-based efficacy of these devices. Materials and methods: This article reviews the current literature on RF, its uses and clinical effectiveness, and a practical guide for application of the assorted RF devices. Results and conclusion: Results have been favorable for the different clinical uses of RF, but many studies are nonrandomized, noncomparative trials that use subjective means of evaluation. Overall, nonablative RF is a safe, tolerable, and effective tool for skin rejuvenation and cellulite treatment that produces modest results. RF should serve as an alternative but not as an equivalent substitute to surgery.