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IJIR: Your Sexual Medicine Journal
https://doi.org/10.1038/s41443-018-0024-8
ARTICLE
An initial study on the effect of functional electrical stimulation in
erectile dysfunction: a randomized controlled trial
Cristiane Carboni 1●Alexandre Fornari1●Karoline C. Bragante1●Marcio A. Averbeck 1●
Patrícia Vianna da Rosa1●Rodrigo Della Mea Plentz1
Received: 7 April 2015 / Revised: 27 December 2017 / Accepted: 12 February 2018
© Macmillan Publishers Limited, part of Springer Nature 2018
Abstract
Erectile dysfunction (ED) affects approximately 150 million men worldwide. Functional electrical stimulation (FES) therapy
has shown a high regenerative capacity for smooth muscle cells and, therefore, is being increasingly adopted. FES can be a
beneficial treatment option when the cause of ED is related to degeneration of cavernous smooth muscle. To evaluate the
impact of FES on erectile function in men with erectile dysfunction. Twenty-two patients with ED participated in this
randomized clinical trial. Participants were randomly assigned to two groups: intervention (IG) or control (CG). IG
participants underwent FES therapy (50 Hz/500 µs) for a total of 4 weeks, divided into two weekly sessions lasting 15 min
each, with intensity lower than the motor threshold. CG participants were treated with placebo FES and followed the same
routine as the IG. Erectile function was assessed by the validated International Index of Erectile Function (IIEF-5) and
Erection Hardness Score (EHS), applied before and after treatment, and quality of life, by the WHOQOL questionnaire.
Statistically significant differences in IIEF-5 and EHS were found between the IG and CG after treatment (p< 0.05), as well
as a within-group difference in the IG when comparing the post-treatment periods (p< 0.0001) The WHOQOL revealed a
significant difference between CG and IG after treatment (p< 0.05), as well as a within-group difference in the IG after
treatment (p< 0.0001), except in the Environment domain, in which there was no difference between the pre- and post-
treatment periods (50.9 ± 2.8 pre vs. 52.3 ± 3.1 post). This trial showed that FES therapy may improve erectile function and
quality of life in men with ED.
Introduction
Erectile dysfunction (ED) is defined as the persistent failure
to achieve and sustain erections of sufficient rigidity for
penetration during sexual intercourse [1]. The etiology of
ED can be either psychogenic (such as anxiety or depres-
sion, which can potentially diminish the awareness of sen-
sory experience) or organic (vasculogenic and neurological
abnormalities, for example). Sexual dysfunction can affect
patients’lives in a variety of ways, including disorders in
interpersonal relationships, interference with sex life,
problems with partners, and increased mental stress, making
ED a major quality of life (QoL) issue [2].
Despite the availability of several pro-erectile drugs,
there are many men who, for one reason or another, do not
derive benefit from these agents. Indeed, up to 35% of men
with ED do not respond to phosphodiesterase type 5
(PDE5) inhibitors [3], and discontinuation rates are report-
edly high (35 to 45%) [4,5]. The reasons for non-adherence
to treatment include fear of possible side effects and high
drug costs [6]. Consequently, there is an unmet need for the
development of alternative, conservative approaches for ED
management.
Physical therapy interventions offer noninvasive meth-
ods that are painless, inexpensive, and easy to perform.
Studies [7,8] have shown positive results for men who
attended a pelvic-floor reeducation program for patients
with ED. The understanding of possible conservative
treatments for ED is connected to erection physiology. Even
when dealing with diverse forms of ED, the major potential
change can occur in the penile endothelium [9]. This is
*Cristiane Carboni
criscarboni@hotmail.com
1Department of Health Science and Rehabilitation, Federal
University of Health Sciences of Porto Alegre–UFCSPA,
Porto Alegre, Rio Grande do Sul, Brazil
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important to highlight because the penile endothelium is the
site of secretion of nitric oxide (NO), considered the main
factor involved in immediate relaxation of smooth muscle
cells of the penile blood vessels and corpus cavernosum.
NO generated in the endothelium plays a relevant role in
erection maintenance and in endothelial dysfunction, con-
tributing to many subgroups of ED. Animal model studies
have shown that functional electrical stimulation (FES) has
a regenerative effect on the endothelium, with increased NO
release [10,11]. The regeneration of the cavernous smooth
muscle prompted by FES should result in the spontaneous
return of erectile capacity, if no other factors are involved in
the etiology of ED [12]. Within this context, the aim of this
study was to evaluate the effect of FES in the treatment of
ED.
Materials and methods
This study was approved by the Ethics Committee in
Research of the Universidade Federal de Ciências da Saúde
de Porto Alegre, number 926.000. This study was a ran-
domized controlled clinical trial (ClinicalTrials.gov identi-
fier NCT02284659). We randomized 22 patients, aged 40 to
65 years, with known ED (defined as a score of less than 22
on the IIEF-5), who had been in a stable relationship for
more than 6 months and not taking any ED medication. The
exclusion criteria adopted were: neurogenic ED (due to
spinal cord injury, Parkinson’s disease, multiple sclerosis,
prostatectomy); hypogonadism (total testosterone < 300 ng/
dl); decompensated diabetes mellitus (fasting blood glucose
> 200 mg/dl and/or glycated hemoglobin > 8%); decom-
pensated systemic arterial hypertension (SBP > 160 and/or
DBP > 100); morbid obesity; diagnosis of coronary heart
disease and/or cerebrovascular disease; and inability to
understand the study objectives/technique or to provide
informed consent.
If patients were previously taking any commercially
available drug or non-drug treatment for ED (e.g., injection
therapy, topical applications, herbal, or alternative medi-
cines, vacuum-assisted erection devices), such treatments
should have been terminated at, or before, the screening
visit and should not have been used at any time during the
study until the final evaluation. Patients who were on PDE5
inhibitors were asked to complete a 4-week wash-out period
before enrollment in the trial and not to use it until the last
evaluation after finishing the treatment.
Randomization was carried out in two steps: generation
of random numbers in each group, using the RANDOM
subroutine of the PEPI software suite (computer programs
for epidemiologists); and allocation concealment, which
was ensured by placing numbers in letter-sized manila
envelopes.
Participants were randomly assigned to two groups:
intervention (IG) or control (CG). The intervention group
received FES therapy (50 Hz/500 µs) for a total of 4 weeks,
divided into two weekly sessions lasting 15 minutes each,
with intensity set lower than the motor threshold that was
assessed individually. Two self-adhesive electrodes mea-
suring 3 cm each were used. One electrode was placed at the
base of the penis, while the second was attached 2 cm below
the first one. The control group was treated with placebo
FES machine (the red light functioning but there was no
power). Both groups attended sessions twice a week for a
period of 4 weeks, for a total of 8 FES sessions. Erectile
function was assessed by the validated International Index
of Erectile Function (IIEF-5) and Erection Hardness Score
(EHS) instruments. Quality of life (QoL) was assessed with
the validated WHOQOL-BREF questionnaire. All of the
questionnaires were applied before and immediately after
the treatment. The instruments were completed by a blinded
investigator, according to the protocol to which the patient
had been randomized. Only the physiotherapist who applied
the technique was aware of group allocation. Participants
had no treatment costs.
Statistical analysis
Statistical analysis was performed in SPSS Version 22.0
(IBM, Chicago, IL, USA). Data are reported as mean ±
SEM. The generalized estimating equations model was used
to test for significant differences in different visits and time
points, according to each treatment. Differences were
declared significant if p< 0.05.
Results
During the study period, 22 patients with ED visited a
private outpatient physical therapy service. All participants
met the inclusion criteria and none were excluded. The
22 subjects completed the study as shown in the CONSORT
flow diagram of patient randomization and analysis (Fig. 1).
Both groups showed a similar distribution of demo-
graphic variables at baseline (Table 1). Within-group ana-
lysis of results in the CG and collected through the EHS and
IIEF-5 questionnaires, administered before and after treat-
ment, showed no statistical difference (Table 2). Within-
group assessment of the results in the intervention group,
collected through the same instruments, demonstrated sta-
tistically significant differences (p< 0.001) (Fig. 2), as well
as variation in pre- and post-treatment scores between the
groups (p< 0.05) (Table 2), (Fig. 2).
Regarding the quality of life questionnaire (WHOQOL-
BREF), CG participants exhibited statistically significant
improvement in the psychological (47.3 ± 2.2 pre-post 50.4
C. Carboni et al.
±2,p< 0.0001*) and personal relationships (39.5 ± 3.5 pre-
post 43.6 ± 4.5, p< 0.0001*) domains. Other domains
showed no statistically significant difference.
Fig. 1 CONSORT flow diagram
of patient randomization and
analysis
Table 1 Characteristics of the sample
Variable Total sample IG
(n=11)
CG
(n=11)
p
Age 58.5 ± 5.3 58.6 ± 5.3 58.4 ± 5.8 .940
Race .534
White 19 (86.3) 10 (90.9) 9 (81.8)
Black 3 (13.7) 1 (9.1) 2 (18.1)
Scholarship 5 (4–8) 5 (4–8) 5 (4–8) 1.0
Smoker 12 (54.5) 5 (45.4) 7 (63.6) .392
Alcoholic 5 (22.7) 3 (27.2) 2 (18.1) .611
Table 2 Comparison between groups and intra groups regarding EHS
and IIEF-5 questionnaire
Placebo Intervention
Variable Pre Post Diff Pre Post Diff
EHS 1.64 ±
0.19
1.82 ±
0.17
.18 1.73 ±
0.13
2.82 ±
0.3*
1.1†
IIEF-5 11.4 ± 1.3 11.4 ± 1.4 0 11 ± 1.2 16 ± 1.7*5†
Value are Mean ± SEM
Generalized Estimating Equations Model was used to test for
significant differences at different visits and time points according to
each treatment
EHS erection hardness score, IIEF-5 International index of erectile
function-5, Diff mean difference post-treatment
*p< .0001 from Pre in each questionnaire, †p< 0.05 Comparison
between questionnaire changes
Fig. 2 Individual changes in the EHS score (a) and IIEF-5 score (b)
An initial study on the effect of functional electrical stimulation in erectile dysfunction: a. . .
Within-group analysis of the IG showed significant dif-
ferences in all areas, except the environment domain (50.9 ±
2.8 pre-post 52.3 ± 3.1). On between-group analysis of
WHOQOL-bref domains, the only area in which no sig-
nificant differences were observed was the environment
domain (Table 3).
Discussion
The results of this trial showed two statistically significant
improvements in the intervention group. First, according to
IIEF-5 and EHS scores, there was a statistically significant
difference in the erectile function in the relationship
between the IG pre- and post-treatment with the CG (p<
0.05) (Table 2). Secondly, there was a statistically sig-
nificant difference between the pre-treatment and post-
treatment time points in the IG (p< 0.0001) (Table 2). In the
WHOQOL-BREF questionnaire, only the environment
domain showed no significance difference in the IG, while
in the CG, there was no difference in any questionnaires.
Individual analysis of each participant revealed a placebo
effect in some of them, but the statistical analyses did not
show any difference in final score.
Upon sexual stimulation, penile erection, occurring in
response to the activation of pro-erectile autonomic path-
ways, is greatly dependent on adequate inflow of blood to
the erectile tissue and requires coordinated arterial
endothelium-dependent vasodilatation and sinusoidal
endothelium-dependent cavernosal smooth muscle relaxa-
tion [13]. NO is the principal peripheral pro-erectile neu-
rotransmitter, released both by parasympathetic-nitrergic
autonomic nerves and by the sinusoidal endothelium to
produce cyclic GMP (cGMP) and relax cavernosal smooth
muscle, ultimately resulting in increased intracavernosal
pressure [10]. Studies [10,14] in animals support the view
that FES causes NO and cGMP formation in the corpus
cavernosum, as assessed by monitoring the simultaneous
formation of nitrite (the spontaneous oxidation product of
NO) and cGMP. This is one possible explanation for the
positive results of the present study, in which both erection
hardness and erectile function were evaluated. We intended
to translate these principles to the bedside by applying them
to real-world patients with ED. Electron microscopy studies
have already shown that ED is often caused by cavernous
smooth-muscle degeneration [15,16]. In these patients,
drugs, penile prosthetics, or the application of a vacuum
device seemed to be the only treatment possible. Con-
sidering experimental studies on cavernous smooth-muscle
cells [17], we now have the knowledge that smooth-muscle
growth is easily inducible and that FES is an established
method for muscle regeneration [2]. Therefore, FES should
be considered as a treatment for ED.
In 1995, Stief et al. [12] conducted a similar study and
found similar results in the intervention group, but as there
was no control group, the placebo effect could not be
evaluated. However, the aforementioned study found that
some patients who had exhibited an insufficient response to
vasoactive drugs started to respond after the intervention.
Unfortunately, this possibility was not tested in our study.
In 2000, Myung-cheol Gil et al. [18] reported a statistically
significant improvement in erectile function, maintenance of
erection, intercourse satisfaction, and overall satisfaction
after FES treatment for ED.
ED is a complex and multidimensional condition, asso-
ciated with psychological and relationship concerns,
including decreased QoL and self-esteem and an increased
incidence of depression and interpersonal relationship pro-
blems [19,20] which demonstrates the importance of
evaluating QoL in this group of patients. Laumann et al.
[21] have noted that health status, stress, life satisfaction,
and deterioration of general health and emotional functions
are strongly correlated with sexual dysfunction. As in our
study, they concluded that the social relationships and
psychosocial well-being domains of QoL are particularly
impaired in men with ED. Therefore, we believe that, by
Table 3 Comparison between
groups and intra groups
regarding WHOQOL-BREF
questionnaire
Placebo Intervention
Variable Pre Post Diff Pre Post Diff
WQ–PH 50 ± 2.1 50 ± 2.1 0 52.3 ± 3 67.7 ± 4.1*15.4†
WQ–P 47.3 ± 2.2 50.4 ± 2*3.1 47.3 ± 2 67.3 ± 2.9*20†
WQ–SR 39.5 ± 3.5 43.6 ± 4.5*4.1 41.8 ± 2.4 66.8 ± 4*25†
WQ–E 50.9 ± 2.9 53.2 ± 3 2.3 50.9 ± 2.8 52.3 ± 3.1 1.4
Value are Mean ± SEM
Generalized Estimating Equations Model was used to test for significant differences at different visits and
time points according to each treatment
WQ WHOQOL-BREF, PH physical health, Ppsychological, SR social relationships, Eenvironment,
Different mean difference Post-treatment
*p< .0001 from Pre in each treatment, †p< 0.05 Comparison between treatment changes
C. Carboni et al.
restoring sexual function, one can also improve QoL levels.
Although we had good QoL outcomes in the intervention
group, the small number of sessions prevents a definitive
conclusion; long-term results are needed before we can
claim that our protocol restores sexuality-related QoL. It is
hard to explain both lack of placebo effect in the CG and the
good improvement in the QoL of the IG. Looking indivi-
dually some of the control had a bit improvement but was
not significant. And the few sessions that was done might
gave a feeling of enthusiasm for the intervention. But this is
just speculations. We would need a bigger study to have
more conclusive data about the results.
Our findings suggest that FES for ED is feasible and has
some beneficial effect on erectile capacity and QoL in our
patients. One limitation of our study is the small sample
size, although it was sufficient to show a clear statistical
difference in terms of recovery of erectile function on
comparison to the control group. Another limiting factor
was the length of follow-up, which was insufficient to allow
evaluation of long-term results. Further studies should be
carried to corroborate our results, aiming to improve the
methods of evaluation establishing the physiopathology
pathways of the FES in the NO release, and finding selec-
tion criteria for patients suitable for this treatment.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
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