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OPEN
ORIGINAL ARTICLE
A clinical study to assess the effectiveness of a hyaluronic acid-
based procedure for treatment of premature ejaculation
A Littara
1,2
, B Palmieri
3,4
, V Rottigni
3,4
and T Iannitti
4,5
Premature ejaculation is a sexual debilitating condition affecting a large number of men worldwide and leading to important
dysfunctions influencing the patients’ affective and emotional life. Hyaluronic acid is a natural and safe compound that has been
widely used not only in the aesthetic medicine clinic, but also for treatment of osteoarthritis. The present study shows the
effectiveness of a hyaluronic acid-based procedure for treatment of premature ejaculation. A hundred and ten male patients were
treated with hyaluronic acid injections in the deep dermis of their glans penis to increase the volume and the circumference of their
penis to prevent male premature ejaculation and improve the patients’ and their partners’ sexual satisfaction. The intravaginal
ejaculation latency time increased significantly from a baseline value of 88.34±3.14 s to 293.14±8.16 s after 6 months from the
procedure. Maximal glandular circumference increased from 98.51±0.71 mm to 114.35±0.66 mm after 6 months from the
procedure. At 6-month follow-up, patients’ self-rated satisfaction was 5.3±0.07 (range: 4–6). At the follow-up, partners’ self-rated
satisfaction was 5.1±0.09 (range: 3–6). The present clinical study showed that hyaluronic acid injection is a promising treatment for
premature ejaculation. The effect of the procedure in the long-term follow-up needs to be clarified.
International Journal of Impotence Research (2013) 25, 117–120; doi:10.1038/ijir.2013.13; published online 4 April 2013
Keywords: augmentation; filler; glans; hyaluronic acid; penis
INTRODUCTION
Premature ejaculation (PE) is a common sexual debilitating
dysfunction affecting 20–30% of all men worldwide.
1,2
A
definition of PE has not been standardized yet
3
because of
the large and controversial debate surrounding this term.
However, in medical practice, this term is commonly defined as
‘the ejaculation that regularly occurs at or around initial vaginal
penetration’,
4
and it is not the result of a prolonged absence from
sexual activity.
5
To achieve a precise diagnosis, the specialist often
relies only on the patient’s history without further laboratory or
physiological tests.
1
PE pharmacological treatment includes the
use of antidepressants, local anesthetic agents and phospho-
diesterase type 5 inhibitors; currently, dapoxetine represents the
only short-acting selective serotonin reuptake inhibitor licensed
for PE treatment.
1
Filler materials have been extensively used for
soft tissue augmentation in aesthetic surgery, but it is only
recently that they have found an important application in the field
of glans penis augmentation allowing to achieve a volume
sufficient to prevent PE.
2,6
Abdallah et al.
2
evaluated the effect
of hyaluronic acid in 60 men affected by PE, demonstrating
that intravaginal ejaculation latency time (IELT) increased 1 month
after the injection of the compound in their penis. Furthermore,
in 2008, another study
6
reported positive results in a 5-year
long-term study in which hyaluronic acid gel was injected in
38 men. They demonstrated that IELT decreased if compared to
6-month follow-up, but it was still higher if compared with the
pretreatment period. The patients and their partners reported
high satisfaction for the procedure consisting in 76% and 63%,
respectively.
Aim
The aim of this study was to investigate the effectiveness of
hyaluronic acid injection in the deep dermis of the glans penis to
increase the volume and the circumference of the penis to
prevent male PE and improve the patients’ and their partners’
sexual satisfaction. The rationale for this procedure is to increase
the dermis thickness of the glans embedding the nervous fibres in
highly cross-linked hyaluronic acid atmosphere to reduce
sensitivity of penile reflexes.
MATERIALS AND METHODS
Patients
A total of 171 male patients were screened between June 2009 and March
2011. A hundred and ten male patients, aged between 25 and 42 years
(32.78±0.33; mean±standard error of the mean (s.e.m.)), affected by PE,
were included in this study. For the purposes of the present investigation,
PE was defined as involuntary ejaculation during foreplay or within 1 min
of penetration on at least 50% of occasions when attempting intercourse.
7
Patients were selected at our clinic where the study was performed.
Inclusion criteria were a stable, monogamous and heterosexual
relationship for at least 12 months. Exclusion criteria were a history of
medication that can affect ejaculation 6 months before the beginning of
the study, a history of drug abuse within 2 years before enrollment for the
procedure, a history of or current major psychiatric disorder (psychiatric
consultation was conducted at the time of enrollment), such as mood and
anxiety disorders, schizophrenia, other psychotic disorders, alcoholism,
erectile dysfunction and patients’ or partners’ decreased interest in sexual
intercourse or other forms of sexual dysfunction. No other medication of
psychotherapy was allowed during the study period.
1
Centro di Medicina Sessuale, Milan, Italy;
2
Istituto di Laser-Chirurgia Sessuale, Milan, Italy;
3
Department of General Surgery and Surgical Specialties, University of Modena and
Reggio Emilia Medical school, Surgical Clinic, Modena, Italy;
4
Poliambulatorio del Secondo Parere, Modena, Italy and
5
Institute for Membrane and Systems Biology, University of
Leeds, Leeds, UK. Correspondence: Dr T Iannitti, Institute for Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, UK.
E-mail: tommaso.iannitti@gmail.com
Received 13 April 2012; revised 9 October 2012; accepted 8 February 2013; published online 4 April 2013
International Journal of Impotence Research (2013) 25, 117 –120
&
2013 Macmillan Publishers Limited All rights reserved 0955-9930/13
www.nature.com/ijir
Surgical procedure
The present study was performed according to the Helsinki declaration
and local internal review board approval was obtained (it is available for
viewing upon request from the Editor-in-Chief). All patients signed
the informed consent. Each patient, comfortably sitting, was injected
with a 28-G needle containing 1 ml of 1% lidocaine and prilocaine
(Astra Pharmaceuticals, Milan, Italy) to induce local anesthesia. The
circumference of the glans penis (deep connective tissue of the corpus
spongiosum) was divided into three circles (from the base of the glans at
a 1-cm distance from each other). The circles were then divided into
quarter circles. An injection, containing 1ml hyaluronic acid (Variofill;
Adoderm GmbH, Langenfeld, Germany) was performed in the deep
dermis into every quarter circle with a 27-G needle for a total of
12 injections performed in a single session (Figure 1). The patients’
and partners’ satisfaction was rated on the basis of a scale 1–10
(1 ¼dissatisfied ; 10 ¼satisfied). IELT, a subjective measure defined as the
time between the start of vaginal intromission and the start of
intravaginal ejaculation, was evaluated for each couple. Evaluations
about the increase of glans circumference and patients’ and partners’
satisfaction were also performed. Following the procedure, the patients
did not receive any further aesthetic treatment.
Patients and partners were asked to self-rate their satisfaction with
sexual intercourse before and after the procedure, using a scale from 1 to 6
(1 ¼not satisfied; 6 ¼very satisfied). This information was collected by an
allied health-care professional and kept in our clinic database.
Statistical analysis
All data are represented as the means±s.e.m., and were first
checked for normality using the Anderson–Darling test. All statistical
analysis was conducted using Minitab, v15, Leeds, UK. A paired
t-test was used to compare IELT and maximal glandular circumference
before and after treatment. A value of Po0.05 was considered
significant.
RESULTS
At baseline, patients’ self-rated satisfaction with sexual inter-
course was 1.2±0.04 (Figure 4a). Partners’ self-rated satisfac-
tion with sexual intercourse was 1.3±0.05 (Figure 4b).
Treatment was well tolerated. No dropout or uncompleted
procedure was reported. No pain was observed when perform-
ing local anesthesia. No inflammatory signs or other adverse
reactions were observed in all cases. The IELT increased
Figure 1. (a–c) The circumference of the glans penis is virtually subdivided into three circles (starting from the base of the glans penis at a
distance of 1 cm from each other). Then, each circumference is further subdivided into quarter circles where 1 ml of hyaluronic acid is injected.
0
50
100
150
200
250
300
350
Before treatment After treatment
***
IELT (s)
60
90
120 ***
Maximal glandular
circumference (mm)
a
b
Figure 2. (a). IELT (s) and (b) maximal glandular circumference (mm)
before and after surgical procedure. Data are presented as the
group mean±s.e.m.
***
Po0.001.
A hyaluronic acid-based procedure for premature ejaculation
A Littara et al
118
International Journal of Impotence Research (2013), 117 – 120 &2013 Macmillan Publishers Limited
significantly from 88.34±3.14 s to 293.14±8.16 s after 6 months
from the procedure (Po0.001; Figure 2a). Maximal glandular
circumference, measured by tapeline, increased from 98.51±
0.71 mm as measured before treatment, to 114.35±0.66 mm at
6months(Po0.001; Figure 2b; Figure 3). At 6-month follow-up,
patients’ self-rated satisfaction with sexual intercourse was
5.3±0.07 (Po0.001; Figure 4a). At the follow-up, partners’ self-
rated satisfaction with sexual intercourse was 5.1±0.09 (Po0.001;
Figure 4b).
DISCUSSION AND CONCLUSIONS
The present study shows that hyaluronic acid injection can be
effectively used for treatment of PE, allowing to achieve a
significant increase in IELT. At 6-month follow-up, IELT was still
significantly higher, if compared with baseline values. The
maximal glandular circumference was significantly increased at
6-month follow-up. Self-rated patients’ and partners’ sexual
satisfaction was rated as 5 or 6 by 90 and 74 subjects, respectively,
at 6-month follow-up. According to the present study, the
procedure is well tolerated without adverse reactions. This article
describes an original hyaluronic acid-based approach to treat PE
and well confirms the favourable outcome previously reported in
an experimental study in rabbits and dogs
8
where hyaluronic acid
was injected into the glans penis proving its potential for
glandular augmentation. In fact hystological analysis showed
that hyaluronic acid can still be found in the lamina propria of the
glans penis after 6 months.
8
Another two studies performed in
men by the same research group,
9,10
also support the use of
hyaluronic acid as a safe and effective approach for glans penis
augmentation and treatment of PE. Findings from our study
also support the use of hyaluronic acid for treatment of PE.
Further studies, with a follow-up extending beyond 6 months, are
necessary to determine with precision the long-term therapeutic
capacity of this treatment. Hyaluronic acid has been widely
used in aesthetic surgery, and complications are very rare and
promptly manageable by expert surgeons. Therefore, it is possible
that such a procedure, based on the protocol we are proposing,
may be integrated in the aesthetic clinic and performed on a
routine basis.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
ACKNOWLEDGEMENTS
This work was not supported by grants. Written informed consent was obtained from
the patients for publication of the data and images included in this manuscript. A copy of
the written consent is available for review by the Editor-in-Chief of this journal.
AUTHORS’ CONTRIBUTION
The authors contributed equally to this work. The authors hereby certify that all
work contained in this manuscript is original. The authors claim full
responsibility for the contents of the article.
Figure 3. Clinical situation (a) before and (b) after hyaluronic acid injection in the glans penis.
0
1
2
3
4
5
6
***
Patients' self-r ated satisfac tion
with sexual interc ourse
Before Treatment After Treatment
0
1
2
3
4
5
6
***
Partners' self -rated satisf acti on
with sexual interc ourse
a
b
Figure 4. Patients’ (a) and partners’ (a) self-rated satisfaction with
sexual intercourse before and after surgical procedure. Data are
presented as the group mean±s.e.m. ***Po0.001.
A hyaluronic acid-based procedure for premature ejaculation
A Littara et al
119
&2013 Macmillan Publishers Limited International Journal of Impotence Research (2013), 117 – 120
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