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Chang et al. BMC Urology (2024) 24:237
https://doi.org/10.1186/s12894-024-01633-2 BMC Urology
*Correspondence:
I-Ni Chiang
inichiang@gmail.com
1Department of Urology, College of Medicine, National Taiwan
University Hospital, National Taiwan University, No. 7, Zhongshan S. Rd.,
Zhongzheng Dist., Taipei City 100, Taiwan
2College of Medicine, National Taiwan University Hospital, National Taiwan
University, Taipei, Taiwan
Abstract
Background Among the emerging treatments for erectile dysfunction (ED), platelet-rich plasma (PRP), known for its
ability to enhance tissue repair and regeneration, stands out as a promising therapeutic approach. In this innovative
study, we aimed to assess the ecacy of intracavernous injections of platelet lysate (PL), a derivative of PRP, in
improving erectile function among ED patients.
Methods We enrolled twenty-six patients, aged between 35 and 70 years (mean age 51.6 ± 11.3 years), who had
been experiencing ED for over six months and had an International Index of Erectile Function-5 (IIEF-5) score of 21 or
less. Participants received autologous PL injections intracavernously every two weeks for a total of ve administrations.
We assessed Erection Hardness Score (EHS) and International Index of Erectile Function-5 (IIEF-5) bi-weekly for 16
weeks and conducted penile Doppler ultrasounds pre- and post-treatment to record peak systolic velocity (PSV) and
resistance index (RI).
Results Before treatment, the mean EHS was 2.15 ± 0.88 and IIEF-5 was 10.92 ± 5.28. Remarkable improvements
were observed post-treatment, with the EHS signicantly increasing to 3.15 ± 0.83 (p < 0.05) and IIEF-5 to 17.23 ± 5.26
(p < 0.05). Penile Doppler ultrasound exhibited an increase in both PSV and RI post-treatment, with the rise in RI being
statistically signicant.
Conclusions Our ndings indicate that intracavernous injections of PL substantially enhance erectile function, as
evidenced by improvements in EHS, IIEF-5, and the RI of penile Doppler ultrasound, without hemorrhagic events or
other adverse reactions apart from temporary pain at the injection site during the 16-week follow-up period. These
encouraging results suggest that PL injections are a safe and eective treatment modality for patients with moderate
ED, potentially providing a less invasive and more physiologically friendly alternative to current ED management
strategies.
Trial registration The study received approval from the Institutional Review Board of National Taiwan University
Hospital (IRB Number 202008061RIPC, date of registration 08/28/2020).
Keywords Erectile dysfunction, Platelet-rich plasma, Platelet lysate, Intracavernous injection
Clinical ecacy of intracavernous injection
of platelet lysate for erectile dysfunction
Yi-KaiChang1, I-NiChiang1*, Hong-ChiangChang1, Yi-HuiChen2 and Shih-Chieh JeChueh1
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Chang et al. BMC Urology (2024) 24:237
Introduction
Erectile dysfunction (ED), characterized by the persis-
tent inability to attain or sustain an erection sufficient for
satisfactory sexual performance, is a multifactorial con-
dition with both physical and psychosocial contributors.
Traditional management strategies encompass lifestyle
adjustments, cardiovascular exercise, administration of
phosphodiesterase-5 (PDE5) inhibitors with differing
pharmacokinetics, vacuum erection devices, intracavern-
ous alprostadil injections, and penile prosthesis implan-
tation. In a breakthrough for regenerative medicine,
low-intensity shock wave therapy has been introduced as
an innovative treatment, primarily targeting vasculogenic
ED due to its potential to enhance penile blood flow and
stimulate neovascularization [1].
In recent years, a surge in both preclinical and clini-
cal research has focused on the therapeutic potential
of platelet-rich plasma (PRP) in the realm of ED. PRP, a
preparation obtained from centrifuged autologous blood,
is essentially a concentrated source of platelets, encom-
passing various growth factors and cytokines known
to augment tissue regeneration and healing [2]. An
advanced form of PRP is platelet lysate (PL), achieved by
lysing the platelets, thereby ensuring the comprehensive
release of their reservoir of growth factors. is configu-
ration not only maximizes the availability of growth fac-
tors but also maintains an exceedingly low white blood
cell count, less than 1%, minimizing the risk of immune
reactions and inflammatory responses. PL has been
reported to be effective in treating osteoarthritis, radic-
ular pain, and promoting wound healing due to its high
concentration of growth factors and low levels of white
blood cells, which contribute to accelerated tissue regen-
eration, enhanced wound healing, and reduced inflam-
matory response [3].
Recent studies have illuminated the promise of PRP
and its derivatives in ED management. For instance, a
systematic review by Mohammad et al. demonstrated
that PRP therapy could significantly enhance erectile
function scores in men, paralleling the effects of other
common ED treatments without accompanying systemic
side effects [4]. Similarly, a review and study in 2022 con-
solidated evidence from multiple trials, underscoring the
potential benefits of PRP injections in improving erectile
function, particularly among patients with vasculogenic
ED [5, 6].
Furthermore, a 2023 study by Shaher et al. investigated
the safety and efficacy of PRP injections in men with ED
and concluded that the treatment was associated with
significant improvements in erectile function and penile
hemodynamics, without any serious adverse events [7].
In another compelling study by Tai et al. in 2023, the
findings suggested a potential role for PRP therapy not
only in managing ED in rat model but also in potentially
reversing underlying pathophysiological mechanisms,
emphasizing rat the regenerative capacity of PRP [8].
Additionally, a few research papers provided evidence
supporting the concept that combining PRP therapy with
other regenerative strategies, such as stem cell therapy or
shock wave treatment, might offer synergistic benefits,
paving the way for comprehensive regenerative therapeu-
tic protocols for ED [9, 10].
In the context of these scientific advances and the
potential of regenerative medicine, our study aims to
explore the efficacy of intracavernous injections of PL
in treating ED. We assessed this by comparing pre- and
post-treatment Erection Hardness Score (EHS), the
International Index of Erectile Function-5 (IIEF-5), and
penile Doppler ultrasound findings, seeking not only to
corroborate the findings of previous research but also to
contribute new insights into the evolving landscape of
ED therapy.
Materials and methods
Patient selection and ethical approval
e study received approval from the Institutional
Review Board of National Taiwan University Hospi-
tal (IRB Number 202008061RIPC). Inform consent
were given and signed by all the patients. Male partici-
pants experiencing erectile dysfunction for more than
6 months, with an International Index of Erectile Func-
tion-5 (IIEF-5) score of ≤ 21 and aged between 30 and 70
years, were enrolled for the platelet lysates (PL) study.
Exclusion criteria included coagulopathy, prior penile
surgery or trauma, pelvic radiation therapy within the
last 12 months, previous pelvic surgery, and psychogenic
erectile dysfunction (Fig.1).
Platelet lysates (PL) preparation
Twenty mL of peripheral blood was collected from each
patient and infused into Aeon CPKit tubes (Aeon Bio-
therapeutics Corp., Taipei, Taiwan) in each session.
Tubes filled with 10 mL of blood were then centrifuged
at 1650g for 8min and gently inverted repeatedly. Tube
filled with 10 mL of blood was then centrifuged at 1650g
for 8min and gently inverted repeatedly. e tubes were
then centrifuged multiple times at 1650g for 8min until
platelet-rich fibrin formed. Centrifugation was per-
formed 1 to 2 times until the platelet-rich fibrin was com-
pressed into a thin layer on top of the separation gel, and
PL was released from the fibrin. Eight to 10 mL of PL was
collected from 2 tubes and prepared for injection.
Platelet lysates (PL) injection
Autologous PL was administered every two weeks for a
total of 5 sessions. All injections were performed by the
same clinician. Eight to 10 mL of PL was injected using
a 30-gauge needle at equal proportions into the bilateral
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Chang et al. BMC Urology (2024) 24:237
distal, middle, and proximal corpus cavernosum, totaling
6 injection sites (Fig.2).
Penile doppler ultrasound
Penile Doppler ultrasound with intracavernous alprosta-
dil injection was conducted pre-treatment and 16-week
post-treatment (Fig.3).
Data analysis: questionnaire and penile doppler
ultrasound
e pre-treatment evaluation included the Erection
Hardness Score (EHS), IIEF-5, and penile Doppler
ultrasound with peak systolic velocity (PSV) and resis-
tance index (RI). EHS and IIEF-5 were assessed every
two weeks for 16 weeks. Two months after the 5th PL
Fig. 2 Schematic representative of platelet lysate (PL) injections. Six Injection sites viewed from underneath of penis indicate by syringe icons (A). Injec-
tion is shown in cross-section view of penis (B)
Fig. 1 Flow diagram regarding the experimental procedure and criteria of inclusion and exclusion
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Chang et al. BMC Urology (2024) 24:237
treatment, patients were also evaluated with post-treat-
ment penile Doppler ultrasound. All data differences
were analyzed using one-way ANOVA, and differences
between groups were assessed using paired t-tests. A P
value of < 0.05 was considered statistically significant.
Results
Between 2021 and 2022, a total of 30 patients with erec-
tile dysfunction participated in the PL treatment study.
Four patients were excluded due to a history of previ-
ous penile surgery, penile trauma, or current use of
antipsychotics.
Among the 26 patients who received five intracav-
ernous injections of PL, the mean age was 51.6 ± 11.3
years (ranging from 35 to 70 years). Pre-treatment
mean Erection Hardness Score (EHS) and International
Index of Erectile Function-5 (IIEF-5) were 2.15 ± 0.88
and 10.92 ± 5.28, respectively. Following treatment, EHS
increased significantly to 3.15 ± 0.83 (p < 0.05), and IIEF-5
increased to 17.23 ± 5.26 (p < 0.05) ( Table 1; Fig.4). Sub-
jectively, 80.7% of patients reported an improvement in
sexual performance, describing enhancements such as
easier erection, increased hardness, prolonged erection,
more morning erections, easier maintenance of erection,
decreased plaque, and increased girth. Among patients
with improvement, pretreatment IIEF-5 ranged from 4 to
21, while those without improvement had a pretreatment
IIEF-5 ranging from 5 to 10. Considering patient charac-
teristics, including hyperlipidemia, hypertension, diabe-
tes mellitus, and testosterone levels, only hyperlipidemia
showed a negative impact on PL treatment.
Both EHS and IIEF-5 showed significant improve-
ment two weeks after the first PL injection (Figs.4 and
5). Furthermore, EHS and IIEF-5 continued to gradu-
ally improve with repeated injections (Fig. 6; Table 2).
We subdivided the initial IIEF score to mild, moderate,
and severe ED and found IIEF-score increased in all
groups. e patients with mild to moderate ED improved
with one injection of PL. e patients with severe ED
improved after at least three injections (Fig. 7). e
details of IIEF-score were listed in Table2.
Post-treatment peak systolic velocity (PSV) and resis-
tance index (RI) from penile Doppler ultrasound both
increased compared to pre-treatment values, with RI
showing statistically significant improvement (Table 3).
Table 1 Patients’ characteristics
Total Positive Negative P-Value
N 26 21 5
Age 51.6 ± 2.3 51.1 ± 2.5 53.4 ± 5.5 0.7
Duration of ED (Year) 4.7 ± 1.2 5.09 ± 0.5 1.8 ± 0.4 0.24
BMI 24.8 ± 0.5 24.5 ± 0.5 26.1 ± 1.4 0.26
Testosterone 4.7 ± 1.2 5.4 ± 1.5 3.4 ± 1.0 0.15
Benign prostatic hyperplasia 12 9 3 0.51
Hypertension 7 6 1 0.71
Smoking 6 5 2 0.33
Hyperlipidemia 9 5 4 0.016 *
CVA 1 1 0 0.635
CAD 3 3 0 0.38
DM 2 2 0 0.492
(All data repr esent mean ± SEM)
Fig. 3 Doppler ultrasound Images of vascular ow in penis
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Chang et al. BMC Urology (2024) 24:237
No hemorrhagic events or other side effects were
observed.
Discussion
Our study demonstrated a substantial increase in Inter-
national Index of Erectile Function-5 (IIEF-5) scores (by
an average of 6.31 points) in patients after five sessions
of PL injections. Notably, there was no deterioration in
Erection Hardness Score (EHS) or IIEF-5, and no compli-
cations were reported post-injection. Patients with mild
to moderate ED showed improvements after the first
injection of PL, while those with severe ED experienced
improvements after the third injection. Continuous
improvements were observed in patients with mild, mod-
erate, or severe ED. In consideration of patients’ char-
acteristics, hyperlipidemia showed significant negative
Fig. 5 EHS scores on week 0, 2, 4, 6, 8 and 16 after PL injections
Fig. 4 International Index of Erectile Function (IIEF-5) (A) and Erection Hardness Score (EHS) (B) scores on week 0 and 16 after PL injections
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Chang et al. BMC Urology (2024) 24:237
effects on PL therapeutic effects for ED. Patients with
ED should receive at least 3 to 5 PL injections to achieve
satisfactory outcomes, although hyperlipidemia may
compromise these results. is offers valuable clinical
insights for physicians considering PL cavernous inter-
vention for ED patients. Doppler ultrasound analyses
also indicated significant improvements in the Resistive
Index (RI) following the treatment sessions. In summary,
PL injections have proven effective in enhancing erectile
function from both objective and subjective standpoints,
thereby improving the overall quality of life for patients
with erectile dysfunction.
Today, innovative treatments such as Platelet-Rich
Plasma (PRP), Low-Intensity Shockwave erapy (Li-
SWT), and stem cell therapy are at the forefront of
erectile dysfunction (ED) management [11, 12]. PRP is
procured from blood and contains platelet concentra-
tions that are significantly higher, about 2 to 7 times, than
that found in normal plasma, making it rich in growth
factors [13, 14].
e therapeutic potential of blood-derived PRP and PL
in regenerative medicine is noteworthy, given the com-
position of platelets’ releasates. ese include adhesive
proteins, angiogenic factors, growth factors, chemokines,
clotting factors, inhibitors, integral membrane proteins,
immune mediators, and other bioactive substances.
Key among these are platelet-derived growth factors
(PDGF), transforming growth factor-β (TGF-β), insu-
lin-like growth factor (IGF), fibroblast growth factor-2
(FGF-2), and vascular endothelial growth factor (VEGF)
[15]. ese growth factors are integral for processes like
Table 2 EHS score and scores to each questions in IIEF-5 questionnaire on week 0, 2, 4, 6, 8,16 after PL injections. All data represent mean ± SEM(n=26).
Symbol a, b, c, d and e indicate P<0.05 when compared to scores on week 0, 2, 4, 6, 8, respectively
Fig. 6 Scores to question 1 to 5 in IIEF-5 questionnaire on week 0, 2, 4, 6, 8 and 16 after PL injections (A, B, C, D, and E)
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Chang et al. BMC Urology (2024) 24:237
wound healing and angiogenesis, the growth of new
blood vessels [16].
In the field of clinical urology, the application of PRP
has transcended experimental phases, showing promise
in the treatment of conditions like erectile dysfunction
[17], both male and female stress urinary incontinence
[18, 19], persistent BK virus-induced hemorrhagic cys-
titis [20], and more. PRP has demonstrated efficacy in
mid-shaft hypospadias repair by reducing urethral steno-
sis and post-operative infection rates [21], and in offer-
ing protection against recurrent urinary tract infections
by improving the expression of cytoskeletal and barrier
function proteins, including CD34, Shh, CK20, M2, and
M3 [22]. Remarkably, patients with interstitial cystitis
showed significant symptom improvement and a change
in urinary markers after receiving PRP injections [23].
Experimental models also indicate the potential of PRP
in mitigating urethral stricture by reducing mucosal
inflammation and spongiofibrosis [24], protecting rat tes-
tes from ischemia-reperfusion injury [25], and even pro-
viding renal protection in cases of obstructive uropathy
[26].
Animal studies further substantiate the regenera-
tive properties of PRP. Ding et al. observed that PRP
facilitated cavernous nerve regeneration, improved
intracavernous pressure, and increased the presence
of myelinated axons and NADPH-diaphorase-positive
nerve fibers in a rat model [27]. Another study demon-
strated that regular intracavernous PRP injections over
four weeks improved erectile function parameters in
hyperlipidemia rats, outperforming the group without
PRP treatment [28]. Additionally, Wu et al. reported
that PRP injections post-bilateral cavernous nerve injury
enhanced erectile function recovery and decreased cellu-
lar apoptosis [29]. Further, an optimized PRP preparation
protocol showed superior therapeutic outcomes in tissue
recovery [30], and high levels of C-X-C motif chemokine
ligand 5 (CXCL5) in PRP were found to ameliorate ED by
preventing penile smooth muscle atrophy [31].
Transitioning from animal models to human applica-
tion, Matz et al. reported positive outcomes with PRP
injections in patients with ED and Peyronie’s disease
between 2012 and 2017, noting improvements in IIEF-5
scores without any significant complications other than
Table 3 Resistant index (RI) and peak systolic velocity (PSV) were
measured and analyzed by Doppler ultrasound on week 0 and 16
after PL injections
Time, weeks 0 16 P-value
RI 0.81 ± 0.02 0.87 ± 0.02 0.01
PSV 39.39 ± 3.12 46.41 ± 3.62 0.07
(Each value is r epresented by mean ± SEM f or n = 26. P < 0.05 indicates signic ant
dierence f rom the value of week 0.)
Fig. 7 IIEF-5 questionnaire scores at weeks 0, 2, 4, 6, 8, and 16 following PL injections in patients with mild, moderate, or severe ED. Values represent the
mean ± SEM for n = 11, 9, and 6 in patients with mild, moderate, or severe ED, respectively. Symbols a, b, and c indicate P < 0.05 when compared to week
0 scores in patients with mild, moderate, or severe ED, respectively
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Chang et al. BMC Urology (2024) 24:237
injection-site pain [2]. Other studies, including those
by Zaghloul et al. and Poulios et al., echoed these find-
ings, showing significant improvements in IIEF scores in
patients with ED who were refractory to traditional phos-
phodiesterase-5 (PDE5) inhibitors [32, 33]. Furthermore,
Geyik et al. suggested that combining Li-SWT with PRP
could enhance treatment outcomes, including a pro-
longed intravaginal ejaculatory latency time (IELT) [10].
e regenerative capabilities of PRP, which promote
angiogenesis and tissue repair, are particularly relevant in
the context of ED, often caused by inadequate blood flow or
nerve damage. Huang et al. [28] conducted a comprehensive
study, which underscored the potential of PRP in treating
ED, particularly due to its angiogenic properties. e study
suggested that the growth factors in PRP could reverse
endothelial dysfunction, a common contributor to ED.
Moreover, the safety profile of PRP is an essential aspect
of its applicability. A systematic review by Panunzio et al.
[34] in 2023 emphasized the minimal invasiveness and
low adverse event rates of PRP injections, making them a
compelling treatment option for patients who might not
respond to conventional therapies or for those who are
seeking alternatives to pharmacological treatments.
e synergy between PRP therapy and other ED treat-
ments also warrants discussion. Towe et al. [35] studied
the combination of PRP with other regenerative thera-
pies, including stem cells and shockwave therapy, and
found that the combined treatment modalities could
potentially have a synergistic effect, offering a new ave-
nue for patients who have not responded to singular
treatment modalities.
Despite the promising results of PRP therapy in pre-
clinical studies and clinical trials, there remains a need
for larger-scale, randomized, double-blinded, placebo-
controlled studies to validate the efficacy and safety of
PRP in the management of ED. A large-scale randomized
controlled trial should be considered and conducted to
evaluate the results of this study. A study by Fadadu et
al. [36] emphasized the importance of standardization
in platelet-rich plasma (PRP) preparation methods. ey
highlighted the significant variability in these methods,
which can impact the concentration of platelets and lev-
els of certain growth factors, potentially influencing the
outcomes of treatments.
Finally, the cost-effectiveness of PRP treatments is an
important consideration for widespread adoption. Britt
et al. [37] examined the economic aspects of PRP therapy
for the management of ED and concluded that although
PRP therapy holds promise, the associated costs of the
procedure are substantial. e authors advocate for
larger-scale randomized control trials to assess the long-
term efficacy of PRP in managing ED. Such trials may
provide essential information to determine whether PRP
should be considered a routine treatment.
Conclusion
In conclusion, while our study and others highlight the
potential benefits of PRP and PL therapies in manag-
ing ED, further investigations are needed to standardize
treatment protocols, assess long-term efficacy and safety,
evaluate synergy with other treatments, and analyze cost-
effectiveness. As these therapies continue to evolve, they
may offer new hope for patients with ED, particularly
those for whom conventional treatments are ineffective,
contraindicated, or unwanted.
Abbreviations
ED Erectile Dysfunction
PRP Platelet-Rich Plasma
PL Platelet Lysate
EHS Erection Hardness Score
IIEF-5 International Index of Erectile Function-5
PSV Peak Systolic Velocity
RI Resistance Index
PDE5 Phosphodiesterase-5
Li-SWT Low-Intensity Shockwave Therapy
PDGF Platelet-Derived Growth Factors
TGF-β Transforming Growth Factor-β
IGF Insulin-like Growth Factor
FGF-2 Fibroblast Growth Factor-2
VEGF Vascular Endothelial Growth Factor
CXCL5 C-X-C motif chemokine ligand 5
IELT Intravaginal Ejaculatory Latency Time
Supplementary Information
The online version contains supplementary material available at https://doi.
org/10.1186/s12894-024-01633-2.
Supplementary Material 1: Additional le 1. File format: .xls. Title of data:
Table 2. EHS score and scores to each question in IIEF-5 questionnaire on
week 0, 2, 4, 6, 8,16 after PL injections. Description of data: All data rep-
resent mean ± SEM(n=26). Symbol a, b, c, d and e indicate P<0.05 when
compared to scores on week 0, 2, 4, 6, 8, respectively.
Supplementary Material 2
Supplementary Material 3
Acknowledgements
The authors appreciate the contributions of all the healthcare teams involved
and all the patients enrolled in this study.
Author contributions
All the authors contributed equally to conceptualization and study design,
data acquisition, data analysis and interpretation, writing—original draft
preparation, writing—review and editing. All authors have read and agreed to
the published version of the manuscript.
Funding
This research did not receive any specic grant from funding agencies in the
public, commercial, or not-for-prot sectors.
Data availability
Data is provided within the supplementary information les.
Declarations
Ethics approval and consent to participate
The study received approval from the Institutional Review Board of National
Taiwan University Hospital (IRB Number 202008061RIPC, date of registration
08/28/2020). Participation in this study is entirely voluntary. Prior to any data
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Page 9 of 9
Chang et al. BMC Urology (2024) 24:237
collection, all participants are provided with detailed information regarding
the purpose, procedures, potential risks, and benets of the research. They
are also informed about their rights as participants, including the right to
withdraw from the study at any time without penalty.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Received: 25 April 2024 / Accepted: 21 October 2024
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