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- Original Article -
Peyronie's disease: a silent consequence of diabetes mellitus
A. Tefekli1, E. Kandirali2, B. Erol1, M. Tunc1, A. Kadioglu1
1Department of Urology, Istanbul University, Istanbul Medical Faculty, Istanbul 343 90, Turkey
2 Department of Urology, Izzet Baysal Medical Faculty, Abant Izzet Baysal University, Bolu 14 280, Turkey
Aim: To investigate the clinical characteristics of patients with Peyronie's disease (PD) and diabetes mellitus (DM).
Methods: During an 8-year period, a total of 307 men seen at our outpatient clinic were diagnosed with PD. Clinical
characteristics, penile deformities and the erectile status of patients with PD and DM together
(n = 102) were retrospectively analyzed and compared to patients with PD alone with no risk factors for systemic vascular diseases
(n = 97). Results: The prevalence of PD among men with DM and sexual dysfunction was 10.7 %. The mean age
of diabetic patients with PD was (55.9 ± 8.9) years; in the no risk factor group it was (48.5 ± 9.0) years
(P < 0.05). The median duration of DM was 5 years. The majority of diabetic patients with PD (56.0 %) presented in the chronic
phase (P < 0.05), and they were more likely to have a severe penile deformity
(> 60°) than the no risk factor group
(P < 0.05). In the diabetic group, the most common presenting symptom was penile curvature (81.4 %), followed
by a palpable nodule on the shaft of the penis (22.5 %) and penile pain with erection (14.7 %). A total of 19.6 % of
patients were not aware of their penile deformities in the diabetic group. Erectile function, provided by history and in
response to intracavernosal injection and a stimulation test, was significantly diminished in patients with PD and DM
(P < 0.05). Conclusion: DM probably exaggerates the fibrotic process in PD. Diabetic patients with PD have a
higher risk of severe deformity and erectile dysfunction (ED). PD seems to be a silent consequence of DM and
should be actively sought in diabetic men. (Asian J Androl 2006 Jan; 8: 75-79)
Keywords: Peyronie's disease; diabetes mellitus; erectile dysfunction; penile deformity; fibrosis
Correspondence to: Dr Ates Kadioglu, M.D., Department of
Urolo-gy, Istanbul University, Istanbul Medical Faculty,
Istanbul 34390, Turkey.
Tel: +90-212-6351-203, Fax: +90-212-6358-184
Received 2004-11-15 Accepted 2005-04-12
Peyronie¡¯s disease (PD) is a localized connective
tissue disorder that primarily affects the tunica albuginea
of the penis and is characterized by an initial
inflammatory reaction followed by fibrous inelastic scar
formation . The result is a fibrous plaque on the shaft of the
penis that contains an excessive amount of collagen and
fibroblastic proliferation . Penile pain with erection
and a palpable nodule on the shaft of the penis are other
clinical hallmarks during the acute phase of the disease,
which lasts for approximately 12-18 months . The
chronic phase commences when the penile deformity stabilizes and pain diminishes. Erectile dysfunction (ED),
due either to difficulty in penetration as a result of a
disabling penile deformity or diminished erectile capacity
resulting in an inability to maintain or sustain a
satisfactory penile erection, may be a presenting symptom and
is reported in 20.0 %-54.4 % of men with PD in different series .
The disease is considered to have a multifactorial
etiology in nature. The most widely accepted theory is
that it is caused by an abnormal fibrotic reaction of the
tunica albuginea to repetitive microtrauma to the erect or
flaccid penis, with inherited predisposition to
exaggerated fibrotic response . Recent studies have also
documented the role of several cytokines, such as
transforming growth factor-b (TGF-b), basic fibroblast growth
factor and platelet derived growth factor in the pathogenesis
and fibrotic reactions of extracellular matrix changes in
PD [1, 4-7]. Diabetes mellitus (DM) is also associated
with abnormalities in extracellular matrix composition, such
as collagen accumulation and fibrosis . The
stimulatory influence of hyperglycemia on factors related to
extracellular matrix remodeling has been documented in
experimental studies . Penile corporeal tissues from
diabetic men also demonstrate increased fibrosis .
Furthermore, DM is a leading risk factor for sexual
dysfunction and 18.3 %-33.0 % of men with PD have been
reported to have DM [2, 11].
However, the clinical relationship between DM and
PD is still obscure. Thus, the aim of this study is to
in-vestigate the demographic findings of patients with both
PD and DM and look at how DM affects the clinical characteristics, presenting symptoms and erectile status
of patients with PD.
2 Materials and methods
During an 8-year period, a total of 5 942 men with
sexual problems were seen at our outpatient andrology
clinic. They were evaluated with a detailed sexual and
medical history and multiple serum analyses, to
investigate the presence of DM, hypertension,
hypercholestero-lemia, hypertriglyceridemia and ischemic heart disease.
Physical examination was focused on abnormalities of
external genitalia and the extent of palpable induration on
According to the National Institute of Health (NIH)
Consensus , patients with a consistent inability to
attain and maintain a penile erection sufficient to permit
satisfactory sexual intercourse were diagnosed as
having ED. All patients in our study were given an
intracav-ernous injection of 60 mg papaverine hydrochloride
combined with manual genital self-stimulation (Combined
Injection and Stimulation [CIS] test), performed in
private to induce maximal erection and to overcome
sympathetic overactivity due to anxiety, in order to assess the
degree of tumescence, as well as the location and degree of
curvature of the penis . The criteria for a positive
erectile response to the CIS test were determined by the
occurrence of an erection (buckling pressure
> 500 gr) within 10 min and maintaining this state for at least
10 min. In cases where the penile deformity exceeded 30°, the bucklometer
was not used to assess the axial rigidity of the penile
erection. A vacuum erection device (VED) was used to
achieve full erection in patients with a negative response
to the CIS test. If present, the degree of curvature of
the penis was measured with a protractor during
maximum erection in response to the CIS test and/or VED,
when patients described the erection they had achieved as
similar as or better than they had been at home. Penile
deformities were documented by photographs or drawing.
A modified Kelami¡¯s classification was used to categorize
penile deformities as follows: mild deformity, a curvature
of 30° or less; moderate, a curvature of 31-60°; severe, a
curvature greater than 60° [2, 11].
Of the patients with ED, 16.0 % (n = 951) were found
to have DM (92 type I DM, 859 type II DM). They
were all further evaluated in detail by an experienced
diabetio-logist. The erectile status of patients with uncontrolled
DM was assessed after their serum glucose and HgbA1C
levels normalized. During the same period, 307 out of a
total of 5 942 patients were found to have PD. The
clinical characteristics of these patients were also analyzed
and 102 of them (33.2 %) (12 type I DM, 90 type II DM) were found to have DM. No risk factor could be
identified in 97 men (31.6 %). The remaining men with
a risk factor other than DM, such as hypertension,
hyper-cholesterolemia, hypertriglyceridemia or ischemic heart
disease, were excluded from the study. The patients with
PD and DM characteristics (Group 1) were compared to
patients without risk factors (Group 2).
The clinical parameters and erectile status of patients
in each group were analyzed and statistical analyses were
performed using unpaired t-test and the
c2 test. P < 0.05 was considered to be statistically significant. Data were
expressed as Mean ± SD.
Of the 5 942 men presenting with sexual problems
during the 8-year period, 951 (16.0 %) had DM, 5.1 %
(n = 307) of the 5 942 men with sexual dysfunction were
diagnosed to have PD. The prevalence of DM among men with PD was 33.2 %
(n = 102), and the prevalence of PD in the diabetic population with ED was calculated
to be 10.7 % (102/951).
Of the patients admitted to our clinic with sexual
problems, 897 of 951 (94.3 %) with DM and 167 of
307 (54.4 %) with PD complained of ED. The remaining
patients complained of sexual problems such as
premature ejaculation and penile deformity without PD.
The mean age, degree of deformity, presenting
symptoms and duration of PD of both groups are summarized
in Table 1. Overall, the mean age of patients with PD
was (52.8 ± 9.3) years. The mean age of patients with
PD and DM (Group 1) and those with no risk factors
(Group 2) was (55.9 ± 8.9) years and (48.5 ± 9.0) years,
respectively (P < 0.05). The median duration of DM in
men enrolled to the study was 5 years (range 3 months-15 years).
In the diabetic group, the most common presenting
symptoms were penile curvature (81.4 %), a palpable
nodule on the shaft of the penis (22.5 %) and penile pain
with erection (14.7 %), usually combined with other
symptoms (Table 1). Although the mean degree of
deformity was similar in both groups, a higher percentage
of diabetic patients with PD exhibited severe penile
deformity greater than 60° (Table 1), which was
statistically significant (P < 0.05). Dorsal curvature was the
most common type of deformity in both groups. A total
of 20 (19.6 %) men with DM (mean age 63.7 ± 7.3 years),
and 9 (9.2 %) men with no risk factors were not aware of
their penile deformity, and were identified during standard
investigation for ED. This difference was also statistically
significant (P < 0.05, Table 1). The presenting symptoms in
Group 2 were penile curvature (91.0 %), penile pain with
erection (29.0 %) and palpable nodule (24.3 %). Penile
pain with erection as a presenting symptom was
encountered significantly less often in men with DM, when
compared with those with no risk factors (Table 1).
In the diabetic group, the median period between the
initial diagnosis of DM and the occurrence of PD-related
symptoms was 3 years (range 1 month-15 years). Overall, 62.9 % of patients with PD with no risk factors
and 44.6 % of patients with PD with DM presented in
the acute phase (P < 0.05, Table 1).
Evaluations of erectile capacity by history and CIS
test are summarized in Table 2. In Group 1, 83.0 %
complained of ED by history and 69.0 % had a poor response
to the CIS test. In Group 2, 41.9 % complained of ED
by history and 30.8 % had a poor response to the CIS
test (P < 0.05).
ED is an increasingly common clinical problem around the world and is known to be a frequent
complication of DM. The overall incidence of ED in the
general population between the ages of 40 years and 70 years
is reported to be 52 %. Men with DM develop ED at an
earlier age with a significantly high prevalence, ranging
from 20 % to 85 % . In a recent study, the
prevalence of undiagnosed DM was found to be higher in men
with ED than that in the general population . Both
neurogenic and vascular factors are important
determinants in the pathogenesis of ED. DM also affects both
systems and frequently results in ED as a long-term
complication. Numerous studies have shown
histopathological changes responsible for ED in diabetic
patients . Several authors described ED as another "silent
complication" of DM .
In addition to the functional problems of the penis,
structural abnormalities also attract attention, and PD is
the most important acquired deformity of the penis.
Although it has been considered a rare condition,
large-scale epidemiological studies have demonstrated high
prevalence rates of PD, up to 3.2 % .
Recently, molecular studies have documented the role
of several cytokines, such as TGF-b, as detrimental
factors for collagen accumulation and extracellular matrix
composition alterations . Studies on patients with DM
have also shown extracellular matrix alterations and
collagen accumulation to be responsible for several
complications such as diabetic nephropathy [6, 8, 9]. Bollineli
et al.  clearly indicated a regulatory role of
TGF-b in renal glomerular collagen synthesis, and suggested a
possible causal role for enhanced collagen synthesis in the
diabetic rat. A systemic change of extracellular matrix
metabolism is observed in DM, and it is found in the
penis of men with PD, where TGF-b also plays a major
role in the pathogenesis . Thus, DM seems to be a
major risk factor of PD. The further difficulty in wound
healing observed in DM may also be a part of this pathology, and all these mechanisms together suggest
that DM exacerbates the pathogenesis of PD. However,
a recent study demonstrated that there was no statistical
relationship between penile curvature severity and risk
factors, including DM . On the contrary, DM had a
statistically significant negative impact on the severity of
penile deformity and erectile capacity, assessed by
history and CIS test in our study (Table 2). This
discordance with the paper by Usta et al.  can be explained
by the different demographic characteristics of the study
groups, the type and frequency of sexual intercourse, as
well as ethnic differences between populations. This
should be investigated in further large-scale, multicenter
studies by multivariate analysis.
A number of studies and clinical reviews have
investigated erectile function in men with DM . Men with
DM face problems related to sexual dysfunction at an early
age. However, our results indicate that diabetic patients
with PD are diagnosed in their mid-50s and their mean age
is higher than those with no risk factors (Table 1).
Patients with PD and DM also present in the later stages of
the disease. This may be related to the fact that diabetic
patients with ED recognize and seek help for their penile
deformities later than those without ED or risk factors.
These men may also have more crucial problems related
to DM which they have to deal with urgently before
addressing their sexual dysfunction. This may be another
contributing factor in their presenting in the later stages of PD.
Penile pain with erection is a significant presenting
symptom in PD . However, our results have shown
that this symptom is not prevalent among diabetic
patients with PD (Table 1). This may be another factor
leading to late presentation and may be explained by the
fact that they may not have sufficient rigid erections and
that neurological problems may lessen their pain perception. In addition to significantly different
presenting symptoms, a total of 19.6 % patients with PD and
DM together and 9.2 % patients with PD and no risk
factors were not aware of their penile deformity, and
were identified during standard investigation for ED. This
difference was also statistically significant. The incidence
of incidentally diagnosed PD in men presenting with ED
was reported to be 16.0 % in a cohort of 448 cases ,
and this ratio correlated well with our results.
Our results show that diabetic patients with PD are
more likely to have a severe penile deformity exceeding
60° (Table 1). It can be speculated that systemic changes
in extracellular matrix metabolism and increased
TGF-b production in response to hyperglycemia [8, 9] and
relevant advanced glycation end products  in patients
with DM and PD exacerbate fibrotic changes in the penis.
Another explanation may be the fact that insufficient
erections during intercourse in diabetic patients may lead to
increased trauma to the penis, resulting in increased
fibrotic reaction . All of these factors underline the
importance of early diagnosis of problems related to
erection in diabetic men, in order to initiate appropriate
treatment in the acute phase. Medical treatment has been
documented to improve deformities in 30 % of all
patients with PD . However, further studies are needed
to establish the efficacy of medical treatment in diabetic
patients with PD.
Recent experimental studies have documented encouraging results in the prevention of fibrosis and ED.
Decorin, an anti-TGF-b agent previously used in the
prevention of experimental diabetic nephropathy, has been
used in the treatment of an experimental PD-like
condition in rats, and its antifibrotic activity has been
reported . In another study, the protective effect of amino
guanidine on erectile function in diabetic rats has been
demonstrated . With our increasing knowledge of the
pathogenesis of PD in diabetic patients, significant
improvements in the prevention of fibrotic changes of the penis
and other organs related to DM will be achieved.
There are several controversies regarding erectile
function in men with PD. The prevalence of sexual
dysfunction as a presenting symptom is reported in
different series to range from 20.0 % to 54.4 % [2, 3].
Although the excessive angulations due to curvature,
painful erection, tender plaque and performance anxiety may
all contribute to ED, it has been shown that penile
vascular abnormalities are responsible for ED in 61 %-70 %
of patients with PD [3, 13]. The role of veno-occlusive
dysfunction and arterial disease has also been shown in
PD with ED, although it is not easy to determine the
exact etiologic factor in every case [3, 13]. Furthermore,
patients with PD, presenting most commonly in their 50s,
may only reflect the conditions of potency of age-matched
patients without PD [2, 3]. Although our results suggest
a high prevalence of penile vascular abnormalities,
further objective studies, preferably with penile Doppler
ultrasonography, are needed to clarify vascular
abnormalities in diabetic patients with PD. However, the same
management algorithm for ED is valid in this group of
In conclusion, PD may be considered another silent
consequence of DM, with a prevalence of 10.7 % in
diabetic patients with ED. Diabetic patients with PD have
strikingly different characteristics. They usually present
with severe penile deformity in their mid-50s, most
often with ED. Penile pain with erection is less commonly
observed, and 19.1 % are not aware of their penile
deformity. All of these factors underline the importance
of evaluation of erectile function as well as penile
deformity in diabetic men.
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