# When fibrosis intersect: Association and risk factors between Peyronie's and Dupuytren's diseases

Valentine Lethuillier, Benoît Peyronnet, Claire Richard, Charles-Karim

Bensalah, Romain Mathieu, François Robin, Antoine Faix, Jean-Luc Roux, Lucas Freton

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► To cite this version:

Valentine Lethuillier, Benoît Peyronnet, Claire Richard, Charles-Karim Bensalah, Romain Mathieu, et al.. When fibrosis intersect: Association and risk factors between Peyronie's and Dupuytren's diseases. French Journal of Urology, 2024, 34 (14), pp.102759. 10.1016/j.fjurol.2024.102759. hal-04846514

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Original article

# When fibrosis intersect: Association and risk factors between Peyronie's and Dupuytren's diseases

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# Quand les fibroses se croisent : lien et facteurs de risque entre les maladies de Lapeyronie et Dupuytren

Valentine Lethuillier<sup>a,*</sup>, Benoit Peyronnet<sup>a</sup>, Claire Richard<sup>a</sup>, Charles-Karim Bensalah<sup>a</sup>, Romain Mathieu<sup>a</sup>, François Robin<sup>b</sup>, Antoine Faix<sup>c</sup>, Jean-Luc Roux<sup>d</sup>, Lucas Freton<sup>a</sup>

## ARTICLE INFO

**Keywords:**

Penile induration

Dupuytren contracture

Fibrosis

Risk factors

## ABSTRACT

**Introduction:** Peyronie's and Dupuytren's diseases are benign but are source of significant functional impairment leading to considerable suffering. In this study, the aim is to investigate the association between Peyronie's and Dupuytren's diseases as well as their common and specific risk factors.

**Material and methods:** From July 2022 to March 2024, we conducted a multicentric observational study on 450 patients. Patients followed up for Peyronie's and/or Dupuytren's disease were given a questionnaire that included a consent form, in order to screen one or the other associated disease and explore all risk factors.

**Results:** Among the 278 patients followed for Dupuytren's disease, 35 (12.3%) had Peyronie's disease. Of the 172 patients with initial Peyronie's disease, 50 (29.1%) were diagnosed with Dupuytren's disease. Eventually, 85 patients had both pathologies (18.9%). High blood pressure was significantly more prevalent in patients with both diseases, compared to subjects with Peyronie's disease only (37.7% vs. 38.4% vs. 24.4%; P = 0.02). The same observation was made regarding smoking (62.3% vs. 60.7% vs. 48.8%; P = 0.05) and daily alcohol consumption (52.9% vs. 41.7% vs. 35.8%; P = 0.04). Patients diagnosed with isolated Dupuytren's disease were more likely to be diabetic (13.6% vs. 9.41%; P = 0.42). Blue eyes and family history were significantly more often reported in Dupuytren's patients (33.9% vs. 22.8%; P = 0.03; P < 0.001). Ledderhose disease was significantly more prevalent in patients with both diseases or isolated Dupuytren's disease (21.2% vs. 12.4% vs. 3.3%; P = 0.0003).

**Conclusion:** This study confirms the association between Peyronie and Dupuytren diseases. Smoking, alcohol daily consumption and hypertension are more prevalent in case of associated diseases. Blue eyes and family history are significantly more frequently found in case of Dupuytren's contracture. More powerful studies including a control group are necessary.

**Level of evidence:** 2.

© 2024 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

## RÉSUMÉ

**Mots clés:**

Maladie de Lapeyronie

Maladie de Dupuytren

Fibrose

Facteurs de risque

**Introduction** : Dans cette étude, l'objectif était d'évaluer l'association entre les maladies de Lapeyronie et de Dupuytren ainsi que leurs facteurs de risque communs et spécifiques.

**Matériel et méthodes** : Nous avons mené une étude observationnelle transversale multicentrique (un centre hospitalier universitaire, une clinique mutualiste et deux cliniques privées en France). Les patients suivis en

<footnote><sup>a</sup> Département d'urologie, CHU de Rennes, Rennes, France</footnote>

<footnote><sup>b</sup> Département de rhumatologie, CHU de Rennes, Rennes, France</footnote>

<footnote><sup>c</sup> Département d'urologie, clinique Saint-Roch Montpellier, Montpellier, France</footnote>

<footnote><sup>d</sup> Département d'orthopédie, clinique Saint-Roch Montpellier, Montpellier, France</footnote>

<footnote>* Corresponding author. Service d'urologie, CHU Pontchaillou Rennes, 2-3, rue Henri-Le-Guilloux, 35000 Rennes, France.</footnote>
consultation pour une maladie de Lapeyronie et/ou de Dupuytren entre juillet 2022 et mars 2024 ont reçu un questionnaire intégrant un consentement, visant à dépister l'une ou l'autre des maladies associées et à explorer l'ensemble des facteurs de risque.

**Résultats** : Sur cette période, 450 patients sur 686 sollicités ont été inclus. Parmi les 278 patients suivis pour une maladie de Dupuytren, il existait une maladie de Lapeyronie chez 35 (12,6 %). Chez les 172 patients suivis initialement pour une maladie de Lapeyronie, une maladie de Dupuytren a été diagnostiquée chez 50 sujets (29,1 %). Au total, 85 patients étaient atteints des deux pathologies (18,9 %). L'hypertension artérielle, le tabagisme et la consommation quotidienne d'alcool étaient significativement plus prévalents chez les patients ayant les deux maladies associées par rapport aux sujets ayant une maladie de Lapeyronie isolée (37,7 % vs. 38,4 % vs. 24,4 % ; *p* = 0,02 / 62,3 % vs. 60,7 % vs. 48,8 % ; *p* = 0,05 / 52,9 % vs. 41,7 % vs. 35,8 % ; *p* = 0,04). Les patients avec une maladie de Dupuytren avaient plus souvent les yeux bleus que les patients avec une maladie de Lapeyronie isolée (33,9 % vs. 22,8 % ; *p* = 0,03). Des antécédents familiaux de Dupuytren étaient significativement plus souvent retrouvés chez les patients atteints d'une maladie de Dupuytren isolée ou associée (*p* < 0,001). La maladie de Ledderhose était significativement plus prévalente chez les patients atteints des deux maladies ou de Dupuytren isolé (21,2 % vs. 12,4 % vs 3,3 % ; *p* = 0,0003).

**Conclusion** : Cette étude confirme l'association entre les maladies de Lapeyronie et de Dupuytren. Les facteurs de risque communs déjà connus tels que le tabac, l'alcool et l'hypertension artérielle sont plus prévalents en cas d'association des pathologies par rapport à une maladie de Lapeyronie isolée. La prévalence de patients aux yeux bleus était plus élevée chez les hommes atteints de maladie de Dupuytren.

**Niveau de preuve** : 2.

© 2024 Les Auteurs. Published by Elsevier Masson SAS. This article is published in Open Access under a Creative Commons Attribution 4.0 License (http://creativecommons.org/licenses/by/4.0/).

# 1. Introduction

Peyronie's disease is a progressive fibrosing condition of the tunica albuginea, around the corpora cavernosa of the penis. It affects 0.4% to 20% of men in the general population, with an average age at onset around 53 years [1-5].

Various risk factors have already been identified, such as genital trauma, smoking, daily alcohol consumption, obesity, and high blood pressure [6-15].

Dupuytren's disease is the most common specific fibrosing organ disease [16]. Reported prevalences vary widely, ranging from 0.6% to 31.6% in the general population. It is more common in men, affecting 12% of the population over 55 years old and up to 29% in patients over 75 years old [17,18].

The disease has a multifactorial origin, mostly influenced by a significant family history [19,20], along with several non-genetic factors such as smoking, daily alcohol consumption, and diabetes [21]. It has been also hypothesized that autoimmune diseases, psoriasis, and repeated microtrauma could play a role in its pathophysiology [22,23].

Despite the fact that they are benign, these diseases cause significant physical and psychological suffering due to major functional impairment [24,25].

The likely association between these diseases was first reported in 1828 by Abernethy [26-29]. Indeed, their pathophysiology is very similar, involving processes such as inflammation, collagen degradation, ossification, and myofibroblast differentiation. Some studies suggest that men affected by one condition may be at higher risk of developing the other [31-33].

In both diseases, the role of a genetic factor has been described [34-38], although specific common genes implicated in both diseases have yet to be identified.

To date, and to our knowledge, no study has yet analyzed the association of these diseases reciprocally in a large number of patients, as well as all their potential risk factors.

This research gap is likely related to the complexity of Peyronie's diagnosis.

Indeed, it is an intimate subject that is not systematically discussed with patients, and its clinical diagnosis through palpation requires a certain level of expertise.

We used two different patient recruitment processes, in order to separate specific and common risk factors as well as to study each association independently.

The objective of our study was to investigate the association as well as the specific and common risk factors between Dupuytren's disease and Peyronie's disease.

# 2. Material and methods

## 2.1. Study design

We conducted a multicentric, cross-sectional, observational study using data from the urology departments of a University Hospital Center, three private practices, and the orthopedic department of a private practice in France.

Included patients were men aged 18 years or older, able to provide written consent, and diagnosed with either Peyronie's disease and/or Dupuytren's disease by a urologist or orthopedic surgeon. Patients were excluded from the study if they had a history of penile implant, were unable to answer to the questionnaire, or could not provide informed consent.

### 2.1.1. Questionnaire and data collection

The questionnaires were given at the four centers in clinics. Additional information were collected from the medical records (Supplementary material).

From July 2022 to March 2024, all patients seen for Peyronie's disease at the department of urology of one University Hospital Center and three private practices were offered inclusion in the study by completing a questionnaire (via email or paper) in order to identify associated Dupuytren's disease and various risk factors. Dupuytren's disease was systematically assessed during clinical examination by the urologist.

Likewise, all patients followed in the orthopedic department of a private practice for Dupuytren's disease were offered to complete a questionnaire to determine potential risk factors and any associated Peyronie's disease.

The questionnaire consisted of 23 questions written in French language, regarding patients' characteristics, lifestyle, risk factors, potential symptoms of Peyronie's/Dupuytren's disease, as well as the onset date of the disease. This questionnaire was elaborated in collaboration with expert urologists and orthopedists focusing on their experience, combined with literature data.

Penile curvature was measured by the urologist based on photographs during erection, with a goniometer-equipped application.

We assume that curvature degree is underestimated by an associated erectile dysfunction. When patients had severe erectile dysfunction, a
Doppler with induced by prostaglandin injection erection was asked in order to have an optimal assessment of the curvature degree.

Erectile dysfunction was assessed using the Erection Hardness Score.

Penetration difficulties were assessed by asking the patient whether sexual intercourse had been possible since the onset of the disease.

We did not distinguish between penetration difficulties related to the psychological impact of the curvature and those directly associated with the deformation itself.

## 2.2. Ethics

Patients provided written consent using the questionnaire (via email or paper).

An ethics committee reviewed and approved the study protocol (CERU).

The study was registered with the Commission Nationale Informatique et Libertés (CNIL) under the reference : 2234178v0.

## 2.3. Statistical analysis

Proportions were reported for nominal variables, median and ranges were used for continuous variables. Comparisons between groups were performed using $\chi^2$ test for discrete variables and using analysis of variance (ANOVA) for continuous variables with Bonferroni's correction for multiple comparisons. Statistical analyses were performed using JMP v.14.0 software (SAS Institute Inc, Cary, NC, USA) and Statistical Package for the Social Sciences (SPSS) 28.0 software.

All tests were two-sided with a significance level at $P < 0.05$.

# 3. Results

## 3.1. Patients' characteristics

From July 2022 to March 2024, we included 450 men.

Among the 278 patients initially diagnosed with Dupuytren's disease, 35 had Peyronie's disease (12.6%). Among the 172 patients followed for Peyronie's disease, Dupuytren's disease was diagnosed in 50 men (29.1%). In total, 85 patients were affected by both conditions, which represents 18.9% of the whole cohort (Table 1).

Dupuytren patients' median age at onset was 54.5 years (range: 42.1–66.9).

Regarding isolated Peyronie's disease, the median age at onset was 56 years (range: 17–73). When diseases were associated, median age at Peyronie's onset was 58 years (range: 30–78).

## 3.2. Common risk factors

Regarding common risk factors, hypertension was significantly more prevalent in patients with both diseases compared to those with isolated Peyronie's disease (37.7% vs. 38.4% vs. 24.4%; $P = 0.02$). The same observation was made regarding smoking (62.3% vs. 60.7% vs. 48.8%; $P = 0.05$) and daily alcohol consumption (52.9% vs. 41.7% vs. 35.8%; $P = 0.04$).

Ledderhose disease was significantly more prevalent in patients with both diseases (18/85 men) or isolated Dupuytren's disease (30/242 men)

<caption>**Table 2**</caption>

Results concerning common risk factors for both diseases comparing the 3 groups (Peyronie's only, Dupuytren's only and both diseases).

<table><thead><tr><th>Risk factor</th><th>Peyronie<br>n = 123</th><th>Dupuytren<br>n = 242</th><th>Peyronie-<br>Dupuytren<br>n = 85</th><th>P<br>value</th></tr></thead><tbody><tr><td>Smoking</td><td>60<br>(48.8%)</td><td>147<br>(60.7%)</td><td>54 (62.3%)</td><td>0.05</td></tr><tr><td>Daily alcohol</td><td>44<br>(35.8%)</td><td>101<br>(41.7%)</td><td>45 (52.9%)</td><td>0.04</td></tr><tr><td>High blood<br>pressure</td><td>30<br>(24.3%)</td><td>93 (38.4%)</td><td>32 (37.7%)</td><td>0.02</td></tr><tr><td>Diabetes</td><td>12 (9.8%)</td><td>33 (13.6%)</td><td>8 (9.4%)</td><td>0.42</td></tr><tr><td>Dyslipidemia</td><td>31<br>(25.2%)</td><td>68 (28.1%)</td><td>26 (30.6%)</td><td>0.50</td></tr><tr><td>Ledderhose</td><td>4 (3.3%)</td><td>30 (12.4%)</td><td>18 (21.2%)</td><td>0.0003</td></tr><tr><td>Autoimmune<br>disease</td><td>10 (8.1%)</td><td>11 (5.4%)</td><td>4 (4.7%)</td><td>0.49</td></tr><tr><td>Psoriasis</td><td>19<br>(15.5%)</td><td>43 (17.8%)</td><td>22 (25.9%)</td><td>0.14</td></tr></tbody></table>

compared to 4 out of 123 men in those with Peyronie's disease alone (21.2% vs. 12.4% vs. 3.3%; $P = 0.0003$).

The prevalence of an autoimmune disease was 4.7% in patients with both conditions (Table 2).

Eventually, 332 patients were diagnosed with one fibrosant disease (73.8%), 100 men had two of the fibrosant diseases (22.2%) and 18 contracted all three diseases (4%).

## 3.3. Dupuytren's specific risk factors and features

Patients with Dupuytren's disease more often had blue eyes compared to patients with isolated Peyronie's disease (33.9% vs. 22.8%; $P = 0.03$).

When combining green and blue eyes, there were 154 men with clear eyes out of 277 Dupuytren men (isolated or associated) whereas they were 80 over 173 in the global Peyronie's population ($P = 0.065$).

The proportions of manual workers were similar in patients with Dupuytren's disease and in those with Peyronie's disease (35% in isolated Dupuytren's vs. 35.3% in both diseases vs. 41.3% in isolated Peyronie's; $P = 0.40$).

A history of Dupuytren's disease among siblings was reported by 28 men of the Dupuytren-only group (11.7%) and by 11 men affected by both diseases (12.9%) compared to only 3.2% if they only had Peyronie's disease ($P = 0.015$).

A Dupuytren history affecting one or both parents was mentioned by 68 of Dupuytren's isolated men, 31 of patients with both disease versus only 9 of the Peyronie's group (28.5% vs. 36.5% vs. 7.1%; $P < 0.001$).

There was a significant difference between the groups in terms of history of Dupuytren's disease in second-degree relatives.

Indeed, the prevalence was 15% in the isolated Dupuytren population, 18.8% in the group with both diseases versus 4.8% in the Peyronie-only group ($P = 0.004$) (Table 3).

<caption>**Table 1**</caption>

Results concerning the association between the two diseases by studying the initial followed disease and the potential associated fibrosant disease (total number of patients diagnosed with both diseases = 85/450; 18.9%).

<table><thead><tr><th>Initially followed disease/<br>Associated disease</th><th>Peyronie's disease<br>n = 172</th><th>Dupuytren's disease<br>n = 242</th><th>Total<br>n = 450</th></tr></thead><tbody><tr><td>Association with the other fibrosant disease</td><td>50 (29.1%)</td><td>35 (12.6%)</td><td>85 (18.9%)</td></tr><tr><td>No association</td><td>123</td><td>242</td><td></td></tr></tbody></table>
<table><caption>**Table 3**

Results concerning specific risk factors of Dupuytren's disease comparing the 3 groups (Dupuytren's only, Peyronie's only or both diseases).</caption><thead><tr><th>Risk factor</th><th>Dupuytren<br>n = 242</th><th>Peyronie<br>n = 123</th><th>Dupuytren-Peyronie<br>n = 85</th><th>P value</th></tr></thead><tbody><tr><td>Manual profession</td><td>100 (41.3%)</td><td>43 (35%)</td><td>30 (35.3%)</td><td>0.40</td></tr><tr><td>Blue eyes</td><td>82 (33.9%)</td><td>28 (22.8%)</td><td>23 (27.1%)</td><td>0.09</td></tr><tr><td>Green eyes</td><td>49 (20.2%)</td><td>27 (22%)</td><td>25 (29.4%)</td><td></td></tr><tr><td>Clear eyes (blue & green)</td><td>131 (54.1%)</td><td>57 (46.3%)</td><td>46 (54.1%)</td><td>0.20</td></tr><tr><td>Right handed</td><td>211 (88.3%)</td><td>110 (94.8%)</td><td>75 (88.2%)</td><td>0.96</td></tr><tr><td>Family history (brother/sister)</td><td>28 (11.7%)</td><td>4 (3.2%)</td><td>11 (12.9%)</td><td>0.015</td></tr><tr><td>Family history (mother/father)</td><td>68 (28.5%)</td><td>9 (7.1%)</td><td>31 (36.5%)</td><td>&lt; 0.001</td></tr><tr><td>Family history (2nd degree relative)</td><td>36 (15%)</td><td>6 (4.8%)</td><td>16 (18.8%)</td><td>0.004</td></tr></tbody></table>

<table><caption>**Table 4**

Results concerning specific risk factors of Peyronie's disease comparing the 3 groups (Peyronie's only, Dupuytren's only or both diseases).</caption><thead><tr><th>Risk factor</th><th>Peyronie<br>n = 123</th><th>Dupuytren<br>n = 242</th><th>Peyronie-Dupuytren<br>n = 85</th><th>P value</th></tr></thead><tbody><tr><td>Congenital penile curvature</td><td>14<br>(11.1%)</td><td>0</td><td>13 (15.3%)</td><td>&lt; 0.001</td></tr><tr><td>Pelvic traumatism</td><td>1 (0.1%)</td><td>2 (0.1%)</td><td>2 (2.4%)</td><td>0.289</td></tr><tr><td>Endouretral surgery</td><td>16<br>(12.7%)</td><td>23 (9.6%)</td><td>11 (12.9%)</td><td>0.564</td></tr><tr><td>Genital surgery</td><td>15 (2%)</td><td>5 (11.9%)</td><td>1 (1.1%)</td><td>&lt; 0.001</td></tr><tr><td>Pelvic or abdominal surgery</td><td>9 (7%)</td><td>6 (2.5%)</td><td>2 (2.4%)</td><td>0.065</td></tr></tbody></table>

### 3.4. Peyronie's specific risk factors and features

A history of genital surgery was found in 11.9% of the Peyronie's group, 2% in the Dupuytren's group and 1.1% if the patient had the two diseases (P < 0.001).

The prevalence of previous abdominal or pelvic surgery was higher in the Peyronie's population: 7% for isolated Peyronie, 2.5% for isolated Dupuytren and 2.4% for both but this difference was not statistically significant (P = 0.065).

A congenital curvature was found in 11.1% of the men affected by Peyronie's disease only and in 15.3% of patients affected by both diseases (P < 0.001) (Table 4).

The mean curvature degree was 43.6 degree in the Peyronie-only population compared to 39.5 in those with associated Dupuytren's disease (P = 0.14).

Erectile dysfunction was reported by most of patients with Peyronie's disease, whether isolated or not (60.2% if isolated vs. 58.1% if associated with Dupuytren's disease; P = 0.77).

Apparition of the disease resulted (due to erectile dysfunction and/or curvature) in penetration difficulties in more than half of Peyronie's patients (73 patients in Peyronie-only group vs. 49 in the two-disease group, representing 59.4% vs. 57%; P = 0.73).

Overall, 7.3% of Peyronie's only subjects and 11.6% of men with both Peyronie's and Dupuytren's disease had undergone surgery for their penile curvature (P = 0.29).

### 4. Discussion

To our knowledge, our study is one of the few to simultaneously analyze the association of both diseases along with a wide range of common and specific possible risk factors.

#### 4.1. Epidemiological association between the two diseases

Our study findings are consistent with Segundo et al.'s study, showing a prevalence of 12.6% of Peyronie's disease among initially followed for Dupuytren patients.

When we take a look at the general male population, Peyronie's disease prevalence varies from 0.5 to 10% as cited in Dibenedetti et al.'s study.

These results are in favor of a probable association.

Dupuytren's prevalence within general male population reaches up to 18% across all age groups.

In a group followed for Peyronie's disease, Nugteren et al. highlighted a prevalence of 22.1% of men diagnosed with Dupuytren's contracture.

In our study, results strengthen the hypothesis of an association by showing 29.1% of Dupuytren's disease among men affected by Peyronie's disease.

We believe that the difference between Dupuytren's prevalences among Nugteren et al.'s study and our study is due to the fact that urologists are likely more aware now and systematically examine hands.

#### 4.2. Modifiable risk factors

It was postulated in 1997 by El-Sakka et al. that risk factors for systemic vascular diseases could influence the occurrence of Peyronie's disease by causing a hypoxic microenvironment in the erectile tissue, which activates TGF-β secretion, conducting to an aggravation of the fibrosis [31].

It is well known that cardiovascular risk factors impair vessel quality particularly through the formation of atherosclerosis. Penile vessels are often the first to be altered, leading to erectile dysfunction which can also be a potential risk factor for Peyronie's disease.

In our study, over half of the patients with both conditions reported daily alcohol consumption.

This is consistent with Wang et al.'s findings who described alcohol drinking as a clear risk factor for Dupuytren's disease as well as a trigger for flare ups.

Prolonged daily drinking can cause disturbances in body chemistry such as dyslipidemia, which may contribute to blood vessels remodeling, and thus promote hypertension.

These mechanisms explain why smoking, alcohol daily consumption, dyslipidemia or high blood pressure seem to be Peyronie's risk factors.

Indeed, La Pera et al. suggested a correlation between the relative risk of Peyronie's disease and the number of smoked cigarettes per day.

We showed some similar results: 62,3% patients with both diseases, 60,7% diagnosed with Dupuytren's disease only versus 48,8% followed for Peyronie's disease only reported current smoking or recent cessation of smoking.

As their physiopathology is very similar, it is most likely that the same process occurs in Dupuytren's disease.

#### 4.3. Genetic risk factors

When we take a closer look to the results, we notice a higher prevalence of blue-eyed men among Dupuytren's patients, suggesting that men of Caucasian descent may be at higher risk.
Our study has also demonstrated that family history among siblings, second-degree relatives or parents seems to be a significant risk factor for Dupuytren's disease.

These findings are consistent with Nakamoto et al.'s study of 2022 which reported 20% of first-degree family history [16].

The hypothesis for a genetic origin transmitted by Vikings has already been suggested before, reinforced by Nunn et al.'s work which demonstrated that Dupuytren's disease more commonly affects men of Northern Europe.

A meta-analysis conducted in 2023 has identified three genetic risk factors for Dupuytren's disease. The primary gene located on chromosome 7 comes from Neanderthals, encoding a variant of the *EPDR1* gene, which itself codes for a protein potentially involved in myofibroblast contraction [32].

Pathways associated with the pathogenesis of fibrosis in Peyronie's and Dupuytren's diseases include wingless-type mammary-tumour virus integration site (WNT) signaling, extracellular matrix modulation and inflammation [30].

This has led to Qian et al.'s study on gene expression alterations in Peyronie and Dupuytren diseases. They analyzed total RNA samples from Peyronie's plaques, normal tunica albuginea, Dupuytren's nodules, and normal palmar fascia.

It has shown common upregulated gene families in both diseases which were involved in collagen degradation (MMP), ossification (OSFs) and myofibroblast differentiation (RhoGDP dissociation inhibitor 1). A significant association was observed with WNT2 expression in both diseases [37].

All these results further support the crucial role of the genetic factor.

However, despite technological advances and genomics, specific genes implicated in these diseases have not been clearly identified in order to develop targeted therapeutics.

According to an analysis conducted on 3 patients affected by both conditions' families, they appear to be inherited by an autosomal dominant with incomplete penetrance way [33].

In light of these results, it is necessary to underline the importance of screening for modifiable risk factors as well as associated diseases. Indeed, a patient treated for Dupuytren's disease should be informed that he is likely to develop Peyronie's disease or Ledderhose disease, as their functional impact is significant and can be a source of considerable suffering.

The main limitation of our study is the relatively limited sample size preventing to conduct a robust epidemiological analysis.

Additionally, it does not include a control group with 'healthy' subjects, without Peyronie's or Dupuytren's disease.

The primary information bias concerns data collection, which was mostly based on information provided by the patient himself. Furthermore, family history is not always known by patients or discussed with their relatives.

Another important shortcoming is that the questionnaire used was not validated and was devised for the purpose of that study.

The present study was cross-sectional preventing to draw any information of the temporality of those two diseases. Several of the included patients may develop the concurrent disease within the course of the upcoming years hence possibly underestimating the coexistence of the two diseases and of some of the risk factors.

Finally, the available data did not allow to assess whether the coexistence of Peyronie and Dupuytren diseases was associated with specific features of each individual condition.

## 5. Conclusion

This study confirms the association between Peyronie's and Dupuytren's diseases.

There was a higher prevalence of previously known shared risk factors such as smoking, alcohol consumption, and hypertension among patients

affected by both diseases compared to those with isolated Peyronie's disease. There was also a higher prevalence of blue-eyed patients among men with Dupuytren's disease.

The association between Peyronie's and Dupuytren's diseases may then be explained by a common pathophysiology involving modifiable risk factors and a predisposing family background.

The present findings may be helpful for patients' counselling and to build preventive strategies tackling the shared risk factors.

The question of whether the coexistence of the two diseases represents a distinct phenotype with different prognosis and responses to the various treatments available has yet to be elucidated.

## Disclosure of interest

The authors declare that they have no competing interest.

## Appendix A. Supplementary data

Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.fjurol.2024.102759.

## References

[1] Dibenedetti DB, Nguyen D, Zografos L, Ziemiecki R, Zhou X. A population-based study of Peyronie's disease: prevalence and treatment patterns in the United States. Adv Urol 2011;2011:282503.

[2] Schwarzer U, Sommer F, Klotz T, Braun M, Reifenrath B, Engelmann U. The prevalence of Peyronie's disease: results of a large survey. BJU Int 2001;88:727-30.

[3] Segundo A, Gлина S. Prevalence, risk factors, and erectile dysfunction associated with Peyronie's disease among men seeking urological care. Sex Med 2020;8(2):230-6.

[4] Chung E, et al. Prevalence of penile curvature: a population-based cross-sectional study in metropolitan and rural cities in Australia. BJU Int 2018;122(Suppl. 5):42.

[5] Ferretti L, Faix A, Droupy S. Lapeyronie's disease. Prog Urol 2013;23(9):674-84.

[6] Bjekic MD, Vlajinac HD, Sipetic SB, Marinkovic JM. Risk factors for Peyronie's disease: a case-control study. BJU Int 2006;97(3):570-4.

[7] La Pera G, et al. Peyronie's disease: prevalence and association with cigarette smoking. A multicenter population-based study in men aged 50-69 years. Eur Urol 2001;40:525.

[8] Askari M, Mohamad Mirjalili SA, Bozorg M, Azizi R, Namiranian N. The prevalence of Peyronie's disease in diabetic patients -2018- Yazd. Diabetes Metab Syndr 2019;13 (1):604-7.

[9] Casabe A, Bechara A, Cheliz G, De Bonis W, Rey H. Risk factors of Peyronie's disease. What does our clinical experience show? J Sex Med 2011;8(2):518-23.

[10] Kadioğlu A, Gürcan M, Rakhmonovich AF, Dursun M. Surgical management of complex curvature in Peyronie's disease. World J Urol 2024;42(1)276, doi:http://dx. doi.org/10.1007/s00345-024-04936-z PMID: 38689034; PMCID: PMC11061042.

[11] Cosentino M, Di Nauta M, Boeri L, Ferraioli G, Lucignani G, Ricapito A, et al. Conservative treatment of Peyronie's disease: a guide. World J Urol 2024;42(1)317, doi:http://dx.doi.org/10.1007/s00345-024-04975-6 PMID: 38740620.

[12] Alshuaibi M, Zugail AS, Lombion S, Beley S. New protocol in the treatment of Peyronie's disease by combining platelet-rich plasma, percutaneous needle tunneling, and penile modeling: Preliminary results. Fr J Urol 2024;34(1)102526, doi:http://dx. doi.org/10.1016/j.purol.2023.09.013 Epub 2023 Sep 28. PMID: 37777436.

[13] EAU Guidelines. Edn. presented at the EAU Annual Congress, Paris 2024. ISBN 978-94- 92671-23-3.

[14] Ziegelmann MJ, Bajic P, Levine LA. Peyronie's disease: Contemporary evaluation and management. Int J Urol 2020;27(6)504-16, doi:http://dx.doi.org/10.1111/ iju.14230 Epub 2020 Apr 6. PMID: 32253786.

[15] Montorsi F, et al. Summary of the recommendations on sexual dys-functions in men. J Sex Med 2010;7(11):3572-88.

[16] Nakamoto HA, Gonçalves RB, Oliveira LT, Macedo LS, de Sambuy MTC, Rodrigues MP, et al. Epidemiological aspects of Dupuytren's disease in Brazil. Acta Ortop Bras 2022;30(spe1):e244900.

[17] Layton T, Nanchahal J. Recent advances in the understanding of Dupuytren's disease. F1000Res 2019;8:F1000, doi:http://dx.doi.org/10.12688/f1000research.17779.1 Faculty Rev-231. PMID: 30854193; PMCID: PMC6396840.

[18] Alioto RJ, Rosier RN, Burton RI, Puzas JE. Comparative effects of growth factors on fibroblasts of Dupuytren's tissue and normal palmar fascia. J Hand Surg 1994;19 (3):442-52.

[19] Bayat A, Alansar A, Hajeer AH, Shah M, Watson JS, Stanley JK, et al. Genetic susceptibility in Dupuytren's disease: lack of association of a novel transforming growth factor beta(2) polymorphism in Dupuytren's disease. J Hand Surg 2002;27 (1):47-9, doi:http://dx.doi.org/10.1054/jhsb.2001.0689.

[20] Agren R, Patil S, Zhou X, Finn G, Sahlholm K, Pääbo S, et al. Major genetic risk factors for Dupuytren's disease are inherited from Neandertals. Mol Biol Evol 2023;40(6) msad130, doi:http://dx.doi.org/10.1093/molbev/msad130 PMID: 37315093; PMCID: PMC10266526.

[21] Wang Z, Wang Z, Yan Z, Xu Z, Gao A. Smoking, alcohol consumption and risk of Dupuytren's disease: a Mendelian randomization study. BMC Med Genomics 2023;16
(1)212, doi:http://dx.doi.org/10.1186/s12920-023-01650-4 PMID: 37679690;
PMCID: PMC10483747.

[22] Berndt A, Kosmehl H, Mandel U, Gabler U, Luo X, Celeda D, et al. TGF beta and bFGF synthesis and localization in Dupuytren's disease (nodular palmar fibromatosis) relative to cellular activity, myofibroblast phenotype and oncofetal variants of fibronectin. Histochem J 1995;27(12):1014-20.

[23] Gonzalez AM, Buscaglia M, Fox R, Isacchi A, Sarmientos P, Farris J, et al. Basic fibroblast growth factor in Dupuytren's contracture. Am J Pathol 1999;141(3):661-71.

[24] Terrier JE, Nelson CJ. Psychological aspects of Peyronie's disease. Transl Androl Urol 2016;5(3)290-5, doi:http://dx.doi.org/10.21037/tau.2016.05.14 PMID: 27298775; PMCID: PMC4893509.

[25] Thach S, Pommier B, Soulier V. The impact of Peyronie's disease on couples. Fr J Urol 2024;34(4)102595, doi:http://dx.doi.org/10.1016/j.fjurol.2024.102595 Epub ahead of print. PMID: 38442548.

[26] Abernethy J. The consequences of gonorrhea. Lecture on anatomy, surgery and pathology: including observations on the nature and treatment of local diseases, delivered at St Bartholomew's and Christ's Hospitals. 1st ed London (England): James Balcock; 1828 p. 205.

[27] Nugteren HM, Nijman JM, de Jong IJ, van Driel MF. The association between Peyronie's and Dupuytren's disease. Int J Impot Res 2011;23(4)142-5, doi:http://dx.doi.org/10.1038/ijir.2011.18 Epub2011 Jun 2. PMID: 21633367.

[28] Shindel AW, Sweet G, Thieu W, Durbin-Johnson B, Rothschild J, Szabo R. Prevalence of Peyronie's disease-like symptoms in men presenting with Dupuytren's contractures. Sex Med 2017;5(3):e135-41.

[29] Mohede DCJ, Riesmeijer SA, de Jong IJ, Werker PMN, van Driel MF. Prevalence of Peyronie and Ledderhose diseases in a series of 730 patients with Dupuytren disease. Plast Reconstr Surg 2020;145(4):978-84.

[30] Sharma KL, Alom M, Trost L. The etiology of Peyronie's disease: pathogenesis and genetic contributions. Sex Med Rev 2020;8(2)314-23, doi:http://dx.doi.org/10.1016/j.sxmr.2019.06.004 Epub 2019 Sep 17. PMID: 31540807.

[31] El-Sakka AI, Hassoba HM, Pillarisetty RJ, Dahiya R, Lue TF. Peyronie's disease is associated with an increase in transforming growth factor-beta protein expression. J Urol 1997;158(4)1391-4 PMID: 9302128.

[32] Gelbard MK, Rosenbloom J. Fibroproliferative disorders and diabetes: Understanding the pathophysiologic relationship between Peyronie's disease, Dupuytren disease and diabetes. Endocrinol Diabetes Metab 2020;4(2):e00195.

[33] Al-Thakafi S, Al-Hathal N. Peyronie's disease: a literature review on epidemiology, genetics, pathophysiology, diagnosis and work-up. Transl Androl Urol 2016;5:280-9.

[34] Badamente MA, Sampson SP, Hurst LC, Dowd A, Miyasaka K. The role of transforming growth factor beta in Dupuytren's disease. J Hand Surg 1996;21(2):210-5, doi:http://dx.doi.org/10.1016/s0363-5023(96)80102-x.

[35] Nyberg Jr. LM, Bias WB, Hochberg MC, et al. Identification of an inherited form of Peyronie's disease with autosomal dominant inheritance and association with Dupuytren's contracture and histocompatibility B7 cross-reacting antigens. J Urol 1982;128:48-51, doi:http://dx.doi.org/10.1016/S0022-5347(17)52751-2.

[36] Gabrielsen JS. Peyronie's disease: is it genetic or not? Transl Androl Urol 2020;9 (Suppl. 2)S262-8, doi:http://dx.doi.org/10.21037/tau.2019.10.21 PMID: 32257867; PMCID: PMC7108984.

[37] Qian A, Meals RA, Rajfer J, Gonzalez-Cadavid NF. Comparison of gene expression profiles between Peyronie's disease and Dupuytren's contracture. Urology 2004;64 (2):399-404, doi:http://dx.doi.org/10.1016/j.urology.2004.04.006.

[38] Allen-Brady KL, Christensen MB, Sandberg AD, Pastuszak AW. Significant familial clustering of Peyronie's disease in close and distant relatives. Andrology 2022;10(7) 1361-7, doi:http://dx.doi.org/10.1111/andr.13223 Epub 2022 Jul 13. PMID: 35770847; PMCID: PMC9481671.