Peyronie’s disease is a benign acquired fibrotic condition of the tunica albuginea that leads to penile curvature, pain, palpable plaque, and erectile dysfunction, with prevalence increasing with age (1,2,5). Overall, penile deformity represents the most common initial symptom of Peyronie’s disease, occurring in 52–94% of patients. Penile pain is the second most frequent symptom, reported by approximately 20–70% of patients during the early phase of the disease (16). Consistent with the literature, penile deformity was the most common initial symptom in our study (65.7%), followed by pain (20.4%) and erectile dysfunction (13.9%) as the second and third most frequent presenting symptoms, respectively. Kadioglu et al., in a population-based study, reported dorsal and lateral curvatures as the most common deformities, with dorsal curvature observed in 45.6% and lateral curvature in 29.3% of patients (17). Similarly, Moreno and Morgentaler found that the primary direction of curvature was dorsal in 66.9% of cases, followed by ventral in 12.4% and lateral in 8.3% (7). In line with these findings, the most frequent curvature pattern in our cohort was also dorsal curvature, which was identified in 56.5% of patients. (Table 2).
It is widely recognized that PD plaque development may originate from penile trauma or repeated microvascular injury during erection (6,18), leading to an imbalance between profibrotic and antifibrotic pathways. This dysregulation—particularly involving transforming growth factor‑β1 (TGF‑β1)—promotes excessive collagen deposition and subsequent plaque formation (19); however, the pathogenesis of PD is likely multifactorial, involving an interplay among genetic predisposition, mechanical injury, local inflammatory processes, and dysregulated wound healing (13). Clinical studies have identified several comorbid conditions that cluster with PD, including diabetes mellitus, hypertension, dyslipidemia, hypogonadism, smoking, Dupuytren’s contracture, and other systemic fibrotic or autoimmune disorders, suggesting that local penile pathology develops on a background of systemic vascular and connective tissue susceptibility (8,20,21).
The relationship between testosterone and PD has attracted particular interest over the past decade. Androgens are known to influence tissue repair and collagen metabolism, with experimental and clinical data linking androgen deficiency to impaired wound healing and increased fibrosis (22,23). These findings support a theoretical basis for the hypothesis that low testosterone may predispose to fibrotic tissue remodeling and PD development. Moreover, testosterone deficiency may contribute indirectly to PD via diminished erectile rigidity, thereby increasing susceptibility to repetitive penile trauma during sexual activity (24). Additionally, androgens have been shown to positively regulate nitric oxide (a potent anti-fibrotic mediator), which further supports the protective role of testosterone against fibrotic processes (25).
However, the clinical evidence regarding the association between testosterone levels and PD has been conflicting. Moreno and Morgentaler reported that 74% of men with PD had low testosterone (defined by either total or free testosterone), with a significant correlation between low free testosterone and penile curvature severity (54.3° vs. 37.1°, p = 0.006) (7). Similarly, Nam et al. found that patients with testosterone deficiency had a significantly greater mean degree of penile curvature than those with normal testosterone levels (32.0 ± 16.9° vs. 21.8 ± 15.4°, p = 0.033), and a higher prevalence of moderate to severe curvature (40% vs. 23.7%, p = 0.015), proposing mechanisms such as reduced nitric oxide activity and upregulated TGF-β1 expression in hypogonadal states (26). Cavallini et al. reported that PD patients had lower bioavailable testosterone compared to controls, with larger plaque size in hypogonadal men, while penile curvature did not differ significantly. They also reported improved treatment outcomes with combined testosterone replacement and intralesional verapamil (8).
In contrast, more recent studies have largely failed to confirm these associations, aligning closely with our findings. Kirby et al. found no difference in curvature severity between hypogonadal and eugonadal PD patients (35.4° vs. 34.0°, p = 0.70) and comparable testosterone levels between men with PD and age-matched men with isolated erectile dysfunction (328 vs. 332 ng/dL, p = 0.98), suggesting that low testosterone may represent a common feature of sexual dysfunction rather than a PD-specific phenomenon (11). Mulhall et al., in a rigorous analysis of 184 men with PD undergoing intracavernosal injection-induced erections, found no association between total or free testosterone levels and the magnitude of penile deformity (r = −0.01, p = 0.95) (12). Similarly, Candela et al. analyzed 149 men with chronic-phase PD and observed no correlation between testosterone levels and penile curvature across testosterone quartiles (p = 0.31), with only disease duration independently predicting deformity severity (9). Can et al. also found no significant association between testosterone and plaque dimensions or curvature degree in 147 PD patients, despite lower mean testosterone levels compared to controls (3.9 ± 1.1 vs. 4.2 ± 1.7 ng/mL, p = 0.062) (27). In a recent study, Schneider et al. evaluated the impact of testosterone on collagenase clostridium histolyticum (CCH) treatment outcomes in 36 men with PD and found that neither baseline testosterone levels nor hypogonadal status (<300 ng/dL) predicted treatment response, with no significant difference in curvature improvement between hypogonadal and eugonadal groups (p = 0.41) (28). Our study, consistent with these studies, reinforces the prevailing evidence that serum testosterone levels are not associated with objective measures of PD severity. In our cohort of 108 men, 38.9% were classified as hypogonadal according to EAU guidelines (total testosterone <12 nmol/L or approximately 3.5 ng/mL). Despite this substantial prevalence of low testosterone, we observed no significant differences between hypogonadal and eugonadal groups in horizontal curvature (13.6° vs. 11.2°, p = 0.53), vertical curvature (29.4° vs. 27.9°, p = 0.71), plaque size (8.4 mm vs. 9.3 mm, p = 0.54), or disease phase distribution. Furthermore, correlation analysis revealed no association between total or free testosterone levels and either the degree of penile curvature or plaque dimensions, suggesting that hormonal status does not influence the anatomical manifestations of PD.
In the literature, several studies have investigated comorbidities associated with PD (17,29), including hyperlipidemia as a potential risk factor, though findings remain inconsistent. While Rhoden et al. found no correlation between serum lipid profiles and PD, Can et al. reported significantly elevated LDL levels in PD patients (27,30). In our study, no significant differences were observed between eugonadal and hypogonadal groups regarding hypertension, diabetes, coronary artery disease, or COPD. However, hypogonadal men exhibited significantly lower SHBG and estradiol levels, along with higher HbA1c and triglyceride values. These findings suggest that hypogonadism may be associated with a distinct metabolic profile characterized by impaired glucose regulation and dyslipidemia, potentially contributing to PD pathophysiology through altered tissue repair and increased fibrotic remodeling (29).
Our study has several limitations. First, the retrospective design may have introduced selection bias. Second, the absence of a healthy control group and comparisons exclusively between PD subgroups may limit the generalizability of our findings. Third, plaque measurements by multiple radiologists may have introduced inter-observer variability, potentially affecting the consistency of radiological assessments.
DISCUSSION
Peyronie’s disease is a benign acquired fibrotic condition of the tunica albuginea that leads to penile curvature, pain, palpable plaque, and erectile dysfunction, with prevalence increasing with age (1,2,5). Overall, penile deformity represents the most common initial symptom of Peyronie’s disease, occurring in 52–94% of patients. Penile pain is the second most frequent symptom, reported by approximately 20–70% of patients during the early phase of the disease (16). Consistent with the literature, penile deformity was the most common initial symptom in our study (65.7%), followed by pain (20.4%) and erectile dysfunction (13.9%) as the second and third most frequent presenting symptoms, respectively. Kadioglu et al., in a population-based study, reported dorsal and lateral curvatures as the most common deformities, with dorsal curvature observed in 45.6% and lateral curvature in 29.3% of patients (17). Similarly, Moreno and Morgentaler found that the primary direction of curvature was dorsal in 66.9% of cases, followed by ventral in 12.4% and lateral in 8.3% (7). In line with these findings, the most frequent curvature pattern in our cohort was also dorsal curvature, which was identified in 56.5% of patients. (Table 2).
It is widely recognized that PD plaque development may originate from penile trauma or repeated microvascular injury during erection (6,18), leading to an imbalance between profibrotic and antifibrotic pathways. This dysregulation—particularly involving transforming growth factor‑β1 (TGF‑β1)—promotes excessive collagen deposition and subsequent plaque formation (19); however, the pathogenesis of PD is likely multifactorial, involving an interplay among genetic predisposition, mechanical injury, local inflammatory processes, and dysregulated wound healing (13). Clinical studies have identified several comorbid conditions that cluster with PD, including diabetes mellitus, hypertension, dyslipidemia, hypogonadism, smoking, Dupuytren’s contracture, and other systemic fibrotic or autoimmune disorders, suggesting that local penile pathology develops on a background of systemic vascular and connective tissue susceptibility (8,20,21).
The relationship between testosterone and PD has attracted particular interest over the past decade. Androgens are known to influence tissue repair and collagen metabolism, with experimental and clinical data linking androgen deficiency to impaired wound healing and increased fibrosis (22,23). These findings support a theoretical basis for the hypothesis that low testosterone may predispose to fibrotic tissue remodeling and PD development. Moreover, testosterone deficiency may contribute indirectly to PD via diminished erectile rigidity, thereby increasing susceptibility to repetitive penile trauma during sexual activity (24). Additionally, androgens have been shown to positively regulate nitric oxide (a potent anti-fibrotic mediator), which further supports the protective role of testosterone against fibrotic processes (25).
However, the clinical evidence regarding the association between testosterone levels and PD has been conflicting. Moreno and Morgentaler reported that 74% of men with PD had low testosterone (defined by either total or free testosterone), with a significant correlation between low free testosterone and penile curvature severity (54.3° vs. 37.1°, p = 0.006) (7). Similarly, Nam et al. found that patients with testosterone deficiency had a significantly greater mean degree of penile curvature than those with normal testosterone levels (32.0 ± 16.9° vs. 21.8 ± 15.4°, p = 0.033), and a higher prevalence of moderate to severe curvature (40% vs. 23.7%, p = 0.015), proposing mechanisms such as reduced nitric oxide activity and upregulated TGF-β1 expression in hypogonadal states (26). Cavallini et al. reported that PD patients had lower bioavailable testosterone compared to controls, with larger plaque size in hypogonadal men, while penile curvature did not differ significantly. They also reported improved treatment outcomes with combined testosterone replacement and intralesional verapamil (8).
In contrast, more recent studies have largely failed to confirm these associations, aligning closely with our findings. Kirby et al. found no difference in curvature severity between hypogonadal and eugonadal PD patients (35.4° vs. 34.0°, p = 0.70) and comparable testosterone levels between men with PD and age-matched men with isolated erectile dysfunction (328 vs. 332 ng/dL, p = 0.98), suggesting that low testosterone may represent a common feature of sexual dysfunction rather than a PD-specific phenomenon (11). Mulhall et al., in a rigorous analysis of 184 men with PD undergoing intracavernosal injection-induced erections, found no association between total or free testosterone levels and the magnitude of penile deformity (r = −0.01, p = 0.95) (12). Similarly, Candela et al. analyzed 149 men with chronic-phase PD and observed no correlation between testosterone levels and penile curvature across testosterone quartiles (p = 0.31), with only disease duration independently predicting deformity severity (9). Can et al. also found no significant association between testosterone and plaque dimensions or curvature degree in 147 PD patients, despite lower mean testosterone levels compared to controls (3.9 ± 1.1 vs. 4.2 ± 1.7 ng/mL, p = 0.062) (27). In a recent study, Schneider et al. evaluated the impact of testosterone on collagenase clostridium histolyticum (CCH) treatment outcomes in 36 men with PD and found that neither baseline testosterone levels nor hypogonadal status (<300 ng/dL) predicted treatment response, with no significant difference in curvature improvement between hypogonadal and eugonadal groups (p = 0.41) (28). Our study, consistent with these studies, reinforces the prevailing evidence that serum testosterone levels are not associated with objective measures of PD severity. In our cohort of 108 men, 38.9% were classified as hypogonadal according to EAU guidelines (total testosterone <12 nmol/L or approximately 3.5 ng/mL). Despite this substantial prevalence of low testosterone, we observed no significant differences between hypogonadal and eugonadal groups in horizontal curvature (13.6° vs. 11.2°, p = 0.53), vertical curvature (29.4° vs. 27.9°, p = 0.71), plaque size (8.4 mm vs. 9.3 mm, p = 0.54), or disease phase distribution. Furthermore, correlation analysis revealed no association between total or free testosterone levels and either the degree of penile curvature or plaque dimensions, suggesting that hormonal status does not influence the anatomical manifestations of PD.
In the literature, several studies have investigated comorbidities associated with PD (17,29), including hyperlipidemia as a potential risk factor, though findings remain inconsistent. While Rhoden et al. found no correlation between serum lipid profiles and PD, Can et al. reported significantly elevated LDL levels in PD patients (27,30). In our study, no significant differences were observed between eugonadal and hypogonadal groups regarding hypertension, diabetes, coronary artery disease, or COPD. However, hypogonadal men exhibited significantly lower SHBG and estradiol levels, along with higher HbA1c and triglyceride values. These findings suggest that hypogonadism may be associated with a distinct metabolic profile characterized by impaired glucose regulation and dyslipidemia, potentially contributing to PD pathophysiology through altered tissue repair and increased fibrotic remodeling (29).
Our study has several limitations. First, the retrospective design may have introduced selection bias. Second, the absence of a healthy control group and comparisons exclusively between PD subgroups may limit the generalizability of our findings. Third, plaque measurements by multiple radiologists may have introduced inter-observer variability, potentially affecting the consistency of radiological assessments.