PREDICTORS OF DEPRESSION IN MEN WITH PEYRONIE’S DISEASE SEEKING EVALUATION

Abstract

Background:

Peyronie’s disease (PD) has negative impacts on the psychosocial status of men including depression warranting clinical evaluation in up to 50% of men.

Aim:

To examine predictors of depression in patients with early PD seeking evaluation.

Methods:

All PD patients at a high-volume PD practice underwent screening and curvature assessment after intracavernosal injection. Complex deformity was defined as any degree of multiplanar curvature, curvature >60 degrees, or presence of hourglass deformity. Men completed the PD questionnaire (PDQ), a validated depression questionnaire (CES-D) as well as the Self-Esteem and Relationship (SEAR) questionnaire. Scores of ≥16 on CES-D were considered indicative of moderate/severe depression. Predictors of the presence of depression were defined using univariable and multivariable logistic regression.

Outcomes:

Demographic, bother and curve related predictors of depression in men with PD.

Results:

408 men completed all questionnaires. Mean age was similar between depressed and non-depressed groups (57±10 years overall, p=0.60 between groups). Proportions of erectile dysfunction were similar between groups (p=0.96). Mean PD duration was similar between groups (19±35 months overall, p=0.46 between groups). Mean degree of curvature was 38±2 degrees in the depressed vs 33±1 degrees in the non-depressed groups (p=0.03). A complex deformity was seen in 64.5% in the depressed vs 61.5% in the non-depressed (p=0.56). A total of 110 (27%) patients had CESD scores ≥16. 74% depressed men were in relationships compared to 84% non-depressed men (p<0.01). Other characteristics including bother, pain, duration of disease, curve complexity and instability were similar between the two groups. On univariable analysis, factors protective against depression included being partnered (OR 0.42, 95%CI 0.24–0.75, p<0.01) and higher total SEAR scores (OR 0.95, 95%CI 0.94–0.97, p<0.01). Elevated PDQ domain scores were associated with depression (Psychologic Symptoms 1.05, 95%CI 1.02–1.10, p<0.01; Pain 1.08, 95%CI 1.03–1.12, p<0.01; Bother 1.11, 95% CI 1.05–1.68, p<0.01) as well as baseline history of depression (OR 2.93, 95%CI 1.67–5.14, p<0.001). On multivariable analysis, only total SEAR score remained protective against depression (OR 0.96, 95%CI 0.94–0.97, p<0.001).

Clinical Implications:

Providers must recognize that men with PD seeking evaluation have meaningful rates of depression for which early recognition is necessary.

Strengths & Limitations:

Retrospective review of a large prospectively collected dataset from a single center of men with PD utilizing a validated screening tool for depression.

Conclusion:

While no significant demographic, bother or curve related factors predicted depression in early PD men seeking evaluation, it remains a significant problem warranting further prospective evaluation.

INTRODUCTION

Peyronie’s disease (PD), originally described by François Gigot de la Peyronie in 1743, represents a benign and localized condition with scar (plaque) development within the tunica albuginea resulting in penile deformity and/or length/volume loss.¹ With a prevalence of up to 9% of men, the condition encompasses both an acute and chronic phase.² Men may also experience painful erections, sexual bother, erectile dysfunction (ED), partner reported pain, and most devastatingly an inability to engage in penetrative sexual relations.^3–5

In addition to physical and sexual symptoms of PD, many men also experience emotional and psychological distress.⁶ Thus far, the majority of studies in this realm have focused on ED rather than PD. However, PD is associated with significant impact on patient quality of life, self-esteem, social isolation, relationship strain and stigmatization.^6,7 PD has been shown to have direct impacts on mental health including clinical depression as well as negative relationship effects and some men with PD may benefit from seeing a mental health specialist.^6,8,9 Only two previous reports have reported on the direct impact of PD on mental illness, one of which reported on emotional and psychological problems, and the other reported rates of depression using a validated questionnaire. Both of these reported rates of approximately 50% or greater of mental illness.^10,11 While these reports briefly explore some predictive factors related to PD, higher risk populations and more broad predisposing characteristics remain to be identified, and therefore represents a deficiency in the literature.

Given the aforementioned data, this study endeavored to examine factors which predict the occurrence of depression based on a validated questionnaire in patients with PD seeking evaluation.

METHODS

Study Population:

Standardized clinical data was collected in a highly structured fashion for all PD patients presenting to a high-volume sexual medicine practice at a single institution. The collected data was retrospectively reviewed. Patients were included if they had 1) documented PD based on the presence of a palpable plaque assessed by an experienced sexual medicine physician, 2) underwent a curvature assessment at the time of intracavernosal injection at the time of their duplex ultrasound, and 3) completed all questionnaires described below. All PD, demographic and comorbidity data were recorded. Study approval was obtained from the institutional review board (IRB) at Memorial Sloan Kettering Cancer Center (Protocol 16–405). Data recorded included: partner status, patient and partner age, sexual orientation, erectile dysfunction (defined as a score of ≥ 6 on a 10 point scale correlating to rigidity sufficient for penetration), patient-reported bother, objective bother (defined as a PDQ score ≥ 9), presence of subjective patient pain (flaccid or erect) and disease duration (months).

Patient Care Pathway:

All patients received the same standardized intake forms and completed standardized questionnaires. Patients were then assessed by a sexual medicine clinician, followed by a curvature assessment as described below. Based on the findings of this assessment, appropriate and relevant treatment options are discussed. Follow-up for their PD is dependent on the treatment option chosen by the patient.

Penile Deformity Assessment:

Deformity assessments were completed in-office using intracavernosal injections of the vasoactive agent, trimix. Curvature was measured in degrees using a goniometer placed at the point of maximum curvature. Penile deformity was considered complex if the curvature was multiplanar, if >60 degrees in magnitude or if hourglass deformity was present. Instability was objectively recorded using manual axial loading of the glans penis at maximal rigidity following intracavernosal injection.

Questionnaires:

All PD patients routinely completed three validated questionnaires at their initial visit prior to seeing any clinician. The Self-Esteem and Relationship (SEAR) questionnaire is a validated instrument for the assessment of the psychosocial impact of ED and includes four domains including sexual relationship, confidence, self-esteem and overall relationship based on 14 questions measured on a five-point scale.¹² The Center for Epidemiologic Studies Depression Scale (CES-D) is employed as a screening tool for depression and depressive disorder and consists of 20 questions on a four-point scale with four reverse scored elements.¹³ A score of ≥16 was utilized as a cut-off for the presence of clinically meaningful depression.¹⁴ Those with a score ≥16 were referred to a psychologist for psychological assessment. Finally, all patients completed the Peyronie’s Disease Questionnaire (PDQ) to assess the psychosexual consequences of PD which consists of 15 questions with three domains including psychological and physical symptoms, penile pain and bother on a five-point Likert scale.^15,16

Statistical Analysis:

Logistic regression modelling was used to define risk factors for the development of depression. Age was treated as a continuous variable, sexual orientation was separated into each sub-category (heterosexual, gay and bisexual) and assessed as a dichotomous variable. Being partnered, subjective and objective bother and pain were treated dichotomously. ED was also treated dichotomously. PD duration was evaluated as a continuous variable, as well as assessed dichotomously as greater or less than 1 year. History of depression and curvature factors were all treated dichotomously including presence of complex curvature. Instability was categorized as mild, moderate and severe but each category was treated dichotomously. All questionnaire data was treated continuously including an overall CES-D score, subdomain PDQ scores, and both subdomain and total SEAR scores. Univariable modelling was completed for all variables. Factors for multivariable models included age, partner status, duration of PD, history of depression, complexity of deformity, PDQ domain scores, total SEAR score and ED. Statistical significance was determined as p-value <0.05. All analysis was completed using Stata v14.

RESULTS

Study Population:

408 men have completed all questionnaires to-date. A total of 110 men (27%) had CES-D ≥16 and composed the depression group. Group comparisons are highlighted in Table 1. Overall mean age was 57 ± 10 years, with no significant differences between the two groups (p=0.60). Mean duration of PD was similar between groups (p=0.46) with an overall duration of 18.8 ± 35.4 months. Mean degree of curvature was statistically significantly different (but not clinically meaningfully different) between groups with 38 ± 2 degrees in the depressed group versus 33 ± 1 degree in the non-depressed group (p=0.03). No significant differences in the frequency of complex deformity was seen (65% in the depressed group versus 62% in the non-depressed group, p=0.56). Pre-existing depression rates were present in 107 (26%) of the total cohort, with a significantly greater portion in the depressed group (26% versus 11% in the non-depressed group, p<0.01). Of those with history of depression, 34 (56%) were on anti-depressants at the time of assessment, and their mean CES-D score was 15.7 ± 12.6 in comparison to the remaining 27 (44%) not on anti-depressants whose score was 16.6 ± 11.1 (p=0.78).

Table 1:

Demographic and Curvature Characteristics by Group

	Depression* (n=110)	No Depression (n=298)	p-value
	n(%)	n(%)
Demographics
Age (mean, SD)	56.4 ± 10.4	57.1 ± 11.3	0.601
Heterosexual	94 (85.5)	267 (89.6)	0.054
Bisexual	0 (0.0)	1 (0.3)	0.538
Gay	11 (10.0)	15 (5.0)	0.074
Undefined	-	-
Partnered	81 (73.6)	250 (83.9)	0.003
Significant Bother (PDQ>/=9)	69 (62.7)	184 (61.7)	0.154
Patient Bother	7 (6.4)	30 (10.1)	0.667
Pain	32 (29.1)	77 (25.8)	0.819
Duration (months) (mean, SD)	21.7± 52.3	18.1± 0.4	0.463
Duration (>1 year)	26 (23.6)	78 (26.2)	0.444
History of Depression	29 (26.4)	32 (10.7)	<0.001
Erectile Dysfunction	23 (20.9)	63 (21.1)	0.959
Deformity
Complex	71 (64.5)	183 (61.4)	0.562
≧2 planes	35 (31.8)	80 (26.8)	0.152
Hour Glass Deformity	18 (16.4)	34 (11.4)	0.181
>60 degrees	13 (11.8)	30 (10.1)	0.461
Instability (any)	51 (46.4)	129 (43.3)	0.525
Instability Moderate	19 (17.3)	53 (17.8)	0.647
Instability Severe	11 (10.0)	21 (7.0)	0.439

^*CES-D score ≥16

Of the depressed men, 74% were partnered compared to 84% in the non-depressed group (p<0.01). Although not significantly different, a larger proportion of depressed men identified as gay (10%) versus the non-depressed group (5%) (p=0.07). No significant differences were seen with respect to rates of erectile dysfunction, degree of bother, pain, duration of disease or proportion of those with PD duration >1 year. With respect to curve characteristics, no significant differences were seen between groups with regard to curve complexity and instability. Duration of disease was not significantly different at time of presentation between groups (21.7 ± 52.2 months in the depressed group versus 18.1 ± 30.4 months in the non-depressed group, p=0.46).

Questionnaire Data:

Questionnaire scores are shown in Table 2. The mean CES-D score was 23.9 ± 7.7 in the depressed group versus 6.29 ± 4.72 in the non-depressed group (p<0.001). PDQ scores for all domains were higher (worse) in the depressed group versus the non-depressed group (p<0.01). SEAR scores were also all significantly lower (worse) for depressed men versus non-depressed men (p<0.001).

Table 2 –

CES-D, PDQ and SEAR Scores By Group

	Depression* (n=110)	No Depression (n=298)	p-value
	mean (SD)	mean (SD)
CES-D	23.9 ± 7.7	6.3 ± 4.7	<0.001
PDQ-Psych	10.0 ± 7.0	7.7 ± 5.9	0.003
PDQ-Pain	6.4 ± 6.6	3.9 ± 5.0	<0.001
PDQ-Bother	9.3 ± 5.1	6.8 ± 4.8	<0.001
SEAR Total	37.4 ± 21.6	60.3 ± 22.1	<0.001
SEAR Sexual Relationships	29.8 ± 23.2	48.7 ± 28.2	<0.001
SEAR Confidence	47.8 ± 25.3	75.2 ± 20.8	<0.001
SEAR Self Esteem	44.5 ± 25.1	75.1 ±21.8	<0.001
SEAR Overall Relationship	56.9 ± 34.3	75.5 ± 28.7	<0.001

^*CESD ≥16

Depression Predictors:

On univariable analysis (Table 3), factors that were protective against depression in men with PD were: being partnered (OR 0.42, p<0.01) and higher total SEAR scores (OR 0.95, p<0.01). Factors not associated with depression included: penile pain (OR 1.06, p=0.82), age (OR 0.73, p=0.34), curvature complexity (OR 1.14, p=0.56), penile instability (OR 1.17, , p=0.53), PDQ score ≥9 (OR 1.58, p=0.16) and duration of PD (OR 1.00, p=0.47). Across all PDQ domains, higher (worse) scores were associated with depression (psychologic symptoms - OR 1.05, p<0.01; pain - OR 1.08, p<0.01; bother – OR 1.11, p<0.01). A baseline history of depression also predicted depression (OR 2.93, 95%CI 1.67–5.14, p<0.001). Multivariable analysis is highlighted in Table 4. Only the total SEAR score remained protective against depression (OR 0.96, p<0.001).

Table 3 –

Univariable Analysis of Predictors of Depression

	Odds Ratio (95% CI)	p-value
Demographics
Age (mean)	0.73 (0.38–1.39)	0.337
Heterosexual	0.47 (0.21–1.02)	0.059
Gay	2.07 (0.92–4.66)	0.079
Undefined	-	-
Being partnered	0.42 (0.24–0.75)	0.003
Significant Bother (PDQ ≥9)	1.58 (0.84–2.95)	0.156
Patient Bother	1.63 (0.17–15.51)	0.669
Pain	1.06 (0.63–1.79)	0.819
Duration (mean)	1.00 (1.00–1.01)	0.467
Duration (>1 yr)	0.81 (0.47–1.39)	0.445
History of Depression	2.93 (1.67–5.14)	<0.001
Erectile Dysfunction	0.97 (0.58–1.69)	0.959
Deformity
Complex	1.14 (0.73–1.80)	0.562
>2 planes	1.43 (0.87–2.35)	0.153
Hour Glass Deformity	1.53 (0.82–2.87)	0.183
>60 degrees	1.30 (0.65–2.61)	0.461
Instability (any)	1.17 (0.72–1.88)	0.525
Instability Moderate	0.87 (0.48–1.58)	0.647
Instability Severe	1.36 (0.63–2.94)	0.441
Questionnaires
CES-D (mean)	-	-
PDQ-Psych	1.05 (1.02–1.10)	0.004
PDQ-Pain	1.08 (1.03–1.12)	0.001
PDQ-Bother	1.11 (1.05–1.68)	<0.001
SEAR Total (mean)	0.95 (0.94–0.97)	<0.001
SEAR Sexual Relationships	0.97 (0.96–0.98)	<0.001
SEAR Confidence	0.95 (0.94–0.96)	<0.001
SEAR Self Esteem	0.95 (0.94–0.96)	<0.001
SEAR Overall Relationship	0.98 (0.97–0.99)	<0.001

Table 4 –

Multivariable Analysis of Predictors of Depression

	Odds Ratio (95% CI)	p-value
Age (continuous)	1.00 (0.97–1.05)	0.784
Orientation (Heterosexual vs gay/bi)	1.12 (0.24–5.18)	0.886
PDQ ≥9	0.54 (0.19–1.58)	0.262
Pain	1.46 (0.67–3.21)	0.344
Complex vs. Simple Curve	1.09 (0.44–2.67)	0.852
Instability (mod/sev vs. mild/none)	0.85 (0.34–2.10)	0.718
SEAR Score (continuous)	0.96 (0.94–0.97)	<0.001
Partnered vs. Single	2.38 (0.68–8.38)	0.177
Duration of PD (continuous)	1.00 (0.99–1.02)	0.459
History of Depression	1.87 (0.69–5.09)	0.211
Erectile Dysfunction	0.62 (0.24–1.62)	0.333

DISCUSSION

PD has both significant sexual and physical symptoms but is also associated with a psychosocial impacts including depression, altered self-image, social isolation and relationship strain.⁷ Our study examined factors predictive of depression based on a validated questionnaire in patients with PD seeking evaluation and is the largest series exploring this outcome, to date. Higher PDQ scores and history of depression were predictive of depression (based on CESD) and being partnered and higher total SEAR scores were protective against depression (based on CESD).

Approximately one third of men in this study had clinical depression as defined by a CES-D score ≥16. This is lower than the previously reported rates of up to 50%, although the single prior study using CES-D used a cut-off score of 14 rather than 16.^6,10 Of note, patients in our study were not diagnosed by a trained psychiatrist but rather completed the screening tool (CES-D questionnaire).¹⁷ Furthermore, while the CES-D questionnaire is a highly utilized tool for screening of depression, the cut-off has been criticized as a score ≥16 may not apply to all populations, but at this threshold has a reported sensitivity of 87% and specificity of 70%.^13,14

Very few previous reports in the literature have examined the relationship between PD patients and mental illness including psychological and emotional problems.¹¹ In a series by Smith et al. in 245 similar but slightly younger men (mean 54.4, range 19.4–75.6), rates of emotional and relationship problems were 81% and 54%, respectively, as defined by an answer to two yes/no questions (“Do you feel the presence of PD has affected your emotional status?” and “Has the presence of PD affected your relationship with your sexual partner?”).¹¹ In comparison to our series, we screened for depression based on a validated screening questionnaire but rates were <30% in our cohort. Our depression rate was lower than that found (48%) in another series by Nelson et al. studying 92 men, which as previously mentioned is likely the result of the use of a lower CES-D cut-off of 14 and perhaps also related to the slightly younger mean cohort age of 54 years.¹⁰ Predictors of emotional problems in the series by Smith et al. included loss of penile length and inability to have intercourse.¹¹ In our series, higher PDQ scores (pain, bother and physical and psychological symptoms) were predictive of depression. In the series by Nelson et al. being single and penile shortening were associated with depression.¹⁰ Even with our higher CES-D cutoff score, we also found that being unpartnered was a risk factor for depression in men with PD.

In our series, depressed patients were less likely to be partnered and less likely to be in a relationship. Depressed men have been shown to avoid intimacy in relationships and loss of these relationships may trigger depression.¹⁸ Sources of depression specifically in men with PD may include loss of sexual confidence, reduced attractiveness, impaired sexual ability, performance anxiety, altered physical image, stigmatization and isolation.¹⁹ Being gay in our series trended towards a two-fold odds of being depressed (OR 2.07, p=0.08) and heterosexuality trended towards protective against depression with these men experiencing about half the odds of depression (OR 0.47, p=0.06). In the general population, gay men are at increased risk of mental health issues and in those with PD, they are furthermore at increased risk of both isolation and stigmatization secondary to avoidance of sexual contact.^6,20

No significant differences were seen for penile curvature characteristics between groups and subsequently were not predictive with statistical modelling. The absence of any significant differences confirms the wide heterogeneity of PD with respect to degree of curvature, complexity and associated instability.²¹ However, in the depressed group there was a trend towards more complex deformity (64.5% in depressed vs 61.4%) and multiplanar curves (31.8% in depressed vs 26.8%).

Our results show demonstrate no differences in ED between groups and no associations with depression as defined by their CESD questionnaires. Unfortunately erectile function assessment in this population is challenging as the international index of erectile function (IIEF) questionnaire was not designed or validated for men with PD.²² Men with PD may have penile instability, loss of sustaining their erection and may be non-functional secondary to their curvature, which may confound with the definition of ED.²³ Despite known associations of ED with psychological disease, assessment of ED in this PD population remains challenging.

Both the PDQ and SEAR scores were predictive of depression. The PDQ is a validated and useful clinical diagnostic and treatment tool in PD.²⁴ While both total score and all three subdomains were predictive; the strongest relationship was seen with respect to bother, with worsening bother associated with higher rates of depression. Studies outside of sexual medicine have indicated that men in general who have concern over penile appearance are at increased risk of mental health and depression.^25,26 The SEAR questionnaire has been shown to have reasonable correlations to the Psychological General Well Being Index (PGWB) and Short Form Health Survey (SF-36) with respect to some of the mental health domains.¹² SEAR scores were significantly lower in the depressed group, and all domains were predictive on univariable analysis, with a higher (better) total score protective against depression on multivariable analysis. Symptoms such as low self-esteem and reduced confidence, captured by the questionnaire, have known associations with depression.²⁷

The clinical implications of these data are obvious. Given the prevalence of PD in the general population, and subsequent rates of depression in this group, it is important that these patients have any mental health issues addressed and that patients are referred for appropriate management in an expedient fashion. Furthermore, since baseline depression was a clear predictor in our series, this additionally reinforces the importance of early recognition, screening and identification of these patients given the potential and unpredictable compounded risks. The subsequent implications of untreated depression are multiple and include: increased economic burdens (cost of medical care, decreased work productivity and lower quality of life), long term severity of disease, reduction of obtaining disease remission, and increased disability (as a consequence of untreated chronic disease).^28–31 As men often underutilize primary care service, men may be more likely to seek care when related to their sexual health³² and thus, urologists may be the primary clinicians involved in early recognition and diagnosis of patients with depression through simple screening of their PD patients and early specialist referral. In addition to this, urologists may also act as a link between and work closely with their PD patients and mental health professionals with expertise in PD. Larger and multi-center studies are warranted to further identify potential predictive factors for depression in this subset of men to permit earlier identification, counselling and intervention.

Limitations of our study include the retrospective nature of the review. However, all data was collected prospectively and every patient was asked a standardized series of demographic and clinical questions. With respect to psychological disease, our study only assessed depression and we are therefore limited by the absence of data on related conditions such as anxiety. Furthermore, the SEAR questionnaire is not currently validated in the PD population, and our study is also limited by its single institution design and single provider analysis. Strengths include a large series of patients and the use of validated instruments.

CONCLUSION

No statistically significant demographic, bother or curve related factors predict depression based on a validated questionnaire in early PD seeking evaluation. Only lower SEAR scores were predictive of depression on multivariable analysis.