madman
Super Moderator
Peyronie’s Disease and Testosterone: A Narrative Review (2022)
Douglas Schneider, Andrew S. Afyouni, and Faysal A. Yafi*
Abstract
The pathophysiology of Peyronie’s disease (PD) remains incompletely understood; current hypotheses point to a combination of predetermined genetic factors and tissue ischemia. Testosterone has been shown in pre-clinical studies to have anti-inflammatory properties and influence collagen metabolism, prompting various clinical studies examining its effect on disease development and impact on the severity of PD. We seek to review these studies to determine if testosterone levels are associated with PD. A comprehensive literature search of PubMed, Scopus, CENTRAL, Embase, and Web of Science was conducted with the search terms ‘‘Testosterone AND (Peyronie OR Peyronie’s OR Peyronies).’’ Titles and abstracts were screened for relevance, and included studies were then manually reviewed. A narrative review was chosen due to the low number of available studies. A total of 381 studies were identified, of which 202 were duplicates, leaving 179 that underwent title and abstract screening. Fulltext review was conducted for 52 studies, and a total of 15 studies were identified that examined or compared the relationship between testosterone levels and either the prevalence or severity of PD; some studies examined both. Three of the 12 studies examining the development of PD with relation to testosterone support an association between hypogonadism and PD, while another four possibly support an association, and five do not support such an association. Of the nine studies that examine the severity of PD, three studies support a statistically significant association between PD severity and hypogonadism, while six do not support such an association. After a comprehensive review of the literature, no definitive statement can be made regarding a relationship between PD and testosterone deficiency. Studies examining such a link suffer from significant heterogeneity and retrospective bias. There is a need for more prospective randomized studies to further elucidate a possible relationship.
Introduction
Historically, Peyronie’s disease (PD) was often misconceived by urologists as being a rare condition. Reports published between 1991 and 2005 initially stated its prevalence to be <1% in the older adult male U.S. population.1,2 However, contemporary studies state rates ranging from 3% in asymptomatic males up to 16% for males seeking evaluation for erectile dysfunction (ED).3–5
PD is a localized connective tissue disorder of the penis defined by penile plaques and deformities.6 In addition, PD is associated with the onset of ED in roughly 20–50% of men, and penile deformities and compromised rigidity can make penetrative intercourse a difficult if not impossible task. These set of symptoms can severely impact the quality of life, mental health, and relationship status of patients and their partners.7
The pathogenesis of PD is hypothesized to be based on an intersection of genetic factors and tissue ischemia, either traumatic or during the course of normal sexual intercourse.8,9 Fibrous collagenous plaques are deposited within the tunica albuginea that may hinder the expansion of the tunica during penile erection. This may lead to penile shortening, bending, and indentation.
At present, the mainstays of PD management are intralesional injection of collagenase clostridium histolyticum (CCH), the only Food and Drug Administration-approved drug for the management of PD, as well as surgical therapy for patients in the chronic phase of the disease. In patients with adequate erectile function, plication of the tunica albuginea, incision and/or partial excision, and grafting can be offered, depending on the degree of curvature and the nature of the initial destabilizing deformity.10 In patients with ED not responsive to oral therapy, insertion of an inflatable penile prosthesis with or without straightening procedures is at present offered.11
Numerous other oral and intralesional treatments have been described in the literature, but the evidence supporting their use is equivocal at best, as reflected by the current American Urological Association (AUA) guidelines solely recommending oral nonsteroidal anti-inflammatory drugs for acute pain management.12–19 As the current options for PD management are limited, further research into the pathophysiology of PD is a promising avenue for the development of future medical therapies.
One such promising avenue for the investigation of PD pathogenesis involves a better understanding of the role androgens play in PD. Traditionally, androgens, such as testosterone, are known to affect collagen metabolism and wound healing in the body, a target that is well suited to the collagenous and fibrous nature of PD plaques.20 Testosterone has anti-inflammatory properties and influences collagen metabolism and there has been a small subset of studies in the past few years that have examined the relationship between low testosterone levels and keloid development.20,21 It has also been shown that androgens, such as testosterone, prevent transforming growth factor-beta 1 (TGF-b1) expression, which is a modulator of fibrosis.
We seek to review the current clinical literature regarding the relationship between androgens and both the prevalence and severity of PD.
*Studies assessing the prevalence of PD
*Studies assessing the severity of PD
Conclusion
After a comprehensive review of the literature, no definitive statement can be made regarding a relationship between PD and testosterone deficiency. Studies examining such a link suffer from significant heterogeneity and retrospective bias; further prospective standardized research should be pursued to truly determine if there is a link between hypogonadism and PD.
Douglas Schneider, Andrew S. Afyouni, and Faysal A. Yafi*
Abstract
The pathophysiology of Peyronie’s disease (PD) remains incompletely understood; current hypotheses point to a combination of predetermined genetic factors and tissue ischemia. Testosterone has been shown in pre-clinical studies to have anti-inflammatory properties and influence collagen metabolism, prompting various clinical studies examining its effect on disease development and impact on the severity of PD. We seek to review these studies to determine if testosterone levels are associated with PD. A comprehensive literature search of PubMed, Scopus, CENTRAL, Embase, and Web of Science was conducted with the search terms ‘‘Testosterone AND (Peyronie OR Peyronie’s OR Peyronies).’’ Titles and abstracts were screened for relevance, and included studies were then manually reviewed. A narrative review was chosen due to the low number of available studies. A total of 381 studies were identified, of which 202 were duplicates, leaving 179 that underwent title and abstract screening. Fulltext review was conducted for 52 studies, and a total of 15 studies were identified that examined or compared the relationship between testosterone levels and either the prevalence or severity of PD; some studies examined both. Three of the 12 studies examining the development of PD with relation to testosterone support an association between hypogonadism and PD, while another four possibly support an association, and five do not support such an association. Of the nine studies that examine the severity of PD, three studies support a statistically significant association between PD severity and hypogonadism, while six do not support such an association. After a comprehensive review of the literature, no definitive statement can be made regarding a relationship between PD and testosterone deficiency. Studies examining such a link suffer from significant heterogeneity and retrospective bias. There is a need for more prospective randomized studies to further elucidate a possible relationship.
Introduction
Historically, Peyronie’s disease (PD) was often misconceived by urologists as being a rare condition. Reports published between 1991 and 2005 initially stated its prevalence to be <1% in the older adult male U.S. population.1,2 However, contemporary studies state rates ranging from 3% in asymptomatic males up to 16% for males seeking evaluation for erectile dysfunction (ED).3–5
PD is a localized connective tissue disorder of the penis defined by penile plaques and deformities.6 In addition, PD is associated with the onset of ED in roughly 20–50% of men, and penile deformities and compromised rigidity can make penetrative intercourse a difficult if not impossible task. These set of symptoms can severely impact the quality of life, mental health, and relationship status of patients and their partners.7
The pathogenesis of PD is hypothesized to be based on an intersection of genetic factors and tissue ischemia, either traumatic or during the course of normal sexual intercourse.8,9 Fibrous collagenous plaques are deposited within the tunica albuginea that may hinder the expansion of the tunica during penile erection. This may lead to penile shortening, bending, and indentation.
At present, the mainstays of PD management are intralesional injection of collagenase clostridium histolyticum (CCH), the only Food and Drug Administration-approved drug for the management of PD, as well as surgical therapy for patients in the chronic phase of the disease. In patients with adequate erectile function, plication of the tunica albuginea, incision and/or partial excision, and grafting can be offered, depending on the degree of curvature and the nature of the initial destabilizing deformity.10 In patients with ED not responsive to oral therapy, insertion of an inflatable penile prosthesis with or without straightening procedures is at present offered.11
Numerous other oral and intralesional treatments have been described in the literature, but the evidence supporting their use is equivocal at best, as reflected by the current American Urological Association (AUA) guidelines solely recommending oral nonsteroidal anti-inflammatory drugs for acute pain management.12–19 As the current options for PD management are limited, further research into the pathophysiology of PD is a promising avenue for the development of future medical therapies.
One such promising avenue for the investigation of PD pathogenesis involves a better understanding of the role androgens play in PD. Traditionally, androgens, such as testosterone, are known to affect collagen metabolism and wound healing in the body, a target that is well suited to the collagenous and fibrous nature of PD plaques.20 Testosterone has anti-inflammatory properties and influences collagen metabolism and there has been a small subset of studies in the past few years that have examined the relationship between low testosterone levels and keloid development.20,21 It has also been shown that androgens, such as testosterone, prevent transforming growth factor-beta 1 (TGF-b1) expression, which is a modulator of fibrosis.
We seek to review the current clinical literature regarding the relationship between androgens and both the prevalence and severity of PD.
*Studies assessing the prevalence of PD
*Studies assessing the severity of PD
Conclusion
After a comprehensive review of the literature, no definitive statement can be made regarding a relationship between PD and testosterone deficiency. Studies examining such a link suffer from significant heterogeneity and retrospective bias; further prospective standardized research should be pursued to truly determine if there is a link between hypogonadism and PD.
