madman
Super Moderator
Abstract
Background: Penile echo-color Doppler ultrasound (PCDU) is the gold standard for the diagnosis of arterial erectile dysfunction (ED). Its reliability in patients with anxiety was questioned, due to false-positive results. Aim: To assess the penile hemodynamic response to intracavernous injection (ICI) of alprostadil in patients with anxiety-related ED.
Methods: Patients with non-organic ED and a 5-item International Index of Erectile Function (IIEF-5) score ranging between 5 and 7 were enrolled. They were asked to compile the 7-item Generalized Anxiety Disorder (GAD-7) questionnaire to assess the degree of anxiety and were divided according to the GAD-7 score in Group 1 with a minimal level of anxiety (n = 20), Group 2 with mild anxiety (n = 20), Group 3 with moderate anxiety (n = 20), and Group 4 with severe anxiety (n = 20). Peak systolic velocity (PSV) and the end-diastolic velocity (EDV) were sampled in all patients, through PCDU in the flaccid state, and 5, 10, 15, and 20 min after ICI of alprostadil at the standard dose of 10 µg.
Results: In penile flaccidity, the patients showed a mean PSV of 8.0 ± 4.0 cm/s. The degree of anxiety was found to significantly influence both PSV and EDV at all assessed time-points. Particularly, it was negatively associated with the PSV at time 5 (r = −0.9, p < 0.01), 10 (r = −0.9, p < 0.01), 15 (r = −0.9, p < 0.01), and 20 (r = −0.7, p < 0.01) minutes, and positively with the EDV at time 5 (r = 0.7, p < 0.01), 10 (r = 0.6, p < 0.01), 15 (r = 0.5, p < 0.01), and 20 (r = 0.3, p < 0.01) minutes. Although all patients showed a mean dynamic PSV > 25 cm/s (which excluded an arterial ED according to the current guidelines), a peculiar hemodynamic pattern was found in patients with severe anxiety. In these patients, normal PSV values were reached only after 20 min from ICI, suggesting a “late-responder” profile.
Conclusion: If further studies confirm the existence of a distinct hemodynamic profile in patients with severe anxiety, sampling the PSV and the EDV values could be proposed, for detecting patients with severe anxiety-related ED. Dynamic PCDU could be considered an accurate diagnostic test in patients with non-organic ED since zero false-positive results were found in the present study. PSV in the flaccid state is not able to discriminate between arterial- or non-organic ED.
1. Introduction
Erectile dysfunction (ED) is defined as the persistent failure to achieve or to maintain a penile erection satisfactory for sexual performance [1]. Both organic and psychogenic causes, either alone or in combination, are recognized to play a role in its pathogenesis [2]. Penile erection results from a complex series of events requiring the integrity of the cavernous arteries and their smooth musculature, the tunica albuginea, the spongiosal, circumflex and cavernous veins, and the correct release, availability, and balance of neurotransmitters involved in the relaxation of the arteries and arterioles’ smooth muscles [3]. In the penile flaccid state, cavernous smooth musculature is tonically contracted, allowing only a minimal arterial blood flow required for nutritional purposes. Sexual stimulation prompts the release of nitric oxide (NO), synthesized by the neuronal NO synthase (nNOS) enzyme via the parasympathetic nervous system. NO modulates the intracellular levels of cyclic GMP into the smooth muscle cells, in turn inducing vascular relaxation and, consequently, the increase of arterial blood flow, which leads to erection [3]. Anxiety associates with an exaggerated adrenergic tone. Cavernous muscle cells express α-adrenergic receptors and, once activated by the sympathetic neurotransmitters, they lead to arterial smooth muscle contraction and hinder penile erection. Several lines of evidence support the negative impact of anxiety on sexual performance and erectile function [4–6], and this negative influence is widely accepted [3,7].
Penile echo-color Doppler ultrasound (PCDU) examination after intracavernous injection (ICI) of prostaglandin (Pg) E1 or derivatives (e.g., alprostadil) is a second-line diagnostic test available for patients with ED. This test allows us to see single images, differently from the penile Duplex Doppler ultrasound (PDDU), where Color Doppler images are combined with the grayscale (B-mode) ones. This leads to the visualization of duplex ultrasonography images, needed for simultaneous visualization of the anatomy of the area [8]. Although due to the lack of standardization of the sampling location [9] and cut-off values, a relevant effort was made through decades to identify PCDU waveforms predictive of arterial or venous ED [3]. In greater detail, PCDU allows the measurement of peak systolic velocity (PSV) and end-diastolic velocity (EDV) in the cavernous artery, following the injection of alprostadil. Both of these parameters describe the blood flow characteristics in the cavernous artery during erection and are currently used for the diagnosis of vasculogenic ED. Accordingly, a restriction of the cavernous artery lumen (e.g., due to an arterial plaque or to a greater media-intima thickness) leads the arterial blood flow to slow down, and the PSV value decreases accordingly. In this regard, a PSV cut-off value ranging from 25 to 35 cm/s was suggested as the limit [10]. Conversely, in the case of venous ED (blood is drained too fast by the penile dorsal vein), EDV increases (>5 cm/s) [3].
Despite efforts to make the PCDU analysis an accurate method for the diagnosis of organic ED, scanty data are currently available on the PCDU outcome in anxiety-related ED. Anxiety is able to negatively impact the quality of erection. Accordingly, a pioneer study described how psychogenic factors impact erectile response to the intracavernous injection of papaverine [11]. Subsequently, another study described a lack of erectile response to ICI of alprostadil, at a dose of 20 µg, in patients with anxiety-related ED [12]. Anxiety-related ED affects young patients (≤30 years) more commonly than middle-aged ones [4]. However, how exactly anxiety influences the PCDU parameters and if a high state of anxiety associates with a specific hemodynamic response is unknown. Therefore, we undertook a cross-sectional study to evaluate whether the PSV and the EDV before and after the ICI of alprostadil, are influenced by the degree of anxiety in patients with non-organic ED. The results of this study can help identify a typical anxiety-related penile hemodynamic pattern of response to alprostadil.
4. Discussion
This study showed for the first time the different penile hemodynamic patterns in patients with non-organic ED, depending on the presence and degree of anxiety. We found that patients with a moderate or a severe anxiety disorder were younger than those with a minimal or a mild degree of anxiety. Furthermore, anxiety was found to influence the dynamic PCDU parameters after alprostadil ICI. The degree of anxiety correlated negatively with PSV and directly with dynamic EDV at all time-points of assessment. Interestingly, patients with the highest degree of anxiety (Group 4) had a distinct penile hemodynamic pattern, achieving normal PSV values only 20 min after alprostadil ICI. Similarly, this group of patients showed higher mean EDV values, after 5 and 10 min, as compared to the other groups. These ultrasound hemodynamic parameters confer the appearance of a “low-responder” pattern in patients with severe anxiety.
5. Conclusions
In conclusion, we showed that anxiety is able to affect penile hemodynamics in patients with non-organic ED, depending on the degree of the anxiety disorder. Patients with severe anxiety show a “late-responder” penile hemodynamic pattern, with distinct PSV and EDV parameters, at all times of assessment. Furthermore, although PSV in a flaccid state was below 13 cm/s in all patients, a dynamic PSV value >25 cm/s was found in all cases 20 min after ICI. Therefore, these results suggest that (i) if further studies confirm the existence of a distinct hemodynamic pattern in patients with severe anxiety, PSV and EDV measurements might be proposed to diagnose patients with severe anxiety-related ED; (ii) PCDU scan after alprostadil ICI could be considered an accurate diagnostic test in patients with non-organic ED, since we found zero false-positives when the evaluation was performed up to 20 min and a cut-off value of 25 cm/s was considered; and (iii) PSV in a flaccid state was not able to diagnose between arterial and non-organic ED.
Background: Penile echo-color Doppler ultrasound (PCDU) is the gold standard for the diagnosis of arterial erectile dysfunction (ED). Its reliability in patients with anxiety was questioned, due to false-positive results. Aim: To assess the penile hemodynamic response to intracavernous injection (ICI) of alprostadil in patients with anxiety-related ED.
Methods: Patients with non-organic ED and a 5-item International Index of Erectile Function (IIEF-5) score ranging between 5 and 7 were enrolled. They were asked to compile the 7-item Generalized Anxiety Disorder (GAD-7) questionnaire to assess the degree of anxiety and were divided according to the GAD-7 score in Group 1 with a minimal level of anxiety (n = 20), Group 2 with mild anxiety (n = 20), Group 3 with moderate anxiety (n = 20), and Group 4 with severe anxiety (n = 20). Peak systolic velocity (PSV) and the end-diastolic velocity (EDV) were sampled in all patients, through PCDU in the flaccid state, and 5, 10, 15, and 20 min after ICI of alprostadil at the standard dose of 10 µg.
Results: In penile flaccidity, the patients showed a mean PSV of 8.0 ± 4.0 cm/s. The degree of anxiety was found to significantly influence both PSV and EDV at all assessed time-points. Particularly, it was negatively associated with the PSV at time 5 (r = −0.9, p < 0.01), 10 (r = −0.9, p < 0.01), 15 (r = −0.9, p < 0.01), and 20 (r = −0.7, p < 0.01) minutes, and positively with the EDV at time 5 (r = 0.7, p < 0.01), 10 (r = 0.6, p < 0.01), 15 (r = 0.5, p < 0.01), and 20 (r = 0.3, p < 0.01) minutes. Although all patients showed a mean dynamic PSV > 25 cm/s (which excluded an arterial ED according to the current guidelines), a peculiar hemodynamic pattern was found in patients with severe anxiety. In these patients, normal PSV values were reached only after 20 min from ICI, suggesting a “late-responder” profile.
Conclusion: If further studies confirm the existence of a distinct hemodynamic profile in patients with severe anxiety, sampling the PSV and the EDV values could be proposed, for detecting patients with severe anxiety-related ED. Dynamic PCDU could be considered an accurate diagnostic test in patients with non-organic ED since zero false-positive results were found in the present study. PSV in the flaccid state is not able to discriminate between arterial- or non-organic ED.
1. Introduction
Erectile dysfunction (ED) is defined as the persistent failure to achieve or to maintain a penile erection satisfactory for sexual performance [1]. Both organic and psychogenic causes, either alone or in combination, are recognized to play a role in its pathogenesis [2]. Penile erection results from a complex series of events requiring the integrity of the cavernous arteries and their smooth musculature, the tunica albuginea, the spongiosal, circumflex and cavernous veins, and the correct release, availability, and balance of neurotransmitters involved in the relaxation of the arteries and arterioles’ smooth muscles [3]. In the penile flaccid state, cavernous smooth musculature is tonically contracted, allowing only a minimal arterial blood flow required for nutritional purposes. Sexual stimulation prompts the release of nitric oxide (NO), synthesized by the neuronal NO synthase (nNOS) enzyme via the parasympathetic nervous system. NO modulates the intracellular levels of cyclic GMP into the smooth muscle cells, in turn inducing vascular relaxation and, consequently, the increase of arterial blood flow, which leads to erection [3]. Anxiety associates with an exaggerated adrenergic tone. Cavernous muscle cells express α-adrenergic receptors and, once activated by the sympathetic neurotransmitters, they lead to arterial smooth muscle contraction and hinder penile erection. Several lines of evidence support the negative impact of anxiety on sexual performance and erectile function [4–6], and this negative influence is widely accepted [3,7].
Penile echo-color Doppler ultrasound (PCDU) examination after intracavernous injection (ICI) of prostaglandin (Pg) E1 or derivatives (e.g., alprostadil) is a second-line diagnostic test available for patients with ED. This test allows us to see single images, differently from the penile Duplex Doppler ultrasound (PDDU), where Color Doppler images are combined with the grayscale (B-mode) ones. This leads to the visualization of duplex ultrasonography images, needed for simultaneous visualization of the anatomy of the area [8]. Although due to the lack of standardization of the sampling location [9] and cut-off values, a relevant effort was made through decades to identify PCDU waveforms predictive of arterial or venous ED [3]. In greater detail, PCDU allows the measurement of peak systolic velocity (PSV) and end-diastolic velocity (EDV) in the cavernous artery, following the injection of alprostadil. Both of these parameters describe the blood flow characteristics in the cavernous artery during erection and are currently used for the diagnosis of vasculogenic ED. Accordingly, a restriction of the cavernous artery lumen (e.g., due to an arterial plaque or to a greater media-intima thickness) leads the arterial blood flow to slow down, and the PSV value decreases accordingly. In this regard, a PSV cut-off value ranging from 25 to 35 cm/s was suggested as the limit [10]. Conversely, in the case of venous ED (blood is drained too fast by the penile dorsal vein), EDV increases (>5 cm/s) [3].
Despite efforts to make the PCDU analysis an accurate method for the diagnosis of organic ED, scanty data are currently available on the PCDU outcome in anxiety-related ED. Anxiety is able to negatively impact the quality of erection. Accordingly, a pioneer study described how psychogenic factors impact erectile response to the intracavernous injection of papaverine [11]. Subsequently, another study described a lack of erectile response to ICI of alprostadil, at a dose of 20 µg, in patients with anxiety-related ED [12]. Anxiety-related ED affects young patients (≤30 years) more commonly than middle-aged ones [4]. However, how exactly anxiety influences the PCDU parameters and if a high state of anxiety associates with a specific hemodynamic response is unknown. Therefore, we undertook a cross-sectional study to evaluate whether the PSV and the EDV before and after the ICI of alprostadil, are influenced by the degree of anxiety in patients with non-organic ED. The results of this study can help identify a typical anxiety-related penile hemodynamic pattern of response to alprostadil.
4. Discussion
This study showed for the first time the different penile hemodynamic patterns in patients with non-organic ED, depending on the presence and degree of anxiety. We found that patients with a moderate or a severe anxiety disorder were younger than those with a minimal or a mild degree of anxiety. Furthermore, anxiety was found to influence the dynamic PCDU parameters after alprostadil ICI. The degree of anxiety correlated negatively with PSV and directly with dynamic EDV at all time-points of assessment. Interestingly, patients with the highest degree of anxiety (Group 4) had a distinct penile hemodynamic pattern, achieving normal PSV values only 20 min after alprostadil ICI. Similarly, this group of patients showed higher mean EDV values, after 5 and 10 min, as compared to the other groups. These ultrasound hemodynamic parameters confer the appearance of a “low-responder” pattern in patients with severe anxiety.
5. Conclusions
In conclusion, we showed that anxiety is able to affect penile hemodynamics in patients with non-organic ED, depending on the degree of the anxiety disorder. Patients with severe anxiety show a “late-responder” penile hemodynamic pattern, with distinct PSV and EDV parameters, at all times of assessment. Furthermore, although PSV in a flaccid state was below 13 cm/s in all patients, a dynamic PSV value >25 cm/s was found in all cases 20 min after ICI. Therefore, these results suggest that (i) if further studies confirm the existence of a distinct hemodynamic pattern in patients with severe anxiety, PSV and EDV measurements might be proposed to diagnose patients with severe anxiety-related ED; (ii) PCDU scan after alprostadil ICI could be considered an accurate diagnostic test in patients with non-organic ED, since we found zero false-positives when the evaluation was performed up to 20 min and a cut-off value of 25 cm/s was considered; and (iii) PSV in a flaccid state was not able to diagnose between arterial and non-organic ED.
