**8. Diagnostic approach of erectile dysfunction**

The diagnosis of erectile dysfunction in SSc patients is not always easy. We are following the common steps starting with taking a detailed history. Then assessment with appropriate questionnaires and dynamic penile Duplex ultrasound is required. The ambiguity lies in the fact that penile vascular damage occurs in almost all SSc patients, regardless of clinical symptoms and the questionnaire results that often do not match with vascular findings. Thus, it is always better to carry out both investigations: the duplex ultrasound to document the degree of vascular involvement and self-administered questionnaire. The International Index of Erectile Function is the standardized and most widely used tool for evaluating erectile dysfunction. As mentioned above, penile temperature in SSc patients is lower than in healthy individuals. Since cutaneous temperature depends on cutaneous blood flow and thermal exchanges with deeper tissues, these findings could suggest the presence of functional alterations of both tissue properties and blood flow. Therefore, assessing changes in thermal properties and temperature control processes of the penis in SSc patients could provide a potential clue in diagnosis of erectile dysfunction. It has to be noted that with the progression of micro/macrovascular damage in the natural course of the disease, a concomitant penile fibrosis and veno-occlusive dysfunction occur and usually lead to difficult-to-treat ED. We should pay attention in cases where the reduced blood flow is observed, for example, on the hands (Raynaud's phenomenon), because it can suggest that the penile arterial flow will be also altered, and it may be a sign of initial stage of ED in SSc patients [61, 62].

### **9. Treatment and recommendation for erectile dysfunction**

It is not a mistake to initiate ED treatment by eliminating general cardiovascular risk factors including lifestyle, psychological, or drug-related factors, but such treatment is often unsatisfactory. This step usually has beneficial effect on erectile function in the general population [63]. Phosphodiesterase-5 (PDE-5) inhibitors are recommended as a first-line option for pharmacotherapy. In non-SSc men, this group of drugs causes the relaxation of smooth muscle cells and temporarily increases arterial blood flow in the penis. However, to achieve an erection, sexual stimulation is required, because this class of drugs is not considered as an initiator of erection. Several types of PDE-5 inhibitors are currently available. The most commonly used are sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra). Except these, newer molecules of PDE-5 inhibitors can be used, for example, mirodenafil, udenafil, and avanafil. All types of PDE-5 inhibitors are effective and safe regarding the treatment of ED in the normal population. The differences are only in their half-lives, when, for instance, tadalafil is effective for up to 36 hours whereas the effectiveness of sildenafil is only 12 hours. The choice of a PDE5-I depends on the frequency of intercourse and the patient's personal experience [64, 65]. However, research on the efficacy of PDE-5 inhibitors is very limited in SSc patients [5]. Proietti et al. reported that once-daily tadalafil improved both erectile function and vascular measures of cavernous arteries in men with SScrelated erectile dysfunction. Also, an increase in frequency of morning erections

**127**

*Sexual Dysfunction in Patients with Systemic Sclerosis DOI: http://dx.doi.org/10.5772/intechopen.86219*

tion of digital ulceration [66].

infection [5, 64, 65].

**10. Conclusion**

and decrease in plasma ET1 levels were found. They suggest that daily tadalafil dose could play a potential role in preventing progression of penile fibrosis and erectile dysfunction in male SSc patients [58]. Furthermore, long-acting PDE-5 may lead to a decrease in the frequency and severity of Raynaud's phenomenon and the promo-

Patients who do not respond to PDE-5 inhibitors may be offered to try vacuum constriction devices. It was reported that patients who used the vacuum therapy system for a month to increase blood oxygenation in the corpora cavernosa and then employed the vacuum constriction device to maintain penile erection for sexual intercourse significantly improved their erectile function and sexual satisfaction [67]. However, there are no reports about the use of this system in patients with SSc. Another option for the treatment of erectile dysfunction is prostaglandin analogues, which can be administered via intracavernous injections or intraurethral application. Alprostadil is a stable form of prostaglandin E1 that increases the concentration of cyclic adenosine monophosphate and decreases the intracellular calcium concentration, resulting in the relaxation of smooth muscle cells. Several studies reported the efficiency of alprostadil in the general population, but in terms of SSc patients, it was reported that a substantial percentage of SSc patients did not

respond adequately to intracavernous prostaglandin E1 injections [68].

to have a positive effect on the treatment of ED in male SSc patients.

When pharmacotherapy fails and the patient wants a permanent solution, the surgical implantation of a penile prosthesis may be considered as the third-line option. Penile prosthesis improved erectile dysfunction in over 70% of men in the general population. Available prostheses are either malleable (semirigid) or inflatable (two or three pieces), but it should be considered that there are two main complications of penile prosthesis implantation—the mechanical failure and

Most of the treatment options described above have not been verified in patients with systemic sclerosis yet. In spite of the fact that erectile dysfunction is common in men with systemic sclerosis, demographics, risk factors, and ED treatments have not been sufficiently investigated. Only a small case series has described unsatisfactory results with on-demand sildenafil (25–50 mg). The higher dose of sildenafil has not been investigated. Tadalafil has been slightly better evaluated in the treatment of SSc-related erectile dysfunction. The efficiency of 20 mg tadalafil on demand and 20 mg tadalafil in a fixed alternate day regimen has been compared. The results showed that flow-mediated dilatation and peak systolic velocities of cavernous arteries at penile duplex ultrasound improved significantly with the alternate day treatment; but no significant changes were observed after the on-demand tadalafil dosing. In addition, the alternate day regimen also reduced the plasma levels of ET-1 and vascular cell adhesion molecule as markers of endothelial function [68]. Therefore, long-term administration of tadalafil and its constant plasma level seems

Sexual dysfunction is a common problem in both men and women with systemic

sclerosis. Erectile dysfunction is the dominant issue in males, which seems to be tightly linked to vascular dysfunction. Sexual dysfunction in the female patient is not less prevalent, but it is considerably more complex and it has been less studied. Several diagnostic approaches have been established to assess sexual dysfunction. Also, there are some treatment options available, but most of them have not been sufficiently verified in patients with systemic sclerosis. Further research regarding

sexual dysfunction in patients with systemic sclerosis is strongly needed.

*New Insights into Systemic Sclerosis*

thyroid hormones in SSc patients [5, 11, 59, 60].

**8. Diagnostic approach of erectile dysfunction**

population. Other causes such as hormonal abnormalities or neurological causes have not been confirmed. No disturbances have been found in follicle-stimulating hormone, luteinizing hormone, serum testosterone, prolactin, estradiol, and

The diagnosis of erectile dysfunction in SSc patients is not always easy. We are following the common steps starting with taking a detailed history. Then assessment with appropriate questionnaires and dynamic penile Duplex ultrasound is required. The ambiguity lies in the fact that penile vascular damage occurs in almost all SSc patients, regardless of clinical symptoms and the questionnaire results that often do not match with vascular findings. Thus, it is always better to carry out both investigations: the duplex ultrasound to document the degree of vascular involvement and self-administered questionnaire. The International Index of Erectile Function is the standardized and most widely used tool for evaluating erectile dysfunction. As mentioned above, penile temperature in SSc patients is lower than in healthy individuals. Since cutaneous temperature depends on cutaneous blood flow and thermal exchanges with deeper tissues, these findings could suggest the presence of functional alterations of both tissue properties and blood flow. Therefore, assessing changes in thermal properties and temperature control processes of the penis in SSc patients could provide a potential clue in diagnosis of erectile dysfunction. It has to be noted that with the progression of micro/macrovascular damage in the natural course of the disease, a concomitant penile fibrosis and veno-occlusive dysfunction occur and usually lead to difficult-to-treat ED. We should pay attention in cases where the reduced blood flow is observed, for example, on the hands (Raynaud's phenomenon), because it can suggest that the penile arterial flow will be also altered, and it may be a sign of initial stage of ED in SSc patients [61, 62].

**9. Treatment and recommendation for erectile dysfunction**

It is not a mistake to initiate ED treatment by eliminating general cardiovascular

risk factors including lifestyle, psychological, or drug-related factors, but such treatment is often unsatisfactory. This step usually has beneficial effect on erectile function in the general population [63]. Phosphodiesterase-5 (PDE-5) inhibitors are recommended as a first-line option for pharmacotherapy. In non-SSc men, this group of drugs causes the relaxation of smooth muscle cells and temporarily increases arterial blood flow in the penis. However, to achieve an erection, sexual stimulation is required, because this class of drugs is not considered as an initiator of erection. Several types of PDE-5 inhibitors are currently available. The most commonly used are sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra). Except these, newer molecules of PDE-5 inhibitors can be used, for example, mirodenafil, udenafil, and avanafil. All types of PDE-5 inhibitors are effective and safe regarding the treatment of ED in the normal population. The differences are only in their half-lives, when, for instance, tadalafil is effective for up to 36 hours whereas the effectiveness of sildenafil is only 12 hours. The choice of a PDE5-I depends on the frequency of intercourse and the patient's personal experience [64, 65]. However, research on the efficacy of PDE-5 inhibitors is very limited in SSc patients [5]. Proietti et al. reported that once-daily tadalafil improved both erectile function and vascular measures of cavernous arteries in men with SScrelated erectile dysfunction. Also, an increase in frequency of morning erections

**126**

and decrease in plasma ET1 levels were found. They suggest that daily tadalafil dose could play a potential role in preventing progression of penile fibrosis and erectile dysfunction in male SSc patients [58]. Furthermore, long-acting PDE-5 may lead to a decrease in the frequency and severity of Raynaud's phenomenon and the promotion of digital ulceration [66].

Patients who do not respond to PDE-5 inhibitors may be offered to try vacuum constriction devices. It was reported that patients who used the vacuum therapy system for a month to increase blood oxygenation in the corpora cavernosa and then employed the vacuum constriction device to maintain penile erection for sexual intercourse significantly improved their erectile function and sexual satisfaction [67]. However, there are no reports about the use of this system in patients with SSc.

Another option for the treatment of erectile dysfunction is prostaglandin analogues, which can be administered via intracavernous injections or intraurethral application. Alprostadil is a stable form of prostaglandin E1 that increases the concentration of cyclic adenosine monophosphate and decreases the intracellular calcium concentration, resulting in the relaxation of smooth muscle cells. Several studies reported the efficiency of alprostadil in the general population, but in terms of SSc patients, it was reported that a substantial percentage of SSc patients did not respond adequately to intracavernous prostaglandin E1 injections [68].

When pharmacotherapy fails and the patient wants a permanent solution, the surgical implantation of a penile prosthesis may be considered as the third-line option. Penile prosthesis improved erectile dysfunction in over 70% of men in the general population. Available prostheses are either malleable (semirigid) or inflatable (two or three pieces), but it should be considered that there are two main complications of penile prosthesis implantation—the mechanical failure and infection [5, 64, 65].

Most of the treatment options described above have not been verified in patients with systemic sclerosis yet. In spite of the fact that erectile dysfunction is common in men with systemic sclerosis, demographics, risk factors, and ED treatments have not been sufficiently investigated. Only a small case series has described unsatisfactory results with on-demand sildenafil (25–50 mg). The higher dose of sildenafil has not been investigated. Tadalafil has been slightly better evaluated in the treatment of SSc-related erectile dysfunction. The efficiency of 20 mg tadalafil on demand and 20 mg tadalafil in a fixed alternate day regimen has been compared. The results showed that flow-mediated dilatation and peak systolic velocities of cavernous arteries at penile duplex ultrasound improved significantly with the alternate day treatment; but no significant changes were observed after the on-demand tadalafil dosing. In addition, the alternate day regimen also reduced the plasma levels of ET-1 and vascular cell adhesion molecule as markers of endothelial function [68]. Therefore, long-term administration of tadalafil and its constant plasma level seems to have a positive effect on the treatment of ED in male SSc patients.

### **10. Conclusion**

Sexual dysfunction is a common problem in both men and women with systemic sclerosis. Erectile dysfunction is the dominant issue in males, which seems to be tightly linked to vascular dysfunction. Sexual dysfunction in the female patient is not less prevalent, but it is considerably more complex and it has been less studied. Several diagnostic approaches have been established to assess sexual dysfunction. Also, there are some treatment options available, but most of them have not been sufficiently verified in patients with systemic sclerosis. Further research regarding sexual dysfunction in patients with systemic sclerosis is strongly needed.
