Sexual Inhibition, Excitation Changes During PDE5I Therapy
Sexual Inhibition, Excitation Changes During PDE5I Therapy
Adequate sexual arousal is required if the use of PDE5Is is to result in penile erection. According to the Dual Control Model, sexual arousal could be adversely affected by impaired sexual excitability and/or active inhibition of sexual responsiveness. The relationship between impaired EF and sexual excitability and inhibition is not well understood, although high correlations between arousal and penile erection are generally reported, perhaps reflecting the fact that both psychological and genital arousal are necessary for men to engage in sexual intercourse. However, arousal does not always result in penile erection, and erection can occur in the absence of arousal. The importance of arousal as an etiological factor in ED has not been determined, although evidence suggests that the two may be related. Janssen et al. found that men who reported experiencing ED, but were not receiving treatment for the condition, had lower SES scores and higher SIS1 and SIS2 scores than men who reported normal EF. They subsequently compared results of 146 men attending sexual clinics for ED treatment with data generated in the initial study, and showed that SES and SIS1 scores in the clinical group were very similar to the scores of men in the non-clinical sample who reported experiencing ED.
The primary aim of this study was to determine whether ongoing therapeutic failure resulted in changes in excitability and inhibition that impacted upon arousal in PDE5I users. The results showed that such changes do occur. When the group results are compared, there is evidence for a general increase in arousal in men with better EF, and a decrease in those with poorer EF. However, the findings should be interpreted with caution, given that there was considerable variability in individual results in both groups.
Furthermore, the results of this study call into question the significance of excitation and inhibition measured using the SIS/SES scales in determining EF. SIS/SES scores were of little value in predicting EF at recruitment. For men in Group MM, no SIS/SES variables were predictive. For men in group M, only inhibition measured on the SIS2 scale was predictive, with better EF resulting in higher SIS2 scores. This observation seems reasonable given that men with better EF are more likely to have the opportunity to engage in sexual intercourse. As a result, the risk of adverse consequences of sexual activity increases. Bancroft et al. hypothesised that 'men with high SIS2 are more likely to react with ED to fears of rejection or partner hostility'. Although the data from this study do not provide sufficient information to enable this proposition to be tested, it should be noted that men in Group M who experienced larger increases in EF over the course of the study also experienced increases in SIS2 score. This suggests that increasing inhibition, as measured on the SIS2 scale, does not necessarily have an adverse effect on EF. SIS2 scores were not predictive of the change in EF recorded by subjects in Group MM. It is possible that the men in this group, who had poorer EF and therefore less likelihood of intercourse occurring, were less affected by fears of the consequences of sexual activity.
For subjects in Group M, increases in SES scores across the 3 months of the study were associated with decreases in EF, indicating that improvements in excitability did not translate into improved EF. This finding contrasts with the previously reported laboratory observation that SES is positively correlated with genital arousal. The reasons underlying the differences in responses cannot be determined from the results of the present study.
In the initial study validating the SIS/SES scales, Janssen et al. found a weak negative correlation between SES and SIS1, which lead them to conclude that excitation and inhibition are relatively independent of each other. The findings were repeated in the present study, albeit with stronger correlations. In both groups, higher SIS1 scores at recruitment were predictive of lower SES scores. However, changes in SES scores across the study were not predicted by changes in SIS1 or SIS2 scores in either group, supporting the view that the three measures are independent of each other.
Overall, the models predicting EF scores at recruitment accounted for ~5% of the overall variance. These findings suggest that arousal is likely to of limited importance in determining EF in men with established ED.
The observation that men continued to use PDE5Is despite the failure to achieve normal EF warrants consideration. The ongoing use of medication is in agreement with previously reported observations that men with more severe ED were more likely to have used PDE5Is to address the problem, and to believe that the problem was important enough to justify pharmacological treatment. The medications may also have resulted in some benefit that made their use worthwhile. It is possible that all men experienced an initial improvement in EF that justified the ongoing use of medication despite the failure to achieve normal EF. The attitudes of a patient's sexual partner may also have been important, as there is increasing evidence that partners influence treatment seeking and utilisation. Partner pressure has been specifically identified as a reason for seeking treatment for ED.
The observation that improved EF was associated with an increase in SIS2 in some men may be relevant to clinical management of psychogenic ED. Men who receive both psychological therapy and PDE5Is have been shown to have greater improvements in EF than men who receive PDE5Is alone. However, the results of this study indicate that counsellors should be aware of the possibility that the strength of inhibitions may change over the course of PDE5I therapy. Failure to address changing inhibitions may limit the value of psychological interventions.
The impact of the underlying psychological changes that contributed to the increased fear of rejection, humiliation or betrayal was not examined in this study. The possibility that the improvements in EF may have had adverse effects on aspects of the subject's relationships cannot be excluded. It is also possible that improved EF brings to light sexual problems afflicting the partners of men with ED. Partners have been reported to have a higher incidence of problems related to desire, arousal and sexual satisfaction than the partners of men with normal EF. This suggests that ED and female sexual dysfunction are interdependent. Successful use of PDE5Is by men has been shown to improve various aspects of sexual function in their partners. It is therefore possible that failure by male subjects to respond to PDE5Is may have an adverse impact on female sexual function, and that the manifestations of female dysfunction, such as a lack of interest in sexual activity, may result in increased fear of rejection in men.
There are several limitations to this study that may affect the interpretation of its results. The first is that the age and history of the patients, the type of medication used and the dosage could not be controlled, nor could relationship issues that may have impacted upon excitability and/or inhibition. It is also possible that different GPs used different diagnostic processes to diagnose psychogenic ED. The dropout rate in this study (54 subjects out 240, or 22.5%) was relatively high. It was however, roughly comparable with rates of ~18% reported in other studies. The higher dropout rate in Group MM (25.0%) may have reflected a decision by these men to cease PDE5I therapy due therapeutic failure, and may have had an impact on results, particularly if the dropouts represented the men who experienced the greatest adverse psychological effects of the failure to achieve normal EF. A further limitation relates to the fact the men in this study had been diagnosed with psychogenic ED. In these men, low excitation or high inhibition may be fundamental to the development of ED. In men who develop ED due to organic causes, a loss of excitation and/or increased inhibition may be a consequence of the underlying condition. Therefore, we do not have evidence to suggest that the results of this study are applicable across the entire spectrum of men with ED.
In conclusion, the results of this study have shown that excitation and inhibition measured on the SIS/SES scales are of limited value in predicting EF in men with established ED who are refractory to treatment. It has also shown that improvements in EF can be associated with increases in inhibition due to fear of the consequences of sexual activity, and decreases in sexual excitability.
Discussion
Adequate sexual arousal is required if the use of PDE5Is is to result in penile erection. According to the Dual Control Model, sexual arousal could be adversely affected by impaired sexual excitability and/or active inhibition of sexual responsiveness. The relationship between impaired EF and sexual excitability and inhibition is not well understood, although high correlations between arousal and penile erection are generally reported, perhaps reflecting the fact that both psychological and genital arousal are necessary for men to engage in sexual intercourse. However, arousal does not always result in penile erection, and erection can occur in the absence of arousal. The importance of arousal as an etiological factor in ED has not been determined, although evidence suggests that the two may be related. Janssen et al. found that men who reported experiencing ED, but were not receiving treatment for the condition, had lower SES scores and higher SIS1 and SIS2 scores than men who reported normal EF. They subsequently compared results of 146 men attending sexual clinics for ED treatment with data generated in the initial study, and showed that SES and SIS1 scores in the clinical group were very similar to the scores of men in the non-clinical sample who reported experiencing ED.
The primary aim of this study was to determine whether ongoing therapeutic failure resulted in changes in excitability and inhibition that impacted upon arousal in PDE5I users. The results showed that such changes do occur. When the group results are compared, there is evidence for a general increase in arousal in men with better EF, and a decrease in those with poorer EF. However, the findings should be interpreted with caution, given that there was considerable variability in individual results in both groups.
Furthermore, the results of this study call into question the significance of excitation and inhibition measured using the SIS/SES scales in determining EF. SIS/SES scores were of little value in predicting EF at recruitment. For men in Group MM, no SIS/SES variables were predictive. For men in group M, only inhibition measured on the SIS2 scale was predictive, with better EF resulting in higher SIS2 scores. This observation seems reasonable given that men with better EF are more likely to have the opportunity to engage in sexual intercourse. As a result, the risk of adverse consequences of sexual activity increases. Bancroft et al. hypothesised that 'men with high SIS2 are more likely to react with ED to fears of rejection or partner hostility'. Although the data from this study do not provide sufficient information to enable this proposition to be tested, it should be noted that men in Group M who experienced larger increases in EF over the course of the study also experienced increases in SIS2 score. This suggests that increasing inhibition, as measured on the SIS2 scale, does not necessarily have an adverse effect on EF. SIS2 scores were not predictive of the change in EF recorded by subjects in Group MM. It is possible that the men in this group, who had poorer EF and therefore less likelihood of intercourse occurring, were less affected by fears of the consequences of sexual activity.
For subjects in Group M, increases in SES scores across the 3 months of the study were associated with decreases in EF, indicating that improvements in excitability did not translate into improved EF. This finding contrasts with the previously reported laboratory observation that SES is positively correlated with genital arousal. The reasons underlying the differences in responses cannot be determined from the results of the present study.
In the initial study validating the SIS/SES scales, Janssen et al. found a weak negative correlation between SES and SIS1, which lead them to conclude that excitation and inhibition are relatively independent of each other. The findings were repeated in the present study, albeit with stronger correlations. In both groups, higher SIS1 scores at recruitment were predictive of lower SES scores. However, changes in SES scores across the study were not predicted by changes in SIS1 or SIS2 scores in either group, supporting the view that the three measures are independent of each other.
Overall, the models predicting EF scores at recruitment accounted for ~5% of the overall variance. These findings suggest that arousal is likely to of limited importance in determining EF in men with established ED.
The observation that men continued to use PDE5Is despite the failure to achieve normal EF warrants consideration. The ongoing use of medication is in agreement with previously reported observations that men with more severe ED were more likely to have used PDE5Is to address the problem, and to believe that the problem was important enough to justify pharmacological treatment. The medications may also have resulted in some benefit that made their use worthwhile. It is possible that all men experienced an initial improvement in EF that justified the ongoing use of medication despite the failure to achieve normal EF. The attitudes of a patient's sexual partner may also have been important, as there is increasing evidence that partners influence treatment seeking and utilisation. Partner pressure has been specifically identified as a reason for seeking treatment for ED.
The observation that improved EF was associated with an increase in SIS2 in some men may be relevant to clinical management of psychogenic ED. Men who receive both psychological therapy and PDE5Is have been shown to have greater improvements in EF than men who receive PDE5Is alone. However, the results of this study indicate that counsellors should be aware of the possibility that the strength of inhibitions may change over the course of PDE5I therapy. Failure to address changing inhibitions may limit the value of psychological interventions.
The impact of the underlying psychological changes that contributed to the increased fear of rejection, humiliation or betrayal was not examined in this study. The possibility that the improvements in EF may have had adverse effects on aspects of the subject's relationships cannot be excluded. It is also possible that improved EF brings to light sexual problems afflicting the partners of men with ED. Partners have been reported to have a higher incidence of problems related to desire, arousal and sexual satisfaction than the partners of men with normal EF. This suggests that ED and female sexual dysfunction are interdependent. Successful use of PDE5Is by men has been shown to improve various aspects of sexual function in their partners. It is therefore possible that failure by male subjects to respond to PDE5Is may have an adverse impact on female sexual function, and that the manifestations of female dysfunction, such as a lack of interest in sexual activity, may result in increased fear of rejection in men.
There are several limitations to this study that may affect the interpretation of its results. The first is that the age and history of the patients, the type of medication used and the dosage could not be controlled, nor could relationship issues that may have impacted upon excitability and/or inhibition. It is also possible that different GPs used different diagnostic processes to diagnose psychogenic ED. The dropout rate in this study (54 subjects out 240, or 22.5%) was relatively high. It was however, roughly comparable with rates of ~18% reported in other studies. The higher dropout rate in Group MM (25.0%) may have reflected a decision by these men to cease PDE5I therapy due therapeutic failure, and may have had an impact on results, particularly if the dropouts represented the men who experienced the greatest adverse psychological effects of the failure to achieve normal EF. A further limitation relates to the fact the men in this study had been diagnosed with psychogenic ED. In these men, low excitation or high inhibition may be fundamental to the development of ED. In men who develop ED due to organic causes, a loss of excitation and/or increased inhibition may be a consequence of the underlying condition. Therefore, we do not have evidence to suggest that the results of this study are applicable across the entire spectrum of men with ED.
In conclusion, the results of this study have shown that excitation and inhibition measured on the SIS/SES scales are of limited value in predicting EF in men with established ED who are refractory to treatment. It has also shown that improvements in EF can be associated with increases in inhibition due to fear of the consequences of sexual activity, and decreases in sexual excitability.
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