Hyperthyroidism and Erectile Dysfunction
Hyperthyroidism and Erectile Dysfunction
While dysthryoidism has been reported to be associated with sexual dysfunction, and thyroid hormone disorders in general have been understood to alter the reproductive axis, to the best of our knowledge this is the first large-scale population-based study conducted investigating the relationship between ED and hyperthyroidism. After adjusting for monthly income, geographic location, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity and alcohol abuse/alcohol dependence syndrome, we found that the OR of prior hyperthyroidism among cases was 1.64 (95% confidence interval=1.37–1.96, P<0.001) than that of controls. After stratifying for age, the association between hyperthyroidism and ED was only significant among three age groups (40–49, 50–59 and 60–69). The greatest magnitude of association was detected among subjects aged between 60 and 69 years who were found to be 1.84 times as likely to have been previously diagnosed with hyperthyroidism than matched controls.
The prevalence of ED increases with age on account of several reasons. A greater share of the older men in this study likely suffered from ED on account of factors that were unrelated to hyperthyroidism. One such factor may involve decreased testosterone levels. While it is possible that hyperthyroidism may have an additional effect on age-related decreases in testosterone and free testosterone, these decreases are well understood to be naturally occurring phenomena in the absence of other endocrine disorders. Another possible diluting factor may involve the increased peripheral vascular resistance resulting from the narrowing of the lumen on account of accumulations on vessel walls. Such increased resistance has been shown to result in structural changes to the penile vasculature, including both arterial and erectile tissues. As we were not able to control for these factors, they may have diluted the association between ED and hyperthyroidism detected in this study.
This study supports the conclusions of the two previous studies investigating the association between dysthyroidism and ED. The pioneering study investigating the relationship between dysthyroidism and ED was a multi-center study conducted in Italy, which analyzed the sexual function, including ED, among 34 men with hyperthyroidism and 14 with hypothyroidism. Upon presentation with dysthyroidism, they screened each subject for hypoactive sexual desire, ED, premature ejaculation and delayed ejaculation. They then performed a follow-up screening 8–16 weeks following restoration of euthyroidism. In addition to improvements in premature ejaculation, delayed ejaculation and ejaculation latency time, there were significant changes among subdomains of IIEF.
The second investigation was performed on 71 men and a similar number of controls selected from one thyroid outpatient hospital in Greece. Of the cases, 27 had hyperthyroidism and 44 had hypothyroidism. The mean ages of the hypothyroidism patients were 52.6 and 55.9 years, respectively, thus leaving the majority of them over Graves' most common age of onset. They used a validated Sexual Health Inventory for Men 5-iitem questionnaire based on the IIEF questionnaire to realize that approximately 80% of the patients suffering from thyroid dysfunction also suffered from ED. This can be compared with 34% of the controls. Most interestingly, following treatment restoring euthyroidism, only 30% of their cases were left suffering from ED, a figure similar to the control group.
The finding from the above two studies that the restoration of euthyroidic conditions can rescue sexual function not only further confirms that dysthyroidism exerts a contributory effect toward the development of ED, but also more specifically helps to identify the downstream effects of dysthyroidism as the major contributory factors in the association with ED. It has been demonstrated that hypothyroidism may result in subsequent decreases in serum testosterone, dehydroepiandrosterone and DHEA sulfate, and while the basal levels of steroids and sex hormone-binding globulin levels have been demonstrated to be significantly higher in male subjects with hyperthyroidism than that in normal men, their basal bioT levels have been shown to be lower than that in controls. Similar hormonal disturbances can also be seen in women. One previous study investigating sexual function in women did find that women with hyperthyroidism also exhibited increased depressive symptoms, increased sex hormone-binding globulin levels and decreased fT levels, all of which being associated with female sexual dysfunction. Thus, it is the work of future studies to investigate the mechanisms underlying the association between hyperthyroidism in men and ED.
The primary strength of our study lies in its longitudinal database and large sample population, which mitigate the effect of the selection biases inherent in studies utilizing data taken from voluntary registries or hospital-referred study patients. Also, over 98% of Taiwan's residents are of Han Chinese ethnicity. While the homogeneity of the population may exempt our study from potential confounding by race, it also limits the generalizibility to other ethnic groups.
This study suffered from several limitations that should be addressed. The first is the use of ICD-9 coding in the administrative database to diagnose ED. Although ED diagnoses in Taiwan are based on the results of a self-administered IIEF-5 questionnaire, the raw scores are not available in the database and we were therefore unable to include any measure for severity in this investigation. Administrative databases are notorious for receiving criticism concerning their diagnostic validity; however, one study by Lin et al. has verified the high validity of diagnoses in the Taiwan Health Insurance Database.
Secondly, on account of cultural taboos associated with discussing sexuality in Taiwan, many patients may not wish to see a specialist despite suffering from ED. Not only may this help account for the seemingly low-incidence of ED when compared with studies from western countries, but could also lead to the possibility that some of the controls in this study were also suffering from ED. However, if such a bias exists in the data, the results of our analysis would be biased towards the null. Further adding to the diagnostic validity of ED in this study, not only may a Taiwanese be reluctant to admit suffering from a shameful condition, but there is also no incentive to be diagnosed as pharmaceutical treatment for ED is not covered under the NHI program.
Third, some clinically relevant patient and lifestyle information, such as smoking status, alcohol consumption and dietary habits, martial status and body mass index, was not available through the administrative data set. Although we did adjust for urbanization level, which may reflect lifestyle, as well as both obesity and alcohol abuse/dependence syndrome, the association between hyperthyroidism and ED may be partially explained by the residual confounding of unadjusted factors.
Finally, although we commented on a number of possibilities regarding the mechanisms underlying the associations between ED and hyperthyroidism detected in this study, the administrative database we used to source our hyperthyroidism cases lacked information detailing their etiological classifications and raw hormone levels. Therefore, the mechanistic possibilities explored in this paper were entirely speculative and future studies will need to be conducted to better elucidate the underpinning of these associations.
This study succeeded in contributing to the body of evidence surrounding the association between dysthyroidism and sexual dysfunction, and most specifically to that between ED and prior hyperthyroidism. As previous work demonstrated that the restoration of euthyroidism recovered sexual function, it is the suggestion of the authors that clinicians follow the advice of previous studies and not begin treatment for ED among hyperthyroid patients until after first completing 6 months of treatment for hyperthyroidism and the restoration of euthyroidism. Furthermore, it is suggested that patients with long-standing hyperthyroidism complaining of ED first be questioned regarding their adherence to their hyperthyroid treatment regimen and have their thyroid levels checked before proceeding to treatment for ED. Finally, it is suggested that similar studies be conducted in other countries or regions to validate the novel findings of this study.
Discussion
While dysthryoidism has been reported to be associated with sexual dysfunction, and thyroid hormone disorders in general have been understood to alter the reproductive axis, to the best of our knowledge this is the first large-scale population-based study conducted investigating the relationship between ED and hyperthyroidism. After adjusting for monthly income, geographic location, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity and alcohol abuse/alcohol dependence syndrome, we found that the OR of prior hyperthyroidism among cases was 1.64 (95% confidence interval=1.37–1.96, P<0.001) than that of controls. After stratifying for age, the association between hyperthyroidism and ED was only significant among three age groups (40–49, 50–59 and 60–69). The greatest magnitude of association was detected among subjects aged between 60 and 69 years who were found to be 1.84 times as likely to have been previously diagnosed with hyperthyroidism than matched controls.
The prevalence of ED increases with age on account of several reasons. A greater share of the older men in this study likely suffered from ED on account of factors that were unrelated to hyperthyroidism. One such factor may involve decreased testosterone levels. While it is possible that hyperthyroidism may have an additional effect on age-related decreases in testosterone and free testosterone, these decreases are well understood to be naturally occurring phenomena in the absence of other endocrine disorders. Another possible diluting factor may involve the increased peripheral vascular resistance resulting from the narrowing of the lumen on account of accumulations on vessel walls. Such increased resistance has been shown to result in structural changes to the penile vasculature, including both arterial and erectile tissues. As we were not able to control for these factors, they may have diluted the association between ED and hyperthyroidism detected in this study.
This study supports the conclusions of the two previous studies investigating the association between dysthyroidism and ED. The pioneering study investigating the relationship between dysthyroidism and ED was a multi-center study conducted in Italy, which analyzed the sexual function, including ED, among 34 men with hyperthyroidism and 14 with hypothyroidism. Upon presentation with dysthyroidism, they screened each subject for hypoactive sexual desire, ED, premature ejaculation and delayed ejaculation. They then performed a follow-up screening 8–16 weeks following restoration of euthyroidism. In addition to improvements in premature ejaculation, delayed ejaculation and ejaculation latency time, there were significant changes among subdomains of IIEF.
The second investigation was performed on 71 men and a similar number of controls selected from one thyroid outpatient hospital in Greece. Of the cases, 27 had hyperthyroidism and 44 had hypothyroidism. The mean ages of the hypothyroidism patients were 52.6 and 55.9 years, respectively, thus leaving the majority of them over Graves' most common age of onset. They used a validated Sexual Health Inventory for Men 5-iitem questionnaire based on the IIEF questionnaire to realize that approximately 80% of the patients suffering from thyroid dysfunction also suffered from ED. This can be compared with 34% of the controls. Most interestingly, following treatment restoring euthyroidism, only 30% of their cases were left suffering from ED, a figure similar to the control group.
The finding from the above two studies that the restoration of euthyroidic conditions can rescue sexual function not only further confirms that dysthyroidism exerts a contributory effect toward the development of ED, but also more specifically helps to identify the downstream effects of dysthyroidism as the major contributory factors in the association with ED. It has been demonstrated that hypothyroidism may result in subsequent decreases in serum testosterone, dehydroepiandrosterone and DHEA sulfate, and while the basal levels of steroids and sex hormone-binding globulin levels have been demonstrated to be significantly higher in male subjects with hyperthyroidism than that in normal men, their basal bioT levels have been shown to be lower than that in controls. Similar hormonal disturbances can also be seen in women. One previous study investigating sexual function in women did find that women with hyperthyroidism also exhibited increased depressive symptoms, increased sex hormone-binding globulin levels and decreased fT levels, all of which being associated with female sexual dysfunction. Thus, it is the work of future studies to investigate the mechanisms underlying the association between hyperthyroidism in men and ED.
The primary strength of our study lies in its longitudinal database and large sample population, which mitigate the effect of the selection biases inherent in studies utilizing data taken from voluntary registries or hospital-referred study patients. Also, over 98% of Taiwan's residents are of Han Chinese ethnicity. While the homogeneity of the population may exempt our study from potential confounding by race, it also limits the generalizibility to other ethnic groups.
This study suffered from several limitations that should be addressed. The first is the use of ICD-9 coding in the administrative database to diagnose ED. Although ED diagnoses in Taiwan are based on the results of a self-administered IIEF-5 questionnaire, the raw scores are not available in the database and we were therefore unable to include any measure for severity in this investigation. Administrative databases are notorious for receiving criticism concerning their diagnostic validity; however, one study by Lin et al. has verified the high validity of diagnoses in the Taiwan Health Insurance Database.
Secondly, on account of cultural taboos associated with discussing sexuality in Taiwan, many patients may not wish to see a specialist despite suffering from ED. Not only may this help account for the seemingly low-incidence of ED when compared with studies from western countries, but could also lead to the possibility that some of the controls in this study were also suffering from ED. However, if such a bias exists in the data, the results of our analysis would be biased towards the null. Further adding to the diagnostic validity of ED in this study, not only may a Taiwanese be reluctant to admit suffering from a shameful condition, but there is also no incentive to be diagnosed as pharmaceutical treatment for ED is not covered under the NHI program.
Third, some clinically relevant patient and lifestyle information, such as smoking status, alcohol consumption and dietary habits, martial status and body mass index, was not available through the administrative data set. Although we did adjust for urbanization level, which may reflect lifestyle, as well as both obesity and alcohol abuse/dependence syndrome, the association between hyperthyroidism and ED may be partially explained by the residual confounding of unadjusted factors.
Finally, although we commented on a number of possibilities regarding the mechanisms underlying the associations between ED and hyperthyroidism detected in this study, the administrative database we used to source our hyperthyroidism cases lacked information detailing their etiological classifications and raw hormone levels. Therefore, the mechanistic possibilities explored in this paper were entirely speculative and future studies will need to be conducted to better elucidate the underpinning of these associations.
This study succeeded in contributing to the body of evidence surrounding the association between dysthyroidism and sexual dysfunction, and most specifically to that between ED and prior hyperthyroidism. As previous work demonstrated that the restoration of euthyroidism recovered sexual function, it is the suggestion of the authors that clinicians follow the advice of previous studies and not begin treatment for ED among hyperthyroid patients until after first completing 6 months of treatment for hyperthyroidism and the restoration of euthyroidism. Furthermore, it is suggested that patients with long-standing hyperthyroidism complaining of ED first be questioned regarding their adherence to their hyperthyroid treatment regimen and have their thyroid levels checked before proceeding to treatment for ED. Finally, it is suggested that similar studies be conducted in other countries or regions to validate the novel findings of this study.
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