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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2007-2259
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The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 5 1815-1819
Copyright © 2008 by The Endocrine Society

Erectile Dysfunction in Patients with Hyper- and Hypothyroidism: How Common and Should We Treat?

Gerasimos E. Krassas, Kostas Tziomalos, Fotini Papadopoulou, Nikolaos Pontikides and Petros Perros

Department of Endocrinology, Diabetes, and Metabolism (G.E.K., K.T., F.P., N.P.), Panagia General Hospital, 55132 Thessaloniki, Greece; and Endocrine Unit (P.P.), Freeman Hospital, Newcastle upon Tyne NE7 7DN, United Kingdom

Address all correspondence and requests for reprints to: Professor Gerasimos E. Krassas, M.D., Ph.D., F.R.C.P., Chairman, Department of Endocrinology, Diabetes, and Metabolism, Panagia General Hospital, North Plastira, 22, North Krini, 55132 Thessaloniki, Greece. E-mail: krassas{at}the.forthnet.gr.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
Context: Erectile dysfunction (ED) is associated with numerous diseases and aging.

Objective: The objective of the study was to investigate the impact of hyper- and hypothyroidism on male sexual health by using the Sexual Health Inventory for Males (SHIM).

Design: Seventy-one men, 27 hyper- and 44 hypothyroid and a similar number of controls were included in the study. A validated SHIM 5-item questionnaire was administered to all participants. Patients were asked to respond before and a year after initiation of treatment for thyroid dysfunction. A score between 25 and 22 is considered normal, between 21 and 11 diagnostic of mild to moderately severe ED, and 10 or less diagnostic of severe ED.

Results: Fifty-six men with thyroid dysfunction (78.9%; 19 hyperthyroid and 37 hypothyroid) had a SHIM score of 21 or less, compared with 24 controls (33.8%) (P < 0.0001). Twenty-one patients with ED (37.5%) had SHIM scores 10 or less, indicative of severe ED, compared with six controls (25%) (P < 0.01). ED was more prevalent in patients with hyperthyroidism and hypothyroidism, compared with controls (P < 0.001 and P < 0.0001, respectively). Positive correlation was found between SHIM scores and serum free T4 (r = 0.413, P = 0.005) and negative for TSH (r = –0.669, P < 0.001). After treatment a significant increase of SHIM scores was noted in both hyperthyroid (P < 0.0001) and hypothyroid (P < 0.0001) patients.

Conclusions: ED is extremely common in males with dysthyroidism. Treatment of the latter restores erectile function. Screening for thyroid dysfunction in men presenting with ED is recommended, whereas specific treatment for ED should be postponed in such patients for at least 6 months after achieving euthyroidism because the latter might be responsible for ED.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
Erectile dysfunction (ED), the consistent or recurrent inability to attain or maintain penile erection adequate for sexual intercourse (1), is a common male disability associated with numerous diseases and aging. The introduction of relatively safe and effective oral therapy in the form of selective phosphodiesterase-5 inhibitors has largely increased patient and physician interest in the evaluation and treatment of this disorder (2). The relationship between ED and thyroid disturbances has not been studied, although hyper- and hypothyroidism are often highlighted as common endocrine conditions associated with ED (2).

A minimum duration of symptoms of 3 months is usually required for accepting the diagnosis of ED, although in cases of trauma or surgically induced ED, this criterion may be waived. Although objective testing or partner reports may be used to support the diagnosis of ED, these cannot replace the patient’s self-report in classifying the dysfunction or establishing the diagnosis (2, 3).

The aim of this study was to investigate the impact of hyper- and hypothyroidism on male sexual health by using the Sexual Health Inventory for Males (SHIM), a 5-item questionnaire that focuses on a man’s ability to attain and then maintain an erection. The SHIM is a useful, quick, and inexpensive tool for diagnosis of ED (4). Validated questionnaires (like SHIM used in the present study) have been used widely to assess erectile function and generate reliable data.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
We administered the validated SHIM 5-item questionnaire (Table 1Go), based on the International Index of Erectile Function questionnaire to 76 consecutive men with thyroid dysfunction, all attending the thyroid outpatient clinic of Panagia General Hospital (Thessaloniki, Greece). Although objective measurements of erectile function were not performed in this study, the SHIM questionnaire is established as a reliable tool in assessing erectile function. Five of 76 patients did not wish to participate in the study. The characteristics of those five patients did not differ from the participants. Of the remaining 71 men, 27 had clinical hyperthyroidism and 44 clinical hypothyroidism (TSH > 10 mU/liter). Of the 27 hyperthyroid patients, 18 had Graves’ disease, whereas the remaining nine had toxic nodular or multinodular goiter. Patients with diabetes mellitus, cardiovascular disease (history of myocardial infarction, coronary angioplasty, or coronary artery bypass grafting), or urological diseases were excluded from the study. None of the patients was on thyroid medication before recruitment. Mean age of patients was 51.2 ± 10.3 yr SD, range 24–65 yr (Table 2Go). A similar number of normal individuals, all without thyroid, cardiovascular, or urological disease or diabetes mellitus, matched for age, was also investigated (Table 2Go). They comprised largely medical and nursing hospital staff. Free T4 (FT4), TSH, free testosterone (FTesto) and prolactin (PRL) serum concentrations were measured in all patients and controls. FTesto was used as a screening test because this is not the most accurate measure for male androgens. However, our policy in our clinic is that if the patient has an abnormal FTesto test, then a further investigation is provided, measuring total testosterone and SHBG. From those two, the androgen index is also calculated. Patients or controls with abnormal levels of those hormones were excluded from the study.


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  		TABLE 1. Sexual Health Inventory for Men (SHIM)1

 

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  		TABLE 2. SHIM scores and serum thyroid hormones at baseline and after treatment

 
About one third of the patients and controls were taking medications (mainly β-blockers, statins, diuretics, antihypertensive agents, or mild sedatives) (Table 2Go). Elevated levels of FT4 and suppressed TSH levels were diagnostic for hyperthyroidism, whereas increased levels of TSH and decreased levels of FT4 confirmed the diagnosis of hypothyroidism. Thirty-seven patients with hypothyroidism had positive thyroid antibodies (Table 2Go). FT4, TSH, FTesto, and prolactin (PRL) were measured by RIA. The serum levels of FT4, TSH, antithyroid peroxidase and antithyroglobulin antibodies were measured by standard, commercial RIA kits (Brahms, Henningsdorf, Germany). Normal range for FT4 is 7–18 pg/ml and 0.3–4.0 mU/liter for TSH. Interassay variation for FT4 and TSH was 3.6 and 4.3%, respectively. FTesto and PRL were measured by commercial RIA kits (Biosource, Fleurus, Belgium; and Immunotech, Prague, Czech Republic, respectively). The normal range for FTesto is 8.7–54.7 pg/ml and 60–400 µIU/ml for PRL. Interassay variation for FTesto and PRL was 4.7 and 5.1%, respectively. Regarding SHIM (Table 1Go), we added the numbers corresponding to questions 1–5 and if the score was between 17 and 21, then the diagnosis of mild ED was confirmed, and if the score was between 11 and 16, then the diagnosis of moderately severe ED was established. Finally, if the score was 10 or less, then the diagnosis of severe ED was confirmed. Question 2 focuses mainly on difficulties achieving erections whereas question 3 on difficulties maintaining erections. After the questionnaire was completed, treatment for thyroid dysfunction was commenced, either with antithyroid drugs if the patient suffered from hyperthyroidism, or T4 if from the diagnosis was hypothyroidism. A year after the initiation of treatment and when all the patients were euthyroid, the same questionnaire was distributed to all patients.

All participants provided written informed consent. The study was approved by the ethics committee of our institution and was performed in accordance with the principles of the Declaration of Helsinki.

Statistical analysis

All data were analyzed using the statistical package SPSS (version 10.0; SPSS Inc., Chicago, IL). The Mann-Whitney and {chi}2 tests were used for comparisons of quantitative and qualitative variables between groups, respectively. Associations between continuous variables were explored using Spearman’s rank order correlation coefficient. The Wilcoxon signed rank test was used to test the effect of therapy on the SHIM score. In all cases, a two-tailed P < 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
Fifty-six men with thyroid dysfunction (78.9%; 19 hyperthyroid and 37 hypothyroid) had a SHIM score of 21 or less (indicating some degree of ED), compared with 24 controls (33.8%) (P < 0.0001). Twenty-one of the patients with ED (37.5%) had SHIM scores of 10 or less, indicative of severe ED, compared with six of 24 controls (25%) (P < 0.01). Of the 21 patients with severe ED, eight were hyperthyroid and 13 hypothyroid. A significantly greater number of patients with hyperthyroidism had ED, compared with controls (P < 0.0001). The same applied to hypothyroid patients (P < 0.0001). No difference in SHIM scores was found between hyper- and hypothyroid patients. In patients with hypothyroidism, SHIM scores correlated positively with FT4 levels (r = 0.413, P = 0.005) and negatively with TSH levels (r = –0.669, P < 0.001). In contrast, SHIM scores did not correlate with either FT4 or TSH levels in patients with hyperthyroidism. After treatment of the thyroid dysfunction, a significant increase of SHIM scores was noted in both hyperthyroid (P < 0.0001) and hypothyroid (P < 0.0001) patients. Specifically, only 20 patients had a SHIM score of 21 or less, and of these, only seven had severe ED (SHIM score ≤ 10). Seven of these 20 patients were hyperthyroid and the rest were hypothyroid (Table 2Go and Fig. 1Go). No difference in SHIM scores was found between treated thyroid patients and controls at 1-yr follow-up. Also, no difference was found between hypothyroid patients having positive thyroid antibodies and those with negative antibodies. Finally, no difference was observed between Graves’ patients and those having nodular or multinodular toxic goiter.


Figure 1
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  		FIG. 1. Distribution of subjects in each study group according to the degree of ED at baseline and after treatment of thyroid dysfunction.

 

   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
Male reproductive function requires normal libido, normal erectile function, intact hypothalamic-pituitary-target endocrine gland axes, and normal spermatogenesis and accessory organs of ejaculation (3). Anecdotal reports suggest an association between libido and/or impotence and hyper- and hypothyroidism (5), but no controlled data have been published so far. By using a validated SHIM 5-item questionnaire, based on the International Index of Erectile Function questionnaire, we found that approximately 80% of our patients with thyroid dysfunction had ED, compared with 34% of controls. ED was severe in 21 patients (37.5%). Our findings are consistent with the concept that hyper- and hypothyroidism contribute to ED. After restoration of euthyroidism, 30% of our patients had ED, which was similar to controls. The intention of this study was to document the prevalence of ED in dysthyroid patients and identify any associations between thyroid and ED. Having made the above observations, additional studies are necessary to unravel the mechanisms by which thyroid dysfunction leads to ED. Validated questionnaires alone are routinely used in assessing erectile function. Indeed, the same (6) or alternative validated questionnaires as in our study (7, 8, 9) have been used in several other studies without inclusion of confirmatory objective tests of ED. We are therefore satisfied that the methodology used in assessing erectile function is sufficiently robust.

ED is common. In the Massachusetts Male Aging Study (MMAS), a community-based survey of men between 40 and 70 yr of age, 52% of all respondents reported some degree of ED: 17% mild, 25% moderate, and 10% complete (10). The MMAS described a crude incidence rate of 25.9 cases per 1000 man-years with a mean follow-up of 8.8 yr. As expected, incidence rates (cases per 1000 man-years) increased with patient age, with an incidence from 12.4 for men aged 40–49 yr to 46.4 for men aged 60–69 yr (10).

Although the role of androgens in maintaining normal erectile function has been viewed traditionally as permissive, there is increasing evidence that androgens are fundamental not just for sexual behavior but also for various physiological and signaling pathways regulating erection (11). In the MMAS, of the 17 hormones measured, dehydroepiandrosterone (DHEA) sulfate levels seemed to be most closely associated with erectile function (12).

A variety of drugs including psychotropics, antihypertensives, diuretics, and others, may cause ED. In our study approximately one third of patients and controls were on medication. Patients and controls were on similar classes of drugs, so drug effects are unlikely to account for the differences in the two groups.

As was mentioned above, the mechanism by which thyroid dysfunction can cause ED has not been investigated in this study because it was outside the scope of our investigation. However, one can hypothesize that ED may result from a complex interplay between altered erectile nerve function, cognitive decline, illness-related stress, and decreased interpersonal interaction (13, 14). Abnormalities of endocrine function may also have implications on erectile function. For hypothyroid patients such abnormalities have been described. Specifically, it is well established that hypothyroidism may be associated with a decrease in serum testosterone, DHEA, and DHEA sulfate (15). In our study, correction of thyroid dysfunction led to restoration of erectile function in most patients. Thus, screening for thyroid dysfunction in men presenting with ED is recommended. Furthermore, specific treatment of ED with selective phosphodiesterase-5 inhibitor should be postponed for at least 6 months after restoration of euthyroidism.

Conclusions

This study demonstrates, for the first time in a controlled manner, that ED is extremely common in males with thyroid disturbances and treatment of the primary disease can restore normal erectile function. Moreover, a significant positive correlation was found between SHIM scores and FT4, and a negative correlation between SHIM scores and TSH. Our study also showed that after 8–9 months of euthyroidism, the prevalence of ED declined significantly to levels comparable with those of controls. Screening for thyroid dysfunction in men presenting with ED is recommended, whereas specific treatment of ED should be postponed in patients with thyroid dysfunction until euthyroidism has been reached for at least 6 months because the latter might principally be responsible for ED.


   Acknowledgments
 
We thank cordially Professor D. Hatzichristou, who gave us indirectly the idea for conducting this study. Also, we thank Mrs. Anna Gialantzi for her excellent secretarial assistance.


   Footnotes
 
Disclosure Statement: G.E.K., K.T., F.P., N.P., and P.P. have nothing to declare.

First Published Online February 12, 2008

Abbreviations: DHEA, Dehydroepiandrosterone; ED, erectile dysfunction; FT4, free T4; FTesto, free testosterone; MMAS, Massachusetts Male Aging Study; PRL, prolactin; SHIM, Sexual Health Inventory for Males.

Received October 9, 2007.

Accepted February 5, 2008.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

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  3. Lewis RW, Fugl-Meyer KS, Bosch R, Fugl-Meyer AR, Laumann EO, Lizza E, Martin-Morales A 2004 Definitions, classification, and epidemiology of sexual dysfunction. In: Lue TF, Basson R, Rosen R, Giuliano F, Khoury S, Montorsi F, eds. Sexual medicine: sexual dysfunctions in men and women. 2004 edition. Paris: Health Publications; 39–72
  4. Kloner RA, Mullin SH, Shook T, Matthews R, Mayeda G, Burstein S, Peled H, Pollick C, Choudhary R, Rosen R, Padma-Nathan H 2003 Erectile dysfunction in the cardiac patient: how common and should we treat? J Urol 170:S46–S50
  5. Krassas GE, Pontikides N, Deligianni V, Miras K 2002 A prospective controlled study of the impact of hyperthyroidism on reproductive function in males. J Clin Endocrinol Metab 87:3667–3671[Abstract/Free Full Text]
  6. Marberger M, Roehrborn CG, Marks LS, Wilson T, Rittmaster RS 2006 Relationship among serum testosterone, sexual function, and response to treatment in men receiving dutasteride for benign prostatic hyperplasia. J Clin Endocrinol Metab 91:1323–1328[Abstract/Free Full Text]
  7. Bliesener N, Albrecht S, Schwager A, Weckbecker K, Lichtermann D, Klingmüller D 2005 Plasma testosterone and sexual function in men receiving buprenorphine maintenance for opioid dependence. J Clin Endocrinol Metab 90:203–206[Abstract/Free Full Text]
  8. Gray PB, Singh AB, Woodhouse LJ, Storer TW, Casaburi R, Dzekov J, Dzekov C, Sinha-Hikim I, Bhasin S 2005 Dose-dependent effects of testosterone on sexual function, mood, and visuospatial cognition in older men. J Clin Endocrinol Metab 90:3838–3846[Abstract/Free Full Text]
  9. O’Connor DB, Archer J, Wu FC 2004 Effects of testosterone on mood, aggression, and sexual behavior in young men: a double-blind, placebo-controlled, cross-over study. J Clin Endocrinol Metab 89:2837–2845[Abstract/Free Full Text]
  10. Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB 2000 Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts male aging study. J Urol 163:460–463[CrossRef][Medline]
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  13. Lundberg PO, Brackett NL, Denys P, Chartier-Kastler E, Sønksen J, Vodusek DB 1999 Neurological disorders: erectile and ejaculatory dysfunction. In: Jardin A, Wagner G, Khoury S, Giuliano, Padma-Nathan H, Rosen R, eds. Erectile dysfunction. London: Health Publication; 591–649
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