Erectile dysfunction and HTLV-I infection: a silent problem

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Abstract

The human T-lymphotropic virus type I (HTLV-I) is a retrovirus associated with a chronic myelopathy known as HTLV-I-Associated Myelopathy or Tropical Spastic Paraparesis (HAM/TSP). The main objective was to assess the frequency of erectile dysfunction (ED) in HTLV-I-infected individuals from Salvador and other cities from Bahia, Brazil, as well as to verify if sexual dysfunction correlates with urinary symptoms and overall neurological impairment. From January 2001 to April 2004, 218 HTLV-I carriers (111 male and 107 female subjects) had complete clinical, neurological, and urological evaluation. They were assessed using standardized questionnaires to determine urinary complaints (Urinary Distress Inventory) and ED (Brief Male Sexual Function Inventory). Neurological impairment was established by Expanded Disability Status Scale (EDSS) from 0 to 10. HAM/TSP was considered as EDSS≥2. A total of 17 males had clinically defined HAM/TSP (group 1). From the 94 HTLV-I-infected males, 62 were selected (group 2) and paired by age with patients in group 1. A total of 79 individuals were selected for this study. The age ranged from 35 to 81 y (mean=47.9±9.65). The percentage of ED in the studied population was 40.5%. In the HAM/TSP group, ED frequency was 88.2%. The associations among sexual dissatisfaction, erectile dysfunction, urinary symptoms (frequency, nocturia, and urgency) and EDSS≥2 were statistically significant. In HAM/TSP, there is a slow and progressive degeneration of the lateral funiculus of the spinal cord. HTLV-I-infected individuals present a high frequency of ED and it is closely associated to urinary symptoms and the overall neurological picture. The HTLV-I carriers already had prominent compromise of the sexual activity.

Introduction

The Human T-lymphotropic virus type I (HTLV-I) is a retrovirus associated with a chronic myelopathy known as HTLV-I-Associated Myelopathy or Tropical Spastic Paraparesis (HAM/TSP).1, 2 This virus is also implicated in the pathogenesis of adult T-cell leukemia/lymphoma (ATL) and has been related to some other immunomediated inflammatory diseases.3 The HTLV-I infection occurs through contaminated blood transfusions, sexual intercourse with an HTLV-I-positive person, contaminated needles, or breast-feeding. HTLV-I-associated myelopathy is characterized by spastic paraparesis with generalized increased deep tendon reflexes, bilateral Babinski's sign, deep sensation abnormalities, and severe bladder dysfunction.4

The neurological presentation begins insidiously after a variable latency period. The first complaints are generally related to the motricity and are associated with a functional asymmetric crural limitation, weakness, rigidity and sensitivity loss in the lower limbs, and lumbar pain. These symptoms and signs indicate the spinal cord involvement. Urinary and intestinal disturbs as well as erectile dysfunction (ED)5, 6 may also be present.

ED is commonly found in men and is related to age, medication, comorbidity, and lifestyle factors. It is a common complaint that makes patients seek urological care. About 18 million Americans aging 40–69 y were estimated to be affected with some degree of ED.7 In The Netherlands, a recent study disclosed an ED prevalence of 17% among the general population (according to the WHO definition).8

The estimated prevalence of ED in Salvador, Brazil is 39.5%. Even though ED has often been reported in patients with HAM/TSP, this problem has been somehow neglected in the past, partly because of the perceived private nature of this matter. Hence, the frequency of this affection in this population has not been established.

The purpose of this study was to evaluate the frequency of ED in HTLV-I-infected individuals from a multidisciplinary HTLV-I outpatient department and verify if the sexual dysfunction correlates with urinary symptoms and overall neurological impairment.

Materials and methods

From January 2001 to April 2004, 218 HTLV-I-infected individuals (111 male and 107 female subjects) were evaluated at the Hospital Universitário Professor Edgard Santos (HUPES)/Universidade Federal da Bahia (UFBA) multidisciplinary HTLV-I outpatient department. The HTLV-I-positive individuals were referred from blood banks after a positive screening or from other neurological services throughout the state. In all cases, the diagnosis of HTLV-I infection was established by ELISA (Cambridge Biotech Corp., Worceste, MA, USA) and confirmed by Western blot analysis, differentiating HTLV-I from HTLV-II (HTLV blot 2.4, Genelab, Singapore). The HTLV-I-positive individuals were then evaluated by several specialists in an ordered and consecutive fashion. They went through a complete clinical, neurological, and urological evaluation.

Neurological disability was established by Expanded Disability Status Scale (EDSS).9 This scale is a good predictor of neurological impairment in multiple sclerosis (MS) for it evaluates the compromise of multiple systems, such as pyramidal, sensory, bladder, bowel, visual, cerebellar, and mental functions. Owing to similarities in the pathogenesis and clinical picture of MS and HAM/TSP, this scale has been widely used to evaluate disease severity in HAM/TSP patients.18 The scale ranges from 0 (normal) to 10 (death due to HAM/TSP). HTLV-I-associated myelopathy was clinically defined as EDSS≥2. Patients were initially divided into two groups: HTLV-I carriers (group 1), composed of individuals who did not fulfill the criteria for HTLV-I-associated myelopathy (EDSS<2), and HAM/TSP patients (group 2) who had EDSS≥2. Further, the individuals in the first group were divided into subgroups 1A (EDSS=0) and 1B (0<EDSS<2). A total of 17 males had clinically defined HAM/TSP (group 2). From the 94 HTLV-I-infected males, 62 were selected (group 1) and paired by age with patients in group 2. They were also assessed using standardized questionnaires to determine urinary complaints (Urinary Distress Inventory—UDI)10 and ED (Brief Male Sexual Function Inventory—BMSFI).11 The BMSFI is a validated questionnaire used to assess ED. It consists of questions regarding sex drive, erectile and ejaculatory function, sexual problems with drive, erections and ejaculation as well as overall satisfaction with sex life. ED was defined according to the WHO definition as follows: an ED is a continuous or repetitive inability to achieve or maintain an erection sufficient for a satisfying sexual activity.12

The criteria to take part in this study were: male gender, 35 y of age or older, and HTLV-I-positive serology (ELISA and Western blot). Individuals who had other neurological disorders, renal insufficiency, hepatic failure, or psychiatric disorders; patients taking any kind of medicine that acts in the central nervous system (CNS) or that interferes with normal urinary tract function; as well as those who did not sign the informed consent or did not follow the protocol were not enrolled for this study. Collected data were inserted in a data bank and analyzed with the help of two statistical packages (SPSS version 11.5 and GraphPad Prism version 3.0). The Pearson chi-square and Fisher's Exact Test were used to verify univariate differences between the groups. The Mann–Whitney U test was used to verify differences in age between groups. A statistical significance was considered if P<0.05. Prevalence ratio was used to estimate the magnitude of ED occurrence among HAM/TSP patients as compared to HTLV-I carriers.

This study was submitted to the Ethical Committee of the Hospital Universitário Professor Edgard Santos/Universidade Federal da Bahia.

Results

In total, 79 individuals were enrolled in this study. Age ranged from 35 to 81 y (mean=47.9 y; s.d.±9.65). The subjects' classification according to EDSS, as well as the group division and mean age±s.d. can be seen in Table 1. There was no statistically significant difference in age among groups and subgroups (subgroups 1A × 1B: Mann–Whitney U test, P=0.65; subgroup 1B × group 2: Mann–Whitney U test, P=0.22; groups 1 × 2: Mann–Whitney U test, P=0.08).

Table 1 Mean age and classification of HTLV-I-seropositive individuals according to EDSS score

A total of 29 patients (36.7%) said they did not have an erection firm enough for penetration in half of the attempts or more in the last 30 days. A total of 30 men (38.0%) answered they did not manage to complete the intercourse in half of the attempts or more. In all, 27 individuals (34.2%) complained of both problems. Regarding the sexual satisfaction, 36 patients (45.5%) answered to have none, little, or moderate satisfaction. As for the sexual frequency, 11.4% reported having no days of sexual activity during the past 30 days and 22.8% referred to have from 1 to 4 sexual relationships in the same period. The overall prevalence of ED in the studied population was 40.5% (32 subjects). In the HAM/TSP group, overall ED frequency was 88.2% against 27.4% in the HTLV-I carrier group (Table 2). The comparative analysis among ED questionnaire answers, urinary symptoms, and EDSS are also summarized in Table 2. The frequency of ED in relation to age and neurological disability as measured by EDSS is given in Table 3. The associations among erectile dysfunction, sexual dissatisfaction, urinary symptoms, and EDSS≥2 were statistically significant. There were also statistically significant differences between subgroups 1A (EDSS=0) and 1B (0<EDSS<2) concerning the occurrence of ED and sexual dissatisfaction as well as urinary symptoms (frequency and urgency) (Table 4).

Table 2 Frequency of erectile dysfunction, sexual satisfaction, and urinary symptoms in HTLV-I-infected individuals according to EDSS classification: EDSS<2 versus EDSS≥2
Table 3 Frequency of ED by age and neurological impairment measured by EDSS
Table 4 Frequency of erectile dysfunction, sexual satisfaction, and urinary symptoms in HTLV-I-infected individuals according to EDSS classification: EDSS=0 versus 0<EDSS<2

Individuals in subgroup 1B were also compared to HAM/TSP patients (EDSS≥2). Interestingly, there was no difference regarding the frequency of ED (69.6 vs 88.2%, respectively; Pearson's chi-square, P=0.31). HAM/TSP patients had a prevalence ratio of 3.2 regarding the occurrence of ED as compared to HTLV-I carriers. Among individuals within group 1, those with 0<EDSS<2 (subgroup 1B) had a prevalence ratio of 27.1 regarding ED as compared to those who did not score any point on EDSS assessment (subgroup 1A).

Discussion

Sexual dysfunction has turned out to be an important aspect of the lives of HTLV-I carriers, especially of those with clinically defined HAM/TSP. However, it seems to have been long neglected, probably due to the private nature of the problem, which can inhibit both the patient and the health professional during an interview. This situation might actually be very common once most HTLV-I carriers are primarily assisted by other specialists rather than an urologist.

ED is a frequent pathology in the male population above the age of 40 y, and its prevalence increases with time. Some disorders favor the development of ED, among them certain neurological diseases, such as MS.13 The incidence of ED in patients with MS has been estimated at 70%.14, 15 Little is known about the sexual function compromise in HAM/TSP; however, its pathophysiology seems to be similar to MS. The penis innervation comes from the autonomous nervous system, with sympathetic fibers (thoracolumbar segment T11-L2) and parasympathetic (sacral segments S2–4). There is also somatic innervation, with sensory pathways, and motor nerves that innervate the ischiocavernous and bulbocavernous muscles.16 In MS, there is degeneration of nerves from the S2, S3, and S4 spinal levels. In HAM/TSP, a slow and progressive degeneration of the lateral funiculus of the spinal cord has been consistently described.17, 18, 19 It mainly involves the lateral cortico-spinal tract as well as the descending autonomic fibers from the hypothalamus, spinocerebellar, and spinothalamic tracts, especially at the thoracic level.17 As it happens with MS, in HAM/TSP, there is also a correlation between sexual and bladder dysfunction and it can also be explained by the neurological level involved. These manifestations might represent a heavy burden to these patients with a great impact on their quality of life. This is the first study, to our knowledge, that specifically evaluates the prevalence of ED in HTLV-I carriers and HAM/TSP patients.

ED seems to be a very common problem caused by HTLV-I infection, mainly in those with HAM/TSP. In the present study, the HTLV-I carriers had a lower frequency of ED as compared to HAM/TSP patients. Interestingly, the occurrence of ED did not differ between individuals with HAM/TSP and those who had some symptoms or signs of myelopathy. This observation suggests a very early spinal cord involvement, probably of sympathetic and parasympathetic fibers at the thoracolumbar level.

An important aspect of the present study was the observation of a high percentage of ED among individuals that are genuinely considered as HTLV-I carriers, even at young ages. It is very interesting that individuals in subgroup 1B (0<EDSS<2) already present a high prevalence of ED when compared to those in subgroup 1A (EDSS=0). These differences could not be explained by age or overall compromise of these patients' health, since they present no obvious motor or vesical impairment. No patient had a clinical history of pelvic irradiation, neither presented penile disorders on physical exam. We did not evaluate comorbidities as hypertension, diabetes, or arteriosclerosis; however, patients were paired by age and, therefore, the occurrence of such comorbidities was more likely to be evenly distributed. Furthermore, such comorbidities would not explain the occurrence of the urinary symptoms. Our data indicate ED may occur even before a clinical picture of HAM/TSP is present. Studies are in progress to evaluate if the individuals with these alterations in sexual function and EDSS are those who will more frequently progress to classical HAM/TSP.

Conclusions

HTLV-I-infected individuals present a high prevalence of ED. The frequency of ED in this population was closely associated to the occurrence of urinary symptoms and also to the overall compromise as evaluated by EDSS. Interestingly, the subjects who presented an EDSS between 0.5 and 1.5, inclusive, already had compromise of the sexual activity and satisfaction as well as prominent urinary symptoms, suggesting an early involvement of the sexual and bladder functions in individuals with few clinical symptoms and signs of myelopathy. Unfortunately, the level of knowledge concerning the HTLV-I-related urologic manifestations seems to be still limited among most urologists, even in an endemic area as Brazil, where the HTLV-I infection has an increasing importance. Further studies are also needed to determine if the use of proerectile agents, such as in MS, will be of any help in treating ED among HTLV-I-infected males. Even lesser is known about female sexual dysfunction associated with HTLV-I infection. It also seems to be an interesting field of research and other studies are needed for a better characterization of this disorder among HTLV-I-infected women.

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Acknowledgements

We are indebted to Dr Sidney Glina for reviewing the manuscript, advice and encouragement; Dr Valdir Lisboa from STS for referring eligible patients to our study. We also thank other members of the HTLV-I Multidisciplinary Outpatient Clinic for collaboration during the study: Dr Maria Aurélia Porto and Dr Adelmir Machado. This work was supported by the Brazilian National Research Council (CNPq) and Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). Edgar M Carvalho is a senior investigator of CNPq.

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Correspondence to N Castro.

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Keywords

  • human T-lymphotropic virus 1
  • tropical
  • spastic paraparesis
  • impotence
  • urologic and male genital diseases

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