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ale Sexual Dysfunction

revalence of Erectile Dysfunctionn HTLV-1–Infected Patients and Itsssociation With Overactive Bladder

aulo Oliveira, Néviton M. Castro, André L. Muniz, Davi Tanajura, Julio C. Brandão,urélia F. Porto, and Edgar M. Carvalho

BJECTIVES To determine the prevalence of erectile dysfunction (ED) in human T-cell lymphotropic virustype I (HTLV-I)-infected patients, and its association with overactive bladder (OB).

ETHODS In a cross-sectional study, 111 male patients with positive serology for HTLV-I (by enzyme-linked immunosorbent assay and Western blot) were examined between October 2003 andDecember 2006. Exclusion criteria were age �18 and �80 years, other neurological diseases,penile prosthesis, neoplasm, and psychological and mental disease. Patients were evaluated by aurologist and neurologist. ED was determined by application of the abridged form of 5-itemInternational Index of Erectile Function (IIEF-5). ED was defined as IIEF-5 � 21. OB wasdetermined by International Continence Society criteria. Using the Expanded Disability StatusScale (EDSS) to determine disautonomy status, a neurologist classified all patients as eitherasymptomatic carriers (EDSS � 0), “oligosymptomatic myelopathy” (EDSS � 0 e � 2), orHTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP); (EDSS � 2). Diagno-sis of HAM/TSP was performed according to World Health Organization recommendations.

ESULTS Of the total of 111 patients, 6 were excluded and 105 were analyzed. The mean age was 48 �10.7 years. ED was observed in 55.2%. ED was documented in all patients who had HAM/TSP,in 79% of the group with EDSS � 0 and �2, and in 35.9% of HTLV-1–infected individuals withEDSS � 0. OB was detected in 93.75%, 33.3%, and 4.6%, respectively. Moreover, there was anassociation observed between ED and OB.

ONCLUSIONS ED is a frequent disease in HTLV-I-infected individuals, and the prevalence is directly correlatedto the degree of neurological disability measured by EDSS. ED was strongly associated with OB

symptoms. UROLOGY 75: 1100–1103, 2010. © 2010 Elsevier Inc.

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he human T-cell lymphotropic virus type 1(HTLV-1) is the etiologic agent of HTLV-1–associated myelopathy/tropical spastic paraparesis

HAM/TSP) and of adult T-cell leukemia/lymphoma.1,2

t is estimated that 20 million individuals are infected byTLV-1 worldwide, with high prevalence of infection

n Africa, Central and South America, and Japan.3,4

TLV-1 has been considered an infection with low mor-idity, as less than 5% of infected individuals will de-elop HAM/TSP or ATLL. Other clinical manifestationsuch as arthritis, sicca syndrome, and neurogenic bladderave been reported, but predominantly in patients with

rom the Serviço de Imunologia, Hospital Universitário Prof Edgard Santos, Institutoacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Universidadeederal da Bahia, Salvador-Bahia, BrazilReprint requests: Edgar M. Carvalho, M.D., Professor Edgar M Carvalho, Federalniversity of Bahia, Hospital Universitário 195161, rio Prof Edgard Santos Immunol-

gy Service, Rua João 195163, das Botas s/n, 40110160 Canela Salvador, Brazil.

r-mail: edgar@ufba.br and imuno@ufba.brSubmitted: July 16, 2009, accepted (with revisions): November 21, 2009

100 © 2010 Elsevier Inc.All Rights Reserved

AM/TSP.3 However, more recently, evidence has ac-umulated showing that a large proportion of individualsreviously considered as carriers, have more polyarthral-ia, polyarthritis, dry mouth, neurological complaints,nd urinary symptoms than HTLV-1 seronegative con-rols.5-7 This emphasizes that HTLV-1 may have a higherorbidity than has been reported, and moreover, raises

he possibility that neurogenic symptoms and signs mayrecede the appearance of HAM/TSP.Urologic manifestations of OB are common in patients

ith HAM/TSP. There is also evidence that a largeopulation of HTLV-1 carriers complain of urgency, fre-uency, and urinary loss.4,8,9 Moreover, it has been doc-mented that the abnormalities found in urodynamictudies in patients with HAM/TSP are similar to thosebserved in HTLV-1 carriers with urological com-laints.10 Putting together these observations, OB may ben oligosymptomatic form of myelopathy or an initialanifestation of HAM/TSP.11 Erectile dysfunction

ED) was the first manifestation of HAM/TSP in 1 case

eported,12 and in only 1 previous study using appropriate

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ethodology evaluated this manifestation in HTLV-1–nfected subjects.13

The objective of this study was to determine the prev-lence of ED in HTLV-1–infected subjects with or with-ut HAM/TSP, and its association with OB symptoms.

ATERIAL AND METHODS

articipants of the study were male individuals consecutivelyvaluated in the HTLV-1 multidisciplinary clinic of our insti-ution between October 2003 and December 2006. HTLV-1–nfected individuals were referred by 2 blood banks, and pa-ients with HAM/TSP are referred predominantly by theeurological and infectious diseases clinics of the same hospital.he diagnosis of HTLV-1 was performed by enzyme-linked immu-osorbent assay (Cambridge, Birtek Corporation, Worcester,A) and confirmed by Western blot (HTLV-1 blot 2.4,enelabs, Singapore). Exclusion criteria were age �18 years or80, presence of penile prosthesis, history of prostatectomy,

resence of mental or psychological disorders, and cancer. Thistudy was approved by the Ethical Committee of the institution,nd all patients signed an informed consent. All patients werevaluated by a urologist, 2 clinicians, an immunologist, 2 neu-ologists, and 2 psychologists. Neurological disability was deter-ined by the Expanded Disability Status Scale (EDSS). This

cale ranges from 0 (normal) to 10 (death), and is widely usedo determine the severity of neurological damage in patientsith multiple sclerosis (MS) or HTLV-1 infection. On the basisf EDSS, participants were classified in 3 groups: group 1—pa-ients with EDSS � 2 and diagnosis of HAM/TSP; group—HTLV-1–infected subjects with EDSS � 0 and �2; androup 3—HTLV-1–infected individuals who had EDSS � 0.roup 2 was composed of patients considered as having an

ligosymptomatic HAM/TSP and group 3 of individuals withsymptomatic HTLV-1 infection. The 5-item International In-ex of Erectile Function (IIEF-5)14 was used for determinationf ED. This is a self-administered questionnaire, and evaluations performed by a scale ranging from 0 to 25 points. Individualsith an IIEF � 21 points are considered as having ED. The

IEF-5 also allows for the determination of severity of ED:evere (5-7 points), moderate (8-11 points), mild to moderate11-16 points), and mild (17-21 points). Urinary symptomsere classified according to the International Continence So-iety.15 Criteria for determination of OB were urgency, with orithout urinary loss, and/or increasing urinary frequency (more

han 8 times a day or more than 2 times at night). Urodynamictudies were performed in 13 patients with OB, and overactivityr dyskinesia of the detrusor was documented in 11 of them.he �2 test and the Fisher’s exact test were used to compare theroportions. The prevalence ratio was used to evaluate theathologic association among the groups. The Spearman test

Table 1. Frequency of ED and OB according to the degree

n (%) Years – Limits (mean)

Group 1 16 (15.2%) 37-72 (51.4)Group 2 24 (22.9%) 30-66 (48.9)Group 3 65 (61.9%) 21-65 (46.3)Total 105 (100%) 21-72 (48)

ED � erectile dysfunction; OB � overactive bladder.* P �.001 between groups (Pearson �2).

as used to evaluate a correlation between EDSS and the A

ROLOGY 75 (5), 2010

IEF-5. Results were considered statistically significant whenhe P value was �.05. The statistical analysis was performed inPSS for windows, version 11.0.

ESULTStotal of 111 male patients were evaluated and 6 were

xcluded: 3 as a result of age factor (2 with age �80 andaged �18 years) and the others as a result of prostate

ancer, symptomatic dorsal spinal radiculopathy, and se-uelae of poliomyelitis. The mean age of the 105 patientsas 48 � 10.7 (range, 25-72 years). The prevalence ofD and OB in the 3 groups of patients, determinedccording to the EDSS, is shown in Table 1, and thessociation between ED and OB is shown in Figure 1. Allatients in group 1 (HAM/TSP) had ED, and OB wasbserved in 93.7% of them. There was a significantncrease (P �.01) in both ED and OB when the fre-uency of these abnormalities in group 1 was comparedith that of groups 2 and 3. However, the frequency ofD was higher than that of OB in all 3 groups. The

requency of severe or moderate ED in patients withAM/TSP was 81.3%, significantly higher than that in the

ther 2 groups (P �.01). There was a trend toward higherrequency of severe and moderate ED in patients of group 247.4%), but it was not significantly different from thatbserved in patients of group 3 (30.4%; P �.01).

There was an association between ED and OB. Therevalence of OB in HTLV-1–infected subjects with andithout ED and in those with ED is shown in Figure 1.

igure 1. Association between erectile dysfunction andveractive bladder in The human T-cell lymphotropic virusype 1–infected subjects.

eurologic disability

(%)* OB n (%)* ED Severe or Moderate n (%)

00%) 15 (93.7%) 14 (87.5%)9.2%) 8 (33.3%) 9 (47.4%)5.9%) 3 (4.6%) 7 (30.4%)5.2%) 26 (24.7%) 30 (62.5%)

of n

ED n

16 (119 (723 (358 (5

lthough in the group of patients without ED, OB was

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bserved in only 6.4%, in the group of patients with ED,B was observed in 39.7%, with a prevalence ratio of

.21 (CI 95%, 2.18-18.75), P �.001 (�2 test).The prevalence of ED and OB in the different age

roups is shown in Table 2. ED was documented in all ageroups ranging from 25% in patients aged 20-30 years, to4.3% in patients aged 61-70. OB was also detected in allge groups. There was a trend toward an increase in therequency of ED with age, but there was no differenceetween the frequency of ED in the 31-40 age grouphen it was compared with older age groups (P �.5).nother important point indicating that neurological

nvolvement due to HTLV-1 was more important thange as a cause of ED, was the observation that moderater severe ED was observed in a maximum of 50% of theatients with ED, and 79.3% of them were �60 years old.ecrease in libido was reported by 9 individuals with ED.

n all of them testosterone levels were at normal levels.To better analyze the association of ED in HTLV-1

nfected subjects with the degree of neurological involve-ent, we plot the EDSS score against the IIEF-5 in

igure 2. There was a negative correlation between EDSSnd the IIEF-5, indicating that the higher the EDSS, theigher the degree of ED.

OMMENTD is a frequent health problem in the male populationnd has a direct relationship with age. It is predominantlyssociated with vascular insufficiency, neurological dis-ases, and psychological and psychiatric disorders. It isxpected that patients with HAM/TSP have ED but onlyfew studies have pointed out the importance of ED inTLV-1–infected subjects. Using the Brief Male Sexual

unction Inventory, Castro et al13 observed ED in both:atients with HAM/TSP and in HTLV-1–infected sub-ects without HAM/TSP. Herein, using the IIEF-5, wextend the observation that ED is frequent in HTLV-1nfection, and determine the degree of severity of thisanifestation. Additionally, using the Internationalontinence Society criteria, we documented the fre-uency of OB in HTLV-1–infected subjects and its rela-ionship with ED. This is an important addition to theublished data regarding clinical manifestations associ-ted with HTLV-1 infection, indicating that, contrary to

Table 2. Frequency of erectile dysfunction and overactivebladder in the different age groups

Age (y) Patients ED n (%) OB n (%)

20-30 8 2 (25%) 1 (12.5%)31-40 15 7 (46.7%) 2 (13.3%)41-50 39 21 (53.8%) 9 (23.1%)51-60 28 18 (64.3%) 10 (35.7%)61-70 14 9 (64.3%) 3 (21.4%)71-80 1 1 (100%) 1 (100%)Total 105 58 (55.2%) 26 (24.7%)

he idea that HTLV-1 has a low morbidity, a large b

102

ercentage of individuals who do not have HAM/TSPave symptoms related to HTLV-1 infection.The prevalence of ED is quite variable, depending upon

he method used and the sample studied. However, a morepecific index has been recently used in an attempt toncrease reproducibility and accuracy of the results. In theresent study we used the IIEF-5. It has been previouslyalidated, is specific for ED, and is the more accepteduestionnaire to determine ED in clinical research.16,17 Us-ng the IIEF-5, the prevalence of ED among HTLV-1–nfected subjects was higher than that observed in a previ-us study published by Castro et al13 using the Brief Maleexual Function Inventory. Moreover, the IIEF-5 enables uso determine that a maximum of 50% of the HTLV-1–nfected individuals had moderate to severe ED. Althoughhe IIEF-5 does not allow us to determine the cause of ED,18

here is a correlation between neurophysiologic testing tovaluate ED and the results of the IIEF-5, validating thisethod to detect ED caused by sensorial neuropathy.19

erein, we showed that there is a direct correlation betweenhe EDSS score with the severity of ED. This gives supporto the role of neurological damage in the development ofD in HTLV-1–infected individuals.In the present study, patients were divided in 3 groups

ccording to the EDSS. The EDSS is a good predictor ofeurological impairment in MS because it evaluates the

nvolvement of multiple systems such as pyramidal, sen-ory, bladder, bowel, visual, cerebellar, and mental func-ions. Owing to similarities in the pathogenesis and clin-cal picture of MS and HAM/TSP, this scale has beenidely used to evaluate disease severity in HAM/TSPatients.20 ED occurred in all 3 groups and increased withhe degree of neurological disability being observed in allAM/TSP patients. In subjects from group 3, formed byTLV-1–infected subjects with EDSS � 0, the preva-

ence of ED was in the range of the values that have beenetected in observational studies. In a population-basedtudy in individuals living in the same place where thistudy was conducted, the prevalence of ED was 39%.21

It is known that OB occurs in a large proportion ofatients with HAM/TSP and here we show that ED isbserved in all HAM/TSP patients. In MS, a disease alsossociated with an inflammatory reaction in the Centralervous System (CNS), the prevalence of ED and OB areigh.22 Because patients with HTLV-1–associated OB andAM/TSP have similar abnormalities in the urodynamic

ndings,10 we believed that neuronal damage mediated dur-ng HTLV-1 infection is the cause of urinary manifestationsn HTLV-1–infected individuals. In such a case, neurolog-cal dysfunction of the spinal cord may decrease synapticransmission and the integration of signs involving thepinal cord, the bridge, and the cerebral cortex, leading torectile and urinary problems.

We showed that OB and ED are highly associated, andoth manifestations were found in HTLV-1–infected sub-ects who do not fulfill the criteria for HAM/TSP. OB has

een recognized as the first manifestation of HAM/TSP and

UROLOGY 75 (5), 2010

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t may occur years before the development of HAM/TSP.23

oreover, urinary complaints of OB may be detected in aarge percentage of subjects infected with HTLV-1 who doot fulfill the criteria for HAM/TSP.8 In a case report, EDas also the first manifestation of HAM/TSP.12 Herein, we

how that despite an association between ED and OB, aarge percentage of patients with EDSS �2 had ED, but OBas not documented. This raises the hypothesis that EDould be even an earlier marker of spinal cord involvementn HTLV-1–infected individuals.

ONCLUSIONSTLV-I–infected patients have a high prevalence of ED

hat increases with the degree of neurological involve-ent being observed in all patients with HAM/TSP.here was an association between ED and OB. As min-

mal signs of neurologic damage may determine sexualnd urinary manifestations, both ED and OB may beonsidered a biological marker of neurologic involvementn HTLV-1–infected subjects.

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