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Gender influence on the progression of HTLV-I associated myelopathy/tropical spastic paraparesis
  1. M A S D Lima1,
  2. R B S Bica1,
  3. A Q C Araújo2
  1. 1Federal University of Rio de Janeiro (UFRJ), Clementino Fraga Filho University Hospital (HUCFF), Rio de Janeiro, Brazil
  2. 2Reference Centers on Neuroinfections and HTLV, Evandro Chagas Institute of Clinical Research (IPEC), FIOCRUZ, Rio de Janeiro, Brazil
  1. Correspondence to:
 Marco Antonio S D Lima
 109 Queensberry Street #12, Boston, MA 02215, USA; mdelimabidmc.harvard.edu

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HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic and disabling disease caused by the human T-lymphotropic virus type I. Onset of the disease is insidious and the disease usually progresses slowly over years.1 However, there have been reports of the rapid evolution of HAM/TSP over months or even weeks. The basis for these different progression patterns is poorly understood and only a few studies have dealt with this matter.2 The present study aimed at evaluating a Brazilian HAM/TSP population for possible factors implicated in the progression of the disease.

Methods

We reviewed the files of 338 HTLV-I infected patients evaluated at the outpatient clinic of the Reference Centers for Neurological Infections and HTLV-I, Evandro Chagas Clinical Research Institute (IPEC), FIOCRUZ, Rio de Janeiro, Brazil. Patients were included in the study if they fulfilled the World Heath Organization criteria for HAM/TSP,1 but were excluded if they had concurrent infections or other disabling diseases that could interfere with clinical progression. The eligible patients were submitted to a clinical questionnaire and physical examination between June 2002 and February 2003. Clinical severity was evaluated using the IPEC disability scale (table 1), which was developed exclusively for the prospective assessment of HAM/TSP.3 We evaluated clinical progression using a disease progression index (DPI) defined as the IPEC disability final score divided by the duration of the disease, from onset of symptoms, in years. We used this value to divide our sample into quartiles. Patients whose values were under the 25th percentile were called slow progressors and patients whose values were above the 75th percentile were called fast progressors. Both groups were compared for their demographic and clinical characteristics using Fisher’s test. DPI values were compared using the Mann-Whitney U test. All p values were two sided and an α = 0.05 was employed.

Table 1

 The IPEC disability scale

Results

A total of 250 individuals were excluded due to lack of neurological disease or the presence of concurrent infections. The mean age of the remaining 88 individuals was 53.1 years, and there were more women (68.2%) than men. The mean age at onset was 40.7 years and the mean duration of disease was 12.5 years.

Comparison between the fast (n = 22) and the slow (n = 22) progression groups showed a significantly higher prevalence of women in the former group (p = 0.02). Statistical analysis of other variables failed to show significant differences.

To evaluate the possible role of sex hormones in this difference, because the mean age of menopause is around 50 years,4 we compared men and women according to age at onset of the disease (early onset: <50 years; late onset: ⩾50 years). The mean DPI of women and men were, respectively, 1.79 and 1.17 (p = 0.009) in the early onset group (n = 66; 66% women) and 2.59 and 1.78 (p = 0.731) in the late onset group (n = 22; 68% women), suggesting that women have a faster progression than men if the disease starts before the menopause.

Discussion

This is the first study to suggest that HAM/TSP progresses faster in women than in men. This difference seems to be particularly important in women whose disease started before the menopause. Although gender differences regarding the clinical evolution of HAM/TSP have not been reported before, there has been evidence of a disproportional number of women with this disease. Firstly, there is a worldwide female to male preponderance of HAM/TSP patients ranging from 1.5:1 to 3.5:1.5 Secondly, Nagai et al analysed the proviral load of 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers and found a significantly higher proviral load in female patients when compared to males.6 It is well known that a higher proviral load is associated with the development of clinical disease.

The reason for the gender difference in our study is unknown, but it is possible that sex hormones play a role in the evolution of the disease. To test this hypothesis, we compared the DPI of patients whose disease had started before and after the age of 50, the mean age of the menopause. The finding of a significantly worse evolution in the female group with early onset of disease, coupled with no significant gender difference being observed in the late onset group, suggests that female hormones may be implicated in HAM/TSP pathogenesis and that their presence at higher levels may be associated with a faster clinical progression. Further support for this idea is provided by the beneficial effects of danazol, an androgenic drug, in the treatment of some HAM/TSP cases.7

In summary, we found evidence of worse clinical progression in women with HAM/TSP compared to men. We hypothesise that sex hormones may account for this difference. If confirmed by further studies, this information may lead to a better understanding of the mechanisms involved in HAM/TSP pathogenesis and suggest different treatment options.

References

View Abstract

Footnotes

  • Competing interests: none declared

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