Sex Ratio Of Multiple Sclerosis Research Articles

Regional variation in the incidence rate and sex ratio of multiple sclerosis in Scotland 2010\u20132017: findings from the Scottish Multiple Sclerosis Register

BackgroundFifteen regional studies published over the last six decades surveying prevalence, mortality and hospital admissions have suggested that Scotland is amongst the highest risk nations for multiple sclerosis (MS) in the world. However, substantial intranational variation in rates (between regions) has been described in numerous countries, including in the only previous Scottish national survey, which used hospital admission data, to address this issue. Against this backdrop, the Scottish Multiple Sclerosis Register (SMSR) was established in 2010 to prospectively collect nationally comprehensive incidence data and to allow for regional comparisons.MethodsHere, we present the SMSR and analyse the variation in crude and age–sex standardized incidence rates, lifetime risk (cumulative incidence), and the sex distribution of cases and rates, between the 14 administrative Health Boards or regions of Scotland: 01 January 2010 to 31 December 2017.ResultsThe overall incidence rate for Scotland was 8.76/100,000 person-years (standardized: 8.54). Regional incidence rates varied significantly—up to threefold—between Health Boards (p < 1 × 10–13). The national female-to-male sex ratio was 2.3:1, but this too varied regionally (outlier regions result in a range from 1.0 to 4.2:1). Lifetime risk ranged from 19.9/1000 for females in Orkney (58.98°N) to 1.6/1000 for males in the Borders (55.60°N). Comparison with a previous national survey suggests that these differences are longstanding. In 6 of 14 regions the lifetime risk for women exceeds 1%.ConclusionsThis study introduces a national incidence register: a valuable research tool and the result of substantial public investment. The wide variation in incidence rates and sex ratios between regions, in a relatively homogenous population, raises questions for future study.

Incidence rate and sex ratio in multiple sclerosis in Lithuania.

ObjectivesTo determine the temporal changes in incidence rates of multiple sclerosis (MS) over the past 15 years in Lithuania with prediction up to 2020, and to estimate female‐to‐male sex ratio and its changes among MS patients.Materials and MethodsWe conducted a descriptive incidence study. The crude incidence rates (CIR) were calculated using 15‐year period, sex, age‐groups, and the number of newly registered MS patients. Standardized incidence rates (SIR) were calculated using European standard in order to evaluate the influence of resident structure changes on incidence of MS during the last 15 years. The data were processed using Minitab set to estimate a linear trend model for the temporal changes of 16 parameters.ResultsThe data showed a substantial growth of the incidence rate of MS in Lithuania during the period of 2001–2015. In 2001, MS was diagnosed to 162 new individuals, whereas 343 new cases of MS were diagnosed in 2015. During 2001–2015, the incidence of MS was on average 6.5 (95% CI 5.70–7.30) cases per 100,000 residents, and 4.9 (95% CI 4.46–5.34) and 8.1 (5.86–9.34) for 100,000 male and female, respectively. Female‐to‐male sex ratio in MS in Lithuania had a tendency to increase over the period. Females were affected from 1.5 to 2 times more often than males.ConclusionsIn 2020, the incidence rate of MS is estimated to reach 13 cases per 100,000 persons and females are expected to be diagnosed with MS two times more often than males.

Testosterone Differentially Affects T Cells and Neurons in Murine and Human Models of Neuroinflammation and Neurodegeneration

The high female-to-male sex ratio of multiple sclerosis (MS) prevalence has continuously confounded researchers, especially in light of male patients' accelerated disease course at later stages of MS. Although multiple studies have concentrated on estrogenic mechanisms of disease modulation, fairly little attention has been paid to androgenic effects in a female system, and even fewer studies have attempted to dissociate hormonal effects on the neurodegenerative and neuroinflammatory processes of MS. Herein, we demonstrate the differential effects of hormone treatment on the acute inflammatory and chronic neurodegenerative phases of murine experimental autoimmune encephalomyelitis. Although s.c. treatment with testosterone and aromatase inhibitor applied beginning on the day of immunization ameliorated initial course of disease, similar treatment administered therapeutically exacerbated chronic disease course. Spinal cord analyses of axonal densities reflected the clinical scores of the chronic phase. Invitro, testosterone treatment not only decreased Th1 and Th17 differentiation in an aromatase-independent fashion, but also exacerbated cell death in induced pluripotent stem cell-derived primary human neurons under oxidative stress conditions in an aromatase inhibitor-dependent manner. Thus, through the alleviation of inflammatory processes and the exacerbation of neurodegenerative processes, androgens may contribute to the epidemiologic sex differentials observed in MS prevalence and course.

The change in the sex ratio in multiple sclerosis is driven by birth cohort effects.

Birth cohort effects have greatly shaped long-term trends in multiple sclerosis (MS). This study examined whether birth cohort effects have also determined trends in the sex ratio. Age-period-cohort analyses were applied to Swiss mortality data, 1901-2010, using logit models. Sex was introduced as an additional main effect (overall effect) and in interaction terms with A, P and C. Birth cohort effects strongly impacted the trends of MS risk in Switzerland, with a peak in cohorts born in the 1910s and 1920s. Similarly, birth cohort effects accounted for the change in the sex ratios during the 20th century. The balanced sex ratio at the beginning of the 20th century has been superseded by a ratio with a preponderance of women. Despite similarities in timing, the patterns of overall and sex-specific birth cohort estimates were not congruent. The change in the sex ratio in MS is driven by birth cohort related factors. Overall and sex-specific trends indicate that the appearance of MS has changed dramatically in the 20th century. The driving force behind these trends is related to yet unknown environmental factors.

Does the changing sex ratio of multiple sclerosis give opportunities for intervention?

In several international studies, an increasing women-to-men (w/m) ratio in patients with multiple sclerosis (MS) has been reported. Such sex ratios have been analysed by year of onset or by year of birth. In a Swedish study, data from the Swedish MS register (SMSreg) were used to analyse the w/m ratio in Sweden. The sex ratio was analysed both by year of birth (8834 patients) and by year of onset (9098 patients). No increased w/m ratio was seen in this study. The age-specific sex ratio did not demonstrate any significant changes. However, a new investigation of the sex ratio in Sweden, based on data from all available data sources (19,510 patients), showed a significantly increased w/m ratio of MS in Sweden from 1.70 to 2.67. Environmental factors such as cigarette smoking, hormonal factors and nutrition are of interest in this context, but the cause of the increasing w/m ratio in MS is yet not possible to explain.

New data identify an increasing sex ratio of multiple sclerosis in Sweden

Background: An increasing women-to-men ratio in later birth cohorts of patients with multiple sclerosis (MS) has been observed in several populations and has been hypothesised to be due to one or several environmental factors of importance for disease aetiology. However, in a study based on data from the Swedish MS registry (SMSreg) this ratio was recently reported to be rather stable during the 20th century. Objective: The purpose of this study was to reinvestigate the women-to-men ratio in Sweden based on data from all available data sources, including deceased patients. Method: We combined data from the SMSreg with data from national patient registers. Results: In total we obtained information on 19,510 MS patients born 1931–1985, 13,321 women and 6189 men. The women-to-men ratio increased from 1.70 for patients born in the 1930s to 2.67 for patients born in the 1980s. When comparing the coverage of SMSreg to the full data set, a significantly higher proportion of women born 1931–1935 compared to men born in the same period were found in SMSreg, resulting in a sampling bias hiding the increasing sex ratio in the full material. Conclusion: The women-to-men ratio in MS has increased in Sweden during the 20th century similarly to observations in other western countries.

Mortality in patients with multiple sclerosis

Mortality in patients with multiple sclerosis (MS) is significantly increased compared with the general population. Many questions concerning survival in MS are still unanswered due to the difficulty of comparing information collected at different times and in different geographic areas. The increasing incidence of MS, the improvement in care of the chronically disabled, and different methodologies may explain the lack of coherence among studies' results. Reported times to death from birth and from disease onset/diagnosis are highly variable. Patients older at onset or with primary progressive course have shorter survival; however, data on sex and mortality are contradictory. Changes in sex ratio in MS over time represent one possible explanation. MS is the main cause of death in ≥50% of patients and the incidence of deaths not due to MS varies among countries. Particularly, suicide is substantially increased in patients with MS, and, despite its varying incidence, mainly due to "cultural bias," it should be considered an MS-related cause of death. Recent results of the long-term follow-up study of interferon-β-1b demonstrated a significant reduction of mortality among treated patients. Notwithstanding its long latency, mortality is therefore an unambiguously valid long-term outcome in randomized controlled trials. It usefully combines the net impact of treatment efficacy on longevity and adverse events, which may reduce it.

Sex ratio of multiple sclerosis in persons born from 1930 to 1979 and its relation to latitude in Norway

A remarkable increase in female to male ratio of multiple sclerosis (MS) is recognised in high incidence areas. Norway is a high-risk area for MS, spanning latitudes 58-71 °N. We studied whether the sex ratio has changed over time and whether it differs by clinical phenotype or by latitude. Population-based epidemiological data and data from the Norwegian MS Registry on patients born from 1930 to 1979 were combined in this study. Place of birth was retrieved from the Norwegian Population Registry and information on clinical subtypes was obtained from the Norwegian MS Registry. The female to male ratio ranged from 1.7 to 2.7 (median 2.0) in 5,469 patients born in Norway, and increased slightly by 5-year blocks of year of birth (p = 0.043). The sex ratio was 2.6:1 in 825 patients born 1970-1979, which is significantly higher than in those born 1930-1969 (p < 0.001). In patients with relapsing remitting onset, the sex ratio was 2.4:1, while it was 1.1:1 in those with primary progressive disease. The sex ratio did not differ between the south, the middle and the north of the country. The overall sex ratio of MS is strongly determined by cases with relapsing remitting onset. We did not observe the remarkable increase in sex ratios of MS reported from other high-risk areas. The high sex ratio in the youngest birth cohorts may change as an increasing proportion of cases in this age group is being diagnosed. Sex ratio was not associated with latitude.

Sex ratio of multiple sclerosis in the National Swedish MS Register (SMSreg)

Background: Sex ratio in multiple sclerosis has been reported from several geographical areas. The disease is more common in women. In Europe the female-to-male ratio varies from 1.1 to 3.4. A recent study from Canada has reported a significant increase, with time, in female-to-male ratio in multiple sclerosis over the last 100 years. Objective: The aim of this study was to analyse any change in sex ratio in multiple sclerosis in the Swedish population. Methods: Data from the Swedish MS Register and data from the Swedish National Statistics Office were used to estimate sex ratio by year of birth and year of onset. Results: In the analysis of sex ratio by year of birth there were 8834 patients (6271 women and 2563 men) born between 1931 and 1985. The mean women-to-men ratio was 2.62. No clear trend was noted for the women-to-men ratio by year of birth (Spearman’s rho = 0.345, p = 0.298, n = 11). The number of patients analysed by year of onset was 9098 during the time period 1946 until 2005. The mean women-to-men ratio was 2.57. No significant change in women-to-men ratio (Spearman’s rho = −0.007, p = 0.983, n = 12) with time was observed. Conclusion: There is no evidence for an increasing women-to-men ratio with time amongst Swedish multiple sclerosis patients.

Sex ratio of multiple sclerosis and clinical phenotype

In a longitudinal population-based dataset of patients with multiple sclerosis (MS), we have previously observed a substantial increase in the female to male sex ratio in Canada over the last 50 years. Here, we aimed to determine whether this change in sex ratio is related to the clinical course of MS. We calculated sex ratios by birth year in 11 868 patients with relapsing-remitting (RR) MS and 2825 patients with primary progressive (PP) MS identified as part of the Canadian Collaborative Project on the Genetic Susceptibility to MS. Year of birth was a significant predictor for sex ratio in RR MS (P < 0.0001, chi(2) = 21.2; Spearman's rank correlation r = 0.67), but not for PP MS (P = 0.44, chi(2) = 0.6; Spearman's rank correlation r = 0.11). An increase in the number of female RR MS patients over time accounts for the increasing sex ratio of MS. This has implications for pathogenesis, for assessment of clinical trial results and for disease prevention. The factors underlying the selective increase in MS in females need to be uncovered.