Research:MS in Women

EpubKotzamani et al. Rising incidence of multiple sclerosis in females associated with urbanization. Neurology. 2012 May 16. 

OBJECTIVE: To design and perform a case-control study of multiple sclerosis (MS) in Crete, an island of 0.6 million people, that has experienced profound socioeconomic changes in recent decades.

METHODS: All MS cases occurring on Crete from 1980 to 2008 were ascertained. To search for putative risk factors, a structured questionnaire of 71 variables was employed, with patients with MS (n = 657) being compared to random controls (n = 593) matched for age, gender, and current place of residence.

RESULTS: MS incidence rose markedly on Crete over the past 3 decades. This increase was associated with a major shift in MS distribution among genders (1980: F/M = 0.9; 2008: F/M = 2.1), with females living in towns or having relocated at a young age from the countryside to urban centers being mainly affected. In rural Crete, MS showed lesser increases and gender preference. Of the major changes that accompanied urbanization, smoking among women with MS increased dramatically, while imported pasteurized cow milk virtually replaced fresh goat milk produced locally. Compared to controls, female patients with MS more often used contraceptives and were older at first childbirth. Besides smoking, alcohol drinking and vitamin intake was more common among female patients with MS. Also, the distribution of childhood diseases and chronic medical conditions differed significantly between patients with MS and controls.

CONCLUSIONS: MS incidence rose markedly over 3 decades in a genetically stable population in tandem with a transition from rural to urban living, thus possibly implicating environmental factors introduced by urbanization.

At the turn of the 1900's Canadian data indicate that the sex ratio of female to males was around is 1 to 1 it is now nearer to 3 to 1. In Iran the ratio is 6:1. MS is increasing in women and staying constant in men. Why is this the case? In this study based in Crete there appears to have been a dramatic change over just a few decades to go from 1:1 to 2:1. This is linked to urbanisation. Therefore what aspect of Canadian/British Culture occurred years ago that is only recently occuring in Crete. 

Understanding the risk factors may allow us to think about changing behaviours and preventing MS. There are loads of papers on risk factors.

Smoking is a risk factor for MS

Malosse et al. Correlation between milk and dairy product consumption and multiple sclerosis prevalence: a worldwide study. 

Neuroepidemiology. 1992;11:304-12. Multiple sclerosis (MS) epidemiology suggests that different factors are involved in the clinical expression of the disease. Alimentary cofactors have already been considered, but mainly theoretically. We have studied the relationship between MS prevalence and dairy product consumption in 27 countries and 29 populations all over the world, with Spearman's correlation test. A good correlation between liquid cow milk and MS prevalence (rho = 0.836) was found; this correlation was highly significant (p < 0.001). A low but still significant correlation was obtained with cream or butter consumption (rho = 0.619 and rho = 0.504, respectively). No correlation was found for cheese. These results suggest that liquid cow milk could contain factor(s) - no longer present in the processed milk - influencing the clinical appearance of MS. The possible role of some dairy by-products is discussed in the light of a multifactorial aetiology of MS.

Butcher PJ. Milk consumption and multiple sclerosis--an aetiological hypothesis. Med Hypotheses. 1986;19:169-78. 

Epidemiological studies of Multiple Sclerosis (MS) in the United States have shown an association with urban living and higher socio-economic groups and a higher incidence and earlier age at onset of symptoms in women. This study is based on the proposition that these trends may be a consequence of differences in exposure to an etiological factor around 15 years of age. As a result of variations in related United States and New Zealand data and other pertinent observations the possibility of a link between high childhood milk intake followed by a large or sudden reduction during the adolescent growth spurt, and the subsequent incidence of MS in young adults is proposed. It may be that the elusive environmental variable associated with the incidence of MS is partly a behavioural one related to western social attitudes

Is it milk or Butter or something else other inter-related  ice cream?

OBJECTIVE: Vitamin D may have a protective role in the etiology of multiple sclerosis (MS), but the effect of gestational vitamin D on adult onset MS has not been studied.

METHODS: In 2001, 35,794 mothers of participants of the Nurses' Health Study II completed a questionnaire inquiring about their experiences and diet during pregnancy with their nurse daughters. We studied the association of maternal milk intake, maternal dietary vitamin D intake, and predicted maternal serum 25-hydroxyvitamin D (25(OH)D) during pregnancy and their daughters' risk of developing MS.

RESULTS: MS was diagnosed in 199 women. The relative risk of MS was lower among women born to mothers with high milk or vitamin D intake during pregnancy. The multivariate adjusted rate ratio (RR) of MS was 0.62 (95% confidence interval [CI], 0.40-0.95; p trend = 0.001) for nurses whose mothers consumed 2 to 3 glasses of milk per day compared with those whose mothers consumed <3 glasses per month, and 0.57 (95% CI, 0.35-0.91; p trend = 0.002) for nurses with mothers in the highest quintile of dietary vitamin D intake compared with those in the lowest. The predicted 25(OH)D level in the pregnant mothers was also inversely associated with the risk of MS in their daughters. Comparing extreme quintiles, the adjusted RR was 0.59; (95% CI, 0.37-0.92; p trend = 0.002).

INTERPRETATION: Higher maternal milk and vitamin D intake during pregnancy may be associated with a lower risk of developing MS in offspring.

Adolescence may be an important etiological period in the development of multiple sclerosis (MS), and studies suggest that adequate vitamin D nutrition is protective. Here, the authors examined whether dietary intake of vitamin D during adolescence decreases the risk of MS in adulthood. In 1986 in the Nurses' Health Study and in 1998 in the Nurses' Health Study II (NHSII), women completed a food frequency questionnaire regarding their dietary intake during adolescence. From this, daily intake of vitamin D was calculated. Adolescent diet was available for 379 incident MS cases confirmed over the combined 44 years of follow-up in both cohorts, and for 67 prevalent cases in the NHSII who had MS at baseline (1989). Cox proportional hazards models were used to calculate relative risk estimates and 95% confidence intervals. Total vitamin D intake during adolescence was not associated with MS risk. Intake of ≥ 400 IU/day of vitamin D from multivitamins was associated with a non-statistically significant reduced risk (RR compared to no intake = 0.73, 95% CI: 0.50-1.07, P = 0.11), whereas intake of whole milk, an important source of dietary vitamin D, was associated with an increased risk. The possibility of opposite effects of vitamin D and milk intake on MS risk should be considered in future studies.

BACKGROUND: Experimental and clinical data suggest a protective effect of estrogens on the development and progression of MS.

METHODS: We assessed whether MS incidence was associated with oral contraceptive use or parity in two cohort studies of U.S. women, the Nurses' Health Study (NHS; 121,700 women aged 30 to 55 years at baseline in 1976) and the Nurses' Health Study II (NHS II; 116,671 women aged 25 to 42 years at baseline in 1989). Participants with a diagnosis of MS before baseline were excluded. Oral contraceptive history and parity were assessed at baseline and updated biennially. During follow-ups of 18 years (NHS) and 8 years (NHS II) we documented a total of 315 definite or probable cases of MS. 

RESULTS:  Neither use of oral contraceptives nor parity were significantly associated with the risk of MS. As compared with women who never used oral contraceptives, the age-adjusted relative risk (95% CI) was 1.2 (0.9, 1.5) for past users, and 1.0 (0.6, 1.7) for current users. Similar results were obtained after adjustment for latitude, ancestry, and other potential confounding factors. There was no clear trend of MS risk with either increasing duration of use or time elapsed since last use. Age at first birth was also not associated with the risk of MS.

CONCLUSIONS: These prospective results do not support a lasting protective effect of oral contraceptive use or pregnancy on the risk of MS. The decision to use hormonal contraception should not be affected by its effects on the risk of MS.

OBJECTIVE: To examine the risk of multiple sclerosis in users of combined oral contraceptives. 

DESIGN:  Cohort study conducted between 1968 and 1996 using diagnostic data supplied by general practitioners. 

POPULATION: Royal College of General Practitioners' Oral Contraception Study cohort of initially 46,000 women recruited during the late 1960s. 

METHODS: Directly standardised incidence rates of multiple sclerosis were calculated for current, former and never-users of oral contraceptives using first ever cases of multiple sclerosis reported by the general practitioners. The standardisation variables were age, parity, social class and smoking history. Five-year survival rates in the different contraceptive groups were calculated using standard life table techniques. 

RESULTS: One hundred and fourteen first ever cases of multiple sclerosis had been reported by November 1996 during 564,000 woman-years of observation. The incidence rate in both current and former users was not materially different to that in never-users. Although based on limited evidence there was no suggestion that the five-year survival was affected by a woman's use of combined oral contraceptives. 

CONCLUSIONS: These findings do not suggest a greatly elevated risk of multiple sclerosis during, or after, use of combined oral contraceptives. 

PIP: The influence of oral contraceptive (OC) use on the risk of multiple sclerosis was examined through use of data from a cohort study conducted in the UK in 1968-96. The Royal College of General Practitioners OC Study collected data from general practices throughout the UK on about 46,000 women. By November 1996, 114 new cases of multiple sclerosis were reported in this cohort over 564,000 woman-years of observation. The incidence rates, standardized by age, parity, social class, and smoking history, were 19.8% for current OC users, 21.9% for former OC users, and 17.1% for never users. The 5-year survival rates were 92.9%, 97.9%, and 94.6%, respectively. Although the numbers were not large enough for statistical analysis, there was some suggestion that ever use of OCs containing more than 50 mcg of estrogen increased the risk of multiple sclerosis (22.9% incidence). Overall, however, these findings do not suggest a significantly elevated risk of multiple sclerosis during, or after, use of modern low-dose combined OCs.

There are many risk factors for MS some we know and others that we don't or we don't know how they contribute to the risk.