RA is a common disease with a worldwide prevalence of about 1% with an annual incidence of about 3/10,000 adults. It is two to three times more common in women. There is some evidence that over the last few decades the disease is declining in incidence or severity. Patients with RA have a reduced life expectancy and a one in three chance of becoming disabled, depending on the severity of the disease at onset. The cause of the disease is unknown, although genetic factors account for up to 30% of disease susceptibility. The most important genetic factors are related to HLA-DR4 and DR1, which may have identical regions conferring the risk of disease. Many infectious agents have also been implicated in the etiology of RA, although there is no good epidemiologic evidence to support the laboratory findings. Hormonal and reproductive factors are known to play a major role in disease pathogenesis. Both pregnancy and the oral contraceptive pill are believed to be protective against development of the disease, although they may act by delaying or modifying the course of the disease rather than conferring "immunity".