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Gender distribution in inflammatory bowel disease (IBD) is dependent on the disease subtype, Crohn's disease (CD) or ulcerative colitis (UC). In CD there is a greater prevalence of females, while in UC population-based studies have shown no significant differences.1 However, the gender ratios in CD are highly dependent on the age as well as geographic region.

Three large studies of CD incidence in North America from the 1990s (Kaiser Permanente Health Maintenance Organization [HMO] in Northern California, and population-based studies in Olmsted County, Minnesota and the Province of Manitoba) consistently demonstrated greater female incidences than males, ranging from a ratio 1.2 to 1.4.1–3 Similar gender ratios were also observed in population-based Scandinavian studies with a ratios that ranged from 1.1 (Stockholm County, Sweden) to 1.4 (Copenhagen, Denmark).4–6 More recent data from a study in Northern France reported a female-to-male ratio of 1.2.7 Studies of hospitalized incident cases of CD showed similar patterns.

The gender distribution of CD varies by geography. In a Baltimore-based epidemiology study, the incident African-American CD female-to-male ratio was 2.2. The study of hospitalizations at Kaiser Permanente also demonstrated a greater female predominance among African-American CD patients with a ratio of 1.5 as compared to white patients with a female-to-male ratio of 1.2.2 The same study showed a 3-fold higher incidence of CD among Hispanic females compared to males, although the size of the Hispanic population was relatively low. For both the African-American and Hispanic populations, greater use of the healthcare system by females relative to males may in part be responsible for the larger female predominance than that seen in whites. Notably, a CD prevalence study based on claims data from Puerto Rico observed only a slight and nonsignificant female preponderance (ratio of 1.1:1).8

Epidemiological surveys from east Asian countries, notably Japan and China, show an unexpected reversal of the CD sex ratio. A nationwide survey of hospitals in Japan described 4243 CD patients with a 0.45:1 ratio of females to males.9 Similarly, a summary of epidemiological studies in China showed that nearly all regions reported a lower incidence in females than males, with an overall female-to-male ratio of 0.7:1.10 Separate Chinese regional studies have observed similar gender distribution patterns, with 1 study in Wuhan Province showing a ratio of 0.4:1.0, while another regional hospital-based study revealed a ratio of 0.6.11 It is noteworthy that although the population was small, the female-to-male ratio between Asian-Americans in the Kaiser Permanente study was opposite of that (5.7:1) of the East Asian-based studies (female-to-male ratios all <1). This suggests that geography, cultural, and health utilization factors as well as environmental exposures may be contributing.

Tobacco is one such exposure that varies geographically and is now an accepted risk factor for CD.12 The dramatically higher rate of tobacco use among males compared to females in East Asian countries13, 14 may in part explain the great male CD predominance. It is possible that the above findings may be partially explained by a selection bias in which males are more frequently diagnosed or treated for CD in some Asian societies. This degree of bias, however, may be unlikely since a female predominance has been observed in East Asia for other chronic inflammatory conditions such as rheumatoid arthritis.15, 16

Interestingly, gender differences in CD development appear to be strongly influenced by attained age: the increased sex differences in females seem to be only present after the mid-second decade of life.7 Moreover, among prepubescent children CD is more prevalent in boys than girls.17 The age-specific differences in CD gender distribution raise the possibility that cumulative exposure to estrogen following puberty may play a role in the development of CD. Garcia-Rodriguez et al reported that both long-term hormone replacement therapy and oral contraceptives have been associated with increased risk of CD.18

Even though there is an overall greater incidence of CD among females compared to males, these gender distributions vary between geographic regions of the world and by age. Thus, these factors need to be taken into consideration when making overall generalizations regarding female predominance in CD. Furthermore, the effect modification of age and geography on gender prevalence raised speculation that there may be environmental exposures that are contributing to the higher incidence among females.

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