'Behind blue eyes'†: the association between eye colour and deep infiltrating endometriosis

Study question: Is the prevalence of blue eye colour higher in women with deep endometriosis?

Summary answer: Blue eye colour is more common in women with deep endometriosis when compared with both women with ovarian endometriomas and women without a history of endometriosis.

What is known already: Recent and intriguing evidence suggests that women with deep endometriosis may have particular phenotypic characteristics including a higher prevalence of a light-colour iris. Available epidemiological evidence is however weak.

Study design, size, duration: Case-control study performed in a large academic department specializing in the study and treatment of endometriosis. Individual iris colour was evaluated in daylight and categorized in three grades, namely blue-grey (blue), hazel-green (green) and brown. One observer assessed iris colour. In addition, the women themselves were invited to indicate the colour of their eyes according to the same classification system. Cases with discordant eye colour determinations between the observer and the woman were excluded from the final analysis.

Participants materials, settings, methods: Two hundred and twenty-three women with deep endometriosis (cases), 247 with ovarian endometriomas and 301 without a history of endometriosis were enrolled.

Main results and the role of chance: After exclusion of 52 discordant cases, the proportions of brown, blue and green eye colours were, respectively, 61, 30 and 9% in the deep endometriosis group, 74, 16 and 10% in the endometrioma group and 75, 15 and 10% in the non-endometriosis group. Women in the deep endometriosis group had a statistically significant excess of blue eyes and a reduced proportion of brown eyes compared with the two control groups (P = 0.002 and P < 0.001, respectively). The proportion of blue eyes was almost identical in the ovarian endometrioma group and the non-endometriosis group, and that of green eyes was substantially similar in all study groups. The OR (95% CI) of having blue eyes in women with deep endometriosis compared with women with ovarian endometriosis and with those without endometriosis was, respectively, 2.2 (1.4-3.6) and 2.5 (1.6-3.9).

Limitations, reason for caution: We cannot exclude that some women without a previous diagnosis of endometriosis indeed had the disease. However, this would have led to a reduction of the observed difference in proportion of blue eyes, thus to a potential underestimation of the real strength of the association. Moreover, under-ascertainment is possible with regard to peritoneal disease, but unlikely with deep endometriotic lesions and ovarian endometriomas.

Wider implications of the findings: There are two possible explanations for our findings. Both may have intriguing implications for future research on endometriosis. Firstly, genes involved in the control of iris colour transmission may lie in a region with a strong pattern of linkage disequilibrium with genes involved in the invasiveness of endometriosis. Alternatively, blue eye colour could be considered an indicator of a photo-sensitive phenotype resulting in limited exposure to sunlight and UVB radiation. Limited sunlight exposure is associated with reduced circulating 25-hydroxyvitamin D3, an element that has recently been linked to endometriosis development.