title: 'Behind blue eyes'†: the association between eye colour and deep infiltrating endometriosis.
abstract: OBJECTIVE
  Is the prevalence of blue eye colour higher in women with deep endometriosis?
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  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.
  Two hundred and twenty-three women with deep endometriosis (cases), 247 with ovarian endometriomas and 301 without a history of endometriosis were enrolled.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Istituto Ostetrico e Ginecologico 'Luigi Mangiagalli', Department of Clinical Science and Community Health, Università degli Studi, Milano, Italy paolo.vercellini@unimi.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vercellini
authors.affiliation: Istituto Ostetrico e Ginecologico 'Luigi Mangiagalli', Department of Clinical Science and Community Health, Università degli Studi, Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Buggio
authors.affiliation: Infertility Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Edgardo
authors.initials: E
authors.lastname: Somigliana
authors.affiliation: Istituto Ostetrico e Ginecologico 'Luigi Mangiagalli', Department of Clinical Science and Community Health, Università degli Studi, Milano, Italy.
authors.forename: Dhouha
authors.initials: D
authors.lastname: Dridi
authors.affiliation: Istituto Ostetrico e Ginecologico 'Luigi Mangiagalli', Department of Clinical Science and Community Health, Università degli Studi, Milano, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Marchese
authors.affiliation: Obstetrics and Gynecology Unit, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Viganò
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004715:Endometriosis / Q000473:pathology*; D005127:Eye Color; D005260:Female; D006801:Humans; D010641:Phenotype; D015995:Prevalence
keywords: deep endometriosis; endometriosis; eye colour; ovarian endometrioma; vitamin D