title: Endometriomas and deep infiltrating endometriosis in adulthood are strongly associated with anogenital distance, a biomarker for prenatal hormonal environment.
abstract: Is the length of the anogenital distance (AGD), a biomarker of the in-utero prenatal hormonal environment, associated with the presence of endometriomas and deep infiltrating endometriosis (DIE)?
  
  
  
  Shorter AGD is associated with presence of endometriomas and DIE.
  
  
  
  It is debated whether hormonal exposure to estrogens in utero may be a risk factor for endometriosis in adulthood. AGD is a biomarker of prenatal hormonal environment and observational studies have shown an association between AGD and reproductive parameters in both sexes.
  
  
  
  This case-control study of 114 women with endometriosis (endometriomas and/or DIE) and 105 controls was conducted between September 2014 and May 2015.
  
  
  
  Cases were attending the Endometriosis Unit of the Hospital. Prevalent as well as incident cases, diagnosed by transvaginal ultrasound (TVUS), were included. Controls were women without endometriosis attending the gynecological outpatient clinic for routine gynecological exams. Participants completed health questionnaires, followed physical and gynecological examinations, including TVUS. Measurements from the anterior clitoral surface to the upper verge of the anus (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF) were obtained in all subjects. Unconditional multiple logistic regression was used to estimate the association between AGD measurements and presence of endometriomas and/or DIE while accounting for important confounders and covariates, including age, body mass index, vaginal delivery or episiotomy.
  
  
  
  AGDAF was related to presence of endometriomas and/or DIE. For all cases of endometriosis (endometriomas and DIE), women in the lowest tertile of the AGDAF distribution, compared with the upper tertile, were 7.6-times (95% CI 2.8-21.0; P-trend < 0.001) more likely to have endometriosis. With regard to DIE, women with AGDAF below the median, compared with those with AGDAF above the median, were 41.6-times (95% CI 3.9-438; P-value = 0.002) more likely to have endometriosis.
  
  
  
  In case-control studies, information and selection bias has to be ruled out. Physicians conducting the measurement were blind to the status of the patients. Controls came from the same population as the cases. We adjusted for known and suspected confounders and covariates, but the possibility of residual confounding or chance findings should always be considered. As with all observational studies, causal inference is limited.
  
  
  
  This study suggests that endometriosis, especially the DIE, might have a prenatal origin that may be traced back to the hormonal milieu in which the fetus develops.
  
  
  
  This work was supported by the Ministry of Economy and Competitiveness, ISCIII (AES), grant no. PI13/01237 and the Seneca Foundation, Murcia Regional Agency of Science and Technology, grant no. 19443/PI/14. The authors have no competing interests to declare.
  
  
  
  Not applicable.
authors.affiliation: Division of Preventive Medicine and Public Health, Department of Public Health Sciences, University of Murcia School of Medicine, 30100 Espinardo, Murcia, Spain Institute for Biomedical Research of Murcia, IMIB-Arrixaca, 30120 El Palmar, Murcia, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Mendiola
authors.affiliation: Institute for Biomedical Research of Murcia, IMIB-Arrixaca, 30120 El Palmar, Murcia, Spain Department of Obstetrics & Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, 30120 El Palmar, Murcia, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: Sánchez-Ferrer
authors.affiliation: Department of Obstetrics & Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, 30120 El Palmar, Murcia, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Jiménez-Velázquez
authors.affiliation: Department of Obstetrics & Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, 30120 El Palmar, Murcia, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Cánovas-López
authors.affiliation: Department of Obstetrics & Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, 30120 El Palmar, Murcia, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Hernández-Peñalver
authors.affiliation: Department of Obstetrics & Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, 30120 El Palmar, Murcia, Spain.
authors.forename: Shiana
authors.initials: S
authors.lastname: Corbalán-Biyang
authors.affiliation: Department of Obstetrics & Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, 30120 El Palmar, Murcia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Carmona-Barnosi
authors.affiliation: Institute for Biomedical Research of Murcia, IMIB-Arrixaca, 30120 El Palmar, Murcia, Spain Department of Obstetrics & Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, 30120 El Palmar, Murcia, Spain.
authors.forename: María T
authors.initials: MT
authors.lastname: Prieto-Sánchez
authors.affiliation: Institute for Biomedical Research of Murcia, IMIB-Arrixaca, 30120 El Palmar, Murcia, Spain Department of Obstetrics & Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, 30120 El Palmar, Murcia, Spain.
authors.forename: Aníbal
authors.initials: A
authors.lastname: Nieto
authors.affiliation: Division of Preventive Medicine and Public Health, Department of Public Health Sciences, University of Murcia School of Medicine, 30100 Espinardo, Murcia, Spain Institute for Biomedical Research of Murcia, IMIB-Arrixaca, 30120 El Palmar, Murcia, Spain Department of Preventive Medicine, 'Reina Sofia' University General Hospital, 30003 Murcia, Murcia, Spain amtorres@um.es.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Torres-Cantero
mesh_terms: D000293:Adolescent; D000328:Adult; D001003:Anal Canal / Q000000981:diagnostic imaging / Q000473:pathology*; D015415:Biomarkers; D001837:Body Weights and Measures; D016022:Case-Control Studies; D004715:Endometriosis / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D005836:Genitalia, Female / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: anogenital distance; deep infiltrating endometriosis; endometriomas; endometriosis; estrogens; prenatal exposures