title: Plasma adipokines and endometriosis risk: a prospective nested case-control investigation from the Nurses' Health Study II.
abstract: OBJECTIVE
  Do higher leptin levels and lower adiponectin levels predict subsequent development of endometriosis?
  
  
  CONCLUSIONS
  Plasma leptin and adiponectin levels were not associated with laparoscopically confirmed endometriosis when collected prior to disease diagnosis.
  
  
  BACKGROUND
  Case-control studies have identified altered levels of the inflammatory adipokines leptin and adiponectin in women with endometriosis, but it remains unclear whether inflammation results in endometriosis or whether the presence of endometriosis creates an inflammatory state.
  
  
  METHODS
  Nested, matched, case-control study within the prospective Nurses' Health Study II (NHS II) cohort. Blood samples were collected between 1996 and 1999 from 29 611 female nurses within the cohort. Women who reported endometriosis before blood collection were excluded.
  
  
  METHODS
  Plasma leptin and adiponectin levels were assayed by ELISA. Three hundred and fifty cases of laparoscopically confirmed endometriosis were matched 1:2 with 694 controls of comparable race, age, infertility history, menopausal status and time of blood draw. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression models adjusting for matching factors and BMI.
  
  
  RESULTS
  After adjusting for BMI, there were no statistically significant associations between endometriosis and leptin [RR = 1.2; 95% CI = 0.7-2.0; P-value, test for linear trend (P(trend)) = 0.72], adiponectin (RR = 0.8; 95% CI = 0.5-1.2; P(trend) = 0.48) or the leptin to adiponectin ratio (RR = 0.8; 95% CI = 0.4-1.4; P(trend) = 0.14) when comparing the upper with the lower quartile. Results were unaltered when analyses were stratified by BMI or restricted to cases diagnosed ≥ 4 years after blood draw. To evaluate statistical significance and limit the role of chance to the gold standard of 5%, we present 95% CIs about the RRs, and for P-values calculated for linear tests of trend and tests of heterogeneity, we have set the α-level to be 0.05 (i.e. <0.05 is considered to be statistically significant).
  
  
  CONCLUSIONS
  A limitation of this study is the inability to differentiate the time of endometriosis 'diagnosis' from the time of disease 'onset' due to the impossibility in identifying a precise time point at which the disease process was first initiated at a molecular or cellular level. Additional limitations include lack of information regarding stage of endometriosis and the possibility of asymptomatic disease in the control population.
  
  
  CONCLUSIONS
  The mean age at diagnosis of endometriosis in the study population is 41.7, ≈ 10 years older than the mean age of diagnosis in the general population. While this may limit the generalizability of the results, there is no reason to suspect that the association between adipokines and endometriosis risk should differ at a younger age of diagnosis in an adult population.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 31324 PFP, Iowa City, IA 52242, USA. divya-shah@uiowa.edu
authors.forename: Divya K
authors.initials: DK
authors.lastname: Shah
authors.forename: Katharine F
authors.initials: KF
authors.lastname: Correia
authors.forename: Holly R
authors.initials: HR
authors.lastname: Harris
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Missmer
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D016022:Case-Control Studies; D004715:Endometriosis / Q000097:blood*; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D052242:Adiponectin; D020738:Leptin