title: Are Dieting and Dietary Inadequacy a Second Hit in the Association with Polycystic Ovary Syndrome Severity?
abstract: BACKGROUND
  The composition of the diet is of increasing importance for the development and maturation of the ovarian follicles. In Polycystic Ovary Syndrome (PCOS) healthy dietary interventions improve the clinical spectrum. We hypothesized that dieting and diet inadequacy in the reproductive life course is associated with impaired programming of ovarian follicles and contributes to the severity of the PCOS phenotype.
  
  
  RESULTS
  To determine associations between the use of a self-initiated diet and diet inadequacy and the severity of the PCOS phenotype, we performed an explorative nested case control study embedded in a periconception cohort of 1,251 patients visiting the preconception outpatient clinic. 218 patients with PCOS and 799 subfertile controls were selected from the cohort and self-administered questionnaires, anthropometric measurements and blood samples were obtained. The Preconception Dietary Risk Score (PDR score), based on the Dutch dietary guidelines, was used to determine diet inadequacy in all women. The PDR score was negatively associated to cobalamin, serum and red blood cell folate and positively to tHcy. PCOS patients (19.9%), in particular the hyperandrogenic (HA) phenotype (22.5%) reported more often the use of a self-initiated diet than controls (13.1%; p = 0.023). The use of an inadequate diet was also significantly higher in PCOS than in controls (PDR score 3.7 vs 3.5; p = 0.017) and every point increase was associated with a more than 1.3 fold higher risk of the HA phenotype (adjusted OR 1.351, 95% CI 1.09-1.68). Diet inadequacy was independently associated with the anti-Müllerian Hormone (AMH) concentration (β 0.084; p = 0.044; 95% CI 0.002 to 0.165) and free androgen index (β 0.128; p = 0.013; 95% CI 0.028 to 0.229) in PCOS patients.
  
  
  CONCLUSIONS
  The use of a self-initiated diet and diet inadequacy is associated with PCOS, in particular with the severe HA phenotype. This novel finding substantiated by the association between diet inadequacy and AMH needs further investigation.
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Huijgen
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Reproductive Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Chantal T
authors.initials: CT
authors.lastname: Labee
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Reproductive Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Yvonne V
authors.initials: YV
authors.lastname: Louwers
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.|Department of Biostatistics, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Sten P
authors.initials: SP
authors.lastname: Willemsen
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Régine P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D004032:Diet; D005260:Female; D006728:Hormones / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D015999:Multivariate Analysis; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000473:pathology*; D011247:Pregnancy; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D006728:Hormones