title: Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial.
abstract: BACKGROUND
  Polycystic ovary syndrome (PCOS) is characterized by an adverse metabolic profile. Although dietary changes are advocated, optimal nutritional management remains uncertain. Polyunsaturated fatty acids (PUFAs), particularly long-chain (LC) n-3 (omega-3) PUFAs, improve metabolic health, but their therapeutic potential in PCOS is unknown.
  
  
  OBJECTIVE
  We aimed to determine the associations between plasma PUFAs and metabolic and hormonal aspects of PCOS to investigate the efficacy of LC n-3 PUFA supplementation and to support the findings with mechanistic cellular studies.
  
  
  METHODS
  We selected a cross-sectional PCOS cohort (n = 104) and conducted a principal component analysis on plasma fatty acid profiles. Effects of LC n-3 PUFA supplementation on fasting and postprandial metabolic and hormonal markers were determined in PCOS subjects (n = 22) by a randomized, crossover, placebo-controlled intervention. Direct effects of n-6 (omega-6) compared with n-3 PUFAs on steroidogenesis were investigated in primary bovine theca cells.
  
  
  RESULTS
  Cross-sectional data showed that a greater plasma n-6 PUFA concentration and n-6:n-3 PUFA ratio were associated with higher circulating androgens and that plasma LC n-3 PUFA status was associated with a less atherogenic lipid profile. LC n-3 PUFA supplementation reduced plasma bioavailable testosterone concentrations (P < 0.05), with the greatest reductions in subjects who exhibited greater reductions in plasma n-6:n-3 PUFA ratios. The treatment of bovine theca cells with n-6 rather than with n-3 PUFAs up-regulated androstenedione secretion (P < 0.05).
  
  
  CONCLUSIONS
  Cross-sectional data suggest that PUFAs modulated hormonal and lipid profiles and that supplementation with LC n-3 PUFAs improves androgenic profiles in PCOS. In bovine theca cells, arachidonic acid modulated androstenedione secretion, which suggests an indirect effect of n-3 PUFAs through the displacement of or increased competition with n-6 PUFAs. This trial was registered at clinicaltrials.gov as NCT01189669.
authors.affiliation: Department of Endocrinology, Adelaide and Meath Hospital, Incorporating the National Children's Hospital, Dublin, Ireland.
authors.forename: Niamh
authors.initials: N
authors.lastname: Phelan
authors.forename: Annalouise
authors.initials: A
authors.lastname: O'Connor
authors.forename: Tommy
authors.initials: T
authors.lastname: Kyaw Tun
authors.forename: Neuman
authors.initials: N
authors.lastname: Correia
authors.forename: Gerard
authors.initials: G
authors.lastname: Boran
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
authors.forename: James
authors.initials: J
authors.lastname: Gibney
mesh_terms: D000328:Adult; D000728:Androgens / Q000097:blood* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002417:Cattle; D002478:Cells, Cultured; D015331:Cohort Studies; D018592:Cross-Over Studies; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use*; D043371:Fatty Acids, Omega-6 / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000178:diet therapy*; D019518:Postprandial Period; D025341:Principal Component Analysis; D013799:Theca Cells / Q000378:metabolism; D055815:Young Adult
chemical_list: D000728:Androgens; D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6