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

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) n23 (omega-3) PUFAs, improve metabolic health, but their therapeutic potential in PCOS is unknown. Objectives: We aimed to determine the associations between plasma PUFAs and metabolic and hormonal aspects of PCOS to investigate the efficacy of LC n23 PUFA supplementation and to support the findings with mechanistic cellular studies. Design: We selected a cross-sectional PCOS cohort (n = 104) and conducted a principal component analysis on plasma fatty acid profiles. Effects of LC n23 PUFA supplementation on fasting and postprandial metabolic and hormonal markers were determined in PCOS subjects (n = 22) by a randomized, crossover, placebocontrolled intervention. Direct effects of n26 (omega-6) compared with n23 PUFAs on steroidogenesis were investigated in primary bovine theca cells. Results: Cross-sectional data showed that a greater plasma n26 PUFA concentration and n26:n23 PUFA ratio were associated with higher circulating androgens and that plasma LC n23 PUFA status was associated with a less atherogenic lipid profile. LC n23 PUFA supplementation reduced plasma bioavailable testosterone concentrations (P , 0.05), with the greatest reductions in subjects who exhibited greater reductions in plasma n26:n23 PUFA ratios. The treatment of bovine theca cells with n26 rather than with n23 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 n23 PUFAs improves androgenic profiles in PCOS. In bovine theca cells, arachidonic acid modulated androstenedione secretion, which suggests an indirect effect of n23 PUFAs through the displacement or increased competition with n26 PUFAs. This trial was registered at clinicaltrials.gov as NCT01189669. Am J Clin Nutr doi: 10. 3945/ajcn.110.005538.