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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.
Phelan, N, O'Connor, A, Kyaw Tun, T, Correia, N, Boran, G, Roche, HM, Gibney, J
The American journal of clinical nutrition. 2011;93(3):652-62
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5-10% of women of reproductive age are thought to be affected by polycystic ovary syndrome (PCOS). Women with PCOS don’t ovulate and have high levels of androgens (‘male’ hormones) such as testosterone. Dietary changes are often recommended for women with PCOS, yet the optimal diet for managing the condition has not been defined. Long-chain polyunsaturated fatty acids (PUFAs), in particular omega-3s, may influence various aspects of metabolic health in ways that are beneficial for women with PCOS. The objectives of this study were to determine the link between PUFAs and hormonal aspects of PCOS, to investigate the effects of omega-3 supplementation, and to support the findings with cellular studies. Participants were given 4 mg of either omega-3 supplementation or an olive oil placebo every day for 6 weeks. There was a 6-week rest period, after which the women crossed over to receive the alternative treatment for a further 6 weeks. Women who had higher levels of circulating androgens at the start of the study tended to have both higher omega-6 levels and omega-6:omega-3 ratios. After taking omega-3 supplements, testosterone levels were significantly reduced, particularly in those women who experienced more substantial falls in the ratio of omega-6:omega-3. Alongside this, the researchers found that ovarian cells sourced from cows increased production of androgens when treated with omega-6, but not omega-3. The authors concluded that supplementation with omega-3 PUFAs improves hormonal balance in women with PCOS.
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. OBJECTIVES 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. DESIGN 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.