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
Open accessAbstract
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.
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A randomized cross-over study of 22 women showed that daily 2.4 g of EPA + DHA supplementation for six weeks significantly reduced plasma bioavailable testosterone levels.
“A subsequent randomized cross-over study of 22 women conducted by the same investigators showed that daily 2.4 g of EPA + DHA supplementation for six weeks significantly reduced plasma bioavailable testosterone levels [68].”
From Role of Omega-3 Fatty Acids in Improving Metabolic Dysfunctions in Polycystic Ovary Syndrome (2024) · cites this paper as [68]
A cross-sectional study of 104 white pre-menopausal women with PCOS from Australia showed that a higher plasma concentration of n-6 PUFA and a higher n-6:n-3 ratio was linked to increased circulating androgens.
“A cross-sectional study of 104 white pre-menopausal women with PCOS from Australia showed that a higher plasma concentration of n-6 PUFA and a higher n-6:n-3 ratio was linked to increased circulating androgens [68].”
From Role of Omega-3 Fatty Acids in Improving Metabolic Dysfunctions in Polycystic Ovary Syndrome (2024) · cites this paper as [68]
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- Authors
- Phelan, N., O’Connor, A., Kyaw Tun, T., Correia, N., Boran, G., Roche, H. M., & Gibney, J.
- Affiliations
- Tallaght University Hospital (IE)
- University College Dublin (IE)
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 93
- Issue
- 3
- Pages
- 652-662
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2106165408
- Cited by
- 89
- References
- 7
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 3 · 2023: 6 · 2022: 2 · 2021: 11 · 2020: 7 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 8 · 2015: 6 · 2014: 7 · 2013: 3 · 2012: 5
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- polycystic ovary syndrome, polyunsaturated fatty acids, omega-3 fatty acids, omega-6 fatty acids, n-6/n-3 ratio, dietary supplementation, androgen levels, testosterone, androstenedione, steroidogenesis, theca cells, arachidonic acid, plasma lipid profile, atherogenic lipids, young women
- MeSH terms
- Adult, Androgens, Animals, Cattle, Cells, Cultured, Cross-Sectional Studies, Double-Blind Method, Female, Humans, Ovary, Polycystic Ovary Syndrome, Theca Cells, Cohort Studies, Biomarkers, Fatty Acids, Omega-3, Cross-Over Studies, Postprandial Period, Dietary Supplements, Principal Component Analysis, Fatty Acids, Omega-6, Young Adult
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