Summary 
Polycystic ovarian syndrome (PCOS) is a disorder affecting up to 20% of women of reproductive age worldwide. Women with PCOS often experience menstrual irregularities, abnormally high levels of male hormones (androgens) and develop cysts on their ovaries. These facets can contribute to risk of reproductive dysfunction, cardiovascular disease and type 2 diabetes. DHA plays an important role in this condition, research suggests that higher levels of DHA in people with PCOS can contribute to a better disorder profile or management. 
 
Introduction
Polycystic ovarian syndrome (PCOS) is an endocrine-metabolic disorder where hormonal, metabolic and inflammatory dimensions together create a diverse and complex disorder profile. The most common disorder facets presented by women with PCOS include excessive production of the male sex hormones (called androgens), abnormal hair growth, thinning of hair on the head, cysts on the ovaries, persistent acne, menstrual irregularities, ovulatory failure and infertility. The ovaries in healthy individuals produce androgens (such as testosterone) as a part of the hormonal regulation of the reproductive cycle; this production becomes excessive in PCOS which results in a disbalance of the reproductive hormones. This shift in the reproductive hormones is a reason why abnormal hair growth and thinning of the hair of the head (typically seen in men and not women) are common symptoms seen in PCOS. More importantly, the PCOS disease profile can contribute to risk of pregnancy complications, reproductive dysfunction, cardiovascular disease and type 2 diabetes. It is estimated that  5-20% of women of reproductive age worldwide are affected by PCOS, highlighting the need for proper treatment strategies. Between 40-80% of people with PCOS have obesity; chronic low-grade systemic inflammation is commonly reported as well. As such, one of the most common treatments provided are lifestyle and diet interventions, with a focus on weight management. As DHA is renowned for its anti-inflammatory properties and positive effects on cardiovascular health (the risk of which is increased by PCOS), studies have investigated the role of DHA in PCOS prevalence and treatment, as summarised below. 
 
Research findings:
To investigate the effects of Omega-3 fatty acids in PCOS, Phelan and colleagues set up a two-pronged study strategy (Phelan et al. 2011). First, the fatty acid profiles in blood plasma of a cross-sectional PCOS cohort of 104 women were determined. These were then correlated to circulating markers of PCOS status, such as androgen concentrations (which are excessively produced in PCOS). The authors discovered that a greater plasma concentration of Omega-6 fatty acids (commonly associated with pro-inflammatory effects) and a greater plasma ratio of Omega-6 to Omega-3 fatty acids correlated with higher circulating levels of androgens. Based on these results, Phelan and colleagues set up a double blind clinical trial where Omega-3 supplementation was given to 22 persons with PCOS to measure the effects on metabolic and hormonal markers relevant to PCOS. For a period of 6 weeks, participants received either a daily placebo or Omega-3 supplementation in the form of capsules, receiving 0.76g DHA and 1.14g EPA per day. In the persons receiving the Omega-3 supplementation, greater levels of circulating DHA and EPA were measured after the supplementation period compared to the baseline levels; this effect was not found in the placebo group. Crucially, the supplementation group showed a significant decrease in levels of circulating androgens and bioavailable testosterone, suggesting an improvement of disease profile markers. 
 
In a study by Mousa and fellow investigators, the serum lipid profiles of 42 women with and 36 women without PCOS were measured to research the role of lipids (and the polyunsaturated fatty acids that they can contain) in PCOS-associated markers (Mousa et al. 2022). Amongst the PCOS-associated markers investigated were free androgen index (FAI) and sex hormone-binding globulin (SHBG). SHBG is a glycoprotein that can bind to sex hormones such as testosterone to make them biologically inactive, the FAI is a measurement that indicates how much of the circulating androgens are biologically active (referred to as free androgen). Interestingly, the authors reported that independent of PCOS status, lower concentrations of lipids containing DHA were associated with higher insulin resistance (a marker of type 2 diabetes), higher FAI and lower SHBG. This indicates that DHA has a positive effect on markers of PCOS, independent of PCOS status. 
 
The findings on SHBG were confirmed in a study published by Tian and collaborators (Tian et al. 2023). Here, the serum fatty acid profiles in a cohort of 202 women with PCOS were investigated. The authors reported that SHBG levels positively correlated with DHA, meaning that higher levels of DHA predicted higher levels of SHBG. The authors conclude that this positive correlation supports a beneficial role of DHA in the context of PCOS. 
 
In a Mendelian randomization study, Shao and others set out to investigate the link between Omega-3 fatty acids and the risk of developing PCOS (Shao et al. 2024). Mendelian randomization is a method often used in epidemiology to assess if there is a causal link between a variable such as a circulating nutrient and disease outcome. This is done on the basis of small genetic variances that affect metabolism between people in the study population, which predispose them to have either slightly higher or lower levels of that circulating nutrient. In this study, the authors looked at different genetic variances that predispose people to have higher relative circulating levels of certain nutrients, including Omega-3 fatty acids such as DHA, to see if these have an effect on PCOS risk. This risk is defined as odds ratio, where an odds ratio of >1 increases the risk and a ratio of <1 decreases the risk of the disease. The authors reported that participants with genetic variances predisposing them to have higher levels of circulating Omega-3 fatty acids had a reduced risk of PCOS, with an odds ratio of 0.73.
 
Conclusion
The publications highlighted above show that DHA plays a positive role in the context of PCOS. Across observational, interventional, and genetic studies, higher circulating levels or intake of DHA are associated with favourable hormonal and metabolic profiles in women with PCOS. Clinical trials demonstrate that DHA supplementation can reduce circulating androgens and bioavailable testosterone, improving hormonal balance. Observational research further indicates that DHA is positively correlated with sex hormone-binding globulin and negatively correlated with insulin resistance and free androgen index, suggesting that DHA supports both metabolic and hormonal regulation in PCOS. These findings are strengthened by the Mendelian Randomization study by Shao and colleagues, who showed that higher levels of circulating Omega-3 fatty acids (such as DHA) are associated with a decreased risk of PCOS. 
 
References
Mousa, Aya, Kevin Huynh, Stacey J. Ellery, Boyd J. Strauss, Anju E. Joham, Barbora de Courten, Peter J. Meikle, and Helena J. Teede. 2022. “Novel Lipidomic Signature Associated With Metabolic Risk in Women With and Without Polycystic Ovary Syndrome.” The Journal of Clinical Endocrinology & Metabolism 107(5):e1987–99. doi:10.1210/clinem/dgab931. 

Tian, Ye, Jingjing Zhang, Mingyue Li, Jie Shang, Xiaohong Bai, Huijuan Zhang, Yanxia Wang, Haitao Chen, and Xueru Song. 2023. “Serum Fatty Acid Profiles Associated with Metabolic Risk in Women with Polycystic Ovary Syndrome.” Frontiers in Endocrinology 14. doi:10.3389/fendo.2023.1077590. 

Phelan, Niamh, Annalouise O’Connor, Tommy Kyaw Tun, Neuman Correia, Gerard Boran, Helen M. Roche, and James Gibney. 2011. ‘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’. The American Journal of Clinical Nutrition 93(3):652–62. doi: 10.3945/ajcn.110.005538.

Shao, Fang, Shijia Xu, Haiyang Zhao, Furong Zhang, Xin Wang, and Hui Wang. 2024. ‘Causal Relationship between Fertility Nutrients Supplementation and PCOS Risk: A Mendelian Randomization Study’. Frontiers in Endocrinology 15. doi: 10.3389/fendo.2024.1420004.