Endocrine Abstracts

Background: Woman with Polycystic Ovarian Syndrome (PCOS) are at risk of developingmetabolic syndrome (MetS), insulin resistance, dyslipidemia, Type 2 Diabetes and Cardiovascular Disease. Atherogenic dyslipidemia occurs in > 70% of women with PCOS which includes high fasting plasma TG, LDL-C, non-HDL-C or ApoB, and low HDL-C. In addition to diet and lifestyle as the first-line intervention, metformin is commonly prescribed for impaired glucose sensitivity. However, metformin has limited effects on blood lipids in women with PCOS. Furthermore, treatments for dyslipidemia are limited due to safety in young women of reproductive age. Fish oil (FO) and icosapentyl ethyl supplementation, rich in eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), has been shown to reduce fasting TG, but the effectiveness of FO in combination with metformin is unknown in conditions of the MetS and PCOS. The aim of this pilot study was to determine the effect of FO in combination with Metformin on fasting blood lipids in high-risk women with PCOS.

Methods: Participantswere female, age 18–30 years, diagnosed with PCOS who were recruited from the community and endocrine clinics in Edmonton, as part of a randomized clinical trial (n = 30). Participants were randomized into intervention groups including: 1) dietary supplementation with fish oil (FO; containing 2520 mg EPA + 1680 mg DHA/d, n = 13), 2) fish oil + metformin (FO + Metformin 1500 mg/d, n = 7) or 3) metformin alone (n = 7) for 12 weeks. Inclusion criteria consisted of PCOS diagnosis using NIH-AEPCOSS criteria, BMI > 25 kg/m², elevated fasting plasma triglycerides (> 150 mg/dl), impaired insulin sensitivity (glucose 100–125 mg/dl) and/or diagnosed with T2D (glucose > 126 mg/dl). Statistical analysis was completed via 2-way RM-ANOVA (GraphPad 8.0).

Results: FO + Metformin treatment significantly reduced fasting plasma TG from baseline compared to other treatment groups (Combination 2.45 ± 0.43 vs 1.64 ± 0.25*, Metformin alone 1.7 ± 0.2 vs 1.5 ± 0.22, FO 2.3 ± 0.19 vs 2.2 ± 0.19 mmol/l). Combination treatments had no significant effects on fasting insulin-glucose indices or androgen hormones. However, these treatments tended to reduce LDL-C and non-HDL-C (~10%), as well as blood glucose, fasting insulin (~5%) and HOMA-IR (~7–10%).

Conclusion: These pilot analyses demonstrate that the FO + Metformin combination treatment significantly reduces fasting plasma TG levels compared to metformin or fish oil alone in high-risk women with MetS and PCOS. A longer-term trial with larger cohort is warranted to determine the efficacy of this treatment to improve plasma TG, apoB-lipoprotein remnants and early subclinical atherosclerotic CVD risk in women with PCOS.