A Study on the Association between Subclinical Hypothyroidism and Polycystic Ovary Syndrome

Abstract

Mei Wang, Xiaofeng Li, Nan Ding, Fang Wang

Background: Polycystic ovary syndrome (PCOS) and hypothyroidism are endocrine and metabolic disorders. Hypothyroidism has been found to be related to changes in blood lipids and insulin insensitivity. However, the relationship between subclinical hypothyroidism (SCH) and endocrine disorders in PCOS patients remains unclear. The incidence of SCH in PCOS patients is increasing. Metabolomics methods have been used to investigate the differences in metabolites and metabolic pathways between normal body weight and overweight (not obese) PCOS patients with SCH. Understanding the association between PCOS and SCH can guide diagnosis and treatment.

Methods: We performed an untargeted serum metabolomics analysis in 62 PCOS patients. From 38 PCOS patients with SCH, 24 were selected and divided into the overweight (n = 13) and normal weight (n = 11) groups. Differential metabolites were identified using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry analysis. The significance of metabolites was evaluated by calculating the variable importance in projection score (> 1 and P < 0.01) from partial least squares discriminant analysis (PLS-DA) and orthogonal PLS-DA models. Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted to investigate the metabolomic pathways. P < 0.05 (Fisher’s exact test) was considered statistically significant.

Results: In PCOS patients with SCH, significant differences in body weight, right ovary volume, homeostasis model assessment for insulin resistance value, insulin level at 2 h after a meal, and triglyceride level were observed between the overweight and normal weight groups. Twenty-six different metabolites were identified, mainly fatty acids and phosphatidylcholines, to have significantly levels in overweight patients with SCH. Moreover, 18 enriched metabolic pathways were identified, mainly biosynthesis of fatty acids and unsaturated fatty acids, digestion and absorption of proteins, aminoacyl-tRNA biosynthesis, and ATP-binding cassette (ABC) transporters.

Conclusion: The interaction between body mass index and thyroid-stimulating hormone affects the metabolic status of PCOS patients. Overweight PCOS patients with SCH may have the worst metabolic status. The overweight and normal weight groups showed differences in glycerol phospholipid, sterol lipid, phosphatidylcholine, and androsterone sulphate levels. PCOS with SCH affects endocrine metabolism and ester metabolism through fatty acid biosynthesis, protein digestion and absorption, and ABC transporters.

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