Increased circulating conjugated primary bile acids are associated with hyperandrogenism in women with polycystic ovary syndrome Original paper

What was studied?

This study explored the relationship between circulating bile acid profiles and hyperandrogenism in women diagnosed with polycystic ovary syndrome (PCOS). Specifically, the researchers investigated whether changes in the concentration and composition of serum bile acids, particularly conjugated primary bile acids, were associated with elevated androgen levels in PCOS patients. Utilizing ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS), the study quantified individual bile acid species in the serum and examined their statistical associations with androgen markers such as total testosterone and androstenedione.

Who was studied?

The study population consisted of 37 women diagnosed with PCOS and 35 age- and BMI-matched healthy control subjects, all recruited from the Endocrinology Department of Drum Tower Hospital, Nanjing, China. The diagnosis of PCOS was based on the Rotterdam criteria, ensuring that participants met at least two of the following: hyperandrogenism, oligo/anovulation, or polycystic ovarian morphology. Subjects were carefully screened to exclude confounding conditions such as diabetes, liver disease, and recent antibiotic use. This rigorous matching and exclusion criteria strengthen the internal validity of the findings.

What were the most important findings?

The researchers identified that women with PCOS had significantly elevated levels of circulating conjugated primary bile acids, specifically glycine-conjugated (GCA and GCDCA) and taurine-conjugated (TCA and TCDCA) species, compared to healthy controls. Interestingly, the total bile acid levels and the total primary bile acid pool were both elevated in PCOS, while secondary bile acids showed no significant difference. The elevated conjugated bile acids also displayed strong positive associations with serum androgen levels, including total testosterone and androstenedione. These associations remained statistically significant even after adjusting for potential confounders such as age, BMI, and insulin resistance (HOMA-IR).

The study also observed that the relative percentage composition of the bile acid pool shifted in PCOS patients, with higher contributions from conjugated primary bile acids like GCA, TCA, and TCDCA and a reduced proportion of secondary bile acids like DCA, LCA, and GLCA. These patterns suggest an altered bile acid metabolism that could be functionally linked to androgen excess in PCOS, potentially through mechanisms involving bile acid receptors such as the farnesoid X receptor (FXR), which has been shown in other research to regulate steroid metabolism.

What are the greatest implications of this study?

This study highlights a novel and potentially important role for bile acid metabolism in the endocrine dysfunction characteristic of PCOS, especially hyperandrogenism. The findings suggest that the gut-liver axis and bile acid signaling could contribute to the development or perpetuation of elevated androgen levels in PCOS, potentially via FXR-mediated inhibition of androgen-to-estrogen conversion in ovarian granulosa cells. If validated in future longitudinal studies, these insights open new avenues for biomarker discovery and therapeutic intervention. Modulating bile acid composition—whether through dietary strategies, microbiome-based therapies, or bile acid sequestrants—could represent a future direction in managing hyperandrogenism and its associated reproductive and metabolic complications in PCOS.