Endocrine Abstracts

Context: Polycystic ovary syndrome (PCOS) is associated with an increased cardiometabolic risk that might not necessarily translate into adverse cardiovascular outcome later in life. Recently, alterations in gut microbial composition have been reported in the syndrome. Microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and its precursors are closely linked with development of atherosclerotic cardiovascular disease, independently of traditional risk factors.

Objective: To assess whether TMAO and its precursors are altered in PCOS and to determine potential impact of oral contraceptive (OC) use on these metabolites.

Materials and methods: The study included 27 overweight/obese patients with PCOS and 25 age- and BMI-matched healthy control women. At baseline, fasting serum TMAO and its precursors were measured after a 3-day standardized diet. Patients received dienogest-ethinylestradiol (2 mg/0.03 mg) therapy along with general dietary advice for three months after which all measurements were repeated. Four patients were excluded from the second analysis due to antibiotic use during the study period.

Results: The median age and BMI of patients and controls were 21 (IQR: 19–22) versus 23 (IQR:20.5–27) years and 30.7 (IQR:27.8–33.3) versus 31.5 (IQR:27.8–37) kg/m² respectively (P=NS for both). Patients had higher total testosterone (T) and free androgen index (FAI) whereas whole body fat mass, fasting plasma glucose, insulin and lipids were similar between the groups. PCOS group showed significantly higher serum levels of TMAO and its precursors: TMAO (2.39 [IQR:2.15–4.49]vs 2.05 [IQR: 1.36–3.33][Mol/L, P=0.042), choline (43.2 [IQR:39.5–48.9] vs. 36.6 [IQR:29.85–41.3][Mol/L, P=0.001), betaine (49.4 [IQR: 38.3–53.3]vs. 39.8 [IQR: 33.8–50.9][Mol/L, P=0.034), and carnitine (10.7 [IQR: 9.9–12.3]vs. 9.7 [IQR:8.15–11.6][Mol/L, P=0.024). TMAO and choline showed correlations with T (r=0.292, P=0.037, and r=0.353, P=0.010). After 3 months of OC use, there were decreases in BMI (30.3 [IQR: 27.5–33.3]vs. 29.4 [IQR:25.8–31.4]kg/m², P<0.001) and FAI levels(11.2 [IQR: 5.6–15.5]vs. 1.74 [IQR:0.76–2.53]ng/dl, P<0.001). TMAO and all its precursors significantly reduced after therapy: TMAO (3.35 [IQR: 2.18–4.93]vs. 2.05 [IQR:1.7–2.93][Mol/L P=0.002), choline (43.6 ([IQR: 39.5–49]vs. 33.8 [IQR: 31.5–36.9][Mol/L, P<0.001), betaine (49.4 [IQR: 39.9–57.1]vs 24.4 [IQR:20.2–32.6][Mol/L P<0.001), and carnitine (10.7 [IQR: 9.9–12.3]vs 8.9 [IQR: 8.2–9.7][Mol/L P<0.001).

Conclusion: This study reports for the first time that TMAO and its precursors are elevated in PCOS which might contribute to increased cardiometabolic risk of the syndrome and that OC use is associated with reduction of these microbiome-dependent metabolites.