Abstract / Summary
Abstract Background Cardiorespiratory fitness in women with metabolic syndrome (MetS) may reflect the combined influence of adiposity, exercise-related substrate-use responses, and thyroid history. However, the relative associations of these factors with maximal oxygen uptake (VO₂max) remain insufficiently characterized, particularly in women with previously diagnosed and predominantly treated subclinical hypothyroidism (SCH). Methods This exploratory cross-sectional study analyzed baseline data from 24 women with MetS, including 16 with previously diagnosed SCH and 8 euthyroid women. Fifteen of the 16 women with SCH were receiving levothyroxine. Body composition was assessed by dual-energy X-ray absorptiometry (DXA), and cardiorespiratory fitness was assessed by cardiopulmonary exercise testing (CPET). The exercise-related respiratory exchange ratio response (ΔRER) was calculated as RER at maximal exercise minus resting RER. Associations with VO₂max were examined using correlation and prespecified exploratory multivariable linear regression. Basal metabolic rate was considered a secondary exploratory outcome. Results Analyses involving VO₂max included 23 participants. VO₂max did not differ significantly between the SCH and euthyroid groups (22.08 ± 3.48 vs. 24.28 ± 3.32 mL·kg⁻¹·min⁻¹). Waist circumference (r = − 0.757, p < 0.001) and body-fat percentage (r = − 0.675, p < 0.001) were inversely correlated with VO₂max, whereas the bivariate association between ΔRER and VO₂max was not statistically significant (r = 0.361, p = 0.091). In the primary multivariable model (R² = 0.749; adjusted R² = 0.709), greater waist circumference remained inversely associated with VO₂max (B = − 0.210, 95% CI − 0.279 to − 0.142; p < 0.001), and greater ΔRER remained positively associated with VO₂max (B = 17.709, 95% CI 5.382 to 30.036; p = 0.007). Thyroid-status group was not statistically significant in this model (B = − 1.525, 95% CI − 3.276 to 0.225; p = 0.084). In a sensitivity model using body-fat percentage instead of waist circumference, adiposity and ΔRER remained significantly associated with VO₂max, while previous SCH diagnosis also reached statistical significance, indicating sensitivity of the thyroid-status estimate to model specification. Conclusions In this small exploratory sample of women with MetS, adiposity and the exercise-related RER response showed consistent associations with VO₂max across multivariable models. Thyroid-status history was not significantly associated with VO₂max in the primary model, but its estimate varied in sensitivity analysis. These cross-sectional findings are hypothesis-generating and apply primarily to women with previously diagnosed, predominantly treated SCH.