Sex- and menopausal status-specific patterns of fat free mass loss and cardiorespiratory fitness after metabolic bariatric surgery: the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (SOPHIA) longitudinal cohort

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ABSTRACT Background Fat-free mass (FFM) loss after metabolic bariatric surgery (MBS) may influence physical function, metabolic health, and quality of life. Whether FFM loss differs by sex and menopausal status and whether it relates to cardiorespiratory fitness (CRF) remain unclear. Objectives This study aimed to investigate patterns of FFM loss in males, premenopausal females, and postmenopausal females after MBS and to assess relationships between FFM and CRF before and after surgery. Methods In this longitudinal cohort study, individuals undergoing primary MBS with ≥18 mo of follow-up were included. Body weight and FFM were measured preoperatively and at intervals ≤72 mo. CRF was assessed using the Åstrand submaximal bicycle test. Changes in total weight loss (%TWL), FFM, and CRF were analyzed using linear mixed models. Associations between FFM and CRF were analyzed using Kendall’s τ and linear mixed models. Results The study included 1022 individuals: 221 males, 614 premenopausal females, and 187 postmenopausal females. Males exhibited the greatest absolute FFM loss, whereas premenopausal females lost the lowest proportion relative to TWL (%FFM/WL). At 24 mo, %FFM/WL was 24.7% in premenopausal females compared with 27.1% in males and 28.7% in postmenopausal females. Despite substantial FFM reductions, maximal oxygen consumption improved significantly in all groups. FFM correlated positively with CRF at baseline and until 24 mo in males and premenopausal females; however, postoperative FFM changes were not independently associated with CRF (β: −0.004; 95% confidence interval: −0.008, 0.001). Conclusions FFM loss after MBS differs by sex and menopausal status: males and postmenopausal females lose a greater proportion of FFM relative to TWL than premenopausal females. Nevertheless, CRF improves across all groups, showing postoperative gains in CRF can occur despite FFM reductions. These findings highlight substantial interindividual variability in the composition of weight loss after MBS, which is not fully explained by biological sex, menopausal status, or baseline adiposity. This trial was registered at Centrale Commissie Mensgebonden Onderzoek (CCMO) as NL751466.018.20 ( https://onderzoekmetmensen.nl/en/node/27224/pdf ).

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