Levothyroxine monotherapy has limited effects on body composition in clinical and subclinical hypothyroidism: a systematic review and meta-analysis

Abstract Clinical (CH) and subclinical (SCH) hypothyroidism reduces the metabolic rate and alter body composition. The current treatment with levothyroxine (LT4) restores the thyroid axis hormonal levels; however, its efficacy in reversing the anthropometric alterations remains unclear. This review was prospectively registered on PROSPERO (CRD42024589156), followed PRISMA guidelines, and aimed to include studies involving CH and/or SCH treated with LT4 monotherapy until achieving physiological hormonal levels. Eligible studies reported pre- and post-LT4 treatment data of BMI, BW, fat mass (FM), and lean mass/fat-free mass (LM/FFM). Each variable was analyzed according to treatment duration, sex distribution, initial and final TSH levels. 35 studies were included, comprising 1,116 individuals with hypothyroidism (672 CH; 444 SCH). In CH, LT4 led to negligible changes in BMI in the general analysis (Standardized mean difference [SMD] -0.18; 95% confidence interval [CI] -0.26, -0.10; mean difference [MD] -0.68 kg/m²), while moderate BMI reductions were observed after 12 months of treatment (SMD − 0.56; CI -0.87, -0.24; MD -2.29 kg/m²). LT4 reduced BW in CH (SMD − 0.24; CI -0.34, -0.15; MD -2.15 kg), primarily in the first 3 months of treatment; it did not change FM and led to a small reduction in LM/FFM (SMD − 0.21; CI -0.37, -0.05). However, LT4 showed no significant effects on BMI, BW, FM, or LM/FFM in SCH, regardless of the analysis. Despite restoring thyroid hormonal homeostasis, LT4 showed limited efficacy in reversing the anthropometric alterations associated with CH and mainly SCH, suggesting that therapies beyond hormonal normalization may be required. Moreover, our data reinforces that LT4 monotherapy must not be prescribed for weight loss.