Levothyroxine for subclinical hypothyroidism in older adults: no evidence of benefit on quality of life or cardiovascular outcomes: a systematic review

Subclinical hypothyroidism (SCH) is highly prevalent in older adults, yet the efficacy of levothyroxine treatment in this population remains uncertain. This systematic review evaluated the efficacy of levothyroxine compared with placebo or no treatment on health-related quality of life (HRQoL) and major adverse cardiovascular events (MACE) in older adults with mild SCH. We conducted a systematic review following PRISMA 2020 guidelines (PROSPERO: CRD420251176144). We searched PubMed/MEDLINE, Embase, Scopus, Cochrane Library, Web of Science, and LILACS from database inception through October 2025. We included randomized controlled trials (RCTs) and prospective cohort studies in adults ≥ 60 years with SCH (TSH 4.5–10 mIU/L, normal free T4). Two independent reviewers performed study selection, data extraction, and risk of bias assessment (RoB 2 for RCTs, Newcastle-Ottawa Scale for cohorts). Due to substantial heterogeneity in HRQoL instruments and study designs, we performed structured narrative synthesis. From 1,247 identified records, eight studies met inclusion criteria (n = 4,892 participants): two RCTs and six prospective cohort studies with follow-up ranging from 60 to 96 months. RCTs demonstrated no significant benefit of levothyroxine on HRQoL (non-significant differences across all SF-36 and EQ-5D domains) or MACE (RR range: 0.88–0.94; all confidence intervals crossing unity). High-quality cohort studies consistently reported no improvement in HRQoL and no significant reduction in MACE risk after multivariable adjustment (HR range: 0.85–0.95; all 95% CIs including 1.0). Current long-term evidence does not support levothyroxine treatment for improving quality of life or reducing cardiovascular events in older adults with mild SCH. These findings support a conservative management strategy of active surveillance over routine treatment in this population.