Sex differences in major cardiovascular outcomes and fractures in patients with subclinical thyroid dysfunction: a systematic review and meta-analysis

Objective: To evaluate whether sex differences in the associations of subclinical hypothyroidism (SH) and subclinical hyperthyroidism (SCH) with the risks of major adverse cardiovascular events (MACE) and fractures. Methods: The PubMed, EmBase, and Cochrane Library databases were searched for eligible studies from inception until November 2021. The relative risk (RR) ratio with the 95% confidence interval (CI) was used to identify sex differences in the associations of SH and SCH with the risks of MACE and fractures. All analyses were performed using a random-effects model. Results: Twenty-four cohort studies (in 3,480,682 patients) were selected for meta-analysis. There were no sex differences in the associations of SH and SCH with the risks of atrial fibrillation, all-cause mortality, cardiac death, coronary heart disease, heart failure, MACE, stroke, fracture. Subgroup analyses indicated a greater risk of MACE in men than in women with SH if follow-up was ≥10.0 years (RR ratio 2.44; 95% CI 1.17–5.10; P = 0.017). The risk of any fracture was greater in men than in women with SH if follow-up was <10.0 years (RR ratio 1.17; 95% CI 1.03–1.34; P = 0.017) and in studies with a high level of adjustment (RR ratio 1.16; 95% CI 1.02–1.32; P = 0.022). However, the risk of hip fracture was lower in men than in women with SH on pooling of studies with low adjustment (RR ratio 0.53; 95% CI 0.29–0.97; P = 0.039). Conclusions: There may be sex-related differences in the risks of MACE, any fracture, and hip fracture in patients with SH.