Impact of sleep restriction on biomarkers of thyroid function: Two pooled randomized trials

Chronic, mildly insufficient sleep is associated with increased cardiometabolic risk, but whether the regulation of thyroid hormones and related growth factors are mechanisms of this association is unclear. We investigated whether 6 wk of mild sleep restriction (SR) alters levels of free thyroxine (FT4), thyroid stimulating hormone (TSH), and fibroblast growth factor-21 (FGF-21), a modulator of FT4, in adults with adequate habitual sleep (AS; 7-9 h/night).

Healthy adults participated in one of two randomized, crossover studies with identical 6-wk intervention phases: AS and SR (1.5 h/night < AS). Fasted blood samples were collected at baseline and endpoint of each phase. Outcomes were concentrations of FT4, TSH, and FGF-21 (women only). Linear mixed models tested the effects of SR vs AS on the outcomes, adjusting for baseline levels, week, sex, and sex-by-condition interaction.

Thirty participants (20 women; 73% racial/ethnic minority; age 21-64 y [M±SD = 36.2 ± 12.8 y]) were included. In the full sample, no effects of SR on FT4 (β±SE = 0.02 ± 0.04, p = 0.654) or TSH (β±SE = -0.02 ± 0.04, p = 0.650) were observed; however, there were sex-by-condition interactions for both FT4 (p-interaction = 0.056) and TSH (p-interaction = 0.049). In sex-stratified analyses, TSH was reduced in SR vs. AS in women (β±SE = -0.11 ± 0.04, p = 0.011, Cohen's f² = 0.55) but not men (β±SE = 0.09 ± 0.08, p = 0.261). Among women (n = 17), FGF-21 was not significantly different between conditions (β±SE = 8.51 ± 17.70, p = 0.638).

Prolonged mild SR reduces TSH in women, whereas FT4 and FGF-21 remain unaffected compared with AS. If sustained, disruptions to the thyrotropic axis in women may contribute to their more pronounced cardiometabolic risk in response to SR compared with men.