Third-trimester estradiol is associated with isolated maternal hypothyroxinemia and attenuated TSH-FT4 coupling: evidence from rats and human astrocytes.

The pituitary T3/T4 ratio showed a numerical increase across gestation but did not reach statistical significance (NP: 0.087 ± 0.014; GD20: 0.111 ± 0.019; P = 0.18; Figure 2B ; Supplementary Table 2 ); given the small number of pituitary samples, modest effects cannot be excluded.

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When modeled by E2 quartiles, the highest quartile (Q4 vs Q1) showed increased odds of IMH (OR = 3.488, P < 0.01), with a significant trend across quartiles (P for trend < 0.05; Table 2B ; Figure 1E ); sensitivity analysis yielded consistent results ( Supplementary Table 1A ).

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