Thyroid hormones and semen quality in infertile men: a large-scale stratified analysis revealing gradient associations

Thyroid hormones (THs) modulate male reproductive function, but their graded associations with multidimensional semen parameters remain poorly defined. This stratified analysis investigated TH levels and semen quality in 5142 infertile men (20-45 years). Serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4) and thyroid-stimulating hormone (TSH) were measured and stratified into quartiles (Q1-Q4). Comprehensive semen analysis included conventional, kinematic and morphological parameters. Multivariable logistic regression was used to assess the risk of specific semen abnormalities. Key findings revealed hormone-specific, graded associations: lower FT3 (Q1-Q2) and TT3 (Q1-Q2) levels were independently associated with increased risk of oligozoospermia (adjusted odds ratios [aORs] ranging from 1.434 to 1.785), while moderate FT3 (Q3) and FT4 (Q3) levels conferred protection against asthenozoospermia (aORs: 0.740 and 0.664, respectively). For teratozoospermia, lower TT3 (Q1) increased risk (aOR: 1.219), whereas moderate FT4 (Q2) was protective (aOR: 0.705). Interestingly, men in the lowest TSH quartile (Q1) exhibited a lower risk of both oligozoospermia and asthenozoospermia. Beyond conventional parameters, FT3 and TT4 demonstrated the most extensive associations with detailed motility, morphology and kinematic measures, including progressive motility, head/tail defects and multiple velocity parameters. These findings suggest that TH levels exhibit graded associations with semen quality in infertile men, with specific strata - even within conventional reference ranges - serving as independent risk factors for distinct semen abnormalities. The observed hormone-specific signatures support the potential integration of comprehensive thyroid profiling into male infertility evaluation, enabling refined risk stratification and personalized clinical management.