Can Thyroid Dysfunction Contribute to Infertility via Lipid Abnormalities?

Thyroid dysfunction alters lipid metabolism and may impair reproduction, raising the possibility that lipid abnormalities contribute to thyroid-related infertility. This review evaluates dyslipidemia as a potential mechanistic link between these conditions. Thyroid hormones regulate hepatic LDL clearance, triglyceride-rich lipoprotein metabolism and HDL remodeling. Overt hypothyroidism commonly increases total and LDL cholesterol, changes that are partly reversible with levothyroxine, whereas lipid abnormalities in subclinical and central hypothyroidism are smaller and less consistent; hyperthyroidism generally lowers total and LDL cholesterol. Independently, adverse circulating lipid profiles are associated with reduced natural fecundability and poorer outcomes in selected assisted-reproduction studies. Experimental evidence identifies biologically coherent pathways involving ovarian steroidogenesis, follicular HDL function, oocyte cholesterol efflux and membrane signaling, endometrial receptivity and sperm membrane integrity. Human evidence supports both the thyroid-lipid and lipid-fertility relationships, but does not establish that lipid abnormalities mediate thyroid-related infertility. Interpretation is complicated by direct thyroid hormone effects, thyroid autoimmunity and metabolic confounding. Taken together, current findings support dyslipidemia as a biologically plausible potential contributor to thyroid-related reproductive dysfunction. Clinically, they suggest considering integrated assessment of thyroid and lipid status in reproductive-age adults and reassessment of the lipid profile after restoration of euthyroidism. Prospective preconception studies incorporating functional lipid measurements and formal mediation analyses are needed.