Can phthalates, parabens, and PFAS disrupt testosterone and thyroid signaling?

Environmental exposure to phthalates, parabens, and per- and polyfluoroalkyl substances (PFAS) significantly disrupts crucial endocrine pathways regulating both androgenic and thyroid systems.

Androgenic pathway disruption

• Inhibited testosterone synthesis: Phthalates (such as DEHP and DBP) and legacy PFAS impair cholesterol transport to mitochondria in testicular Leydig cells by downregulating regulatory proteins StAR and SREBP2. They further suppress key biosynthetic enzymes, including CYP11A1, CYP17A1, and 17β-HSD, directly decreasing systemic testosterone production.
• Reduced hormone bioavailability: Exposure to phthalates, methylparaben, and specific PFAS (such as PFNA and PFOS) is associated with elevated levels of sex hormone-binding globulin (SHBG). Increased SHBG binds circulating testosterone, lowering the active, free, and bioavailable fraction.

Thyroid and immune signaling interference

• HPT axis disruption: Phthalates interfere with thyroid receptor (TRα/TRβ) signaling and deiodinase (DIO1, DIO2, DIO3) activity, shifting the peripheral conversion of thyroxine (T4) to triiodothyronine (T3). Parabens reduce T4 levels and alter thyroid peroxidase (TPO) expression, while PFAS compete for serum transport protein binding sites and inhibit cellular iodide uptake.
• Autoantibody interaction: These compounds alter thyroid immune signaling by modulating thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) titers in a nonlinear, sex-specific manner. Individuals with pre-existing thyroid autoimmunity (TPOAb-positive) or concurrent iodine deficiency exhibit the highest susceptibility to these disruptive effects.

Bottom line

• Bottom line: Phthalates, parabens, and PFAS act as potent endocrine disruptors that reduce bioavailable testosterone by suppressing Leydig cell steroidogenesis and elevating SHBG, while simultaneously dysregulating the thyroid axis and intensifying thyroid autoimmune vulnerabilities.