We reported that estradiol (E2) affects the medial preoptic area in the hypothalamus, a thermoregulatory center, decreases the Tskn (skin temperature) of the tail, and maintains the Tb (body temperature) in the cold in ovariectomized rats. E2 facilitates the thermoregulatory behavior, evaluated by the tail-hiding behavior of rats hiding their tails under their bodies, and suppressed neural activity in the insula of the brain. These results indicate that E2 centrally affects and facilitates autonomic and behavioral thermoregulation in the cold. The effect of E2 on thermoregulatory responses through cold receptors, transient receptor potential melastatin-8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1), were investigated. E2 suppressed the elevation of Tb by the application of menthol, a TRPM8 agonist; however, it did not affect Tb or Tskn of the tail after the application of cinnamaldehyde, a TRPA1 agonist. Thus, E2 modifies thermoregulation via TRPM8. In young women, Tskn decreased in all phases of the menstrual cycle after menthol application to the dorsum of the foot; however, cold unpleasantness occurred only in the preovulatory phase, the higher E2 concentration phase. Thus, E2 induces mental hypersensitivity to the cold through TRPM8. In ovariectomized rats, the effect of E2 on thermoregulation was investigated through the TWIK-related K+ channel (TREK), a new cold receptor. E2 administration increased Tb after the administration of ostruthin, a TREK agonist. These results indicate that E2 modulates thermoregulation in the cold through TRPM8, TREK, and centrally.