Influence of hormone replacement therapy and aspirin on temperature regulation in postmenopausal women

Postmenopausal women receiving estrogen-replacement therapy (ERT) regulate body temperature (T-b) at a lower level than women not receiving hormone re placement therapy (untreated) and women using estrogen plus progesterone th erapy (E + P), but it is not clear if reproductive hormones alter T-b by di rectly acting on central thermoregulatory centers or indirectly via a secon dary mediator(s). The purpose of the present investigation was to examine t he possible involvement of pyrogenic cytokines and cyclooxygenase (COX) pro ducts (e.g., prostaglandins) in the regulation of T-b in three groups of po stmenopausal women (8 ERT, 7 E + P, and 8 untreated). We measured ex vivo s ecretion of cytokine agonists [tumor necrosis factor (TNF)-alpha and interl eukin (IL)-1 beta and -6] and modifiers (IL-2 soluble receptor, IL-1 recept or antagonist, soluble TNF receptor type I, soluble TNF receptor type II, s oluble IL-6 receptor, and soluble glycoprotein 130) from peripheral blood m ononuclear cells and thermoregulatory responses at rest and during 1 h of p assive whole body heating in the postmenopausal women before and after 3 da ys of placebo or aspirin (50 mg . day(-1) . kg(-1)). With and without aspir in, the ERT group had a lower baseline rectal temperature (T-re; 0.44 degre es C, P < 0.004) and a reduced T-b threshold for cutaneous vasodilation (0. 29 degrees C and 0.38 degrees C, P < 0.01) compared with the untreated and E + P groups, respectively. In the placebo condition, waking morning oral t emperature (T-or) correlated with ex vivo secretion of the proteins associa ted with IL-6 bioactivity. Aspirin caused significant reductions in waking T-or in the E + P group and in baseline T-re in the untreated group. Howeve r, the difference in thermoregulation brought about by steroid hormone trea tment could not be explained by these relatively modest apparent influences by cytokines and COX products. Therefore, the altered thermoregulation ind uced by reproductive steroid therapy appears to occur via a mechanism disti nct from a classic infection-induced fever.