title: Influence of hormone replacement therapy and aspirin on temperature regulation in postmenopausal women.
abstract: Postmenopausal women receiving estrogen-replacement therapy (ERT) regulate body temperature (T(b)) at a lower level than women not receiving hormone replacement therapy (untreated) and women using estrogen plus progesterone therapy (E + P), but it is not clear if reproductive hormones alter T(b) by directly acting on central thermoregulatory centers or indirectly via a secondary mediator(s). The purpose of the present investigation was to examine the possible involvement of pyrogenic cytokines and cyclooxygenase (COX) products (e.g., prostaglandins) in the regulation of T(b) in three groups of postmenopausal women (8 ERT, 7 E + P, and 8 untreated). We measured ex vivo secretion of cytokine agonists [tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta and -6] and modifiers (IL-2 soluble receptor, IL-1 receptor antagonist, soluble TNF receptor type I, soluble TNF receptor type II, soluble IL-6 receptor, and soluble glycoprotein 130) from peripheral blood mononuclear cells and thermoregulatory responses at rest and during 1 h of passive whole body heating in the postmenopausal women before and after 3 days of placebo or aspirin (50 mg. day(-1). kg(-1)). With and without aspirin, the ERT group had a lower baseline rectal temperature (T(re); 0.44 degrees 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 temperature (T(or)) correlated with ex vivo secretion of the proteins associated 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. However, the difference in thermoregulation brought about by steroid hormone treatment could not be explained by these relatively modest apparent influences by cytokines and COX products. Therefore, the altered thermoregulation induced by reproductive steroid therapy appears to occur via a mechanism distinct from a classic infection-induced fever.
authors.affiliation: Noll Physiological Research Center, Penn State University, University Park, Pennsylvania 16802-6900, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Brooks-Asplund
authors.forename: J G
authors.initials: JG
authors.lastname: Cannon
authors.forename: W L
authors.initials: WL
authors.lastname: Kenney
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood; D001127:Arginine Vasopressin / Q000097:blood; D001241:Aspirin / Q000008:administration & dosage*; D001833:Body Temperature Regulation / Q000187:drug effects*; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D050822:Cytokine Receptor gp130; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D020249:Hormone Replacement Therapy; D006358:Hot Temperature; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009994:Osmolar Concentration; D017698:Postmenopause; D011374:Progesterone / Q000008:administration & dosage*; D015375:Receptors, Interleukin-2 / Q000097:blood; D019947:Receptors, Interleukin-6 / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012795:Sialoglycoproteins / Q000097:blood; D012867:Skin / Q000098:blood supply; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D015703:Antigens, CD; D016861:Cyclooxygenase Inhibitors; D004967:Estrogens; C507763:IL1RN protein, human; C494199:IL6ST protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D001127:Arginine Vasopressin; D050822:Cytokine Receptor gp130; D011374:Progesterone; D001241:Aspirin