Postmenopausal hormone replacement: effects on autonomic, neuroendocrine, and immune reactivity to brief psychological stressors

Postmenopausal status increases some aspects of women's physiological responses to psychological stress; however, the influences of chronic hormone replacement with estrogen and progestogen on these responses are not known. We investigated possible effects of long-term estrogen replacement therapy (ERT), both with and without progestogen, on physiological reactivity to brief laboratory stressors. We studied three groups of postmenopausal women: 16 on estrogen alone, 14 on estrogen and progestogen, and 25 control participants receiving no replacement therapy. Cardiovascular, neuroendocrine, and immune data were collected at baseline and after speech and math tasks. In all groups, the stressors reduced vagal cardiac control (indexed by respiratory sinus arrhythmia); increased heart rate and plasma epinephrine, adrenocorticotropic hormone, and cortisol levels; and altered T lymphocyte response (measured by mitogen-induced cell proliferation), natural killer cell lysis, and circulating leukocyte subsets. Women on either type of ERT had higher total cortisol levels (reflecting an estrogen effect on cortisol binding globulin) and greater mitogen-induced blastogenesis across measurement periods than controls. They also showed greater vagal withdrawal and less decline in mitogen-stimulated blastogenesis in response to the stressors. Combined estrogen and progestogen was associated with higher epinephrine and lower circulating total lymphocytes, T cells, and CD4+ T cells across measurement periods, and with intermediate levels of vagal withdrawal in response to the stressors. Long-term ERT was associated with enhanced parasympathetic responsiveness to stress, suggesting possible reduced demand for potentially detrimental sympathetic activation; and with higher overall levels and smaller stress-induced reductions of mitogen-stimulated blastogenesis, suggesting up-regulated T cell function.