Autonomic Responses to Psychological Stress: The Influence of Menopausal Status Noha H. Farag, M.D., Wayne A. Bardwell, Ph.D., Richard A. Nelesen, Ph.D., Joel E. Dimsdale, M.D., and Paul J. Mills, Ph.D. Department of Psychiatry University of California, San Diego ABSTRACT Cardiovascular disease is the leading killer of women in de- veloped countries. Menopause, stress, and lack of social support may contribute to the increased risk of heart disease morbidity and mortality in women. This study examined the effects of psy- chological stress and social support on autonomic nervous sys- tem control of the heart in 18 pre- and 34 postmenopausal women. Autonomic activity, as indexed by high-frequency heart rate variability and pre-ejection period, was assessed at rest and during a public speech task. Social support was determined using the Berkman Social Support Inventory. Postmenopausal women had higher heart rate (F = 4.4, p ≤ .04) and less para- sympathetic activity (F = 11.9, p ≤ .001) compared with premenopausal women at rest. In response to stress, sympa- thetic nervous system activity increased in postmemopausal women (F = 6.1, p ≤ .02); however, this effect was no longer sig- nificant when age was used as a covariate in the analysis. Social support did not significantly affect measures of autonomic activ- ity in either the pre- or postmenopausal women. Postmeno- pausal women have greater sympathetic and less parasympa- thetic activity than premenopausal women, which may account for their increased risk of coronary artery disease. (Ann Behav Med 2003, 26(2):134–138) INTRODUCTION Cardiovascular disease accounts for more than 900,000 deaths annually in the United States; 49.2% of those victims are women (1). Coronary artery disease (CAD) is the leading cause of death among women in the United States, and its incidence rises sharply as they advance in age (2). Disordered autonomic regulation of the cardiovascular system is implicated in CAD (3). In women, menopause marks the onset of the change in au- tonomic control of the cardiovascular system whereby there is an increased sympathetic tone (4). There is a complex interaction between physiological changes related to menopause and psychosocial factors. Both stress and poor social support are significant risk factors for acute CAD events (5). The mechanisms by which psychosocial factors contribute to the development of CAD are not fully un- derstood; however, several studies suggest that altered auto- nomic control (i.e., increased sympathetic control, decreased parasympathetic control, or both) is a mechanism that links so- cial isolation with CAD (6,7). Heightened stress reactivity may have an etiological role in CAD (8). Menopausal status also affects cardiovascular reactiv- ity to psychological stressors. Postmenopausal women are more reactive to laboratory stress than their age-matched premeno- pausal counterparts (9). There is a tendency, however, to treat cardiovascular reactivity as a unidimensional construct ranging from low to high reactivity. This is an impractical method be- cause the vagal and sympathetic outflows to the heart may vary reciprocally, nonreciprocally (e.g., coactivation), or independ- ently (10). Classification of an individual as high or low in car- diovascular reactivity ignores possible individual differences in the autonomic origins of this reactivity (11). Heart rate variability (HRV) has been used as an index of au- tonomic function (12). Power spectral analysis of the R–R inter- val (the interval between two consecutive R-waves on an EKG) reveals two major spectral components. The first, the high-fre- quency (HF) component of HRV corresponds to the respiratory sinus arrhythmia and is an index of parasympathetic (PNS) con- trol of the heart (13). The second major spectral component of HRV is the low-frequency component, modulated by both the sympathetic nervous system (SNS) and PNS (14), which makes it difficult to assess the SNS component alone of HRV. An alterna- tive measure for the SNS control of the heart is the pre-ejection pe- riod (PEP). The ventricular myocardium is innervated primarily by the SNS, which makes the interpretation of the PEP less am- biguous with respect to its autonomic origin (15). A number of studies investigating relations between psychosocial risk factors and autonomic nervous system responsivity have used HF–HRV as an index of PNS activity. Only a few of these studies have fo- cused on women. To our knowledge, there is a scarcity of studies examining the relation between psychosocial factors and PEP as an index of SNS activity. In this study we examined the influence of menopausal sta- tus on autonomic regulation of cardiovascular responses to acute psychological stress. We used impedance cardiography to assess PEP as a noninvasive index of SNS activity. Power spec- tral analysis of HRV was used to assess the HF power as an in- dex of PNS control of the heart. We hypothesized that pre- menopausal women would have less SNS and more PNS 134 This work was supported by Grants AG–13332, MO1–RR00827, and HL–57265 from the National Institutes of Health. We thank the research participants. We also gratefully acknowledge the efforts of Dr. Jose Loredo, M.D. in conducting the physical examina- tions for our participants and Elaine Dillon, R.N. for her hard work on this research study. Reprint Address: N. H. Farag, M.D., University of California, San Diego, Department of Psychiatry, UCSD Medical Center, 200 West Ar- bor Drive, CTF-A, 415, San Diego, CA 92103–0804. E-mail: nfarag@ucsd.edu © 2003 by The Society of Behavioral Medicine.