PSYCHOSOCIAL FACTORS, SEX-DIFFERENCES, AND ATHEROSCLEROSIS - LESSONS FROM ANIMAL-MODELS

Objective: Premenopausal women, compared with men, are relatively spar ed from coronary heart disease and the underlying atherosclorosis. Our purpose has been to elucidate the reason for this difference and to e xplore the role of behavioral factors in this phenomenon. Methods: Stu dies employed socially housed cynomolgus macaques (Macaca fascicularis ) fed on atherogenic diet and subjected to behavioral observations. Ov ariectomy, with or without hormone replacement, was used to test speci fic hypotheses about estrogen's role in the protection of females from atherosclerosis and coronary heart disease. Results: Female macaques, like women, are resistant atherosclerosis. However, this resistance i s modified by social status-dominant monkeys develop little atheroscle rosis, whereas subordinates resemble males in the amount of lesion tha t occurs. Subordinate females also are characterized by hypercortisole mia, behavioral dysfunction, and impaired ovarian function; the result ing low concentrations of circulating estrogen perhaps explain their a ccelerated atherosclerosis. Notably, atherosclerosis is exacerbated in ovariectomized monkeys but is suppressed association with pregnancy, a hyperestrogenic state. Moreover, exogenous estrogen (an oral contrac eptive) inhibits atherosclerosis in premenopausal social subordinates. Conclusions: To the extent that our results apply to women, they high light the potential importance of behavioral stressors and their effec ts on estrogen activity in the premenopausal development of atheroscle rosis. The triad of hypercortisolism, ovarian impairment, and psychiat ric morbidity found in monkeys also occurs in women and may represent a high-risk state for disorders of the cardiovascular system and, perh aps, other estrogen-sensitive tissues.