Dominant Social Status and Contraceptive Hormone Treatment Inhibit Atherogenesis in Premenopausal Monkeys

Abstract

Abstract The stress of social subordination is associated with exacerbation of coronary artery atherosclerosis in premenopausal cynomolgus monkeys, possibly as a result of the ovarian dysfunction that reliably accompanies subordinate social status. The primary objective of the current study was to determine whether treatment with an oral contraceptive (OC) provides relative protection from development of atherosclerotic plaques, especially among animals made vulnerable to atherosclerosis by social subordination. In the present study, 193 adult female monkeys (Macaca fascicularis) were placed in social groups of 5 or 6 animals each. Half of the animals were then fed an atherogenic diet to which had been added a triphasic OC, while the remainder received only the atherogenic diet. At the end of 26 months, atherosclerosis was measured in an iliac artery biopsy taken from each monkey. The results demonstrated that among untreated animals subordinate individuals developed significantly more atherosclerosis than did their dominant counterparts ( P <.01); however, OC treatment inhibited atherosclerosis in subordinate animals ( P <.05) and eliminated the difference between dominant and subordinate animals that was observed in the untreated condition. Subordinate social status and OC treatment were both associated with reduced plasma concentrations of HDL cholesterol ( P <.01 for both), and subordinate monkeys also had elevations in LDL cholesterol plus VLDL cholesterol ( P <.01). Nonetheless, the interaction between social status and OC treatment remained significant even after covariance adjustment for variation in plasma lipids. Taken together, these results suggest that social subordination worsens, whereas OC treatment inhibits, atherosclerosis, and that these effects are independent of concomitant variability in plasma lipids.