OBJECTIVE: To determine whether premenopausal social subordination in female monkeys predicts postmenopausal atherosclerosis, and whether any such effect is altered by chronic exposure to contraceptive steroids or postmenopausal hormone replacement.
METHODS: One hundred seventy-seven (177) premenopausal cynomolgus monkeys (Macaca fascicularis) housed in social groups of five or six were fed an atherogenic diet that, for half of the animals, also contained an oral contraceptive (OC). Individuals were judged socially dominant or subordinate based on behavioral observations. After 26 months animals were oophorectomized, biopsied for iliac atherosclerosis, and for the next 36 months were fed one of three atherogenic diets containing soy protein: 1) phytoestrogen-free; 2) phytoestrogens intact; and 3) phytoestrogen-free plus conjugated equine estrogens. Plasma lipids and menstrual cyclicity were also assessed. Finally, all animals were necropsied and the extent of atherosclerosis measured in the coronary and iliac arteries.
RESULTS: The interaction of premenopausal social status and OC exposure predicted postmenopausal coronary artery atherosclerosis (P =.02). Subordinate animals not receiving OCs developed twice the coronary atherosclerosis of similarly untreated dominants (P <.01), an outcome mitigated by premenopausal OC exposure (P <.01). These effects occurred across postmenopausal treatment groups and independent of variation in plasma lipids. The same associations were observed in the iliac arteries, and, to a similar extent, both pre- and post-menopausally. Hormone data suggest that untreated premenopausal subordinates may have been estrogen deficient.
CONCLUSION: Premenopausal social subordination exacerbates postmenopausal atherosclerosis, an effect possibly mediated by estrogen deficiency and shown here to be prevented by premenopausal OC exposure. These results occur irrespective of postmenopausal treatment.
