Disruption of the dopaminergic system has been implicated in the etiology of many pathological conditions, including drug addiction. Here we used positron emission tomography (PET) imaging to study brain dopaminergic function in individually housed and in socially housed cynomolgus macaques (n = 20). Whereas the monkeys did not differ during individual housing, social housing increased the amount or availability of dopamine D2 receptors in dominant monkeys and produced no change in subordinate monkeys. These neurobiological changes had an important behavioral influence as demonstrated by the finding that cocaine functioned as a reinforcer in subordinate but not dominant monkeys. These data demonstrate that alterations in an organism's environment can produce profound biological changes that have important behavioral associations, including vulnerability to cocaine addiction.

FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation.

Although controversy continues, the preponderance of evidence indicates that estrogen replacement therapy favorably influences the risk of coronary heart disease in postmenopausal women. It remains uncertain how this effect is mediated and whether the cyclic addition of a progestin may influence adversely an estrogenrelated cardioprotective effect. We investigated the influence of sex hormone replacement therapy on diet-induced coronary artery atherosclerosis in estrogendeficient (ovariectomized) adult female cynomolgus monkeys. Monkeys were assigned randomly to one of three treatment groups: 1) no hormone replacement (n=17), 2) continuously administered 17-beta estradiol plus cyclically administered progesterone (n=20), and 3) continuously administered 17-beta estradiol (n=18). The physiologic patterns of plasma estradiol and progesterone concentrations were maintained by administering the hormones in sustained-release subcutaneous Silastic implants. The experiment lasted 30 months. At necropsy, coronary artery atherosclerosis was inhibited similarly (reduced by approximately one-half) in animals in both hormone replacement groups (p<0.05). Antiatherogenic effects of hormone replacement were independent of variation in total plasma cholesterol, lipoprotein cholesterol, apoprotein A-1 and B concentrations, high density lipoprotein subtraction heterogeneity, and low density lipoprotein molecular weight. We conclude that physiologic estrogen replacement therapy with or without added progesterone inhibits atherosclerosis progression in ovariectomized monkeys. This may explain why estrogen replacement therapy results in reduced risk of coronary heart disease in postmenopausal women. (Arteriosclerosis 10:1051-1057, November/December 1990) P remenopausal white women are at a low risk of coronary heart disease relative to age-matched white men. Although direct evidence is lacking, it is widely believed that ovarian estrogen is responsible for this gender-related protection. However, there is no direct evidence that endogenous estrogen or progesterone influences the pathogenesis of coronary heart disease or its underlying cause, coronary artery atherosclerosis. Furthermore, it remains uncertain whether coronary risk in women is influenced by physiologic conditions that affect endogenous sex steroid levels.1 While most studies have found evidence for increased severity of coronary artery atherosclerosis and increased coronary risk in postmenopausal women, others have found no relationship. 1 The results of studies of the effects of pregnancy, Received February 20,1990; revision accepted May 14,1990. that coronary risk increases with increasing number of pregnancies and half find no relationship. As regards exogenous estrogen, the preponderance of evidence indicates that estrogen replacement therapy favorably influences coronary risk in postmenopausal women.3 More controversial is whether the cyclic addition of a progestin to an estrogen replacement regimen may adversely influence an estrogen-related protective effect....

The purpose of this experiment was to examine the effects of social environment and social status on coronary artery and aortic atherosclerosis In adult male cynomolgus monkeys (Macaca fascicularls). Thirty experimental animals were assigned to six groups of five members each, and all animals were fed a moderately atherogenic diet (43% of calories as fat, 0.34 mg cholesterol/Cal) for 22 months. Group memberships were changed periodically among 15 monkeys (unstable social condition) and remained fixed throughout the experiment In the remaining animals (stable social condition). Within each condition, individual monkeys were classified as either dominant or subordinate animals, based on dyadic patterns of aggression and submission. At necropsy, the coronary arteries were subjected to pressure fixation and five sections each were taken from the left anterior descending, left circumflex, and right coronary arteries. The mean Intimal area measurement, based on all arterial sections, served as a coronary Index for each animal. Results Indicated that dominant animals in the unstable condition had significantly greater coronary artery atherosclerosis than dominant monkeys housed In stable social groups. Coronary artery atherosclerosis in the unstable dominants was also greater than among similarly housed (I.e., unstable) subordinates. A similar pattern was observed In the abdominal aorta, but was not statistically significant. No significant differences or similar patterns were seen In the thoracic aorta. Additional analyses revealed that the coronary artery effects were not due to concomitant differences In total serum cholesterol or high density llpoproteln cholesterol concentrations, blood pressures, ponderosity, or fasting glucose concentrations among the experimental animals. Behaviorally, manipulation of group memberships intensified agonistic encounters and disrupted patterns of affiliative Interaction between dominant and subordinate monkeys. Overall, these results suggest that social dominance (an Individual behavioral characteristic) Is associated with increased coronary artery atherosclerosis, but only under social conditions that provide recurrent threats to the status of dominant animals (I.e., under behavioral challenge). (Arteriosclerosis 2:359-368,