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Effects of social status and moderate alcohol consumption on mammary gland and endometrium of surgically postmenopausal monkeys

Shively, Carol A. PhD1; Register, Thomas C. PhD1; Grant, Kathleen A. PhD2; Johnson, Jami L. BS1; Cline, J. Mark DVM, PhD1

Articles

Objective: To evaluate the effects of social subordination stress and chronic moderate alcohol consumption on indices of breast and endometrial cancer risk.

Design: Forty-six adult, ovariectomized, cynomolgus monkeys (Macaca fascicularis) were trained to voluntarily drink a placebo or a two-drink/day equivalent of ethanol (0.5 g/kg), 5 days a week for 26 months, the latter resulting in average blood alcohol levels of 42 mg/100 mL. Indices of cell proliferation and sex steroid receptor abundance were measured.

Results: Compared with dominants, socially subordinate females had increased cell proliferation and proportions of glandular (P < 0.02) and epithelial tissue (P = 0.009) and less stroma (P < 0.02) in endometrium, and increased tissue thickness in breast (P < 0.05). There was no evidence of increased risk of breast or endometrial cancer with chronic moderate alcohol consumption, as indicated by markers of cell proliferation and sex steroid receptor abundance. Chronic moderate alcohol consumption did not effect circulating sex steroid concentrations (all P > 0.10). The adipocyte hormones leptin and adiponectin were correlated with indices of cell proliferation and sex steroid receptor abundance.

Conclusions: These observations suggest that social status was more important than chronic moderate alcohol consumption in endometrial and breast biology of surgically postmenopausal females. Endogenous sex steroid metabolism was not significantly affected by chronic moderate alcohol exposure consistent with the lack of estrogen-like effects on breast and endometrium. Social subordination stress was associated with initial cellular changes that may increase endometrial cancer risk. Ovariectomized cynomolgus monkeys may be a useful model for the study of effects of social factors and obesity on breast and endometrial cancer risk.

In ovariectomized monkeys, low social status was associated with cellular changes indicative of increased endometrial cancer risk. Social stress factors may be more important than chronic moderate alcohol consumption to the endometrial and breast biology of surgically postmenopausal female primates.

From the 1Comparative Medicine Section, Department of Pathology and the 2Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC.

Received July 29, 2003; revised and accepted October 7, 2003.

This research was funded by the National Institute on Alcohol Abuse and Alcoholism grant RO1 AA 11204 (C.A.S.) and P50 11997 (K.A.G.) for the alcohol analyses.

Address correspondence to: Carol A. Shively, PhD, Department of Pathology (Comparative Medicine Section), Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040. E-mail: cshively@wfubmc.edu.

©2004The North American Menopause Society