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This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/E270    most recent 00108.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Williams, N. I. Articles by Cameron, J. L. Search for Related Content PubMed PubMed Citation Articles by Williams, N. I. Articles by Cameron, J. L.

Synergism between psychosocial and metabolic stressors: impact on reproductive function in cynomolgus monkeys

Departments of ¹Psychiatry, ²Cell Biology and Physiology, and ³Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; ⁴Divisions of Reproductive Sciences and Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon; ⁵Departments of Gynecology and Obstetrics and Psychiatry, Emory University School of Medicine, Atlanta, Georgia; and ⁶Department of Kinesiology, Penn State University, University Park, Pennsylvania

Submitted 17 February 2006 ; accepted in final form 30 March 2007

The role of energy imbalance versus psychosocial stress in the pathogenesis of female reproductive dysfunction characterized by anovulation and amenorrhea remains controversial. In women, functional hypothalamic amenorrhea can develop in the absence of significant weight loss, excessive exercise, or profound psychosocial disruption. We posited, therefore, that commonplace, seemingly minor stressors that alone would have minimal impact upon reproductive function might interact synergistically such that combinations of stressors would cause a greater impairment of the reproductive axis than any single stressor alone. We then developed a monkey model to test this hypothesis. Adult female cynomolgus monkeys with normal menstrual cycles were randomized into three experimental groups and studied over four menstrual cycles. The groups were: low-level psychosocial stress (i.e., moving to a new housing environment; Move, n = 8), moderate energy imbalance (Exercise + Diet, n = 9); and all stressors in combination (Move + Exercise + Diet, n = 10). Food intake, body weight, menstrual cyclicity, and reproductive hormones were assessed for two control menstrual cycles followed by two experimental cycles during which the monkeys experienced the stressors. Abnormal cycles were considered to be abnormally long or anovulatory cycles. Few abnormal cycles occurred in the Move group (1 of 8 monkeys) and in the Exercise + Diet group (1 of 9 monkeys). In contrast, 7 of 10 monkeys in the Move + Exercise + Diet group displayed at least one abnormal cycle (² = 9.61, P = 0.008). These findings suggest that infertility due to hypothalamic hypogonadism can result from the combination of commonplace, seemingly minor stressors that often escape clinical attention.

exercise; diet; psychosocial stress; reproduction

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