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A novel animal model to study hot flashes: no effect of gonadotropin-releasing hormone

Albertson, Asher J. MS; Skinner, Donal C. PhD

doi: 10.1097/gme.0b013e3181a9f60b

Objective: Menopausal hot flashes compromise the quality of life for most women. The physiological mechanisms underlying hot flashes remain poorly understood, and the absence of an animal model to investigate hot flashes hinders investigations in this field.

Methods: We first developed the sheep as a model to study peripheral skin temperature changes using fever-inducing lipopolysaccharide (LPS; 200 μg/kg) administered to ovary-intact ewes. Because a strong correlation between luteinizing hormone pulses and hot flashes has previously been reported, we then determined whether intravenous gonadotropin-releasing hormone (GnRH; 1 mg), a dose sufficient to elevate cerebrospinal fluid-GnRH concentrations, could modulate ear skin temperature in both ovariectomized and low-estrogen-replaced ovariectomized ewes.

Results: Some ewes responded to LPS in heart rate and abdominal temperature, but there was no significant effect on either parameter or cheek temperature for the group. In contrast, LPS injection caused a significant (P < 0.001) change in skin temperature at the ear. Ear temperature showed no significant change in response to GnRH relative to control injections in both ovariectomized and low estrogen ewes.

Conclusions: We developed a model animal system in the ewe that can accurately detect small changes in peripheral skin temperature. This system has the potential to be extremely useful in future studies investigating the pathology of hot flashes and holds several advantages over previous model systems developed for this research. GnRH per se does not seem to be involved in thermoregulatory events.

Sheep show significant changes in ear temperature in response to thermoregulatory challenges, suggesting that they may be a tractable animal model for the study of postmenopausal hot flashes. No evidence was found for a role of GnRH in the generation of thermoregulatory events in the ewe.

From the Department of Zoology and Physiology and Neurobiology Program, University of Wyoming, Laramie, WY.

Received January 22, 2009; revised and accepted March 9, 2009.

Funding/support: This publication was made possible by Grant RR15640 from the National Center for Research Resources, a component of the National Institutes of Health. A.J.A. was funded, in part, by a grant from the National Science Foundation EPS-9983278.

Financial disclosure/conflicts of interest: None reported.

The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Address correspondence to: Donal C. Skinner, Department of Zoology & Physiology, University of Wyoming, 1000 E University Ave., Laramie, WY 82071. E-mail:

©2009The North American Menopause Society