Menopausal Hot Flashes:
Physiological Mechanisms and Potential of a Primate Model
Robert R. Freedman, Ph.D.
Wayne State University School of Medicine, Detroit, Michigan 48201
The symptoms of a hot flash are characteristic of a heat-dissipation response and consist of sweating on the face, neck, and chest, as well as peripheral vasodilation. Although hot flashes clearly accompany the estrogen withdrawal at menopause, estrogen alone is not responsible since levels do not differ between symptomatic and asymptomatic women. Until recently it was thought that hot flashes were triggered by a sudden downward resetting of the hypothalamic setpoint, since there was not evidence of increased core body temperature. However, we recently obtained such evidence, using a rapidly responding ingested telemetry pill. We then found that the thermoneutral zone, within which sweating and shivering do not occur, is virtually nonexistent in symptomatic women but normal (about 0.4 C) in asymptomatic women. Thus, we believe that small temperature elevations preceding hot flashes acting within a reduced thermoneutral zone constitute the triggering mechanism. We also demonstrated that sympathetic activation is elevated in symptomatic women which, in animal studies, reduces the thermoneutral zone. Clonidine reduces central sympathetic activation, widens the thermoneutral zone, and ameliorates hot flashes. Estrogen virtually eliminates hot flashes but its mechanism of action is not known.
Rhesus monkeys provide an excellent animal model for the study of menopausal hot flashes because their reproductive and thermoregulatory systems are extremely similar to those of humans.
Only 3 previous investigations have been performed to develop animal models of menopausal hot flashes. Dierschke recorded temperature from the ear pinna, forehead, finger, and rectum in 3 rhesus monkeys before and after OVX, during estrogen replacement, and after estrogen removal. Temperature fluctuations of the ear pinna tended to increase following OVX and decrease during estrogen replacement, although the statistical significance of these findings was unclear. However, each phase of the study lasted only a few weeks. In women, HFs do not always occur immediately following OVX and estrogen replacement generally requires 1-2 months to ameliorate HFs. Thus, longer periods of study would be desirable.
Jelinek et al. recorded skin temperature from the forehead in 2 female stumptail macaques. They found statistically significant increases in the number of temperature fluctuations following OVX in both animals. These fluctuations were significantly reduced by administration of estrogen and by clonidine.
Katovich attempted to use fluctuations in rat tail temperature following opiate withdrawal as a model for menopausal HFs. However, this model is not tenable because naloxone infusion does not suppress HFs in symptomatic women and because rats do not undergo menopause.
From the above studies, it is clear that an animal model for menopausal hot flashes has not been established. Future work in nonhuman primates could yield useful data by using longer recording periods for each manipulation, by recording from more sites, by using a variety of pharmacologic and thermal manipulations, and by verifying the effects of hormonal manipulations by assays. Physiological HF markers obtained in OVX animals should be verified in naturally-menopausal animals. Then, invasive studies of hypothalamic function in menopausal HFs could be undertaken to determine the cause(s) of this phenomenon.
Keywords: Menopause, Hot Flashes, Thermoregulation.
Problems or questions regarding this site should be directed to
webmaster@americanaging.org