Am J Obstet Gynecol 1999 Jul;181(1):66-70
Reduced thermoregulatory null zone in postmenopausal women with hot flashes.
Freedman RR, Krell W
Departments of Psychiatry and Behavioral Neurosciences, Obstetrics and Gynecology, and Internal Medicine (Pulmonary), Wayne State University School of Medicine, Detroit, Michigan, USA.

OBJECTIVE: Most menopausal hot flashes are preceded by small elevations in core body temperature. If the thermoneutral zone between the thresholds for sweating and shivering is reduced in women with symptoms, the triggering mechanism for hot flashes could be explained. STUDY DESIGN: We studied 12 postmenopausal women with symptoms and 8 without symptoms. We measured body temperatures with a rectal probe, an ingested telemetry pill, and a weighted average of rectal and skin temperatures. Each woman underwent 3 experimental sessions: determination of the sweating threshold by body heating, determination of the shivering threshold by body cooling, and replication of the sweating threshold with exercise. RESULTS: The women with symptoms had significantly smaller interthreshold zones than did the symptom-free women for all 3 measures of body temperature: rectal temperature, 0.0 degrees C +/- 0.06 degrees C versus 0.4 degrees C +/- 0.18 degrees C (P <.005); telemetry pill temperature, 0.0 degrees C +/- 0.11 degrees C versus 0.4 degrees C +/- 0.18 degrees C (P <.005); and mean body temperature, 0.8 degrees C +/- 0.09 degrees C versus 1.5 degrees C +/- 0.20 degrees C (P <. 0006). Sweat rates were significantly higher among the women with symptoms (0.06 +/- 0.002 mg. cm(-2). min(-1)) than among the women without symptoms (0.03 +/- 0.001 mg. cm(-2). min(-1), P <.05). Sweating thresholds during exercise did not significantly differ from those during body heating. During exercise all the women with symptoms and none of the women without symptoms had hot flashes. CONCLUSIONS: Menopausal hot flashes in women with symptoms may be triggered by small elevations in body temperature acting within a reduced thermoneutral zone.

Am J Human Biol. 2001 Jul-Aug;13(4):453-64. Publication Type: Review
Physiology of hot flashes.
Freedman RR.
Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, Michigan 48201, USA.

Hot flashes are the most common symptom of the climacteric, although prevalence estimates are lower in some rural and non-Western areas. The symptoms 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 no evidence of increased core body temperature. Evidence obtained using a rapidly responding ingested telemetry pill indicates that the thermoneutral zone, within which sweating, peripheral vasodilation, and shivering do not occur, is virtually nonexistent in symptomatic women but normal (about 0.4 degrees C) in asymptomatic women. The results suggest that small temperature elevations preceding hot flashes acting within a reduced thermoneutral zone constitute the triggering mechanism. Central sympathetic activation is also 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.