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The hot flush is the only symptom specifically attributable to the menopause. Hot flushes appear to represent an episodic derangement of thermoregulation as a result of estrogen deficiency but the underlying physiological mechanisms are unknown. We have developed an animal model for the study of hot flushes. Two female monkeys (Macaca arctoides) were trained to accept monitoring of scalp cutaneous temperatures. After baseline temperature recordings were obtained both monkeys were ovariectomized. A few days after operation the previously stable scalp temperature changed to an undulating pattern with cycles lasting approximately 40-50 min. Ethinyl estradiol (20 micrograms orally or im) and (7 alpha,17 alpha)-17-hydroxy-7-methyl-19-nor-pregn-5(10)-en-20-yn-3-one (2.5 mg orally), a steroid with weak estrogenic, progestogenic, and androgenic properties, suppressed the characteristic undulating temperature pattern; this returned after withdrawal of replacement therapy. Clonidine (0.15 mg twice a day) suppressed the cyclic changes for 2 to 3 h. Domperidone and naloxone had no significant effect. This animal model may be useful for the investigation of alternative therapy for the management of menopausal flushes.

The role of endogenous corticoids in fever responses caused by recombinant murine interleukin (IL)-1β and IL-6 was studied in adult male Wistar rats. Adrenalectomy diminished the development of fever after intracerebroven-tricular (icv) injection of these ILs and lowered body temperature. Intraperitoneal administration of the same doses of ILs did not produce fever in intact animals or hypothermia in adrenalectomized rats, thus suggesting a central site of action of IL-1β and IL-6 in these experiments. Chronic replacement with moderate doses of corticosterone restored the fever response in adrenalectomized animals in response to icv administration of IL-1β but only partially reversed the fever caused by IL-6. Adrenalectomized animals acutely treated with corticosterone and thereafter with either IL-1β or IL-6 developed fever more rapidly than did chronically corticosterone-treated animals. In intact animals corticosterone blocked the fever response to icv injected IL-1β. We propose that in the rat corticosterone acts in a bimodal manner on body temperature; it exerts a permissive central effect on the fever response and limits the production of inflammatory mediators in the brain. Conversely, higher corticosterone doses probably reduce the magnitude of the fever response.

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