The present research team recently demonstrated that a circadian rhythm of hot flashes (HFs) follows that of core body temperature(Tc) and that Tc elevations precede the majority of HFs. Tc in humans is regulated by maintaining a balance between heat production (by metabolism) and heat loss (by sweating and cutaneous vasodilation) or heat conservation (by cutaneous vasoconstriction). In Study 1, the investigators, therefore, propose to record measures of metabolic rate and cutaneous temperature to determine if these factors are related to the Tc elevations. They will also measure plasma MHPG (3- methoxy-4-hydroxyphenylglycol) to determine if elevations in this parameter can explain those HFs not preceded by a Tc increase. Tc in homeotherms is regulated within a thermoneutral zone between the Tc thresholds for sweating and shivering. The investigators found that the shivering threshold in postmenopausal women with HFs is elevated rather than lowered as was previously thought. This implies that the thermoneutral zone is narrowed in symptomatic women. This hypothesis would explain the ability of small Tc elevations to trigger the heat loss mechanisms of HFs and would also explain the shivering observed following many HFs. The investigators, therefore, propose to measure the thermoneutral zone in symptomatic and asymptomatic postmenopausal women, to determine if it is narrowed in the former group (Study 2). After the investigators determine the thermoneutral zone for a symptomatic woman, it should be possible to induce a HF by raising her Tc above the sweating threshold. The investigators, therefore, propose to measure the thermoneutral zone in symptomatic and asymptomatic women and then test to see if exercise-induced Tc elevations provoke HFs (Study 3). The investigators have previously demonstrated that central norepinephrine (NE) release is increased in symptomatic women. The investigators have also shown that yohimbine, an alpha (2)-adrenergic antagonist that increases central NE release, provokes HFs in symptomatic women and that clonidine, which acts in the opposite manner, reduces the occurrence of heat-induced HFs. Animal studies have shown that increased brain NE narrows the width of the thermoneutral zone. Conversely, intravenous clonidine reduces NE release and lowers the shivering threshold in man. The investigators, therefore, propose to determine if yohimbine narrows and clonidine widens the thermoneutral zone in symptomatic and asymptomatic postmenopausal women (Study 4). In the investigators' current work they again demonstrated that paced respiration treatment significantly reduces HF frequency, but did not find evidence of decreased sympathetic activation. New work in their laboratory demonstrated reductions in Tc and O(2) consumption during paced respiration training. The investigators therefore propose to measure Tc, metabolic parameters, and skin temperatures to determine if these factors are altered by paced respiration training (Study 5).
| Diwadkar, Vaibhav A; Murphy, Eric R; Freedman, Robert R (2014) Temporal sequencing of brain activations during naturally occurring thermoregulatory events. Cereb Cortex 24:3006-13 |
| Freedman, Robert R (2014) Menopausal hot flashes: mechanisms, endocrinology, treatment. J Steroid Biochem Mol Biol 142:115-20 |
| Freedman, Robert R; Kruger, Michael L; Tancer, Manuel E (2011) Escitalopram treatment of menopausal hot flashes. Menopause 18:893-6 |
| Freedman, Robert R (2010) Treatment of menopausal hot flashes with 5-hydroxytryptophan. Maturitas 65:383-5 |
| Freedman, Robert R; Wasson, Samuel (2007) Miniature hygrometric hot flash recorder. Fertil Steril 88:494-6 |
| Freedman, Robert R; Benton, Mark D; Genik 2nd, Richard J et al. (2006) Cortical activation during menopausal hot flashes. Fertil Steril 85:674-8 |
| Freedman, Robert R; Roehrs, Timothy A (2006) Effects of REM sleep and ambient temperature on hot flash-induced sleep disturbance. Menopause 13:576-83 |
| Freedman, Robert R (2005) Pathophysiology and treatment of menopausal hot flashes. Semin Reprod Med 23:117-25 |
| Freedman, Robert R (2005) Hot flashes: behavioral treatments, mechanisms, and relation to sleep. Am J Med 118 Suppl 12B:124-30 |
| Freedman, Robert R; Subramanian, Marappa (2005) Effects of symptomatic status and the menstrual cycle on hot flash-related thermoregulatory parameters. Menopause 12:156-9 |
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