Pathophysiology and Treatment of Menopausal Hot Flashes

Robert R. Freedman, PhD


Semin Reprod Med. 2005;23(2):117-125. 

In This Article

Physiological Events of the Hot Flash

Peripheral vasodilation, demonstrated by increased skin temperature and blood flow, occurs during hot flashes in all body areas that have been investigated (Fig. 1). Skin temperature increases in the digits, cheek, forehead, upper arm, chest, abdomen, back, calf, and thigh.[8,9,10,11,12] Blood flow in the finger, hand, calf, and forearm also increases during hot flashes.[10,11,12] These changes typically occur within the first few seconds of the reported onset of the flash.[10]

Figure 1.

(A) Core body temperature (means) during menopausal hot flashes. (B) Respiratory exchange ratio (means) during hot flashes. (C) Mean skin temperature (means) during hot flashes. (D) Sternal skin conductance (means) during hot flashes. Time 0 is the beginning of the sternal skin conductance response. Intervals between arrows are significantly different from each other p = 0.05, Duncan's test. (From Freedman RR. Biochemical, metabolic, and vascular mechanisms in menopausal hot flushes. Fertil Steril 1998;70:1-6.)

Sweating and skin conductance, an electrical measure of sweating, also increase during hot flashes (Figs. 1 and 2). Molnar[9] measured the whole body sweat rate to be approximately 1.3 g/min in one subject. We simultaneously recorded measures of sweating and skin conductance from the sternum during 29 hot flashes in 14 women.[13] There was a close temporal correspondence between both measures, which increased significantly (Fig. 2). Measurable sweating occurred in 90% of the flashes.

Figure 2.

(A) Sternal skin conductance (means) during hot flashes. Note expanded time scale. (B) Sweat rate from sternum (means) during hot flashes. (From Freedman RR. Biochemical, metabolic, and vascular mechanisms in menopausal hot flushes. Fertil Steril 1998;70:1-6.)

Increased sternal skin conductance has proved to be the best objective marker of menopausal hot flashes to date. An increase in this measure ≥ 2 μmho (electrical unit of conductance) within 30 seconds corresponded with 95,[13] 90,[14] and 80%[15] of patient reports of hot flashes in four separate studies. No such responses were recorded in premenopausal or asymptomatic postmenopausal women.[13,14] Measurements of finger temperature and blood flow were less predictive of hot flash occurrence.[15]

The skin conductance measurement is particularly useful for the evaluation of treatment studies because it can be recorded outside the laboratory over prolonged periods of time and does not require the patients' intervention. Using the same recording methods with ambulatory monitors, we found an 86% agreement between the skin conductance criterion (2 μmho/30 seconds) and patient event marks.[13] A second study found an agreement rate of 77%.[14] A more recent study using a smaller, solid-state recorder found a concordance rate of 72% in 18 breast cancer patients with hot flashes.[16]

Core body temperature (Tc) also increases prior to hot flashes (Fig. 1), but this was discovered only recently. Tc elevation would appear to be the logical trigger for a hot flash because sweating and peripheral vasodilation constitute heat dissipation responses. However, early studies using esophageal,[10] rectal,[9] and tympanic[11] temperature measurements did not find Tc elevations before hot flashes. This was due to the fact that esophageal and rectal temperatures have long thermal lag times and respond too slowly to correlate with the peripheral physiological events.[17] In addition, tympanic temperature does not reliably measure Tc because it is distorted by facial vasodilation and sweating.[18]

We therefore measured Tc using an ingested radiotelemetry pill, which responds more rapidly than the esophageal and rectal methods. Defining hot flashes using the sternal skin conductance response, we found small, but statistically significant Tc elevations preceding the majority of flashes.[19] We replicated these findings in two subsequent studies, in which we found that significant Tc elevations preceded 76%[8] (Fig. 1) and 65%[20] of the flashes, respectively. Rectal temperature did not significantly change.[20]

The Tc elevations could be caused by increased metabolic rate (heat production) and/or peripheral vasoconstriction (decreased heat loss). We indeed found significant increases in metabolic rate, but they were simultaneous with peripheral vasodilation and sweating; peripheral vasoconstriction did not occur (Fig. 1).[8] Therefore, the Tc elevations are not driven by metabolic rate. Modest increases in heart rate, approximately 7 to 15 beats/minute, do coincide with the increases in metabolic rate.[9,10]


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