Evaluating the role of serotonin in hot flashes after breast cancer using acute tryptophan depletion

Abstract

Objective Among women with breast cancer, hot flashes are frequent, severe and bothersome symptoms that can negatively impact quality of life and compromise compliance with life-saving medications (e.g., tamoxifen, aromatase inhibitors). Clinicians' abilities to treat hot flashes are limited due to inadequate understanding of physiological mechanisms involved in hot flashes. Using an acute tryptophan depletion paradigm, we tested whether alterations in central serotonin levels were involved in the induction of hot flashes in women with breast cancer. Design This was a within subjects, double-blind, controlled, balanced, crossover study. Twenty-seven women completed two 9-hour test days. On one test day, women ingested a concentrated amino acid drink and encapsulated amino acids (no tryptophan) according to published procedures that have been shown to have specific effects on serotonin within 4.5 to 7 hours. On the other test day, women ingested a control drink. Serial venous blood sampling and objective hot flash monitoring were used to evaluate response to each condition. Results Response to acute tryptophan depletion was variable and unexplained by use of selective serotonin reuptake inhibitors, anti-estrogens, breast cancer disease and treatment variables, or genetic polymorphisms in serotonin receptor and transporter genes. Contrary to our hypothesis, hot flashes were not worsened with acute tryptophan depletion. Conclusions Physiologically-documented and self-reported hot flashes were not exacerbated by tryptophan depletion. Additional mechanistic research is needed to better understand the etiology of hot flashes.

Escitalopram treatment of menopausal hot flashes

“…Another recent investigation found no significant effects of acute tryptophan depletion upon HFs 18. Taken together, these results, along with our findings for escitalopram, raise questions regarding the role of the serotonin system in the etiology of HFs.…”

Ameliorating hot flashes/awakenings in the context of breast cancer treatments

“…As pointed out by Carpenter et al, 3 low blood 5-HT is seen after spontaneous or surgical menopause, and estrogen replacement is known to alleviate hot flashes in the context of increasing 5-HT blood concentrations. Estrogen has been observed to affect 5-HT metabolism in multiple ways, including though activating neurons that regulate genes for 5-HT synthesis, transport, and signaling.…”

On hot flash mechanism, measurement, and treatment

“…With regard to hot flash physiology, the article by Carpenter et al 5 in the current issue of Menopause looks at the question of whether tryptophan depletion, resulting in decreased serotonin, would cause increased hot flashes. The authors' innovative hypothesis was not supported by the results of this study.…”