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

Carpenter, Janet S. PhD, RN1; Yu, Menggang PhD2; Wu, Jingwei MS2; Von Ah, Diane PhD, RN1; Milata, Jennifer BSN1; Otte, Julie L. PhD, RN1; Johns, Shelley PsyD3; Schneider, Bryan MD3; Storniolo, Anna Maria MD3; Salomon, Ronald MD4; Desta, Zeuresenay PhD5; Cao, Donghua MS5; Jin, Yan MD5; Philips, Santosh MS5; Skaar, Todd C. PhD5

doi: 10.1097/gme.0b013e318199e9f6
Articles

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 (eg, tamoxifen and 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.

Methods: This was a within-participant, 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, antiestrogens, 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.

Using an acute tryptophan depletion paradigm, alterations in central serotonin levels were tested to see if they were involved in the induction of hot flashes in women with breast cancer. Contrary to our hypothesis, hot flashes were not worsened with acute tryptophan depletion.

From the 1Department of Adult Health, School of Nursing; Divisions of 2Biostatistics and 3Hematology/Oncology, School of Medicine, Indiana University, Indianapolis, IN; 4Department of Psychiatry, School of Medicine, Vanderbilt University, Nashville, TN; and 5Division of Clinical Pharmacology, School of Medicine, Indiana University, Indianapolis, IN.

Received November 12, 2008; revised and accepted December 23, 2008.

Funding/support: This research was supported with an Idea Award from the Department of Defense Breast Cancer Program (BC043199, DAMD W81XWH-05-1-0326) and by the Indiana University General Clinical Research Center (National Institutes of Health M01 RR00750).

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Janet S. Carpenter, PhD, RN, Indiana University, 1111 Middle Drive NU423, Indianapolis, IN 46220. E-mail: carpentj@iupui.edu

©2009The North American Menopause Society