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

Menopause. 2009 Jul-Aug;16(4):644-52. doi: 10.1097/gme.0b013e318199e9f6.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adrenergic Uptake Inhibitors / administration & dosage
  • Adult
  • Aged
  • Amino Acids / administration & dosage
  • Antidepressive Agents / administration & dosage
  • Breast Neoplasms / physiopathology*
  • Breast Neoplasms / therapy
  • Cross-Over Studies
  • Double-Blind Method
  • Estrogen Receptor Modulators / administration & dosage
  • Female
  • Hot Flashes / physiopathology*
  • Humans
  • Middle Aged
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Serotonin / biosynthesis
  • Serotonin / physiology*
  • Tryptophan / administration & dosage*
  • Tryptophan / deficiency*


  • Adrenergic Uptake Inhibitors
  • Amino Acids
  • Antidepressive Agents
  • Estrogen Receptor Modulators
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Tryptophan