The Role of Serotonin in Hot Flashes After Breast Cancer

2014-08-27 03:48:37 | BioPortfolio


The purpose of this proposal is to improve our understanding of the role of tryptophan and serotonin in hot flashes. The main hypothesis is that alterations in tryptophan and serotonin levels are involved in the induction of hot flashes in women with breast cancer and genetic variations in the serotonin receptors and transporters also play a role.


Among women with breast cancer, hot flashes are a frequent, severe and bothersome symptom. For this group, hot flashes are negatively related to mood, affect, and daily activities and can compromise compliance with life-saving medications (e.g., tamoxifen). Over 60% of breast cancer survivors report hot flashes, with 59% stating they are extremely severe and 44% reporting them to be extremely bothersome. Unfortunately, limitations in our understanding of hot flash physiology limit clinicians' abilities to fully treat this symptom. Although the current non-hormonal treatment of choice for hot flashes after breast cancer targets the central serotonin system (e.g., paroxetine, venlafaxine), the role of serotonin in hot flashes has not been directly tested. Because the effectiveness of these agents has been based largely on improvement in subjective reporting of hot flashes, it is not clear whether benefits are due to physiological effects on hot flashes or due to improvements in mood or other related symptoms. In addition, these and other currently available treatments are not acceptable, appropriate, or effective for all women with breast cancer. Understanding the physiological mechanisms involved in hot flashes after breast cancer will enable us to develop more targeted behavioral and/or pharmacological therapies to be used in lieu of, or in addition to, currently available therapies so that we can eradicate hot flashes and improve the quality of life for women with breast cancer.

Results implicating direct effects of tryptophan and serotonin on objective hot flashes will help guide the development of improved interventions for alleviating hot flashes in women with breast cancer. These interventions may target the central serotonin system either behaviorally (e.g., diet) or pharmacologically (e.g., alternative drug therapeutics). If direct manipulation of tryptophan and serotonin does not affect hot flashes, these findings will be equally as useful in guiding future research on non-serotonin related etiologies and interventions. Findings from this study will ultimately be used to eradicate hot flashes as a frequent, severe and bothersome breast cancer treatment related condition, thereby, improving quality of life for all women with breast cancer.

Study Design

Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Basic Science


Breast Cancer


Acute tryptophan depletion, Half-strength tryptophan depletion (Control)


Indiana University Cancer Center
United States




Indiana University

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:48:37-0400

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Medical and Biotech [MESH] Definitions

A dioxygenase with specificity for the oxidation of the indoleamine ring of TRYPTOPHAN. It is a LIVER-specific enzyme that is the first and rate limiting enzyme in the kynurenine pathway of TRYPTOPHAN catabolism.

An enzyme that activates tryptophan with its specific transfer RNA. EC

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A PYRIDOXAL PHOSPHATE containing enzyme that catalyzes the transfer amino group from L-TRYPTOPHAN to 2-oxoglutarate in order to generate indolepyruvate and L-GLUTAMATE.

A metabolite of the essential amino acid tryptophan metabolized via the tryptophan-kynurenine pathway.

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