BACKGROUND: Fatigue is a common and often disabling symptom for cancer patients. 
To date, no pharmacological interventions have shown reliable efficacy in 
treatment of cancer-related fatigue (CF). Thyrotropin-releasing hormone (TRH), a 
key regulator of homeostasis, exerts arousing and analeptic actions in instances 
of behavioral depression. In the present pilot, randomized, placebo-controlled, 
crossover study, we investigated the efficacy and safety of TRH as a treatment 
for CF.
METHODS: Patients with cancer experiencing significant fatigue without medically 
reversible causes were enrolled in this study. The primary outcome measure was 
the visual analog scale for energy (VAS-E) assessed at 3, 7, and 24 h post-study 
medication administration. Secondary outcome measures included the profile of 
mood states (POMS) questionnaire, a 6-min walking test, the hospital anxiety and 
depression scale, the Leeds sleep questionnaire, and assessment of quality of 
life using the Functional Assessment of Chronic Illness Therapy-Fatigue 
(FACIT-F).
RESULTS: Eight patients completed the study. TRH administration was associated 
with significant improvement in fatigue level as measured by the VAS-E, the 
fatigue and vigor subscales of the POMS, and the fatigue subscale of FACIT-F (p 
< 0.05). It was also associated with a positive impact on quality of life. TRH 
administration was associated with transient increases in blood pressure and 
heart rate.
CONCLUSIONS: TRH administration was efficacious, safe, and tolerable in the 
treatment of CF with a positive impact on quality of life. These results provide 
a crucial impetus for pursuing TRH therapeutics to treat CF.