Thyrotropin-releasing hormone as a treatment for cancer-related fatigue: a randomized controlled study

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. 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). 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. 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.