Protirelin (thyrotropin-releasing hormone) appears to be a neuromodulator in the 
extrahypothalamic nervous system and has been suggested as an adjunct in the 
treatment of amyotrophic lateral sclerosis (ALS). Clinical studies have been 
divided on the efficacy of protirelin (TRH) despite strong experimental findings 
that are consistent with a role for the peptide in ALS. Recent findings provide 
evidence of a gender-related specificity in the ability of protirelin to 
potentiate the monosynaptic reflex. While castration in male neonatal rats 
lowered the sensitivity to protirelin, testosterone treatment restored that 
sensitivity. An examination of the clinical studies reveals a failure either to 
identify patients' sex or to separate the results on the basis of sex. These 
findings provide convincing evidence for the potential efficacy of protirelin in 
ALS if the patient's sex and underlying hormonal status are taken into account.