Evaluating the Role of Testosterone in Amyotrophic lateral Sclerosis

Background Dihydrotestosterone (DHT) is implicated in Amyotrophic lateral sclerosis (ALS) pathogenesis. Our previous study found deficiency of DHT in cerebrospinal fluid (CSF) of ALS patients leading us to postulate that DHT was integral to survival of motor neurons . This study explored whether correction of the DHT deficiency using testosterone injections could benefit ALS patients. Methods 9 ALS patients were given intra-muscular testosterone injections with dosages being incremented gradually . As DHT itself does not cross the blood-brain barrier (BBB) , CSF and brain levels of DHT can only be increased through administration of testosterone which crosses the BBB and then gets converted to DHT Results Varying degree of reduction in fasciculations was seen in ALS patients during administration of higher doses of testosterone . Stabilization or increments in ALSFRS-R scores were seen in a fraction of treated patients. Conclusions Testosterone may have a therapeutic role in ALS, especially for control of fasciculations. However more data from randomized controlled trials and meta-analyses evaluating testosterone in ALS would be required before reaching any further conclusion . We also postulate that Neanderthal-Denisovan DNA introgression plays a role in ALS .