Pharmacologically altered androgens, brain activation and response inhibition in a stop-signal task in male heavy drinkers

Heavy episodic drinking (HED) is highly prevalent in men and a major risk factor for Alcohol Use Disorder (AUD). Previous studies indicated an influence of testosterone (T) on AUD, and dihydrotestosterone (DHT) was linked to alcohol consumption, impulsivity, and response inhibition. As the role of androgens in AUD and the modulation thereof is not fully understood, this study investigated the effect of a pharmacological reduction in DHT by inhibition of the 5-alpha reductase II with finasteride on brain activation and response inhibition during a stop signal task. Fifty males with HED participated in a randomized, placebo-controlled, double blind, cross-over, functional magnetic resonance imaging (fMRI) study. Participants received either 5 mg finasteride or placebo, resulting in a 9.6% reduction of DHT levels. Full factorial fMRI models and linear mixed models were used to estimate whole-brain effects of DHT and testosterone following finasteride and placebo on neural correlates of behavioral control ( N = 47 analyzable participants). While no medication effects were observed on behavioral or neural levels, lower levels of DHT and higher levels of testosterone were related to stronger neural activation in temporal regions during response inhibition for successful or unsuccessful stop-trails, respectively. However, no significant influence of hormone levels on behavioral data of the stop signal task was observed. Although the precise mechanisms underlying the effects of pharmacologically altered DHT levels on neural correlates of response inhibition remain unresolved, both DHT and testosterone appear to be specifically associated with neural activation during response inhibition. These preliminary findings may provide a rational for future studies investigating pharmaceutical modulation of androgens as a potential therapeutic approach for problem drinking, and potentially AUD. Clinical trial registration https://drks.de/search/de/trial/DRKS00020569 , identifier DRKS00020569.