# Dihydrotestosterone and Finasteride Effects on Alcohol Cue‐Elicited Brain Activity in Males With Heavy Episodic Drinking

## TL;DR

This study explores how reducing dihydrotestosterone with finasteride affects brain activity and alcohol craving in men who drink heavily.

## Contribution

The study provides new insights into the neurobiological effects of finasteride on alcohol cue processing, independent of dihydrotestosterone levels.

## Key findings

- Finasteride increased brain activation in the caudate nuclei, superior frontal gyrus, and insula during exposure to alcohol cues.
- Finasteride was associated with a stronger wish to not drink alcohol compared to placebo.
- Dihydrotestosterone concentrations were not significantly linked to brain activation or craving.

## Abstract

Preliminary animal and human studies have shown that blood dihydrotestosterone concentrations are increased in males with alcohol use disorder, and 5α‐reductase inhibitors, which decrease dihydrotestosterone concentrations, reduce alcohol consumption. To gain mechanistic insight, we studied the effects of reduced dihydrotestosterone concentrations following pharmacological 5α‐reductase inhibition on alcohol cue‐elicited brain activity and alcohol craving in males with problematic alcohol use. To this end, this randomized, placebo‐controlled, crossover challenge experiment investigated associations between dihydrotestosterone concentrations and brain functional magnetic resonance imaging (fMRI) activity during exposure to visual alcohol cues and alcohol craving following a single dose of 5 mg finasteride versus placebo in 50 males with heavy episodic drinking. We used finasteride because it specifically inhibits 5α‐reductase II activity, which is the main enzyme converting testosterone to dihydrotestosterone. Dihydrotestosterone concentrations were lower in the finasteride condition in comparison to the placebo condition, but not significantly associated with brain activation patterns or craving. In the exploratory analyses, we found higher brain activity during exposure to visual stimuli in the right and left caudate nuclei, the right superior frontal gyrus and the left insula in the finasteride condition versus the placebo condition. Moreover, finasteride versus placebo was associated with a higher wish to not drink alcohol. The results of this experimental study do not support the à priori hypothesis that dihydrotestosterone concentrations play a role in brain activation during exposure to visual alcohol cues, but indicate that finasteride effects may be mediated by other pathways. Future studies are requested to investigate the effects of reduced dihydrotestosterone concentrations over a longer time and to shed light on the molecular mechanisms underlying the here observed effects of finasteride.

Trial Registration: DRKS00020569

In a randomized, double‐blind, placebo‐controlled crossover study, we investigated whether finasteride‐induced reduction of dihydrotestosterone alters alcohol cue‐elicited brain activity and craving in males with heavy episodic drinking. Although dihydrotestosterone concentrations were not associated with neural cue reactivity, finasteride increased brain activation in the right and left caudate nuclei, right superior frontal gyrus, and left insula in response to visual alcohol cues, and enhanced the wish to not drink alcohol. These findings suggest that finasteride effects on alcohol cue processing may be mediated by dihydrotestosterone‐independent neurobiological mechanisms.