Finasteride Probe Reveals How Androgens Shape Brain Control Circuits in Heavy Drinkers

Heavy episodic drinking remains one of the most widespread health risks among men, and scientists have long suspected that male sex hormones play a role in why some drinkers lose control over alcohol. A new randomized, placebo-controlled brain imaging study from Germany now offers the first direct experimental test of that idea, using a single dose of the drug finasteride to chemically lower dihydrotestosterone, or DHT, the most potent androgen in the human body. The findings, published in Frontiers in Systems Neuroscience, reveal that two related hormones leave distinct fingerprints on brain activity during impulse control, even though the drug itself produced no measurable change in behavior.

The research team, led by Marlene Kundlacz and Sarah Gerhardt at the Central Institute of Mental Health in Mannheim together with colleagues at Heidelberg University and the University of Mannheim, recruited fifty men who regularly engaged in heavy episodic drinking, defined by the World Health Organization as consuming at least sixty grams of pure alcohol on a single occasion at least monthly. The scale of the problem they were targeting is considerable: in Europe, 56.5 percent of men over fifteen report such heavy drinking episodes, compared with 24.5 percent of women, and roughly 42 percent of people with heavy episodic drinking eventually develop alcohol use disorder.

The scientific logic behind the experiment rests on a chain of prior observations. Higher testosterone levels have been linked to greater alcohol consumption, and patients with alcohol use disorder show elevated testosterone compared with healthy controls. Dihydrotestosterone, which is produced from testosterone by the enzyme 5-alpha reductase II, binds far more strongly to the androgen receptor and is up to six times more potent than testosterone itself. Critically, a rise in DHT during acute withdrawal treatment has been shown to predict worse twelve-month outcomes in patients with alcohol use disorder, including earlier and more frequent alcohol-related hospital readmissions. A separate clinical trial also found that dutasteride, another 5-alpha reductase inhibitor, reduced alcohol intake in heavy-drinking men, making the pharmacological suppression of DHT a promising but poorly understood therapeutic avenue.

To probe the underlying neural machinery, the researchers designed a rigorous crossover trial registered as DRKS00020569. Each participant attended four study visits. At the first and third visits they received either five milligrams of finasteride or a placebo, and the day after each dose they completed a stop-signal task inside a 3 Tesla MRI scanner at the Central Institute of Mental Health. In this classic test of behavioral control, participants pressed buttons in response to left- or right-pointing arrows, but on twenty percent of trials an upward-pointing arrow appeared shortly afterward, signaling them to abort the already initiated movement. The task lasted just under eleven minutes and comprised 320 go trials and 80 stop trials, with successful inhibition rates held between forty and sixty percent, a range that ensures the task is challenging but achievable.

Blood samples drawn at every visit allowed the team to quantify serum DHT and testosterone using enzyme-linked immunosorbent assays. The single finasteride dose reduced DHT levels by 9.6 percent on average, from 353 to 318 picograms per milliliter, a statistically significant drop, while testosterone levels remained unchanged. That reduction was far smaller than the roughly eighty percent suppression documented with long-term finasteride treatment, a discrepancy the authors attribute to the single-dose design and the timing of blood sampling, which occurred on average nearly twenty-two hours after ingestion, potentially past the point of maximal DHT suppression.

The imaging analysis focused on forty-seven participants with usable data, applying whole-brain flexible factorial models that accounted for the crossover structure of the design, with medication, visit sequence, and time point as factors and individual hormone concentrations as covariates of interest. The results were striking in their specificity. Lower DHT levels were associated with stronger activation in the left middle temporal gyrus when participants failed to inhibit a response, while higher testosterone levels predicted stronger activation in the right middle temporal gyrus during successful inhibitions. Both hormones also showed positive associations with temporal activation when successful stops were contrasted directly against failed ones.

These hemispheric patterns fit neatly with existing models of how the stopping brain is organized. Prior work suggests the right hemispheric network is more involved in attending to the stop signal, whereas the left hemispheric network supports the inhibition of the response itself. The authors therefore propose that testosterone may act primarily on the attentional component of stopping, while DHT relates to the inhibitory process proper. Supporting this interpretation, testosterone has previously been found to correlate positively with brain activation during spatial tasks and mental rotation, which also demand attention, and fetal testosterone exposure has been shown to predict gray matter volumes in the left middle temporal gyrus, the very region where the DHT effect emerged.

Yet the study also delivered a sobering null result: neither the finasteride challenge nor the hormone levels produced any significant change in behavioral performance on the stop-signal task, whether measured as stop-signal reaction time, go reaction time, or stop-signal delay. The authors note that changes in neural activation do not necessarily translate into measurable behavioral differences, as subtle shifts in the recruitment of task-related networks can be detectable with functional MRI while remaining too weak to alter performance. The modest 9.6 percent DHT reduction may simply have been too small to push behavior, and the test-retest reliability of the stop-signal task varies across contrasts and brain regions, which can obscure small medication effects.

The researchers are careful to acknowledge that finasteride’s effects may extend beyond simple androgen suppression. The drug also acts on dopaminergic neurotransmission in the mesolimbic system, influences GABAergic signaling, and has been suggested to interfere with the hypothalamus-pituitary-adrenal axis, potentially reducing stress reactivity and impulsive behavior. Chronic alcohol consumption can additionally promote the aromatization of androgens into estradiol, which has independently been implicated in male problem drinking, meaning the observed testosterone effects could partly reflect estrogenic pathways. Speculatively, the authors also note that testosterone shapes social vigilance and trust, and since alcohol is often used to facilitate social interaction, androgen modulation might have influenced neural activation through social-behavioral routes in the unfamiliar experimental setting.

Despite these caveats, the study stands as the first experimental examination of DHT and the interplay between androgens and inhibitory control in heavy-drinking individuals. The clinical implications are tantalizing: if pharmacological modulation of DHT can shift the neural correlates of response inhibition, and if 5-alpha reductase inhibition has already been shown to improve abstinence and drinking outcomes in some heavy-drinking men, then androgen-targeted therapies could eventually join the arsenal against alcohol use disorder. The authors caution that such applications remain premature. Finasteride is generally well tolerated but has been associated with decreased libido, erectile dysfunction, and, less commonly, mood-related symptoms, and persistent sexual dysfunction has been reported in a subset of patients after discontinuation, though the evidence remains heterogeneous. Larger samples, female participants, clinical populations, and longer treatment durations will all be needed before hormone modulation can be seriously considered as a treatment for problem drinking. For now, the study provides a compelling proof of concept that the brain’s braking system is chemically entangled with the body’s most potent male hormones.

Subject of Research: Effects of pharmacologically reduced dihydrotestosterone on brain activation and response inhibition in male heavy drinkers

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

Article References: Kundlacz, M., Boroumand-Jazi, R., Hoffmann, S., Mühle, C., Reinhard, I., Reichl, M., Wenger, L., Tan, H., Bach, P., Vollstädt-Klein, S., Alpers, G. W., Kiefer, F., Lenz, B., & Gerhardt, S. (2026). Pharmacologically altered androgens, brain activation and response inhibition in a stop-signal task in male heavy drinkers. Frontiers in Systems Neuroscience, 20, Article 1907416. https://doi.org/10.3389/fnsys.2026.1907416

Image Credits: AI Generated

DOI: 10.3389/fnsys.2026.1907416

Keywords: dihydrotestosterone, testosterone, finasteride, response inhibition, stop-signal task, fMRI, heavy episodic drinking, alcohol use disorder, impulsivity, androgens, temporal cortex, clinical trial