Sulphated dehydroepiandrosterone serum levels are reduced in women with alcohol use disorder and correlate negatively with craving: A sex‐separated cross‐sectional and longitudinal study

Previous studies have established a role of sex hormones in alcohol use disorder (AUD).Only few clinical investigations with low numbers of patients with AUD have focused on the sulphated form of dehydroepiandrosterone (DHEA‐S), despite its function as a neuromodulating sex steroid on receptors in the central nervous system (γ‐aminobutyric acid type A, N‐methyl‐D‐aspartate, sigma‐1 receptors). DHEA‐S serum levels were compared between 200 inpatients with AUD (44% women) admitted for withdrawal treatment and 240 healthy controls (45% women) and analysed longitudinally in patients from early abstinence (baseline) to a median of 5 days later. We also correlated DHEA‐S levels with craving, liver enzyme activities, and prospective alcohol‐related readmissions during a 24‐month follow‐up. DHEA‐S concentrations were lower in female patients than in female healthy controls during baseline (70%) and decreased from baseline to follow‐up in the female and male patients groups (down to: women, 92%; men, 76%). Baseline DHEA‐S concentrations correlated with the total and obsessive subscales of the Obsessive–Compulsive Drinking Scale and with maximum visual analogue scale craving scores in female patients (Rho ≤ −0.240) and gamma‐glutamyl transferase activity in female (Rho = −0.292) and male (Rho = −0.391) patients. DHEA‐S did not significantly predict outcome. We found interactions with smoking behaviour and age. This is the first study based on large cohorts of inpatients with AUD undergoing a qualified detoxification treatment to provide sex‐separated evidence for associations of DHEA‐S serum concentrations with AUD and related phenotypes. The results stimulate further investigations whether DHEA‐S directly influences alcohol craving building a basis to develop sex‐sensitive prevention and treatment strategies. HEA‐S serum levels were lower in female patients with AUD than in female healthy controls and decreased during early withdrawal in female and male patients with AUD. DHEA‐S serum levels correlated negatively with craving for alcohol in female patients with AUD and liver enzyme activity in female and male patients with AUD. Here, DHEA‐S was not significantly associated with prospective 24‐month alcohol‐related hospital readmissions in female or male patients with AUD.