The association of prolactin and gonadal hormones with cognition and symptoms in men with schizophrenia spectrum disorder: Divergent effects of testosterone and estrogen

Background: Certain antipsychotics elevate prolactin levels in patients with schizophrenia spectrum disorders (SSD), potentially affecting cognition, symptoms, and hormone levels. This study examines the association between prolactin, testosterone, and estrogen and cognition and symptoms in men with SSD, considering antipsychotic medication. Methods: This cross-sectional study included 128 men with SSD and 44 healthy men from two trials. Patients were divided into a prolactin-sparing (n = 53) and prolactin-raising group (n = 75) based on antipsychotic medication. We examined the association between hormones (testosterone, estrogen and prolactin), and cognition and symptoms using backward linear regression. Three domains of cognition were assessed including: processing speed, verbal fluency, and working memory, while symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Results: Prolactin levels were highest in the prolactin-raising group, followed by the control group, and lowest in the prolactin-sparing group (H = 45.279, p < .001). Testosterone and estrogen levels did not differ significantly between groups. In the prolactin-raising group, prolactin negatively correlated with testosterone (r(73) = −0.32, p = .005). Higher testosterone predicted better cognitive functioning (working memory: β = 0.20, p = .007, verbal fluency: β = 0.30, p = .001) and lower symptom scores (total: β = −0.21, p = .001; negative: β = −0.24, p = .002) in men with SSD. Conversely, higher estrogen levels related to slower processing speed (β = −0.22, p < .001) and higher symptoms scores (β = 0.23, p = .010) in men with SSD. Conclusion: The results suggest positive associations between testosterone and cognition and symptoms in men with SSD, while suggesting that high prolactin levels could relate to lower testosterone levels, possibly worsening cognition and symptoms in men with SSD.