Sex-specific prolactin disturbance and divergent gonadal hormone correlates in first-episode schizophrenia

Hyperprolactinemia and altered prolactin (PRL) levels are well-documented in schizophrenia. However, very few studies have investigated sex-specific differences in the prevalence of PRL disturbances in first-episode patients with schizophrenia. This cross-sectional study investigated sex-specific PRL dysregulation and its interplay with gonadal hormones in first-episode schizophrenia (FES) patients.

One hundred eighty-nine first-episode patients (96 males, 93 females) with minimally treated (≤2 weeks) were recruited. PRL levels and gonadal hormones were measured in all participants.

We found a significantly higher prevalence of abnormal PRL levels in males compared to females (32.3% vs 8.6%, χ2 = 16.2, P < .001). Comparative analysis of gonadal hormones between elevated PRL (n = 39) and normal PRL (n = 150) groups demonstrated elevated follicle-stimulating hormone (Z = 2.7, P = .007) and testosterone (Z = 3.7, P < .001) in the hyperprolactinemic group. In the elevated PRL group, PRL positively correlated with progesterone and testosterone, whereas in the normal PRL group, PRL showed positive associations with estradiol and luteinizing hormone, but negative correlations with progesterone.

Our findings underscore the complex and sex-specific nature of PRL dysregulation and its association with gonadal hormones in FES patients. Significance Statement This work analyses the sex-specific pattern of prolactin (PRL) disturbance in antipsychotic-naïve or minimally treated first-episode schizophrenia (FES), the earliest clinical manifestation of the disorder. While hyperprolactinemia is well documented, its sex-stratified links to gonadal hormones at illness onset remain unclear. We therefore reassessed PRL and gonadal hormone levels in 189 drug-naïve or minimally treated FES patients. Results showed that abnormal PRL levels were almost four times more common in males than in females. Hyperprolactinemic patients displayed elevated testosterone and follicle-stimulating hormone, whereas normal-PRL patients exhibited inverse PRL-progesterone relationships. These findings reveal a sex-divergent neuroendocrine signature at psychosis onset, underscoring the need for sex-specific endocrine monitoring and personalized early intervention strategies that target PRL-gonadal hormone pathways.