Cognitive Function and Serum Hormone Levels Are Associated with Gray Matter Volume Decline in Female Patients with Prolactinomas

Abstract

Background and objectiveCognitive impairments have been reported in patients with hyperprolactinemia; however, there is a lack of knowledge of brain structure alterations relevant to hyperprolactinemia in prolactinomas. Thus, we aimed to identify changes in brain structure in prolactinomas and to determine whether these changes are related to cognitive performance and clinical characteristics.MethodsParticipants were 32 female patients with prolactinomas and 26 healthy controls (HC) matched for age, sex, education, and handedness. All participants underwent magnetic resonance imaging brain scans, neuropsychological assessments, and clinical evaluations. Voxel-based morphometry analysis was used to identify changes in gray matter volume (GMV). Partial correlation analysis and multiple linear regression were performed to determine the relationship between GMV, cognition, and clinical characteristics.ResultsCompared to HC, patients with prolactinomas demonstrated a decrease in GMV in the left hippocampus, left orbitofrontal cortex, right middle frontal cortex (MFC), and right inferior frontal cortex (IFC). In addition, patients performed worse than controls on tests for verbal memory and executive function, and this was significantly related to the GMV of the left hippocampus and right MFC, respectively. Moreover, in the patients, we found a negative relationship between serum prolactin levels and the GMV of the left hippocampus and right IFC, whereas a positive relationship was found between the GMV of the left hippocampus and serum levels of estradiol and luteinizing hormone.ConclusionIn patients with prolactinomas, specific brain structure abnormalities have been identified and are associated with cognitive impairments and dysfunctional hormones. This study enhances our understanding of brain structure changes that may occur with prolactinomas and provides novel and fundamental evidence for previous behavioral findings relevant to hyperprolactinemia.

Grey matter differences associated with age and sex hormone levels between premenopausal and perimenopausal women: A voxel‐based morphometry study

“…Goto et al attributed grey matter shrinkage in the hippocampus to sex hormone levels. Indeed, studies have shown that certain types of hormones, such as PRL and E 2 , have an impact on the hippocampus . In the present study, a majority of the enrolled women had normal sex hormone levels and smaller age differences compared to previous studies .…”

“…Indeed, studies have shown that certain types of hormones, such as PRL and E 2 , have an impact on the hippocampus. 27,50 In the present study, a majority of the enrolled women had normal sex hormone levels and smaller age differences compared to previous studies. 9,10 Therefore, our negative findings in the hippocampus may be caused by less demographic diversity and smaller hormonal fluctuations compared to the previous studies.…”

“…Although sex hormones are well known for their role in procreation and the development of sex organs, they also play a critical role in brain plasticity and overall development with participation in the neuroendocrine phenomena and the establishment of behavioural patterns, including mood and cognition . Studies have confirmed that sex hormone receptors are located in the brain and that the expression of such receptors has a profound impact on brain structure, function and the formation of certain brain regions . These receptors include the PRL receptor, LH receptor and FSH receptor .…”

“…27 Studies have confirmed that sex hormone receptors are located in the brain and that the expression of such receptors has a profound impact on brain structure, function and the formation of certain brain regions. 27,28 These receptors include the PRL receptor, 27 LH receptor 28 and FSH receptor. 29 In addition, VBM studies reported brain morphological changes after hormone therapy, 11,12 which further confirmed the effect of sex hormones on brain morphology.…”

Hormone Levels Are Related to Altered Functional Connectivity in Prolactinomas

“…We have previously investigated the influence of endogenous 56 hormones on brain gray matter and neurocognition in prolactinoma patients. 1 However, functional 57 connections in prolactinoma patients have scarcely been explored. Recently, the resting-state 58 functional magnetic imaging (rsfMRI) has become a useful tool to characterize the brain's 59 functional connectivity (FC) pattern that is considered a potential metric reflecting the temporal 60 dependence of neuronal activation patterns of spatially separated brain areas.…”