ORF45-06 - Structural Remodeling of the Pituitary Gland during the Ovulatory Window

INTRODUCTION
The menstrual cycle is characterized by hormonal fluctuations in estrogen (EST) and progesterone (PRG), regulated by the anterior pituitary gland (PG) via follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Despite its central role, structural changes of the PG across the menstrual cycle remain poorly studied, partly due to limitations in non-invasive biomedical imaging. In this study, we developed a tool to segment the PG on MRI and investigated its volumetric changes throughout the menstrual cycle. We hypothesized that PG volume will increase during the ovulatory window.

METHODS
Two publicly available datasets from two healthy women with regular menstrual cycles were analyzed. In the first, a 23-year-old woman underwent daily cerebral MRI and blood sampling for hormone levels (EST, PRG, FSH, LH) over 30 consecutive days of natural cycling (dataset 28andMe). This protocol was repeated a second time under combined oral contraception (COC). The second dataset included a 37-year-old naturally cycling woman who underwent 25 MRI scans and blood draws over 35 days (dataset NeuroCycle+).
PG volume (VPG) was derived from T1-weighted MRI using an artificial intelligence–based algorithm developed and validated in our laboratory. The volume of the precentral gyrus (VPCG), extracted using FASTSURFER, was used as a control region. All data were converted to z-scores. Temporal variations in VPG and hormone levels were assessed using cross-correlation with time lags ranging from −2 to +2 days. Lastly, we analyzed the VPG around ovulation, focusing on the two days before and after, due to increased pituitary hormone secretion during this period.

RESULTS
In both women, VPG remained stable throughout the cycle except for a relatively large, transient increase in the ovulatory window. These changes were not observed during the COC cycle, nor in the PCG control region.
Cross-correlation analysis revealed that VPG was better correlated with serum LH (R² = 0.41, p = 6.9e−14) compared with FSH (R² = 0.15, p = 0.0030), EST (R² = 0.23, p = 1.4e−5) and PRG (R² = 0.03, p = 0.4).

DISCUSSION
To our knowledge, our results are the first to show transient PG expansion during the ovulatory period possibly associated with the surge in LH and FSH. This volumetric change may reflect the expansion of specialized glandular tissue involved in FSH and LH secretion necessary for ovulation. These findings suggest that the PG may undergo acute structural responses and not only chronic adaptations, such as during pregnancy.
In summary, the PG seems to adapt to the ovulatory window to be able to meet the physiological demands of the critical phase.