Premenopausal bilateral oophorectomy leads to steeper declines in gray matter volume and alterations in perfusion and brain bioenergetics.

Hysterectomy is the second most common surgery among women in the United States, often performed alongside elective oophorectomy. Premenopausal bilateral oophorectomy (PO) causes abrupt endocrine disruption and has been linked to increased neurological risks. However, direct evidence for underlying brain changes is lacking. We conducted a prospective, matched cohort multimodality MRI study of pre- vs. post-surgery women to assess the impact of PO on brain volume, cerebral blood flow (CBF), and energy metabolism. The PO group exhibited steeper declines in hippocampal and parahippocampal volume, steeper and accelerating declines in white matter volume, and accelerated increases in superior frontal CBF compared to controls. The PO group exhibited steeper increases in luteinizing (LH) and follicular stimulating hormone (FSH) compared to controls, which were associated with greater hypothalamic and parahippocampal volume declines, respectively, and with increased medial temporal CBF. These data provide first-time evidence that PO alters brain structural and functional trajectories in some hypothalamic-pituitary-gonadal axis regions compared to normal aging, providing a framework for increased long-term neurological vulnerability. We frame current results as exploratory and hypothesis-generating, intended to provide preliminary effect size estimates and inform the design of future larger-scale, longer-term studies.