Pharmacological Studies of Sex Hormone Suppression

The degree to which female reproductive aging leads to macrostructural changes in human brain morphology, changes in brain connectivity, and ultimately changes in cognitive functioning represents a significant knowledge gap that has yet to be adequately examined.  Ovarian hormone suppression (OHS), a widely used treatment for endometriosis, offers a unique clinical scenario through which to study the impact of estrogen and progesterone changes on the brain and cognition. The treatment allows for the temporary and reversible induction of a postmenopausal-like endocrine status, the effects of which can be observed over the course of a few months, and offers a human analogue of animal studies that have provided substantial evidence for the neuroprotective effects of ovarian hormones and their influence on neural function.  

In this study, with Co-PI Matt Panizzon (UCSD), we are examining 200 adult women with endometriosis (ages 25 to 40), half of whom will undergo OHS via the gonadotropin releasing hormone (GnRH) antagonist Elagolix, and half of whom will follow a non-hormonal treatment plan, in order to gain critical insights into how the depletion of ovarian hormones impacts the brain and cognition. 

This $4.8M project funds one of the largest brain imaging studies of the impact of endocrine manipulation on the human brain, with 400 MRI sessions, an expansive fluid biomarker panel, comprehensive neuropyschological tests, immersive virtual reality measures of spatial navigation, multimodal brain imaging (sMRI, fMRI, ASL, DSI, hippocampal subfield imaging), and clinical/mood assessments. Our goal is that this project will make major contributions to our basic understanding of hormone action in the human brain and provide clinical utility for the millions of women world-wide who consider the use of sex hormone-based treatments during their lifetime.

This work is supported by the National Institutes of Health (R01 AG063843) and the Hellman Fellows Fund.

Learn more: 

Taylor C., Pritschet L., Olsen R., Layher E., Santander T., Grafton S.T., Jacobs E.G. Progesterone shapes medial temporal lobe volume across the human menstrual cycle. NeuroImage (In Press) Preprint available: bioRxiv doi:10.1101/934141

"Science for Women", by Sonia Fernandez, UCSB Current, June 2020