Oral hormonal contraception (OC) is used by more than 100 million women worldwide. OC prevents ovulation by suppressing circulating sex hormones 17β-estradiol and progesterone. There is now 25 years of evidence establishing the critical role of endogenous gonadal hormones in brain morphology and cognitive function. Assessing the health impact of exogenous manipulation of gonadal hormones is long overdue. There has been no systematic investigation into the short- and long-term consequences of oral hormonal contraceptive use on the brain. To determine the consequences of OC use on brain structure and function we need a large-scale database that combines state-of-the-art MRI sequences with detailed reproductive health histories for every individual.

We created a brain imaging database that pairs participants’ high resolution MR data with de-identified data from an extensive reproductive health survey. With collection sites now active at UCSB and UC Berkeley, our database merges data from female and male volunteers who undergo a brain scan at either UC site. This allows us to rapidly build a large-scale repository of brain imaging data to answer our questions regarding the neural impact of OC on an unprecedented scale.

Our analyses are motivated by four essential questions: 

  • Do long-term OC users show structural changes within estrogen-receptor (ER) rich brain regions compared to never-users?
  • Does the duration of OC use predict the degree of structural change?
  • Which specific hormone formulations (e.g. estradiol dosage or androgenicity of the progestin) and OC schedules (monophasics/triphasics) have the biggest impact?
  • Are some women more or less vulnerable to long-term OC effects based on genetic variability?

Addressing these questions at a population-level will guide tightly controlled follow-up studies.

Our next goal is to grow the initiative to include all eight UC campuses with a research dedicated Brain Imaging Center, integrating the brain imaging communities from across the entire University of California system. This would generate data from ~10,000 unique individuals, annually. A dataset of this scale will allow us to examine overlooked biomedical variables – including the effect of hormonal OCs on the brain – that may be determinants in the mental, reproductive, and physical health of women worldwide. 

This work is supported by the SAGE Center for the Study of the Mind, the Hearst Foundation, the Harvey L. Karp Discovery Award, the Hellman Fellows Fund, and the UCSB Academic Senate.