Study of Brain Changes After Stopping or Continuing Second-Generation Combined Oral Contraceptives in Healthy Women Ages 18 to 39

What this Trial Is About

This research aims to understand the possible reversible effects of combined oral contraceptive COC use on the brains serotonin system in healthy women aged 18 to 39. The study focuses on whether stopping COC use leads to an increase in serotonin 4 receptor binding in specific brain areas, measured by PET scans, and over what timeframe this recovery might occur. This trial also explores how stopping COC use may affect mood, memory, sexual desire, insulin sensitivity, anxiety, brain structure, gut microbiome, and sleep. Participants will be randomly assigned to either continue or discontinue their use of a second-generation COC containing 150 micrograms levonorgestrel and 30 micrograms ethinylestradiol for a period ranging from 1 to 52 weeks. They will undergo brain imaging with PET for discontinuers only, MRIfMRI scans, oral glucose tolerance tests, neuropsychological tests, and biological sample collections at the start and follow-up visits. Follow-up timing varies to best capture serotonin receptor recovery, with assessments planned between 1 and 52 weeks after discontinuation or continuation. During the study, participants will complete daily questionnaires about mood, sexual desire, and sleep quality for a month at both baseline and follow-up. Researchers will monitor pill compliance and adjust follow-up assessments if needed. The primary outcome is the change in serotonin 4 receptor binding in key brain regions. Secondary outcomes include changes in memory, brain activity, insulin sensitivity, anxiety, brain structure, gut microbiome, and sleep. The study is designed with interim analyses to optimize timing and will last until December 2030.

Reversible Effects of Oral Contraceptive Removal on Serotonergic Neurotransmission