The goal of this study is to learn about potential reversible effects of combined oral contraceptive (COC) use on the serotonergic brain system. The main question it aims to answer is:
\- If COC discontinuation results in an increase in serotonin 4 receptor binding in caudate, putamen, and hippocampus measured with Positron Emission Tomography from baseline to follow-up ≥ week 8 after discontinuation.
The secondary question it aims to answer is:
\- Over what timeframe the serotonin 4 receptor binding is restored after COC discontinuation to the level previously seen in a group of premenopausal women who had not used hormonal contraception before.
Researchers will compare discontinuation with continuation of a 2nd generation COC containing 150 ug levonorgestrel and 30 microgram to see if COC discontinuation results in an increased serotonin 4 receptor level in the brain.
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Participants will:
* Be randomized to discontinue or continue their COC use for 1-52 weeks. * Undergo an investigational program including brain scans, biological sampling, and neuropsychological testing at baseline and at follow-up.
The study uses a group sequential design with two sequential analyses planned, including an interim analysis after 60% of the brain scans have been acquired, which will be used to decide the timing of the last 40% of the scans - this is performed to best determine when the recovery of the serotonin 4 receptor level occurs.
Healthy women (assigned female at birth) at 18-39 years of age
Currently using a second-generation combined oral contraceptive containing 150 ug levonorgestrel and 30 ug ethinylestradiol for at least 3 months
Current or previous neurological or psychiatric disease, severe somatic disease, or consumption of medical drugs (including psychoactive medication) likely to influence the test results
Non-fluent in Danish or pronounced visual or auditory impairments
Current or past learning disability
Pregnancy within the last year or previous pregnancy lasting into second or third trimester