Striatal dopamine synthesis and cognitive flexibility differ between hormonal contraceptive users and non-users

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine neurotransmission. Yet little is known about hormonal regulation of the dopamine system in the human brain. Using Positron Emission Tomography (PET), we address this gap by comparing hormonal contraceptive users and non-users across multiple aspects of dopamine function: dopamine synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and dopamine release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n=21 naturally cycling; n=15 hormonal contraceptive users), and men (n=20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater dopamine synthesis capacity than naturally cycling participants, particularly in dorsal caudate, and greater cognitive flexibility. Further, across individuals the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or dopamine release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to womens hormone status. Hormonal contraception (in the form of pill, shot, implant, ring or IUD) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the dopamine system. Findings from this study begin to address this critical gap in womens health.