Effects of oral hormonal contraceptives (OC) on human brain structure and behavior
have only recently become a focus of research. Two explorative reports observed larger
regional gray matter (GM) volumes in OC users within the prefrontal cortex, ACC and
fusiform gyri, as well as parahippocampal gyri, hippocampus and cerebellum. These
studies did however not control for the androgenicity of the progestin compound of
OC, did not take into consideration how long OC users had been on their OC, and did
not control for age differences between the OC group and the naturally cycling group.
We compared 20 naturally cycling women during their early follicular cycle phase to
18 users of OC containing androgenic progestins and 22 users of OC containing anti-androgenic
progestins. When controlling for age, we found that in users of anti-androgenic progestins
relative GM volumes within the bilateral fusiform gyri, fusiform face area (FFA),
parahippocampal place area (PPA) and cerebellum, were significantly larger than in
naturally cycling women, while in users of androgenic progestins, relative as well
as absolute volumes within the bilateral middle and superior frontal gyri were significantly
smaller compared to naturally cycling women. These morphological changes were related
to performance in a face recognition task. Face recognition performance was significantly
better in users of anti-androgenic progestins compared to the other groups and significantly
related to absolute as well as relative GM volumes in the FFA and PPA. Total GM volume,
as well as absolute GM volumes within the bilateral fusiform gyri, FFA, hippocampus,
parahippocampus, PPA, middle frontal gyri and ACC were significantly larger, the longer
the duration of OC use, particularly in users of androgenic progestins. Morphological
differences between active and inactive pill phase were observed in users of androgenic
progestins. These findings suggest differential effects of androgenic and anti-androgenic
progestins on human brain structure.