Abstract
Oral contraceptive (OC) effects on the brain have gained increasing interest, but are highly controversial. Previous studies suggest that OC users have larger hippocampi, parahippocampi, fusiform gyri and Cerebelli. Preliminary evidence from one of those studies even suggests an effect of previous contraceptive use on the hippocampi of women who are not current users of OCs. Furthermore, more recent studies postulate an involvement of previous OC treatment in later development of mood disorders. To address the question whether previous OC treatment affects women’s brain structure later in life, high resolution structural images were obtained from 131 naturally cycling women. Among them, 52 women had never used OC before, 52 had previously used one OC for a continuous time period and 27 had previously used multiple contraceptives. The groups did not differ in gray matter volumes. Since endogenous sex hormones modulate gray matter volumes of the hippocampus and basal ganglia along the menstrual cycle, we hypothesize effects of OC use on these areas. Specifically, we hypothesize that a longer duration of previous OC treatment is related to larger hippocampi and larger basal ganglia. Indeed we found the duration of previous OC use to be positively correlated to hippocampal and basal ganglia volumes bilaterally. For the hippocampus, but not for the basal ganglia, this association disappeared after controlling for the time since discontinuation. These results suggest that for the hippocampus, but not for the basal ganglia, effects of previous contraceptive treatment are reversed after a time period comparable to treatment duration. These data question the immediate reversibility of OC effects on brain structure. Accordingly, some changes in the brain due to long-term contraceptive use, while subtle, may be long-lasting.
Highlights
In developed countries about half of the women at childbearing age rely on hormonal contraception and almost every woman has used hormonal contraception at some point in her life[1]
The present study aimed to investigate the effect of previous oral contraceptives (OC) treatment on gray matter volumes in the hippocampus and basal ganglia
Endogenous estradiol has been shown to relate to increased volumes of the hippocampus, while endogenous progesterone has been shown to relate to increased volumes of the basal ganglia[12,13]
Summary
In developed countries about half of the women at childbearing age rely on hormonal contraception and almost every woman has used hormonal contraception at some point in her life[1]. Studies on endogenous sex hormones suggest a progesterone-dependent increase in right basal ganglia volumes and an increase in right fronto-striatal activation during the luteal cycle phase of the menstrual cycle[12,13,14] These structures are likely targets for the actions of synthetic steroids. Brain structural changes in response to OC intake have not been evaluated in a within-subjects design and only few studies have looked at differences in brain structure between OC users and non-users[17,18,19,20,21,22] These studies suggest larger regional gray matter volumes in the hippocampus, parahippocampus, fusiform gyri and Cerebellum in OC users compared to naturally cycling women[17,18,19]. Anti-androgenic progestins may enhance the actions of ethinylestradiol, while androgenic progestins may exert additional effects in the hippocampus via androgen receptors
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