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Estradiol and progesterone vary along the menstrual cycle and exert opposite effects on a variety of neurotransmitter systems. However, few studies have addressed menstrual cycle-dependent changes in the brain. In the present study we investigate menstrual cycle changes in brain activation and connectivity patterns underlying cognition. Thirty-six naturally cycling women underwent functional MRI during two cognitive tasks: spatial navigation and verbal fluency. While no significant performance differences were observed along the menstrual cycle, the changes in brain activation patterns are strikingly similar during both tasks. Irrespective of the task, estradiol boosts hippocampal activation during the pre-ovulatory cycle phase and progesterone boosts fronto-striatal activation during the luteal cycle phase. Connectivity analyses suggest that the increase in right-hemispheric frontal activation is the result of inter-hemispheric decoupling and is involved in the down-regulation of hippocampal activation.

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Hormonal contraceptives are on the market for more than 50 years and used by 100 million women worldwide. However, while endogenous steroids have been convincingly associated with change in brain structure, function and cognitive performance, the effects of synthetic steroids contained in hormonal contraceptives on brain and cognition have barely been investigated. In this article we summarize the sparse findings, describing brain structural, functional and behavioral findings from the literature and suggest that synthetic steroids may contribute to masculinizing as well as feminizing effects on brain and behavior. We try to identify methodological challenges, explain, how results on endogenous steroids may transfer into research on hormonal contraceptives and point out factors that need to be controlled in the study of hormonal contraceptive dependent effects. We conclude that there is a strong need for more systematic studies, especially on brain structural, functional and cognitive changes due to hormonal contraceptive use. The hormonal contraceptive pill is the major tool for population control. Hence, such behavioral changes could cause a shift in society dynamics and should not stay unattended.