Modulation of spatial and response strategies by phase of the menstrual cycle in women tested in a virtual navigation task

• Multiple memory system bias was investigated in young, cycling women.
• Women were tested on a virtual navigation task across the menstrual cycle.
• The mid/late luteal phase biases toward spatial memory.
• Estradiol is associated with enhanced verbal memory.
• Memory bias is influenced by changes in estradiol and progesterone in women.

Different memory systems are employed to navigate an environment. It has been consistently shown in rodents that estrogen impacts multiple memory system bias such that low estradiol (E2) is associated with increased use of a striatal-mediated response strategy whereas high E2 increases use of a hippocampal-dependent spatial memory. Low E2 also enhances performance on a response-based task whereas high E2 levels improve learning on a spatial task. The purpose of the present cross-sectional study was to investigate navigational strategies in young, healthy, naturally cycling women. Participants were split into either an early follicular (i.e., when E2 levels are low), ovulatory (i.e., when E2 levels are high) or mid/late luteal (i.e., end of the cycle, when E2 levels decrease and progesterone levels rise) phase group, using self-reported date of the menstrual cycle. Serum hormone level measurements (E2, progesterone, testosterone) were used to confirm cycle phase assignment. Participants were administered a verbal memory task as well as a virtual navigation task that can be solved by using either a response or spatial strategy. Women tested in the ovulatory phase, under high E2 conditions, performed better on a verbal memory task than women tested during the other phases of the cycle. Interestingly, women tested in the mid/late luteal phase, when progesterone is high, predominantly used a spatial strategy, whereas the opposite pattern was observed in the early follicular and ovulatory groups. Our data suggest that the specific memory system engaged differs depending on the phase of the menstrual cycle and may be mediated by both E2 and progesterone, rather than E2 alone.