The ratio between progesterone and estradiol levels can predict performance in a learning and memory task involving fear extinction, according to a study led by the Institute of Neurosciences of the Universitat Autònoma de Barcelona (INc-UAB).
Published in Neurobiology of Stress, the research involved both mice and healthy human participants—including men, naturally cycling women, and women taking oral contraceptives.
Key Details
The study used a fear-conditioning paradigm. On day one, participants learned to associate a neutral stimulus with a mild electric shock. On day two, researchers assessed fear extinction—the ability to stop fearing the stimulus when it was no longer paired with the shock.
Hormone levels were measured in saliva (humans) and blood (mice). Using a machine-learning model, the team identified that a higher progesterone-to-estradiol ratio before the second session best predicted successful fear extinction in both species.
This predictive value applies to both men and women, as both produce these hormones, though women generally have higher levels.
Among female participants, fear extinction memory was most effective at the end of the follicular phase (just before ovulation), suggesting this period offers a hormonal environment conducive to forming new memories.
Implications
The findings could help identify biologically optimal times for learning or memory-related tasks, such as studying for exams.
The progesterone-to-estradiol ratio may serve as a biomarker to optimize psychological therapy for anxiety- and trauma-related disorders like PTSD, phobias, and panic attacks.
Further validation in larger, diverse cohorts and investigation of other memory types are planned.
The study was conducted in collaboration with the Hospital del Mar Research Institute in Barcelona.