Sex hormones, including estrogens, progestogens, and androgens, exert broad systems-level effects on mammalian biology, reaching far beyond their classic roles in reproduction. The central nervous system is particularly sensitive to circulating sex hormone levels, which are not static, but rather fluctuate across time scales ranging from diurnal to decades (i.e., major hormonal transition periods, including puberty/adolescence, the menstrual cycle, pregnancy, the postpartum period, and menopause). Accumulating reports from both basic science and clinical perspectives highlight that exposure to exogenous hormones, such as via hormone-containing contraceptives in adolescence and adulthood, as well as hormone therapy during and after menopause, also have the potential to result in structural and functional brain changes as well as alter cognitive–behavioral outcomes throughout life. Furthermore, hormone–brain interactions can be influenced by the dynamic interplay between sex hormones and other body systems. For instance, endocrine–immune system interactions may play a role in regulating health outcomes and trajectories of cognitive change.
The brain is a dynamic system with the capacity to respond to and anticipate change throughout the lifespan, which carries implications for many aspects of neurobiology, health, and behavioral outcomes. This Research Topic aims to highlight themes related to mechanisms of endocrine, neural, and cognitive-behavioral changes across the female lifespan. We wish to feature the historically underdiscussed effects of endogenous hormone fluctuations, disruptions to innate cyclicity by means of hormone-containing therapies, and cumulative effects of sex hormone exposures on the brain across the lifetime, with an additional emphasis on endocrine–immune interactions. Collaboration between basic science and clinical researchers is strongly encouraged. As such, we welcome original research report submissions in utilizing animal models and human subjects, as well as review articles encompassing the following topics:
• Longitudinal and cross-sectional brain and behavioral assessments associated with fluctuations in endogenous sex hormones related to:
o puberty
o menstrual cycle
o pregnancy/the maternal brain
o the postpartum period
o the menopause transition/post-reproductive life stage
• Behavioral, pharmacological, and/or neurobiological assessments of exogenous hormone exposures, including estrogen-only, progestogen-only, and combined estrogen+progestogen therapies in the context of hormone-containing contraceptives, menopausal hormone therapies, and gender-affirming hormone therapies
o This includes, but is not limited to: mechanisms of action, timing, duration of administration, composition, and mode of administration
• Novel or alternative treatments to traditional hormone-containing therapies and impacts on brain and behavior
• Neurobiological assessments of brain regions and key neurotransmitter systems impacted by sex hormone exposure/change
• Endocrine–immune interactions at key hormone transition periods in the context of healthy aging, mental health, and disease states
• Brain and behavioral evaluations in the context of the “many menopauses”, including premature ovarian failure, transitional, surgical, or chemo/radiation-induced menopause
• Cognitive and brain changes associated with administration of gender-affirming hormone therapies, with an emphasis on perspectives for longitudinal effects with aging