| |
| author |
Miles Madewell
| | title |
Sex as a Biological Variable in Neuroendocrinology
| | abstract |
The National Institutes of Health (NIH) policy requiring consideration of sex as a
biological variable (SABV) was introduced to address long-standing sex biases in biomedical
research and to improve the generalizability of findings. Although this has increased the
inclusion of females, many studies still treat sex differences descriptively, without explaining the
biological processes that produce variability. This review focuses on whether fluctuations in
ovarian hormones, particularly estradiol, can account for this variability in a systematic,
state-dependent way rather than as unstructured variability. Literature was collected through a
systematic methodology on PubMed Central with a focus on peer-reviewed studies on estradiol's
effects on neural plasticity, circuit function, and behavior in mammalian models, and findings
were considered across hippocampal, corticolimbic, and mesolimbic systems with attention to
differences in hormone state, task design, and behavioral measures. Outcomes vary with circuit
engagement and task demands: in the hippocampus, estradiol is most closely linked to memory
consolidation; in corticolimbic circuits it modulates fear extinction and regulation; and in
mesolimbic systems, it influences motivation and reward sensitivity. Apparent inconsistencies
across studies are better explained by differences in how tasks recruit neural systems and may be
traced to differences in experimental design and the neural systems being tested. This
interpretation is limited by reliance on rodent models, variability in estrous cycle staging, and the
use of ovariectomized designs that simplify endogenous hormonal dynamics. In addition,
focusing on estradiol limits consideration of interacting hormones such as progesterone, which
may alter or counter some of the effects described. Overall, the evidence suggests that
hormone-linked variability resembles organized modulation of neural systems, and considering
hormonal state in this way allows SABV to move beyond group comparisons toward a more
mechanistic understanding of brain–behavior relationships.
| | school |
The College of Liberal Arts, Drew University
| | degree |
B.S. (2026)
|
| advisor |
Christina McKittrick
|
| full text | MMadewell.pdf |
| |
