The Effect of Mild Traumatic Brain Injury on the Hypothalamic-Pituitary-Ovarian Axis: A Narrative Review

Mild traumatic brain injury (mTBI) is the most common type of traumatic brain injury (TBI), with 2.5 million cases reported annually in the United States. mTBI involves diverse signs, symptoms, and functional impairments that typically resolve within 1 month, but may persist. Female sex is one of the most consistent predictors associated with an increased risk of mTBI and worse outcomes, including greater symptom severity and prolonged recovery. Emerging evidence also suggests that females are at greater risk of menstrual cycle dysfunction following mTBI, which could have downstream consequences on reproductive and related women's health outcomes. Researchers have speculated that the underlying mechanism for these detrimental effects is the injury's impact on the hypothalamic-pituitary-ovarian (HPO) axis; however, it is necessary to further clarify the extent of these disruptions, identify consistent patterns across studies, and determine potential implications for reproductive health and hormonal regulation following mTBI. The goal of this narrative review is to understand the effects of mTBI on the HPO axis, identify gaps in the research and clinical practice, and provide recommendations to address these issues in females with mTBI. We summarize: (1) sex differences observed following mTBI, including physiological variables that contribute to these differences, particularly the menstrual and ovulatory cycles in females; (2) pituitary gland functions and hormonal regulations; (3) pituitary and hormonal dysfunction after mTBI; and (4) implications of hormone dysregulation on mTBI recovery. Our review concludes by highlighting methodological gaps, research needs, strategy recommendations, and treatment referrals for patients with HPO axis dysfunction after mTBI.