Hormonal Biomarkers of Exertional Heat Stroke Susceptibility in Females
Abstract
What Is the Problem: Exertional heat stroke (EHS) is characterized by central nervous system dysfunction in hyperthermic subjects during physical activity. The condition can be lethal or result in long-term health complications later in life. The rate at which women will experience EHS is expected to increase markedly in the upcoming years. This prediction is supported by the increasing participation of women in military specialty roles previously accessible only to men. With the lift of the Combat Exclusion Rule on January 24, 2013, women are eligible to serve in front line combat and complete combat operations. From 2020 to 2021, the U.S. armed services reported an increase of ~12% in EHS cases among female Warfighters. This increasing occurrence of EHS in women is of particular concern to the U.S. armed services because EHS is the most severe manifestation of exertional heat illnesses and one of the main causes of death during physical activity. Environmental aspects such as climate change and increases in heat wave’s frequency and duration are additional contributing factors to the increased occurrence of EHS in women. Females are underrepresented in exercise thermoregulation research. The lack of studies addressing physiological responses of females in extreme environments has generated a knowledge vacuum regarding their susceptibility to heat related illnesses. Understanding the fundamental factors associated with EHS response in women is necessary to develop preventative and treatment strategies tailored specifically to this cohort. Currently, there are no reliable biomarkers to predict susceptibility of EHS in females. Our preliminary observations indicate that the ovarian hormones (e.g., estrogen and progesterone) are strong candidates to predict susceptibility to EHS in this cohort. Whether the ovarian hormones affect the efficacy of heat acclimation (HA) and organ damage in response to EHS remains unknown and will be elucidated here. The studies herein proposed cannot be accomplished using human volunteers because it is unethical to experimentally induce EHS in humans. Thus, we will rely on our clinically relevant and highly reproducible mouse model of EHS to accomplish our experimental goals aimed at improving our ability to predict and prevent EHS in females. Objective: We will determine whether ovarian hormones can be used as biomarkers to predict susceptibility to EHS in females. In addition, we will determine the role of ovarian hormones on HA in females. We will use our reliable mouse preclinical model of EHS to study female responses when the ovaries are intact (SHAM) or removed (OVX). In addition, we will use implanted osmotic pumps containing either estradiol or progesterone to determine which of the two hormones are involved in the heat tolerance phenotype observed in females. We will determine whether HA efficacy to protect against EHS is affected by ovarian hormones. How We Address the FY23 Focus Area: The proposed work meets the intent of the award mechanism and focus area of Military Operational Medicine Research Program under the research area of Environmental Health and Protection. We propose to determine whether ovarian hormones can be used as hormonal biomarkers to predict susceptibility to EHS in females. We will also investigate the influence of ovary-related hormones on HA efficacy and subsequent response (e.g., organ damage and dysfunction) to EHS. We hypothesize that ovarian hormones delay EHS occurrence, attenuate organ damage during recovery from EHS, and facilitate HA in females. Applicability: These preclinical studies will provide critical knowledge regarding the role of ovarian hormones in EHS susceptibility and HA efficacy and will provide foundational data that can be transitioned to human studies to develop more sex-specific HA and clinical treatment protocols to reduce lost duty days, decrease medical care costs and accelerate return to duty f
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310769
Entities
People
- Orlando Laitano
Organizations
- United States Army
- University of Florida