Due to historical exclusion of females from research, there are gaps in the understanding of female physiology, how it differs from males, and how sex-specific hormones contribute. As a result, many diagnoses and treatments are based on male physiology and may not be appropriate or effective for females. Females consistently experience greater risk and report worse neurological outcomes in many diseases, including stroke, cardiac arrest, and dementia. As research in females progresses, differences between sexes and changes throughout the lifespan (e.g., puberty, menopause) highlight the importance of understanding the effects of sex and sex-specific hormones on the body. The brain is arguably the most important organ in the body, consuming 20% of the body's total energy. Previous research supports higher blood flow to the brain in females, and research in animals suggests hormones such as estrogen, progesterone, and testosterone are responsible. However, it is extremely difficult to isolate these hormones in humans, due to natural fluctuations (i.e., menstrual cycle). Therefore, the investigators plan to explore the direct role of these sex-specific hormones in regulating blood flow to the brain by blocking hormone production in healthy males and females and giving back testosterone and estrogen, respectively. The investigators will then conduct a range of tests to look at blood flow to the brain at rest and during various stressors. This research will provide crucial insight into how males and females differ in regulation of brain blood flow and inform new treatments and therapies to a wide range of brain injuries and diseases, improving outcomes and reducing the sex disparity in clinical pathways.
Hypertensive (≥140/90 mmHg) or hypotensive (≤90/60 mmHg)
BMI ≥ 30 kg/m2
Fasting blood glucose ≥ 100 mg/dL
Abnormal results on standard blood hematology tests (e.g., complete blood count, comprehensive metabolic panel)
None
Single group
GnRH antagonist
Drugblockade of hormone production
Estradiol (E2)
DrugEstrogen add-back in females
Testosterone
Drugtestosterone add-back in males
Anastrozole (Arimidex)
DrugPrevention of testosterone conversion to estrogen in males
Cerebral blood flow responses to estrogen and testosterone
To determine how cerebral blood flow regulation is altered by estrogen and testosterone concentrations. Measured through doppler ultrasonography, and reported in mL/min.
Cerebral metabolic changes with estrogen and testosterone
Measured as cerebral metabolic rate of oxygen consumption. Determined using arterial and internal jugular vein blood sampling coupled with doppler ultrasound, to determine metabolism directly using the Fick method.
Hormone influences on appetite sensations
How estrogen and testosterone influence appetite sensations (visual analog scale)
How estrogen and testosterone influence energy intake
dietary intake, measured with self-report questionnaire
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