The Role of Estrogen and Testosterone in Determining Brain Blood Flow and Metabolic Regulation in Humans

Summary

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.

Conditions

• Cerebral Blood Flow
• Cerebral Blood Flow Regulation
• Sex Differences
• Exercise
• Vascular

Interventions

DRUG

GnRH antagonist

blockade of hormone production

DRUG

Estradiol (E2)

Estrogen add-back in females

DRUG

Testosterone

testosterone add-back in males

DRUG

Anastrozole (Arimidex)

Prevention of testosterone conversion to estrogen in males

Sponsors & Collaborators

• University of British Columbia

  lead OTHER

Principal Investigators

• Philip Ainslie, PhD · University of British Columbia

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Weeks

Max Age

40 Weeks

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-04-01

Primary Completion

2026-12-31

Completion

2027-12-31

Countries

• Canada

Study Locations