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

Starting soon · Not applicable

Conditions studied: Cerebral Blood Flow, Cerebral Blood Flow Regulation, Sex Differences, Exercise, Vascular

In brief

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.

Key facts

Study ID

NCT07212712

Run by

University of British Columbia

People needed

50

Starts

2026-04-01

Expected to finish

2027-12-31

Last updated by the study team

2026-02-10

Who can join

Age: 0 and older, up to 1. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• The investigators will recruit healthy young (18-40 years) males (n = 25) and females (n = 25). Females must be naturally cycling (i.e., no oral or hormonal contraceptives), not pregnant, and premenopausal. Participants must be normotensive (<140/90 mmHg \& >90/60 mmHg) and have no medical history of cerebrovascular, cardiopulmonary, cardiovascular, neuromuscular, and renal disease assessed by a study questionnaire. A recent physical examination (within 1 year of participation) from a family physician or a completed physical examination by the study doctor is required prior to participation. All subjects will sign an informed consent form prior to participation.
• Participants will be excluded if they meet any of the following criteria:
• 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)
• Males with hypogonadism (total testosterone ≤ 262 ng/dL, per Endocrine Society recommendations)
• Any history of cerebrovascular, cardiopulmonary, cardiovascular, neuromuscular, or renal disease
• Any liver dysfunction or disease
• Taking any cardiovascular medications or medications that would interfere with study medications (e.g., strong organic anion transporting polypeptide 1B1 inhibitors)
• Contraindications or sensitivities to study medications
• Current eating disorder (defined as >2 on the 'SCOFF' questionnaire 67)
• Current smokers
• Females with an irregular menstrual cycle or any medical conditions affecting the menstrual cycle (normal cycle defined as 21-35 days from menstrual cycle diary)
• Females who are pregnant (assessed with pregnancy test at screening and prior to starting medications), breastfeeding, or planning to conceive within 3 months
• Females using hormonal birth control (Copper intrauterine devices [IUDs] will be allowed as they do not change systemic hormone levels)
• Females who are peri- or postmenopausal (as determined by STRAW criteria 68)
• History of hormone-sensitive cancers (i.e., breast, ovarian, uterine or prostate)
• Z-score < -2 as assessed with DXA scan (to determine risk of decrease in bone mineral density)
• Assessed using the Center for Epidemiologic Studies Depression (CES-D) scale, participants with a score > 16 at screening unless otherwise approved by the study MD

Where it is running

• University of British Columbia - Okanagan — Kelowna, British Columbia, Canada

Full record on ClinicalTrials.gov

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