Estrogen and Testosterone for Gender Differences in Physiology

Overseen By Lauren Maier, MSc

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Must not be taking: Cardiovascular medications

Disqualifiers: Hypertension, Hypotension, Smoking, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how brain blood flow differs between males and females due to sex-specific hormones like estrogen and testosterone. Researchers will temporarily block hormone production using a GnRH antagonist, a drug that suppresses hormone production, and then reintroduce these hormones, including Estradiol (E2), to observe their effects on brain blood flow during rest and stress. Healthy men and women who are not on hormonal birth control and have a regular menstrual cycle may be suitable candidates for this study. The goal is to improve treatments for brain-related conditions by tailoring them based on these hormonal differences. As an unphased trial, this study offers participants the opportunity to contribute to groundbreaking research that could lead to personalized treatments for brain-related conditions.

Will I have to stop taking my current medications?

The trial requires that participants do not take cardiovascular medications. If you are on such medications, you would need to stop taking them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that estradiol (E2) can be used safely. One study found that taking 1.4 to 6 mg per week is generally well-tolerated and helps achieve the desired hormone levels, with most individuals experiencing few issues. However, some studies have mentioned possible safety concerns, so consulting healthcare providers is important.

For GnRH antagonists, the information is mixed. Some evidence suggests they might cause heart problems in men, but they seem safer for women. More research is needed to fully understand their safety.

Using testosterone in controlled amounts appears safe, with no serious side effects. Studies suggest that testosterone is generally well-tolerated, especially in women.

Overall, these treatments look promising, but individual reactions may vary. Consulting medical professionals and having regular check-ups during any treatment is crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how manipulating hormone levels can reveal differences in male and female physiology. Unlike typical treatments that maintain consistent hormone levels, this approach temporarily blocks natural hormone production and then adds back specific hormones like Estradiol and Testosterone. This method offers a unique opportunity to understand the role of hormones in the body by using participants as their own controls, potentially shedding light on gender-specific physiological processes.

What evidence suggests that this trial's treatments could be effective for regulating brain blood flow?

This trial will explore the effects of hormone manipulation on physiology. Participants will undergo three phases: first, with no hormone manipulation; second, with a blockade of hormone production using GnRH antagonists; and third, with hormone add-back using Estradiol (E2) and Testosterone. Studies have shown that estrogen is crucial for controlling the female reproductive system and affects blood flow to the brain. Improved blood flow to the brain is linked to better brain health, and research suggests that estrogen might be responsible for this in females. Testosterone, in contrast, influences physical abilities and the immune system. Both hormones are believed to impact brain health by aiding blood flow and overall brain function. Additionally, GnRH antagonists temporarily stop hormone production, allowing researchers to study the specific effects of these hormones. These treatments help scientists explore how male and female bodies, especially their brains, function differently. ^{6 7 8 9 10}

Who Is on the Research Team?

Philip Ainslie, PhD

Principal Investigator

University of British Columbia

Are You a Good Fit for This Trial?

This trial is for healthy males and females interested in contributing to research on how sex hormones like estrogen and testosterone affect blood flow to the brain. Participants should not have any blood vessel disorders or issues with motor skills, and must be willing to undergo hormone treatments.

Inclusion Criteria

All subjects will sign an informed consent form prior to participation

I am a woman not using hormonal birth control, not pregnant, and before menopause.

I am a healthy person aged 18-40.

Exclusion Criteria

Individuals with a current eating disorder (>2 on the 'SCOFF' questionnaire)

I have a history of heart, lung, brain, muscle, or kidney disease.

I am a smoker or take heart medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Hormone Manipulation

Participants undergo hormone manipulation through gonadotropin releasing hormone (GnRH) antagonist and hormone add-back, completing the experiment three times: no hormone manipulation, blockade of hormone production, and hormone add-back.

14 days

Testing

Participants undergo various tests to assess the influence of estrogen and testosterone on cerebral blood flow, ventilatory responses, functional sympatholysis, appetite sensations, neuromuscular responses, and mitochondrial profiles.

14 days

Follow-up

Participants are monitored for safety and effectiveness after hormone manipulation and testing.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Estradiol (E2)
• GnRH antagonist
• Testosterone

Trial Overview The study investigates the direct role of sex-specific hormones (estrogen in females, testosterone in males) on cerebral blood flow regulation. It involves blocking natural hormone production then administering these hormones artificially while monitoring brain blood flow during rest and stress.

How Is the Trial Designed?

Group I: Hormone Manipulation Experimental Treatment 4 Interventions

Participants will act as their own controls, completing the experiment 3 times. First, with no hormone manipulation; second, with blockade of hormone production; third, with hormone add-back.

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9781566/

Level of Estrogen in Females—The Different Impacts at ... Estrogen is known to be responsible for the development and regulation of the female reproductive system and secondary sex characteristics.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0171298523000281

Physiological estrogen levels are dispensable for the sex ... In summary, data from this study confirms that female mice develop stronger innate and adaptive immune responses to allergen-induced airway inflammation, but ...

3. withpower.com withpower.com/trial/phase-vascular-2-2026-46659

Estrogen and Testosterone for Gender Differences in ... Females consistently experience greater risk and report worse neurological outcomes in many diseases, including stroke, cardiac arrest, and ...

4. nature.com nature.com/articles/s41598-025-17874-6

Role of 17β-estradiol injection on growth, physiology, and ... The results clearly indicate that male-female interactions (MF group) without E2 treatment promoted the best overall growth performance, ...

5. biorxiv.org biorxiv.org/content/10.1101/2020.04.27.064451v1.full-text

Transcriptome Sequencing Reveals Sex Differences in ... This revealed that male cells responded more strongly to E2 treatment than female cells. In general, more DEGs were seen from groups treated ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11454064/

6961 Evaluation of Safety and Efficacy of Administration ... These results demonstrate that SC E2 at doses of 1.4-6 mg/week can be administered safely to achieve therapeutic serum E2 levels and suppress serum T levels.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11220669/

Effectiveness and Safety of Different Estradiol Regimens in ... Most transgender women achieved cisgender women testosterone levels within 2 months on 1 or 2 0.1 mg/24 hours estradiol patches. Given no ...

8. link.springer.com link.springer.com/article/10.1007/s44192-025-00216-3

Emerging and accumulating safety signals for the use of ... This paper compiles several emerging and accumulating safety signals in the medical literature. These range from increased rates of previously associated ...

9. academic.oup.com academic.oup.com/clinchem/article/71/8/842/8115917

Comprehensive Review of Estradiol, Progesterone ... Here we examine the role of estrogen in women's physiology, taking a systematic approach to reviewing the literature for modern reference ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S0160412019331873

Trimester-specific, gender-specific, and low-dose effects ... The negative associations between the 1st-trimester concentrations of BPA and E2 were observed among mothers delivering male fetuses, while no significant ...