FORT WORTH, Texas -- A single dose of the female hormone estrogen could protect the brain after a traumatic injury, but researchers won't know for sure until they test it on humans.

That's what they're doing beginning this week as part of a clinical trial at Parkland Memorial Hospital in Dallas. The participants won't know whether they get estrogen or a placebo. And they won't be able to give their OK before receiving it.

The hormone must be given within two hours of a traumatic brain injury, making it virtually impossible to get informed consent, said Dr. James Simpkins, chair of pharmacology and neuroscience at the University of North Texas Health Science Center in Fort Worth. He is working with a researcher from the University of Texas Southwestern Medical Center at Dallas to translate animal studies to humans.

"If we wait until we can get consent from the person when he recovers consciousness, it will be too late,'' Simpkins said. "It is crystal-clear that if one waits six hours, 10 hours or more, the ability to protect the brain goes down dramatically.''

The groundbreaking research will focus on whether estrogen and anti-inflammatory drugs can prevent secondary injuries and improve outcomes in humans. It will involve 50 men ages 18 to 50 who have suffered a brain injury or severe blood loss, most likely after an auto, motorcycle or boating accident.

The study will target men because 70 percent of patients with brain injury or blood loss are young males. Studies have suggested young women, who have high amounts of estrogen, are more resistant to brain trauma than men or older women.

The rapid administration of estrogen holds promise as a way to reduce neurological deficits and increase survival after a devastating injury, said Dr. Jane Wigginton, assistant professor of emergency medicine at UT Southwestern Medical Center.

Studies performed without a patient's consent have long raised ethical concerns. A large trial involving a blood substitute stirred controversy when 13 percent of patients who received it died, compared with 10 percent in the control group. In 2008, the Food and Drug Administration denied approval of the blood substitute, saying it offered no advantage over the current standard of care.

Consent should always be sought, but if a patient is unconscious, the physician should try to locate a guardian who can give permission, said Sarah Breier, associate director of the Missouri University Center for Health Ethics.

"The hope is that they can identify someone who can say, 'Yes, I give you my consent' or, 'No, I don't want you to give any female hormones to my husband,''' she said.

A one-time dose of estrogen is considered safe and has been widely studied in animals and humans for over 60 years, Wigginton said. It's commonly used in patients who have uterine bleeding and prostate cancer.

"I've talked with experts around the world, and nobody can imagine that one dose of this is going to do any harm,'' Wigginton said.

FORT WORTH, Texas -- A single dose of the female hormone estrogen could protect the brain after a traumatic injury, but researchers won't know for sure until they test it on humans.

That's what they're doing beginning this week as part of a clinical trial at Parkland Memorial Hospital in Dallas. The participants won't know whether they get estrogen or a placebo. And they won't be able to give their OK before receiving it.

The hormone must be given within two hours of a traumatic brain injury, making it virtually impossible to get informed consent, said Dr. James Simpkins, chair of pharmacology and neuroscience at the University of North Texas Health Science Center in Fort Worth. He is working with a researcher from the University of Texas Southwestern Medical Center at Dallas to translate animal studies to humans.

"If we wait until we can get consent from the person when he recovers consciousness, it will be too late,'' Simpkins said. "It is crystal-clear that if one waits six hours, 10 hours or more, the ability to protect the brain goes down dramatically.''

The groundbreaking research will focus on whether estrogen and anti-inflammatory drugs can prevent secondary injuries and improve outcomes in humans. It will involve 50 men ages 18 to 50 who have suffered a brain injury or severe blood loss, most likely after an auto, motorcycle or boating accident.

The study will target men because 70 percent of patients with brain injury or blood loss are young males. Studies have suggested young women, who have high amounts of estrogen, are more resistant to brain trauma than men or older women.

The rapid administration of estrogen holds promise as a way to reduce neurological deficits and increase survival after a devastating injury, said Dr. Jane Wigginton, assistant professor of emergency medicine at UT Southwestern Medical Center.

Studies performed without a patient's consent have long raised ethical concerns. A large trial involving a blood substitute stirred controversy when 13 percent of patients who received it died, compared with 10 percent in the control group. In 2008, the Food and Drug Administration denied approval of the blood substitute, saying it offered no advantage over the current standard of care.

Consent should always be sought, but if a patient is unconscious, the physician should try to locate a guardian who can give permission, said Sarah Breier, associate director of the Missouri University Center for Health Ethics.

"The hope is that they can identify someone who can say, 'Yes, I give you my consent' or, 'No, I don't want you to give any female hormones to my husband,''' she said.

A one-time dose of estrogen is considered safe and has been widely studied in animals and humans for over 60 years, Wigginton said. It's commonly used in patients who have uterine bleeding and prostate cancer.

"I've talked with experts around the world, and nobody can imagine that one dose of this is going to do any harm,'' Wigginton said.

This trial is based on years of animal research from the UNT Health Science Center. In animal studies, estrogen has been shown to increase brain cell survival by up to 65 percent, Simpkins said. In 1994, he discovered estrogen can protect nerve cells and reduce neurological damage in rats.

The FDA usually requires informed consent but makes exceptions for emergencies. Before the study, researchers must get community consent and inform the public about how they can opt out of the study. In this case, bracelets will identify those who don't want to participate.

Traumatic head injuries are so devastating and so often affect young adults that when people understand the risks of dying versus trying a drug that has been shown to be safe, they're very supportive of the testing, Wigginton said.

About 50,000 people, or 22 percent of those who sustain a traumatic brain injury, die each year in the United States, according to the Centers for Disease Control and Prevention. More than 80,000 people are left disabled.

The study is expected to last six to eight months, and results will be available to the public. After that, a much larger study, involving hospitals nationwide, is planned.

Doing the study without getting consent could create problems later, but if it helps save lives, people will see it as a small price to pay, Breier said.

The hope is the study will help estrogen become the standard of care for brain injuries worldwide, Simpkins said.

"The vast majority of people who present at ERs with brain trauma either die or have life-altering neurological deficits,'' he said. "We believe we can do better than that.''

A closer look

| The study is open to men 18 to 50 who are taken to Parkland Memorial Hospital after a traumatic brain injury or hemorrhagic shock.

| Participants will receive a single dose of Premarin or a placebo intravenously.

| Anyone who wants to be excluded from the study can call 214-648-6726 to receive a wristband.

-- UT Southwestern Medical Center