Researchers at the University of Alabama, Birmingham (UAB) have made a breakthrough discovery that the female sex hormone, estrogen, may be able to save the lives of wounded soldiers and trauma patients who have suffered up to 60 percent blood loss. Irshan Chaudry, director of the Center for Surgical Research at UAB, has spent 19 years on this sensitive research and recently received a $10 million U.S. Department of Defense contract to begin human safety testing trials of the synthetic estrogen, known as E2.
Untreated blood loss is the primary cause of death for soldiers in battle, and is preventable in many circumstances. Indeed, between 2001 and 2011, more than 80 percent of U.S. soldiers’ deaths during combat resulted from preventable blood loss and septicemia. Often, soldiers are wounded in locations where they can’t be quickly transported to a field hospital, which leaves medics very little time to treat them.
“The golden period after injury, when one needs transport to an ER to have a good benefit of surviving trauma, is one hour,” Chaudry tells mental_floss. “The longer you wait, the more deleterious the effects.” The goal of the treatment is to buy the soldiers enough time to make it alive to a field hospital. “Six hours should be more than adequate to get them to treatment,” he says.
When a person or animal loses blood, minute blood vessels collapse, which results in decreased oxygenation to the tissues. If that is not corrected, the cells gradually die, the organs shut down, and then eventually, so does the entire organism. “Anything we can do to prevent that decrease of microcirculation is good,” Chaudry says. He paraphrases British trauma researcher Harry Berrington Stoner: “The body is like a swamp after blood loss, and anything that can turn it into a running brook is the answer.”
What makes estrogen such a life-saving hormone? Surprisingly, estrogen receptors are found in every cell of the body, and in the mitochondria, in both males and females. “When estrogen receptors are active, they produce more ATP [the “energy currency” of cells], which we need for literally everything we do,” says Chaudry. “When we lose blood through trauma, the production of ATP decreases.”
In 1997, Chaudry and his co-researcher Rene Zellweger discovered the immune-boosting and cardiovascular bolstering effects of estrogen by accident. They were using mice to study infections in trauma-hemorrhaged patients. Instead of male mice, the vendor accidentally sent female mice, which Zellweger did not want to use due to their fluctuating hormones. Yet Chaudry pushed ahead with the study and they found the females were more infection-tolerant—resisting septicemia—than Chaudry had predicted.
Excited, Chaudry ordered more female mice and repeated the experiment. The second time around, the experiment failed. He wondered what was different. "We realized it may have been that we got the females at different points in their cycles,” he says. Sure enough, the first batch of infection-tolerant female mice had been at the proestrus phase of their menstrual cycles, just prior to ovulation, when estrogen levels are highest.
Next, they tested the E2 on blood loss, a common trauma issue, and found that E2 significantly improved cardiovascular and liver function in patients who had lost up to as much as 60 percent of total blood volume; it worked by dilating blood vessels and moving fluid from tissues to blood more efficiently. It also reduced inflammatory cytokines and staved off death or organ failure by three hours.
In 2005, the U.S. Defense Advanced Research Projects Agency (DARPA), held a competition seeking a treatment that would keep a soldier alive for at least three hours after significant, almost universally fatal blood loss [PDF]. Chaudry and his researchers stepped up. They used a version of E2 that was microencapsulated with cyclodextrin—a sugar-like compound—to make it water-soluble.
Since then, Chaudry’s synthetic estrogen has been engineered, with the help of DARPA, to a variant called ethinyl estradiol-3-sulfate, or EE-3-SO4. A syringe of this version can buy mice and horses up to six hours before they show signs of organ failure or death. “There is a lot of edema after trauma, so if we can pull that fluid back from the tissue into blood circulation, it maintains a state of permissive hypotension, enough to sustain life and protect the animals,” he says.
Meanwhile, EE-3-SO4 may have benefits for victims of brain trauma as well. In research, the estrogen also reduced cerebral edema, increased blood flow to the brain, and reduced brain cell death.
Both estrogen variants have the potential for applications in civilian trauma in conditions where they can’t immediately get to a hospital.
Currently waiting to begin the filing process for FDA approval, Chaudry is confident that within a year they will be approved to begin human safety trials. His hope is that eventually all emergency vehicles will carry pre-loaded estrogen syringes, ready at a moment’s notice to literally make the difference between life and death.