Female sex hormones help women survive after trauma

Women who have been severely injured are 14 percent more likely to survive than similarly injured men, according to a new Johns Hopkins study, a difference researchers believe may be due to the negative impact of male sex hormones on a traumatized immune system.

Published in the September issue of The Journal of Trauma, the study is believed to be the largest in humans to date to suggest a survival disadvantage among men from male sex hormones, a hypothesis that has been successfully tested in mice. Both men and women have androgens (male sex hormones, including testosterone) and estrogens, but in different ratios that change over time. The new findings could lead to ways to improve survival in badly injured men, such as giving androgen-blocking drugs to male patients who have been critically injured.

"Female sex hormones appear to give women better resiliency to extreme injury, while male sex hormones seem to worsen their survival after severe trauma" says Adil H. Haider, M.D., M.P.H., an assistant professor of surgery at the Johns Hopkins University School of Medicine and the study's leader. "And if we can come up with ways to manipulate those hormones in men, for example by temporarily blocking sex hormones, we may be able to improve their survival."

Haider and his colleagues analyzed information from the National Trauma Data Bank on more than 48,000 patients who, between 2001 and 2005, were severely injured and arrived at an emergency room with low blood pressure, a sign of significant blood loss. They split the data into three categories — children 12 years and younger, teens and adults ages 13 to 64 and seniors age 65 and older. In the younger patients, those whose sex hormones hadn't developed yet, and in the older patients, whose hormone activity was expected to be significantly diminished, survival did not vary based on gender. It was only the middle group of 13-to-64-year-olds — those most likely to have had the highest levels of estrogen and progestin or testosterone — where women were significantly more likely to survive. The survival advantage was there even when factors such as race, insurance status and source of injury were taken into account.

"The results of the study suggest that female sex hormones provide an advantage and help women survive after trauma," he says. "As expected, the female-to-male advantage is restricted to the group likely to have more sex hormones, rather than in the very young or the old."

Scientists have long suspected that female sex hormones have some kind of immune-enhancing effect, Haider says, something which can be an advantage in trauma but may lie behind the greater prevalence of auto-immune disorders such as lupus, which is seen primarily in women. After trauma, sex hormones appear to have specialized roles in regulating metabolic, cardiovascular and immune reactions. There may be other mechanisms involved as well, Haider says.

The impetus for Haider's study came about several years ago, after Edward E. Cornwell III, M.D., a former Johns Hopkins trauma surgeon and the study's senior investigator, treated a male patient who arrived at the hospital's emergency department with multiple gunshot wounds to the chest and the testicles, which were almost completely destroyed by the shots. The patient had a poor prognosis, but soon after surgery showed a remarkable recovery, Haider recalls. Aware of studies showing that male mice were less likely to survive than female mice after severe trauma — and that castrated mice fared better, surviving at rates similar to female mice — Cornwell suspected this patient's nearly destroyed testicles and the lack of testosterone production that resulted could have been a reason why he survived his severe wounds.

Haider says he hopes this new study leads to future research into the use of sex-based therapies for severe trauma. He says trials should be conducted to explore the survival benefits of using drugs to temporarily block androgens in severely injured or critically ill men. He says such medications are used as part of treatment for prostate cancer and don't have permanent effects in those men.