High levels of estrogen may help protect a woman from mood disorders, while low levels of the hormone can make a woman more susceptible to trauma at certain times in her menstrual cycle, according to new research by Harvard and Emory University neuroscientists.
Depression and anxiety disorders are twice as common in women as in men, but the reason for this gender difference has remained unclear. The new research, however, suggests that women are most at risk for symptoms of post-traumatic stress disorder (PTSD) when their estrogen is low during the menstrual cycle.
“PTSD is a disorder of recovery,” said author Mohammed Milad, associate professor of psychiatry at Harvard Medical School (HMS) and director of the Behavioral Neuroscience Laboratory at Massachusetts General Hospital (MGH).
Men may be less susceptible to mood disorders since testosterone is regularly converted into estrogen in the male brain, resulting in a more steady flow of estrogen.
In healthy women and female rats, estrogen calms the fear response, according to the Harvard researchers, who were led by Kelimer Lebron-Milad, an HMS instructor of psychiatry.
The Emory researchers, led by postdoctoral researcher Ebony Glover, proved that the same is true for women suffering from PTSD. The higher their blood levels of estrogen were when they completed a fear-extinction task, the less likely women were to act startled.
Both studies used “fear-conditioning” experiments, in which the participant is trained to fear a safe “conditioned stimulus” such as a colored shape, paired with a frightening or painful “unconditioned stimulus” like a shock to the finger or a puff of air to the neck or eye.
Overall, women or female rats showed less fear to the neutral stimulus when their estrogen levels were high rather than low.
PTSD is common in women after a trauma such as rape or sexual assault, which studies say are experienced by 25 to 30 percent of women in their lifetimes, and the symptoms last on average four times as long in women as in men after trauma.
This new research suggests the reason for this vulnerability may be the monthly menstrual change in estrogen.
“People are afraid to look into the influence of sex hormones on ‘fear learning’ and extinction,” said Mohammed Milad, “because it’s such a complex system.”
When Milad studied fear as a Ph.D. student, his lab used only male rats. But when he began to study fear in humans as a postdoctoral researcher, he saw that female data were much more variable.
“The data led me there,” to sex differences, Milad said. “Since females add variance, scientists have tended to avoid studying them” in rodent research, he said. Studies of the human brain would tend to combine men and women, assuming that neurological gender differences were minimal. But this attitude is changing.
In addition, since birth control pills affect estrogen levels, they may be used as a future treatment against post-traumatic stress.
The research is published in Biological Psychiatry.
Source: Biological Psychiatry