Estrogen and female anxiety: Study suggests lower levels can lead to more mood disorders

August 10, 2012
Low estrogen levels can make women more vulnerable to trauma at some points in their menstrual cycles, while high levels of the female sex hormone can partially protect them from emotional disturbance, according to new research by Mohammed Milad (left) and Kelimer Lebron-Milad. (Stephanie Mitchell/Harvard Staff Photographer)

Some women’s vulnerability to anxiety and mood disorders may be explained by their estrogen levels, according to new research by Harvard and Emory University neuroscientists presented in this month’s issue of Biological Psychiatry.

Low estrogen levels can make women more vulnerable to trauma at some points in their menstrual cycles, while high levels of the female sex hormone can partially protect them from emotional disturbance, the research suggests. Since birth control pills affect , they might one day be used to help prevent post-traumatic stress.

Depression and anxiety disorders are twice as common in women as in men, but the reason for this gender difference is unclear. The new work, reviewed by Harvard’s Mohammed Milad and colleagues in a commentary, 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 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 at risk because testosterone, the male sex hormone, is converted into estrogen in the male brain, and so is more stable in their brains than in women’s.

Estrogen calms the fear response in healthy women and female rats, 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, showed that the same is true for women suffering from PTSD. The higher the estrogen was in their blood when they trained on a fear-extinction task, the less likely women were to startle.

Both studies used “fear-conditioning” paradigms, in which the subject is trained to fear a safe “conditioned stimulus” such as a colored shape, paired with a frightening or painful “unconditioned stimulus” like a finger-shock or a puff of air to the neck or eye. In both studies, women or female rats showed less fear response to the neutral stimulus when estrogen was high than when it was 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 susceptibility 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 have tended to combine men and women, assuming that neurological are minimal. But this assumption is changing.

“Big boats turn slowly, but this boat is turning,” said Larry Cahill, professor of psychology at the University of California, Irvine, and author of a 2006 review titled “Why Sex Matters to Neuroscience.” People have avoided studying gender differences for social reasons as well as scientific ones, Cahill said, because sex differences have been considered politically taboo. In the 1970s, Cahill said, studying sex differences could get a researcher “excommunicated from academia,” because the assumption was that such differences in the brain were minimal, and it was politically incorrect to suggest otherwise.

“Right now, people are struggling to grow past their biases,” Cahill said. But the result of understanding gender differences should be better health care for women, with treatment tailored to a woman’s needs, including the point in her menstrual cycle.

Birth control pills, in particular the emergency contraceptives known as “morning-after pills,” might be used to prevent post-traumatic stress after an assault, researchers say. This was the conclusion of a study by Cahill’s lab, published this year in the Journal of Forensic Nursing. The study, whose first author was Nikole Ferree, questioned 111 sexual-assault survivors six months after their traumas, and found that those who had taken an emergency contraceptive showed fewer symptoms of PTSD. The drug Ogestrel (which includes both estrogen and progesterone), as opposed to Plan B (estrogen alone), was particularly effective.

“The single biggest bias in neuroscience research is the belief that sex differences are insignificant or small,” Cahill said. “This [research] is the latest salvo in a barrage of information saying to the field that are real, and should affect how we treat clinical disorders in men and .”

Explore further: Period drama! Pop culture makes menstruation 'overly traumatic'

Related Stories

Period drama! Pop culture makes menstruation 'overly traumatic'

July 12, 2012
A study by the University of Melbourne has raised concerns about Hollywood’s treatment of menstruation, and whether it’s frightening girls into believing it is worse than the reality.

Androgen boosts hepatitis B virus replication

February 16, 2012
Androgen enhances replication of hepatitis B virus (HBV), rendering males more vulnerable than females to this virus, according to research published in the February Journal of Virology.

Higher job strain associated with increased cardiovascular risk for women

July 18, 2012
Women with high job strain are 67% more likely to experience a heart attack and 38% more likely to have a cardiovascular event than their counterparts in low strain jobs, according to a study published July 18 in the open ...

Device helps with Sudden Infant Death Syndrome detection

May 9, 2012
University of Texas at Arlington researchers have obtained a patent for a device aimed at saving babies’ lives through improved and rapid detection of Sudden Infant Death Syndrome.

Recommended for you

Probing how Americans think about mental life

October 20, 2017
When Stanford researchers asked people to think about the sensations and emotions of inanimate or non-human entities, they got a glimpse into how those people think about mental life.

Itsy bitsy spider: Fear of spiders and snakes is deeply embedded in us

October 19, 2017
Snakes and spiders evoke fear and disgust in many people, even in developed countries where hardly anybody comes into contact with them. Until now, there has been debate about whether this aversion is innate or learnt. Scientists ...

Dutch courage—Alcohol improves foreign language skills

October 18, 2017
A new study published in the Journal of Psychopharmacology, conducted by researchers from the University of Liverpool, Maastricht University and King's College London, shows that bilingual speakers' ability to speak a second ...

Inflamed support cells appear to contribute to some kinds of autism

October 18, 2017
Modeling the interplay between neurons and astrocytes derived from children with Autism Spectrum Disorder (ASD), researchers at University of California San Diego School of Medicine, with colleagues in Brazil, say innate ...

Study suggests psychedelic drugs could reduce criminal behavior

October 18, 2017
Classic psychedelics such as psilocybin (often called magic mushrooms), LSD and mescaline (found in peyote) are associated with a decreased likelihood of antisocial criminal behavior, according to new research from investigators ...

Taking probiotics may reduce postnatal depression

October 18, 2017
Researchers from the University of Auckland and Otago have found evidence that a probiotic given in pregnancy can help prevent or treat symptoms of postnatal depression and anxiety.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.