Why Do So Many Women Have Anxiety Disorders? A Hormone Hypothesis

Why do so many women suffer from anxiety? Is it something inherent in being female, are we more attuned to our moods? Or is that breath-clenching feeling of impending doom hard-wired?

According to the National Institute of Mental Health, women are 60 percent more likely than men to experience an anxiety disorder over their lifetime. (Obviously, men are not immune: taken together, anxiety disorders are among the most common mental health conditions — they affect about 40 million men and women age 18 and older, or about 18 percent of the U.S. population.)

Mohammed Milad is an associate professor of psychiatry at Harvard Medical School and director of the Behavioral Neuroscience Program at Massachusetts General Hospital. He studies the complex interplay of gender, fear and anxiety. More specifically, he's looking at how hormones, notably estrogen, might play a role in the fear response and our ability to extinguish fear and anxiety.

I spoke with him about his work. Here, edited, is some of our conversation:

RZ: OK, can you just clearly explain the difference between fear and anxiety? Sometimes it's a fine line indeed.

MM: I was thinking about taking my kids camping over the summer, and I was reading about bears and potential bear encounters, and considerations for taking cover and putting your food this distance away from your camping site, etc. Anxiety is when you're camping and you have that heightened awareness — hyper-vigilance  -- that's anxiety, it's sustained, it's continuous, but it's not at the point where it makes you run or look for cover. Fear is when you see the bear; fear is intense, it's immediate, it's right there in front of you.

RZ: Thanks for that. But I'm curious, how did you start studying how men and women are different when it comes to fear and anxiety?

MM: When I was in grad school we used to host kids from middle and elementary school...showing our lab to them, showing them the rats, and one kid, maybe 10, 12 years old, asked, are they male or female rats and I said they're all male rats, and he asked, why, what about the female rats? And I didn't know the answer, so I went to my mentor and asked, why don't we study the females? And the answer, simply put, was they're complicated.

RZ: So the female rats were just too complicated. I get that. But considering far more women than men suffer from anxiety disorders, the fact that you were studying only male rats wasn't such a great approach, was it?

MM: No, so I think that's not an acceptable answer now.

RZ: In your experiments on rats and humans, you and your team use Pavlovian conditioning, as in Pavlov’s dogs, who were famously conditioned into drooling every time they heard a bell because they associated that sound with food. So, in these studies you repeatedly showed a blue light on a screen to men and women who would then receive a mild shock, until they came to expect — and fear — a shock every time they saw the blue light. Then, you stopped giving shocks when the blue light came on, to teach the subjects not to fear it. That’s “fear extinction.” And the next day, the men and women were tested to see if they still had a fear response to the blue light.

The results in these studies were all over the place, but most of the variance in fear response was among women in the experiment, right? The men were much more consistent. Why might that be?

MM: That’s what got me into beginning to think about hormones, because what could account for that other than maybe some women that we're bringing in to the lab were at a particular phase of their menstrual cycle? And when we did that study we found that women who came in when their estrogen is elevated, they had their [fear] extinction capacity much better, in other words, they were able to control their fear, or express much less fear, compared to the women that came in in the early phase of their cycle... when they had low estrogen.

RZ: So just to be clear, high estrogen was linked to better control of fear, and low estrogen meant more potent and longer lasting fear?

MM: Right.

RZ: Ok, so if estrogen helps with fear extinction, and women typically have more estrogen than men, then why aren't men gripped with fear and anxiety all the time?

MM: As our initial hypothesis, we thought that men would behave very much like women with low estrogen, but when we got the data, I was puzzled because men behaved very much like women with high estrogen, and only low-estrogen women showed deficits in the fear extinction. What we have learned is that testosterone in men, in the brain gets converted to estrogen by an enzyme called aromatase. So we think that a lot of the benefit that men get is due to this conversion of testosterone to estrogen.

RZ: It's cool to think that a hormone often thought of as “female,” could be so crucial to a characteristic often thought of as “male”...But you also conducted some research involving women on birth control pills, which, of course, interfere with the body’s normal production of estrogen. How does that affect the fear response?

MM: We did an initial study that made us concerned — we recruited women on birth control, and what we found is that women on birth control pills act like women with low estrogen. In other words, birth control seemed to impair women’s ability to control or extinguish fear.

(Editor's Note: Lots of caveats here; Milad says all of these findings need to be replicated and tested on a much larger scale and are in no way conclusive at this point.)

RZ: After childbirth, that post-partum period is a time when many women have dramatic mood swings, depression, anxiety. Might that be related to the extreme hormonal changes that occur after birth, specifically the drop in estrogen?

MM: Yes, we think it's that drop that perhaps may make women more vulnerable to anxiety disorders.

RZ: And what about the anti-anxiety drugs we're all prescribed now? You did a study on fear extinction and SSRI's, specifically using the generic version of Prozac, fluoxetine. These drugs aren't prescribed with any thought about how hormones come into play...

MM: Right, they are not tailored to the different genders, everyone is taking the same thing. We did a study in female rats with fluoxetine, and what we found is that it's most effective in reducing fear in the female rat only when the rat was in the estrous phase, which is the low estrogen state...So it doesn't always work. And that could provide some data into why aren't all women responding, for example, to Prozac or other medications for anxiety, why there's a huge difference in how people respond.

RZ: So what's next on your research agenda?

MM: We have applied for funding for a study to recruit women with PTSD; we want to pair prolonged exposure therapy with an estrogen pill to see if that helps with fear extinction.

R: Fascinating, and great if that worked. But tell me: what ever happened to that camping trip with your kids?

MM: Yeah, I was thinking about the bear thing...I would be anxious if I was in that park alone with my kids.

R: So did you end up going camping?

MM: No, of course not. I'm highly anxious.

For more on this and related news on anxiety, subscribe to our podcast, The Checkup, a joint venture with Slate. Our next episode, High Anxiety, will come out on Monday.

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Rachel Zimmerman Reporter
Rachel Zimmerman previously reported on health and the intersection of health and business for WBUR. She is working on a memoir about rebuilding her family after her husband’s suicide. 



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