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

(Stuart Anthony/Flickr)

(Stuart Anthony/Flickr)

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. Continue reading

Comfort In Cold: Can Shivering Offer Some Benefits Of Exercise?

Brookline, Mass., 1:30 p.m. (Carey Goldberg/WBUR)

Brookline, Mass., 1:30 p.m. (Carey Goldberg/WBUR)

Just a bit of (cold) comfort if you’re stuck outside today: New research suggests that shivering, your body’s way of trying to stay warm, releases a promising hormone called irisin that appears to be connected to some health benefits of exercise.

(More on that here: A Step Toward Health Benefits Of Exercise In A Pill? and here: Exercise Hormone May Fight Obesity And Diabetes.)

So, if it makes you feel better, perhaps you can think of your chattering teeth and quivering limbs as a quick-tempo workout. (But, forgive the nag, careful not to overdo it into hypothermia and frostbite.)

The Telegraph nicely sums up the findings, though the headline — Shivering Can Help You Stay Slim — sounds far too decisive for an initial study:

A new study from scientists at Sydney University has found that placing volunteers in temperatures of less than 59F (15C) for around 10-15 minutes caused hormonal changes equivalent to an hour of moderate exercise.

These same hormonal changes have been linked to the creation of brown fat, a form of fat that actually burns up energy.

And from the press release:

According to new research into the mechanisms involved, shivering releases a hormone that stimulates fat tissue to produce heat so that the body can maintain its core temperature. This hormone, irisin, is also produced by muscle during exercise. The findings, which are published in the February 4 issue of the Cell Press journal Cell Metabolism, demonstrates that the act of shivering produces calorie-burning brown fat and improves metabolism.

Through experiments conducted in healthy volunteers, Dr. Francesco S. Celi of the National Institute of Diabetes and Digestive and Kidney Diseases and his colleagues found that the irisin, produced when the body shivers, is released in proportion to shivering intensity. Furthermore, the amount of irisin secreted as a result of shivering is of similar magnitude to that of exercise-stimulated secretion. The team also found that when human fat cells in the laboratory were treated with FNDC5, a precursor of irisin, the cells burned more energy and released more heat. Continue reading

Study Finds Oxytocin May Promote Fidelity (If Only Petraeus Knew)

Could General David Petraeus’ career have been spared by a healthy dose of oxytocin?


Researchers from Bonn report that the hormone may promote fidelity by affecting the distance men keep from unknown women they find attractive.

From the news release:

Men in committed relationships choose to keep a greater distance between themselves and an unknown woman they find attractive when given the hormone oxytocin, according to new research in the November 14 issue of The Journal of Neuroscience. The findings suggest oxytocin may help promote fidelity within monogamous relationships.

Oxytocin plays a vital role in triggering childbirth and facilitating nursing. The hormone, which is produced in a region of the brain called the hypothalamus, is also involved in the formation of social bonds. In humans and other animals, this brain chemical is known to promote bonds between parents and children, and between couples. Additionally, previous studies have shown oxytocin increases trust among people. However, scientists had yet to determine what, if any, role oxytocin played in maintaining monogamous human relationships.
Continue reading

Hormone Replacement Therapy 10 Years Later: Calls For ‘Rational Use’

Many findings in medical research have swung back in forth like a pendulum, but the wisdom on Hormone Replacement Therapy for menopausal women must be one of the biggest medical pendulums (or pendula, to be archaic) of all time. First it was a miraculous bottled Fountain of Youth; then it was the epitome of all that is evil about Big Pharma and paternalistic medicine.

Over the last few years, those pendulum swings have seemed to get smaller, and perhaps a new series of articles published in the official journal of the International Menopause Society might diminish them still further.

The press release notes that it was in 2002 that a major study by the first Women’s Health Initiative, whose investigators include Dr. JoAnn Manson at Brigham and Women’s Hospital, caused a dramatic, fear-fueled drop in the use of hormone therapy.

Now a major reappraisal by international experts, published as a series of articles in the peer-reviewed journal Climacteric (the official journal of the International Menopause Society), shows how the evidence has changed over the last 10 years, and supports a return to a “rational use of HT, initiated near the menopause”.

The reappraisal has been carried out by some of the world’s leading experts in the field, including clinicians who worked on the original WHI study. Summarising the findings of the special issue, authors Robert Langer, JoAnn Manson, and Matthew Allison conclude that “classical use of HT” – MHT initiated near the menopause – will benefit most women who have indications including significant menopausal symptoms or osteoporosis.

It quotes Dr. Manson:

“An important contribution of the WHI was to clarify that, for older women at high risk of cardiovascular disease, the risks of HT far outweighed the benefits. This halted the increasingly common clinical practice of prescribing HT to women who were far from the onset of menopause. Unfortunately, these findings were extrapolated to newly menopausal and healthy women who actually had a favourable benefit: risk ratio with HT. The WHI results point the way towards treating each woman as an individual. There is no doubt that HT is not appropriate for every woman, but it may be appropriate for many women, and each individual woman needs to talk this over with her clinician”.

The authors note that the initial press reaction, following the lead of the WHI press release, over-emphasised a relatively small increase in breast cancer, so distorting the overall view of the report.
WHI researcher Professor Matthew Allison (University of California, San Diego), said:

“It is important to put the results of the WHI trials into context. That is, being obese, not exercising or excess alcohol consumption confer higher absolute risks for breast cancer than HT use.”

The press release offers a summary of the issue’s articles; here are the headlines on everything from bone fractures to cancer, lightly edited: Continue reading

A Step Toward Health Benefits Of Exercise In A Pill?

Bruce M. Spiegelman of Dana-Farber in his lab

We’re a long way from being able to bottle the myriad benefits of exercise, but a study just out in the journal Nature looks like a promising step in that direction. It describes the discovery of a naturally occurring hormone christened irisin — pronounced like the name “Iris” with an “in” tacked on the end — that is elevated during exercise in mice and humans.

Irisin appears to be a possible key to the positive effects of exercise on blood glucose and energy expenditure — and thus on Type 2 diabetes and obesity. And because it is naturally occurring, it could be tested in humans fairly soon, perhaps in a couple of years.

But before we get to the science, a word from the study’s senior author, Dr. Bruce Spiegelman of Harvard Medical School and the Dana-Farber Cancer Institute. To all the negativity-mongers (my phrase, not his) out there who will grumble (my verb, not his) that this discovery will just enable more slothfulness, and would be unnecessary if all those couch potatoes would just get off their butts and eat better, please consider:

“The last thing in the world we’re trying to do is substitute for diet and exercise,” Dr. Spiegelman said. But first of all, there are many people who can’t exercise, whether because of paralysis or age or illness, he said. Work on irisin could potentially help them.

Second, yes, everybody should exercise and eat right but they don’t. Obesity and diabetes are worldwide epidemics costing untold billions, he points out. If irisin proves able to help fight them, it could benefit all of us.

Our conversation, lightly edited:

So where did the name irisin come from?

Iris is the Greek messenger goddess who carried messages between humans on earth and the gods on Olympus. We didn’t want to name it for any specific function because we don’t know what all of those are going to be, and what the most important are going to be, so instead we named it for its messenger function.

So what did you already know, and what did you find out?  Continue reading

Study: Hormone Restores Menstrual Cycle In Women With Little Body Fat

You hear about it happening to gymnasts and runners, dancers and anorexics. A woman’s — or girl’s — body fat gets so low that she stops having periods; her reproductive cycle shuts down.

You can imagine how evolution may have worked it this way. In ancient times, if conditions were so bad that you were down to skin and bones, that was not the time to try to feed a baby. But in modern times, women with extremely low body fat may face unwanted infertility, and they have been found to be at higher risk for osteoporosis.

Today, researchers report that leptin — a hormone famed for its role in appetite and obesity — is a key to that loss of menstruation, known as “hypothalamic amenorrhea,” and that giving women synthetic leptin can restore their reproductive function and possibly protect their bones.

The paper’s lead author, Dr. Sharon H. Chou of Beth Israel Deaconess Medical Center, summed up the findings:

Women with hypothalamic amenorrhea, or loss of menstrual periods from excessive exercise, excessive stress, or decreased food intake, have additional neuroendocrine abnormalities and experience bone loss. These women also are found to have low leptin levels, which can be seen as a marker of energy stores. This study shows that replecement of leptin in these women restores menstrual periods, corrects some of the neuroendocrine abnormalities, and may improve bone loss.

And this from a Beth Israel press release:

The findings are reported on-line in the Proceedings of the National Academy of Sciences (PNAS), the week of April 4.
“This condition accounts for over 30 percent of all cases of amenorrhea in women of reproductive age, and is an important problem for which we didn’t have a good solution,” explains senior author Christos Mantzoros, MD, Dsc, Director of the Human Nutrition Unit at BIDMC and Professor of Medicine at Harvard Medical School.
“Our findings now prove beyond any doubt that leptin is the missing link in women with significantly diminished body fat, and that this, in turn, results in numerous hormonal abnormalities.” Without leptin, he explains, menstrual periods cease, the body becomes chronically energy-deprived and women experience bone loss and an increased risk of bone fractures. Continue reading