8

Hormonal Changes

The Impact on Women’s Brain Health

HORMONES HAVE A powerful influence on how our brains develop as well as on our feelings and behaviors and personality traits throughout life. After adolescence, hormone levels remain fairly steady in men, but in women, they fluctuate like clockwork. The constant shifting affects every woman differently, and this must be factored in to any discussion of brain health. Exercise is particularly important for women because it tones down the negative consequences of hormonal changes that some experience, and for others, it enhances the positive. Overall, exercise balances the system, on a monthly basis as well as during each stage of life, including pregnancy and menopause.

The average woman has four hundred to five hundred menstrual cycles in her lifetime, each one lasting four to seven days. If you add them all up, it comes out to more than nine years — a long time for women who suffer premenstrual syndrome (PMS). “You can’t be bitchy and agitated and short-tempered and have a decent life,” says a thirty-eight-year-old colleague I’ll call Patty. “I know the feminists hate it when you say this, but some of us do go crazy.”

Crazy isn’t the word I would use, but it does capture the frustration many women feel when their hormones take over. Approximately 75 percent of women experience some form of premenstrual distress, physical or emotional or both, and Patty is among the subset for whom the symptoms can be severe enough to disrupt their lives (14 percent miss school or work at some point because of PMS). Every month since she was about sixteen, if she doesn’t exercise Patty gets tired, irritable, itchy, anxious, agitated, and aggressive in the days leading up to her period. She has difficulty focusing; she tosses and turns at night; and she craves carbohydrates. Her ankles and belly swell; her face develops a rash; she gets constipated; and her breasts hurt. “That’s when I really push myself,” she says. “The week before my period I have to do an hour of cardio four days a week or I can’t stand myself.”

She learned early on that aerobic exercise dramatically dials back her symptoms. Just shy of five foot ten with a shock of red hair and a bright, broad smile, Patty worked for the Elite modeling agency from childhood through her early twenties. She wasn’t into sports, but beginning in her teens, she exercised almost manically, sometimes three hours a day, to keep her weight down to 110 pounds. Without the exercise, her mom found her impossible to deal with. The absurdity of sticking to that weight convinced her to quit modeling, and she’s since earned a master’s degree in social work. There have been times, even years, when she’s lapsed from her routine, but she always comes back to it. “It helps the most with the mood swings,” she says. “It takes the edge off and gets out that aggression that comes with the hormones.”

Normally tolerant and easygoing, Patty says she gets “snappy” and has a short fuse during PMS. “Her radar goes on hypersensitive,” says her husband, Amon, an architect with neat black hair and rimless eyeglasses. “Her sense of smell, sound, light. Her sense of order. She becomes extremely particular. For example, she wants me to be around her, but I must be around her in a very specific way.”

“He’ll be next to me on the couch,” she says. “I’ll hear him breathing and be like, Do you have a sinus infection or something?”

“Exactly!” he says, laughing. “And she might ask if my father had sinus problems, and then it becomes an entire discussion about my family’s nasal history.”

Patty and Amon are conscientious people who generally communicate well and support each other, which is extremely important for women going through hormonal changes. Amon suggests that they go to the gym together on days she’d rather skip it. “Patty is one of those people in whom you can see the storm clouds building before it comes,” he says.

The term PMS became politicized in the 1970s because some felt that it labeled a natural aspect of women’s lives as a medical issue and created a perception that all women have a psychiatric disorder once a month. The subject was hotly debated by the medical experts who decide what should be included in the Diagnostic and Statistical Manual and what each condition should be called. PMS has been renamed in various editions of the DSM, and in 1994 the entry was changed from the inscrutable late luteal phase dysphoric disorder (LLPDD) to premenstrual dysphoric disorder (PMDD). But the requirements for a medical diagnosis of PMDD are so stringent that they leave out the majority of women who cope with what we all think of as PMS. Call it what you like, but to me the issue is whether any of the 150 symptoms in the DSM interfere with your quality of life.

PMS: NATURAL UPS AND DOWNS

Scientists don’t know precisely what causes PMS, but changes in hormone levels are an obvious place to look for clues. The sex hormones are powerful messengers that travel throughout the bloodstream, and aside from overseeing the development of gender characteristics, they influence the brain in many ways. The cycle begins with signals from the hypothalamus that prompt the pituitary gland to secrete hormones called gonadotropins, which travel to the ovaries and trigger the mass production of estrogen and progesterone.

Estrogen peaks at five times its baseline level just before ovulation and then follows an up-and-down pattern for the two weeks leading up to the period, after which it evens out. Progesterone begins a fitful rise after ovulation (to about ten times its lowest level) and peaks just before menstruation. During pregnancy, estrogen skyrockets to fifty times normal levels, and progesterone increases tenfold. Then during menopause, both hormones decline until they nearly disappear.

The difference between women who suffer from PMS or postpartum depression or tumultuous menopause and those who don’t seems not to be a matter of the level of these hormones but, rather, of the body’s sensitivity to other neurochemical changes they trigger.

For instance, in relation to mood, as well as overall brain function, hormones play an important role in regulating neurotransmitters. Both estrogen and progesterone create more receptors for serotonin and dopamine throughout the limbic system and thus increase these neurotransmitters’ effectiveness. And in just the past few years, scientists have discovered that estrogen signals the production of brain-derived neurotrophic factor (BDNF), which in turn creates more serotonin. While there is much we still don’t know about the complex interplay between shifting hormonal levels and brain function, this link to the neurotransmitter system is shaping up to be pivotal.

In one 2004 study researchers used PET scans to compare neurotransmitter activity in women with and without PMDD. They found that the brains of women with the diagnosis had an impaired ability to “trap” tryptophan in the prefrontal cortex, thus limiting the production of serotonin, which helps regulate mood and behavior such as angry outbursts. In another study, psychiatrists from London’s Kings College purposely depleted tryptophan in a group of women during their premenstrual phase and found that it led to more aggressive behavior when provoked. These were healthy women with no PMS symptoms or mood issues at the time. Each woman was told that if she reacted to a computer cue faster than a competitor in another room, she could adjust the volume of an annoying sound that would penalize the other woman. If she lost, however, she would get buzzed.

In fact, there was no opponent. All of the participants were subjected to the noise — which kept getting louder — half of the time. As the volume increased, the women with depleted tryptophan aggressively cranked up the volume, lashing out at their imaginary opponent. The study concluded that lowering the precursor to serotonin in healthy women increases their tendency toward aggressiveness. “They were much more likely to retaliate than women with normal levels of serotonin,” says Alyson Bond, who conducted the study. “They behaved in a similar way to habitually aggressive people.”

Aggression is just one symptom, and the story of PMS — like that of depression — is more than a one-neurotransmitter drama. A long chain of events connects the production of a hormone to the signal that manifests as feelings or behavior, and any broken or damaged link can spin the outcome in another direction. This is just one reason why PMS, pregnancy, and menopause affect every woman differently. It’s impossible to say where the gap is in Patty’s brain chemistry, for example, but there’s no question that exercise helps close it. “It’s almost like I’m in a fog before my period,” she says. “I could take my ADHD medication, and it won’t do a damn thing. Exercise helps clear my head.”

RESTORING BALANCE

Exercise isn’t necessarily the only answer if you suffer from PMS, but it can dramatically reduce the symptoms and give you a handle on a part of life that feels beyond your control. And with a lifestyle change, medication may not be necessary.

Many women already know this: one survey of more than eighteen hundred women found that at least half of them use exercise to alleviate the symptoms of PMS. In addition to reporting less physical pain, the women who exercise scored better on evaluations of concentration, mood, and erratic behavior.

The notion that exercise alleviates physical symptoms both before and during menstruation is far more accepted than its proposed effects on mood and anxiety. Frankly, there is little experimental evidence to prove specifically that exercise helps the mental symptoms of PMS. Perhaps the best study on the subject comes from the Duke University lab of James Blumenthal, who pioneered much of the research on exercise and depression, and it dates back to 1992.

With a small group of middle-aged women (premenopause), Blumenthal compared how aerobic exercise and strength training affected PMS symptoms. Each group trained for an hour three times a week. The twelve aerobic women did thirty minutes of running at 70 to 85 percent of their aerobic capacity, along with a fifteen minute warm-up and cool-down. The other eleven used weight machines for supervised strength training. Both groups’ physical symptoms improved, but the runners improved significantly more on the mental side. They felt better on eighteen of twenty-three measures, the most significant of which were depression, irritability, and concentration. The sharpest distinction was that the aerobic set showed a less pessimistic outlook and more interest in the world.

One explanation, certainly, is that physical activity increases levels of tryptophan in the bloodstream and thus concentrations of serotonin in the brain. It also balances dopamine, norepinephrine, and synaptic mediators such as BDNF. By stabilizing such a broad number of variables, exercise helps to tone down the ripple effects of shifting hormones.

Exercise also ties into a more nuanced theory of PMS that is just developing. Estrogen and progesterone both get transformed into dozens of hormonal derivatives, some of which are of great interest to neuroscientists because they regulate the brain’s major excitatory and inhibitory neurotransmitters — glutamate and gamma-aminobutyric acid (GABA). During the hormonal fluctuations of the premenstrual phase, the levels of these derivatives relative to one another can get out of whack, which can lead to too much excitement of the nerve cells in the brain’s emotional circuitry. This could happen because too much glutamate is being produced or not enough GABA, but either way, the runaway activity can lead to mood changes, anxiety attacks, aggression, and even seizures.

One recent study found that while hormone levels were the same in women with and without PMS symptoms, their GABA levels were different. Exercise has widespread effects on the GABA system, which puts the brakes on excessive cellular activity as Xanax does. Studies in rats have shown that just one bout of exercise turns on the genes that produce GABA, for instance. Exercise restores the balance between the opposing forces of activity in the brain during a time that is tumultuous for some women. It also fine-tunes the hypothalamic-pituitary-adrenal (HPA) axis, which you may recall from earlier chapters improves our ability to cope with stress. And, not to be overlooked, exercise improves energy and vigor, which impacts all of the other symptoms.

PREGNANCY: TO MOVE OR NOT TO MOVE?

No myth about women’s health has existed for so long as the belief that women should stop exercising during pregnancy. Perhaps because childbirth was a life-threatening event before modern medicine, pregnancy was considered a period of confinement — a time to stay home, reduce activity, and rest in bed. It might be dangerous to disturb the unborn child. Exercise? Out of the question.

It’s only recently that doctors have begun to shift their thinking. In 2002 the American College of Obstetricians and Gynecologists (ACOG) began recommending at least thirty minutes a day of moderate intensity aerobic exercise for pregnant and postpartum mothers. It’s a potentially powerful guideline, given that 23 percent of active women stop exercising when they become pregnant. Equally important, though, is that for the first time the ACOG recommended that sedentary women begin exercising when they become pregnant, largely to counter risks such as diabetes, high blood pressure, and preeclampsia that can develop during gestation and harm both mother and child.

Certainly there are complications for which bed rest is the sensible prescription, so it’s important to speak with your obstetrician before beginning an exercise regimen. Forget ice hockey, racquetball, basketball, and any other contact sports. The same goes for riding horses, mountain biking, practicing a balance beam routine, or doing anything where falling is part of the game. And scuba diving too. Keep in mind, however, that doctors tend to be conservative. In its 2002 recommendations, the ACOG warns against exercise for pregnant women who are overweight, diabetic, heavy smokers, or who have high blood pressure — the very women who need exercise. In these cases, exercise may not be totally out of the question; it’s just that they should start very slowly, working closely with their doctors.

Many expectant mothers don’t have a clear idea of what they can do, and they think in terms of avoiding rather than engaging. If they understood the benefits of exercise — not only in reducing pregnancy risks but also in improving their physical and mental health and that of their babies — then they’d feel much more comfortable being active. The truth is we don’t have all the answers about the effects of exercise on pregnancy, but we do have some good ones.

During pregnancy, estrogen and progesterone levels remain exponentially higher than normal, and in some cases this stabilizes mood and alleviates anxiety and depression. Indeed, pregnancy can change a number of different systems for the better. For instance, some women with attention-deficit/hyperactivity disorder are surprisingly able to sit still and read when pregnant. The body’s reaction to hormones is specific to the individual, though, and some women experience distress.

Whatever the body’s reaction, physical activity lowers stress and anxiety and improves mood and overall psychological health during pregnancy. A 2007 study from England evaluated the effects of a single bout of exercise on the mood of sixty-six healthy pregnant women who were divided into four groups. They either walked on a treadmill, swam, took an arts and crafts class, or did nothing extra. Women in both exercise groups improved their moods, even though they weren’t necessarily problematic to begin with.

It’s also well established that an expectant mother’s state of mind may alter her baby’s development. Stress, anxiety, and depression can have a frighteningly powerful impact on a pregnancy, and, in the extreme, can result in miscarriage, low birth weight, birth defects, or death of the baby. Babies born to unhappy mothers are fussier, less responsive, harder to soothe, and have unpredictable sleep patterns. And in follow-up tests, these babies are more likely to be hyperactive and suffer cognitive impairments. In rodent models, pups born to mothers subjected to stress during pregnancy (by way of shocking their feet) are skittish, clumsy, and less adventurous. And their stress regulation systems are forever altered, leaving them more vulnerable to future problems. Psychiatrist Catherine Monk, of Columbia University, has correlated these changes in human subjects. She found that when pregnant mothers with clinical anxiety are asked to participate in a stressful event, such as making a short speech in front of a group, their fetuses’ heart rates are overreactive and don’t calm down as quickly as fetuses of mothers without clinical anxiety. This is a sure sign that the HPA axis isn’t regulating itself correctly, which means cortisol is on the loose. Also, twitchy HPA axis is a risk factor for future psychiatric issues.

Despite the fact that exercise can prevent a lot of unnecessary complications, many women are still leery of exercising while they’re pregnant: surveys suggest that up to 60 percent remain inactive.

In general, studies report that exercise reduces nausea, fatigue, joint and muscle pain, and fat accumulation. Exercise cuts in half the risk of developing abnormal glucose levels, which can lead to gestational diabetes — a condition that results in overweight babies and prolonged labor. High glucose is also a risk factor for obesity and type 2 diabetes in both the mother and the baby, and these physical conditions are bad for the brain. Fortunately, exercise helps regardless of how active a woman was before pregnancy. One study showed that briskly walking five hours a week reduces the risk of gestational diabetes by 75 percent.

Several years ago a group of German researchers decided to test whether exercise would have any impact on the painful process of labor. They brought a stationary bicycle into the labor suite. Somehow they found fifty women who agreed to pedal for periods of twenty minutes, rate their pain levels, and have their blood tested for endorphins right up until they gave birth. Most of them (84 percent) said contractions were less painful during exercise than at rest, and their ratings were inversely proportional to endorphin levels. The researchers concluded that, “exercising on a bicycle ergometer during labor seems to be safe for the fetus, a stimulus to uterine contractions, and a source of analgesia.”

DON’T FORGET THE BABY

James Clapp, an obstetrician and professor of reproductive biology at Case Western Reserve University, has been studying how exercise affects the child for more than twenty years. His 2002 book, Exercising through Your Pregnancy, is a largely positive endorsement built on long-term studies he’s conducted with several hundred women. He begins by dispelling the myth that exercise is dangerous, noting that in his research there were no differences in weight or skull size between babies born to active and sedentary mothers. With exercise, the fuel line between mother and baby grows, to ensure the fetus gets the nutrients and oxygen it needs. Studies from Clapp and others have shown that newborns of active women are leaner, which you might think is cause for concern, except that the physical differences even out within the first year.

Exercise seems to be more than just not harmful, though. In one study, Clapp compared thirty-four newborns of exercisers to thirty-one of sedentary mothers five days after birth. There’s only so much you can do to gauge behavior at this early stage, but the babies from the exercise group “performed” better on two of six tests: they were more responsive to stimuli and better able to quiet themselves following a disturbance of sound or light. Clapp sees this as significant because it suggests that infants of exercising mothers are more neurologically developed than their counterparts from sedentary mothers. He theorizes that physical activity jostles the baby in the womb, providing stimulation not unlike the effects of touching and holding newborns, which clearly improves brain development. In another comparison at five years of age, he found no differences in behavior and most cognitive measures, but there were statistically significant differences in IQ and oral language skills. The children of exercisers performed better, and his unpublished observations suggest that years later their academic performance is better than kids whose moms were inactive, which is amazing.

There’s no way to conclude just yet why this is the case in humans, but there are tempting clues from lab rats. Most intriguing is a 2003 study showing that rat pups born of exercising moms had higher levels of BDNF immediately after birth, and also at fourteen and twenty-eight days. At the same time, they performed better than controls on learning tasks related to the hippocampus. Essentially, they learned better and faster than rats born of sedentary mothers. One study showed that, for some reason, rat pups of running mothers had fewer neurons in the hippocampus at birth, but they bounced back and outpaced their counterparts. By the end of the first six weeks, the exercise group had 40 percent more cells in the hippocampus. A study in 2006 found that forcing pregnant rats to swim ten minutes a day resulted in more BDNF, greater neurogenesis, and improved short-term memory in their pups. In short, when pregnant rats exercise, neurons in their fetuses’ brains are better able to link up to one another.

Although these findings can’t be applied directly to humans, they certainly fit within the framework of what we’ve learned about exercise and the brain in the past decade. We can’t say that running when you’re pregnant will get your daughter into the best colleges, but on the other hand, these findings suggest that staying physically active improves neurotrophic support for the baby’s brain cells. And, as you’ll recall from earlier chapters, such changes optimize learning, memory, and overall state of mind. For me, the idea that exercising while you are pregnant might have an impact on the future of your baby’s brain — that’s powerful.

In another fascinating line of inquiry, researchers have studied the effects of exercise in combating fetal alcohol syndrome, a devastating disorder that results in stunted growth, retardation, and facial disfigurement. It’s the leading preventable cause of birth defects in the United States, and some studies have shown that if a pregnant woman drinks even moderately, learning, behavioral, and social problems can follow for the baby. The brains of rats born to ethanol-fed mothers have lower levels of BDNF, neurogenesis, and neuroplasticity. The hippocampus is atrophied, and consequently, the pups can’t learn or remember very well. Beyond the hippocampus, alcohol damages glutamate synapses, and this has wide-ranging effects in the brain.

In 2006 researchers from neuroscientist Brian Christie’s lab at the University of British Columbia examined the neurological effects on rats of prenatal exposure to ethanol, and then tested the effects of exercise on those changes. As expected, the pups whose moms consumed ethanol had markedly lower rates of neurogenesis and neuroplasticity. After the pups were born and able to exercise, though, the activity reversed the brain damage to normal, which was startling.

The findings have already had an impact on how doctors recommend handling babies with fetal alcohol syndrome. Parents used to be advised to keep the environment quiet and dark so as not to overstimulate the babies. Now it seems that it’s better to provide physical stimulation and activity, to give the babies’ brains a chance to counteract their neurological deficits.

It never ceases to amaze me how our brains can repair themselves if we keep our bodies moving, as they were designed to do.

POSTPARTUM DEPRESSION: A BOLT OF THE BLUES

Tony and Stacy were desperate. It was a rainy Friday afternoon when the couple decided they needed an elliptical trainer right now, but the NordicTrack store at the mall was out of stock. They had to locate a seedy Boston warehouse to pick it up, and then the seats of their SUV wouldn’t lay flat, so the trainer stuck out the back as rain poured down during the drive home. It must have weighed two hundred pounds, that soggy box, and wrestling it inside the house was just the beginning of Tony’s work for the evening.

“We got home, and I immediately had to put it together,” he says. “It isn’t my strong suit, but at that point I just wanted her to be better.”

They needed a treatment for Stacy’s postpartum depression, which had come out of nowhere after she gave birth to their first child, a son named Carter. For five months now she had been exhausted but unable to sleep soundly; she felt guilty if she left her infant alone; she hated her body; she lost interest in the world; and she was prone to bursting into tears without warning. These symptoms are unrelated to the temporary blues most women experience within the first weeks after delivery, and they’re more common than most people realize. For 10 to 15 percent of new mothers like Stacy, everything seems fine at first, but then postpartum depression strikes, and it can stick around for a year or more. When I mention to my medical and psychiatric colleagues that such a significant number of new mothers suffer postpartum depression — a fact I only learned in researching this book — they are as shocked as I was.

Antidepressants are the typical treatment, but the Lexapro Stacy had tried made her feel numb to everything. She only stayed on it for a few days and was wary of trying another medication. As she and Tony sat in my office on that rainy afternoon, I explained how aerobic exercise works as well as or better than drugs for some people with depression. I only wish all of my patients were as responsive: when they left, they made a beeline to the mall to buy the trainer.

Tony finished putting it together late that evening, and Stacy jumped right on it for a twenty-minute workout.

“Those things are hard when you first start!” she recalls. “I knew it was doing something — you get that burn.”

“I think that’s what grabbed her at first,” Tony says. “The burn and the feeling that it was going to help her appearance. I don’t think she grasped right away that it was helping her mentally and helping her sleep.”

“No, I didn’t.”

“I noticed. I said, Stacy, it’s like night and day. It really is. The first thing it changed was her quality of sleep — ”

“Which of course made me feel better during the day.”

“And then her mood followed.”

“I had a lot more energy. I would feel better when I got off than when I got on it. Even now, after playing with Carter all day long, I’ll feel exhausted, but I make myself do it anyway. And I’m in a better mood and am happier and feel more energetic.”

What makes Stacy’s story dramatic is that before she gave birth, at age twenty-nine, she could most aptly be described as bubbly. She had no history of depression and was “the happiest person” Tony had ever met. They are an incredibly loving couple, young yet old-fashioned, and, above all, they’ve always had a lot of fun together. But after Stacy’s pregnancy, she says, “everything switched around.”

She is tall, blond, athletically trim, and was only five pounds over her normal weight two weeks after giving birth. She looked terrific, which is relevant here only because she didn’t see it that way. On the rare occasions when they went out after Carter was born, Stacy would try on a dozen outfits. “I thought I looked horrendous,” she says. “No matter what anybody said, I didn’t believe it in my heart of hearts.”

“No fooling around; it was nine or ten different shoes and shirts and pants,” Tony says. “She saw a different person in the mirror.”

But there was more at play than a negative self-image. After the initial excitement of bringing Carter home, fatigue set in, and with it came a raft of crummy feelings. Stacy stopped expressing opinions or interest in anything. She moved the crib into their bedroom and woke up every few hours to check on the baby. “I never wanted to leave Carter,” she says. “And I’d always feel guilty if I did.”

New mothers overcome by depression start to question themselves and wonder if there’s something wrong with them. If they’re having trouble, they assume they must be terrible mothers. The instinct is to push away from the world, the baby in particular, and this leads to inner conflict and self-flagellation. Here’s this biological purpose for your being and you’re ashamed that everything is not blissful, convinced you’re the only mother in the world having such feelings. This event that is supposed to be so wonderfully life-fulfilling instead triggers a black cloud.

It took several months of Tony gingerly raising the subject before Stacy recognized that something was off. “I didn’t feel like me anymore,” she says. “I had no idea how I was going to get back to that.”

Stacy had lifted weights occasionally, but as I explained to her and Tony, aerobic exercise is different — and crucial for mood. Now she spends forty-five minutes on her elliptical trainer almost every night. If she misses it for more than a few days, she has trouble sleeping and notices a drop in energy and mood. Does that mean she’s still depressed and just masking it with exercise? Not exactly. It’s just that if symptoms flare up, as they sometimes do during her period, she hits the trainer to make sure they don’t snowball into something worse. Above all, she knows she can handle it. “If I exercise, I’m fine,” she says. “I feel like I’m back to normal.”

GETTING BACK OUT THERE

Scientists know plenty about how aerobic activity curtails the symptoms of general depression (see chapter 5), but new mothers warrant special consideration. It’s not so much the increase in hormones that causes postpartum depression, research suggests, but the effects of withdrawal when they plummet after childbirth. In 2000 Miki Bloch of the National Institute of Mental Health published a study in the American Journal of Psychiatry in which her lab re-created the hormonal conditions of pregnancy in two groups of thirty-something mothers: one with a past history of postpartum depression and one without. (Neither group of eight women had symptoms of depression during the study.) All of the women were given pills to stimulate the production of estrogen and progesterone, and after eight weeks the hormones were secretly replaced with a placebo. The effect was dramatic. During estrogen withdrawal, five of the eight women with a history of postpartum depression experienced a relapse of symptoms; the other group didn’t notice a thing.

Given how powerfully hormones affect neurotransmitters, Bloch proposed that some women’s brains simply can’t compensate for the sudden changes or that the normal signals are amplified in a way that disrupts mood. From this perspective, exercise might be even more effective for new moms experiencing depression than for the general population because it normalizes neurotransmitter levels.

The best study on this issue was conducted in Australia several years ago, with twenty women suffering postpartum depression who’d given birth within the previous year. Half of them were on antidepressants. Researchers chose a form of exercise that is exceedingly convenient for new moms: walking with a stroller. One group of ten women walked with their strollers for forty minutes at 60 to 75 percent of their maximum heart rate three times a week and attended one social support meeting, while the other ten women, in the control group, carried on their normal routines. They all established a baseline score on the Edinburgh Postnatal Depression Scale (EPDS) and were tested again at six weeks, and then at twelve weeks, when the trial ended. Anyone who scores higher than 12 is considered clinically depressed. The stroller-pushers increased fitness and significantly lowered their EPDS scores at both intervals. The exercise group started with a mean score of 17.4, and it dropped to 7.2 and then 4.6. The control group started with a mean of 18.4, dropped to 13.5, and then nudged up again to 14.8.

Statistically, fit mothers have a lower incidence of depression. In one survey of one thousand women in the South of England six weeks after childbirth, the 35 percent who reported doing vigorous exercise three times a week had significantly fewer mood problems. They also had lost more weight, stayed more socially active, and felt more confident and satisfied in being mothers. An exercise routine can help new moms reestablish control over their lives and keep them from feeling overwhelmed. It also provides a great way for them to take time for themselves, which is important in staving off resentment. Like Stacy, about 70 percent of women are dissatisfied with their bodies at six months after childbirth, and obviously exercise can get them back in shape and boost self-image.

Unfortunately, the message that exercise provides something more than physical redemption has been slow to reach doctors and their patients. “People think of exercise in terms of physical health, but not mental health,” says Jennifer Shaw, an obstetrician-gynecologist in Brookline, Massachusetts, who is a clinical instructor at Harvard Medical School. “It’s difficult as a physician to get people to take exercise seriously, as a treatment that actually has medical benefits aside from taking off the pounds.”

The field of obstetrics isn’t really set up to diagnose or treat mental health issues related to pregnancy. Shaw will bring up exercise as a solution to a problem, but she says it’s hard for any physician to find the time to discuss preventive medicine. It can also be dicey, she points out, to suggest exercise to a woman who’s juggling so many new responsibilities and might not be feeling so hot about her body. “The first thing to drop off the list when life gets more complicated for women is exercise,” Shaw says. “I don’t think there’s an appreciation for what it does, but I do think it has a stabilizing effect on mood.”

The worst advice for new mothers who are feeling down is to take it easy. Rest is important, certainly, but not as important as activity. New mothers need support from their husbands to carve out the time to work on their bodies — and their brains — as soon as possible.

MENOPAUSE: THE BIG CHANGE

Strictly speaking, menopause is a one-day event that marks the end of the twelfth month after a woman’s final period. More practically, it represents the span of hormonal changes surrounding that moment. As the ovaries become less reliable with age, production of estrogen and progesterone becomes sporadic and falters. When these hormones fall out of phase, the brain’s delicate balance of neurochemicals gets disrupted.

Symptoms typically kick in several years before menopause, between the midforties and midfifties (the median age for menopause is fifty-one), and might last several years afterward. They include the so-called vasomotor symptoms of hot flashes and night sweats as well as irritability and mood instability. And as with the other hormonal shifts I’ve discussed, there’s no predicting how someone will be affected — some pass through menopause without really noticing, and others are tormented. Most women experience at least a few of the symptoms, and many of those who exercise find that it helps. The great value of exercise for women beyond menopause is that it helps balance the effects of diminished hormones, and as you’ll see in the following chapter, it protects against cognitive decline. From an evolutionary perspective, exercise tricks the brain into trying to maintain itself for survival despite the hormonal cues that it is aging.

Exercise also provides protection, lost to the ebb of natural hormone levels, against health problems such as heart disease, breast cancer, and stroke. It’s rare for premenopausal women to have heart attacks unless they have a genetic predisposition or complications such as obesity or diabetes. This has always been the rationale behind hormone replacement therapy (HRT): estrogen and progesterone protect women against chronic disease, so these hormones need to be replaced after menopause. In recent years, however, this assumption has been overturned, and now many doctors simply won’t prescribe HRT.

The controversy erupted in 2002 when researchers at the National Institutes of Health noticed some alarming statistics for a group of postmenopausal women participating in one of a series of Women’s Health Initiative studies. The women undergoing HRT had a 26 percent higher risk of breast cancer, a 41 percent higher risk of stroke, and a 29 percent higher risk of heart attack.

In the wake of this disturbing news, millions of women stopped taking hormones, and the New England Journal of Medicine published a population survey showing that in 2004 breast cancer rates dropped 9 percent. Then a prominent British study reported that women on HRT have twice the risk of developing dementia, which is a major concern for anyone beyond middle age. However, there are studies supporting the use of HRT for short periods during menopause. The only universal advice for menopausal women is to ask your doctor. Whatever the answer, the contradictions put many women in a painful bind.

CONSIDER THE SYMPTONS

The most common reason women seek HRT is to alleviate the physical symptoms of menopause, specifically hot flashes, and nobody disagrees that it works wonders on this front. Exercise is one alternative, although evidence for its effects on hot flashes and night sweats is inconclusive. Several large observational studies, one of which included sixty-six thousand menopausal Italian women, have shown that lower levels of exercise correlate to more vasomotor symptoms, but other studies have shown no association.

Some ob-gyns will tell you that exercise actually triggers hot flashes. At least with exercise you can safely conduct your own experiment without fear of long-term side effects. Either it helps relieve your symptoms or it doesn’t, but you don’t have to worry about it undermining your health down the line. What gets lost in the question of whether exercise helps menopausal women with hot flashes is the big picture, namely that it guards against heart disease, diabetes, breast cancer, and cognitive decline.

The physical symptoms of menopause exacerbate the mood symptoms, and there’s no question exercise helps in this regard. One woman told me that the most frustrating part of aging is that she feels like her body is out of control. She gained weight, suffered hot flashes and high blood pressure, and her vision deteriorated. On top of that, she feels anxious and depressed at times. What exercise provides is a sense of control, over the physical changes but more so over the emotional ones. “I know that exercise helps to contain many of these symptoms,” she says. “It helps guide me, so that I can be as proactive as possible in dealing with some of these things that are so out of my control.”

As with PMS, in menopause it seems to be the fluctuations, not the levels, of hormones that leave some women vulnerable to anxiety and depression. Women are twice as likely as men to suffer from anxiety and depression to begin with, and that risk increases further when they enter menopause, according to a study conducted by psychiatrist Lee Cohen, a women’s health specialist at Massachusetts General Hospital. As part of a larger effort called the Harvard Study of Moods and Cycles, he followed 460 women, thirty-six to forty-five years old, for six years to compare mood changes as they entered menopause. None had any history of depression, but their risk of developing it doubled during menopause.

In a recent survey of 883 women (ages forty-five to sixty), researchers from the University of Queensland in Australia found a strong correlation between exercise and menopausal symptoms. An astounding 84 percent of the women reported that they exercised two or more times per week, and they had significantly lower rates of the physical and mental symptoms of depression than nonexercisers. Specifically, they felt less tense, tired, and fatigued. They reported fewer headaches and less tightness or pressure in their bodies. Overall, the study concluded, exercise can have a tremendous impact on a woman’s sense of well-being and quality of life.

EXERCISE REPLACEMENT THERAPY

It’s well established that more women suffer from Alzheimer’s disease than men, even when the statistics are adjusted for the fact that women live longer. On the other hand, the protective effects of exercise on cognitive decline seem to be magnified among women. In a 2001 study published in the Archives of Neurology, Danielle Laurin of Quebec’s Laval University analyzed the relationship between exercise and physical activity among a group of 4,615 elderly men and women over the course of five years. Laurin found that women over sixty-five who reported higher levels of physical activity were 50 percent less likely than their inactive peers — women and men alike — to develop any form of dementia.

Until the Women’s Health Initiative came along, scientists believed that HRT protected against cognitive decline, but the evidence doesn’t support that conclusion. Now, one of the questions researchers have begun to tackle is whether exercise and hormones have interactive effects on cognitive decline after menopause. Research from Carl Cotman’s lab at the University of California, Irvine, suggests that estrogen is necessary for exercise to increase levels of BDNF in the prefrontal cortices of female rats. But the design of the study doesn’t necessarily translate to the conditions of menopause in humans — the rats’ ovaries were removed at three months of age, which equates with young, healthy women. The first human reports on this question suggest that estrogen is not an essential ingredient for exercise to protect against cognitive decline. In one study, physiologist Jennifer Etnier, who is now at the University of North Carolina at Greensboro, administered tests of mental processing speed and executive function to 101 postmenopausal women and compared the results to their reported levels of regular aerobic activity. Those who were more physically active had higher scores regardless of whether they had been undergoing HRT.

The most telling study on this subject comes from the lab of psychologist Arthur Kramer at the University of Illinois, Urbana-Champaign, which has been at the forefront of correlating certain cognitive abilities with changes in brain structure identified in MRI scans. He wanted to see whether exercise and HRT interacted in their impact on executive function and the volume of the prefrontal cortex. In a complicated design, he recruited fifty-four postmenopausal women, each of whom agreed to an MRI scan, mental tests of executive function, and a treadmill test of their maximal rate of oxygen consumption (VO2 max) to measure fitness. The data was sorted into four categories based on duration of HRT. The first group had never had hormone treatment, and the rest fell into short-term (ten years or less), midrange (eleven to fifteen years), and long-term (sixteen years or more) treatment.

The results, published in 2005, showed that women in the short-term HRT group performed better on the tests and had greater brain volume than women who had never had therapy or those who had had more than ten years. Which suggests that HRT can, in fact, be protective in the short run. When aerobic fitness was factored in, it had a significant impact on measures of performance and brain volume. Better fitness seems to offset the decline women would otherwise experience if they had never had HRT or if they had had it for more than ten years.

One of the theories from rodent research is that with long-term HRT, estrogen receptors in the brain begin to break down in the hypothalamus, the area that activates the immune response. And if the hypothalamus is not working correctly, women would be more vulnerable to diseases such as cancer. Equally important, long-term estrogen treatment in rodents also causes cellular inflammation, which is a risk factor for Alzheimer’s and is associated with memory impairment.

What Kramer suggests is that exercise seems to enhance the positive effects of short-term HRT, and this fits in with the neuroprotective mechanisms I’ve described throughout the book. Exercise sparks production of neurotransmitters and neurotrophins, creates more receptors for them in key areas of the brain, and turns on genes that keep the positive cycle spinning. That momentum is crucial for any woman, but especially from menopause onward. After all, most women live for decades without their hormones.

ESTABLISH A ROUTINE

At least four days a week, I suggest getting out there and walking briskly or jogging or playing tennis or engaging in some form of activity that will get your pulse up to 60 to 65 percent of your maximum heart rate. You want to keep it there for an hour. People always want to know what type of aerobic activity is best, and the answer is whatever is going to allow you to build it into your lifestyle. The important thing is to stick with it, and make sure you’re elevating your heart rate enough to get the benefits. It’s also important to mix in strength training a couple of days a week, to shore up your bones against osteoporosis.

For younger women with PMS, I would suggest five days a week of aerobic exercise at the same level, but it might be a good idea to mix in more intense bursts like sprinting on two of those days, though not back-to-back. Some of the studies suggest that higher intensity effort has a more dramatic effect on symptoms such as irritability, anxiety, depression, and mood instability. And if your symptoms are particularly bad, and you’re not completely sidelined with cramps, it’s probably a good idea to do something every day during the premenstrual phase of your cycle.

The advice that surprises people the most, I think, is that it’s important to keep up exercise during pregnancy, a recommendation that has finally been endorsed by the American College of Obstetricians and Gynecologists. Its guidelines specify thirty minutes of moderate-intensity aerobic activity every day during pregnancy for healthy women. Obviously, it’s important to get clearance directly from your obstetrician, but it’s safe for most women. Likewise, I can’t stress enough the importance of picking up your routine as soon as possible after the baby is born, ideally within a few weeks. Although it seems contradictory, moving will actually reduce fatigue. And for women like my patient Stacy, it melts away anxiety and depression.

When women are younger, one of the big motivations to exercise is to stay trim, and that’s fine. Use whatever gets you going. But the message I want to leave you with is that even as your body changes, exercise will keep your mind firm and taught. And in this state of mental fitness, you’ll be well equipped to handle the hormonal fluctuations that every woman experiences throughout her life. Not to mention the fluctuations of life itself.