Do hormones really affect women' mood?

In the past fifteen years the field of endocrinology has produced vast amounts of evidence showing that the loss of estrogen that occurs normally during menstrual cycle changes puts women at greater risk for mood, anxiety, and craving disorders. Considering the prevalence of these illnesses among women, we’re fortunate to be gaining a better understanding of them.

Women are more than twice as likely to become depressed. Research shows that they’re also more likely to suffer from anxiety. More develop phobias. It’s the same ratio for agoraphobia: nearly 8% of women become agoraphobic, compared to only 3% of men. More succumb to post traumatic stress syndrome. Seventy percent of those with social phobia are women. What could be happening here?

The cyclic nature of estrogen secretion may account for women’s special vulnerability to mood and anxiety disorders, Dr. Mary Seeman reported, in the Journal of the American Psychiatric Association, in an analysis of dozens of studies on how female hormones affect psychopathology in both men and women.

The theory of “recurrent estrogen withdrawal” proposes that a low estrogen state drives the onset, or worsening, of mood symptoms in women who are predisposed--by virtue of already low serotonin levels--to mood and anxiety disorders. In 1996, researchers at the University of Edinburgh published a report discussing the molecular level at which these changes occur. Struck by estrogen’s “profound effects on mood, mental state and memory” they described the hormone as “nature’s psychoprotectant.” Sufficient levels of estrogen must be present in the brain, that is, if psychic stability is to be maintained. Estrogen’s importance to cognitive processing and memory is not a slight matter. It’s been discovered that actually buffers the brain’s neurons against degeneration.

By the end of the nineties mounting evidence had begun to show a unique and persistent hormone connection to almost all mental illness in women. For example, binging and purging behaviors in bulimics worsened during the premenstruum, when estrogen levels go down. So did panic attacks in women with panic disorder. Impulse disorders, too, seemed to get worse during that week or ten days before the period begins--kleptomaniacs went on more stealing escapades, trichotillomaniacs pulled more hair, skin cutters cut more skin.. All of these illnesses are related to serotonin dysfunction, and, as we’ve seen, serotonin and estrogen are inextricably linked.

In the nineties a Canadian psychologist, Barbara Sherwin, was conducting very interesting studies on how estrogen loss affects cognition and memory. I went to Toronto to spend a day with Dr. Sherwin in her office at McGill University. I needed a mini-course in estrogen and she was willing to give it to me.

From early fetal life, hormone receptors are present in the hypothalamus of the brain. It is here that they begin organizing brain circuitry, setting the stage for puberty, regulating subsequent adult sexual behavior, and controlling the frequency and intensity of emotional disorders. Research in neuroendocrinology has much to tell us about the pre-menopausal malaise that used to be thought the result of women’s sadness over the loss of reproductive function. Now it’s known that the mood and cognitive changes experienced are physical in origin.

Low estrogen affects mood. What I hadn’t known, until speaking with Dr. Sherwin, is that in order to produce serotonin the brain needs estrogen. I didn’t even known that estrogen existed in the brain. “There are estrogen receptors in various organs throughout the body, the brain included,” she explained. “That’s why estrogen loss produces so many different bodily symptoms--loss of skin elasticity, bone shrinkage, mood and cognitive decline”.

When estrogen levels rise, on the other hand, as they do in the first week of menses, their overall effect is to increase the amount of serotonin available in the spaces between the brain’s nerve cells. That improves mood. Within the brain, estrogen may in fact act as a natural antidepressant and mood stabilizer.

Dr. Sherwin introduced me to the work of researchers who were doing important basic science, including Bruce McEwen at Rockefeller Institute, in New York, and Joseph LeDoux, at New York University, who were discovering the molecular changes supporting the view that estrogen had profound effects on the mind and its capacities.

It wasn’t long after my visit with Dr. Sherwin that I learned of an important review of ten years’ worth of studies entitled, Estrogen, Serotonin, and Mood Disturbance: Where is the Therapeutic Bridge? Two researchers in the Perinatal and Reproductive Psychiatry Program at Harvard Medical School had essentially been motivated by the same question that I had: What is the hormone connection to women’s mental health? Joffe and Cohen looked at a hundred-and-twenty five studies on the relationship between women’s reproductive cycle hormone changes and their mental status. In study after study they found that women with histories of depression are apparently more vulnerable to recurrent episodes during periods of “significant reproductive endocrine change”.

Correlation does not prove causality. The fact that someone becomes morbidly depressed exactly on the day ovulation begins and remains that way until the day she starts bleeding doesn’t prove that premenstrual drops in estrogen cause mood changes, but it damn well raised suspicions. Once information from new brain imaging techniques was added to the mix, the case for a hormone connection to women’s mental vulnerabilities became as close to an open and shut case as are you’re likely to get. Neuro-imaging has improved our understanding considerably, indicating lightening flashes of activity in different parts of the brain during what used to be called, dimly, “that time of the month.”

It is the dance between two kinds of hormones, ovarian hormones and brain hormones, that ultimately determines how symptomatic any given woman will become during her menstrual cycle, and at other reproductive risk points as well. If, for example, a woman is genetically coded to have low, or borderline levels of brain serotonin, the estrogen drop that occurs premenstrually may be all it takes to send her serotonin spiraling below the level of optimum functioning, putting her in a mental state that, for all its upsetting symptoms, mysteriously vanishes as soon as her period starts and her estrogen levels go back up.

Why does this happen? Because serotonin needs estrogen for its metabolization in the brain. The two hormones are a dynamic duo, functioning arm in arm. As estrogen levels drop, so does serotonin. When estrogen rises (as it does, for example, once menstruation begins) serotonin levels come right back up with it, and calm is restored. The ebb and flow of womens’ menstrual moods is orchestrated not by the moon but by secretions in her brain and ovaries. What we now know is that the sometimes negative outcome of these secretion changes is not inevitable. Just as science has learned to modify insulin changes and thyroid changes, it can now modify ovarian changes. If you don’t want to blame your mood on your ovaries, blame it on the brain. Blame it on whatever pleases you, just don’t resign yourself to the view that women were born to suffer.

To me it’s fascinating that the individual pieces of this important puzzle were not available to us twenty years ago. And the dynamite effect of putting those pieces together has occurred only in the last decade. Building on previous knowledge and assembling the picture step by step, endocrinologists at places like the Neuropsychiatric Institute in California, and the Reproductive Mood Disorder Program at the University of Texas Medical Center have come to understand that women are not only vulnerable during the premenstruum, they are vulnerable at all the reproductive risk points. Moreover, a woman who suffers at one of these risk points is vulnerable to becoming symptomatic at others. If she has genetically low serotonin in her brain, estrogen drops are going to affect her, simple as that.

Things have taken a more enlightened turn since then, thank God, but we are only now coming to understand what actually happens to women’s mental well-being at times of hormonal stress. Women scientists in particular, including psychiatrists and reproductive endocrinologists like Barbara Sherwin, are making a unique and important contribution to the massive surge of research that is currently shaping a whole new paradigm for understanding the role of hormonally created change in female well-being and mental status.