OB/GYN: Risk Factors Found for Depression Prior to Menopause Social Medicine: Sharp Rise in Disordered Eating in Fiji Follows Arrival of Western TV Clinical Trials: Gene Therapy for Hemophilia Tested Minority Health Policy: Alums to Broaden Access to Care Ethics: Programs Address Ethics in International Research Books: Summer Reading Type of Oncogene-Caused Leukemia Linked to Progenitor Cell Type P53 May Induce Death in Cells with Short Telomeres Certain Dietary Fat May Protect Against Heart Attacks New Channel Suggested in Pheromone Signaling Framework Developed for Diagnosing Coronary Artery Disease Martinos Gift Creates New Imaging Center in HST Appointments to Full and Endowed Professorships In Memoriam: Thomas Sandson Honors and Advances Getting in Touch with the Human Side of Illness Front Page

OB/GYN Risk Factors Found for Depression Prior to Menopause Data Show Nearly 10 Percent of Premenopausal Women Are Clinically Depressed "If we can understand the underlying hormonal mechanisms, we may be able to find a treatment to put women at less of a risk for developing depression," Bernard Harlow says. Among the many myths surrounding menopause is that it presages a blue period in a woman's life—a time of dark moods and, in some cases, deep depression. In fact, women are more likely to become both mildly and severely depressed in the 10 years before their ovaries finally cease their monthly cycle. What researchers haven't yet fathomed is who is most likely to suffer and why.     A new study by Bernard Harlow, HMS associate professor of obstetrics, gynecology and reproductive biology, and his colleagues could help answer these questions and, in general, dispel some of the mystery about menopause and the period leading up to it. The study of 4,161 women in their late 30s and early 40s reveals an unusual mix of factors that singly and together increase a woman's risk of developing major depression. Links to Disease As might be expected, women who underwent the breakup of a marriage—separation, divorce, or the death of a spouse—were more likely to be depressed. This was also true of women who smoked cigarettes. More intriguingly, Harlow and his colleagues found that women who began menstruating at a relatively young age or who had never been pregnant were at significantly greater risk. So too were women with a history of premenstrual symptoms. The findings by the Brigham and Women's researchers appear in the May Archives of General Psychiatry.     What was also surprising, says Harlow, is how high the risk of depression was. Nearly one in 10 women in their study suffered from the constellation of symptoms—loss of appetite, insomnia, inability to concentrate, feelings of sadness, hopelessness, and inertia—that define this debilitating disorder. Previous studies suggested the prevalence was 6 to 8 percent.     "And ours is a very conservative estimate—it doesn't even include the women who were cycling out of depression at the time they were being studied," says Harlow. "What this says is that depression in premenopausal women is a major public health problem." Even more troubling, he says, is that only 40 percent of affected women seek treatment.     The high risk of depression faced by women, nearly twice that faced by men, and the incidence of depression peaking in the early forties, whereas it increases throughout life for men, suggests reproductive changes may play a role. Specifically, researchers suspect it may have to do with a decline in ovarian and hormonal function. Harlow agrees. In fact, he believes a possible key may lie in the number of times a woman undergoes her menstrual cycle and therefore the rate at which she depletes her cache of egg-swaddling follicles.     Harlow explains: Each month a woman's ovaries release not just one but a whole bunch of follicles. "You're letting out lots of eggs, though only one is usually available for conception," he says. Each follicle is a tiny estrogen producing factory. The more frequently a woman cycles—for example, by having shorter periods or never taking oral contraceptives—the sooner she will deplete her supply of follicles. This would also be true of women, like those in Harlow's study, who began menstruating at an earlier age and who never became pregnant.     Interestingly, the smokers in Harlow's study may also have been losing eggs more rapidly. Smoking damages the ovaries, actually killing follicles—and women who smoke are known to reach menopause on average 1 to 2 years earlier than those who do not.     How exactly the decline in estrogen-producing follicles in these women makes them more susceptible to depression is not clear. Estrogen is known to affect the nervous system through estrogen receptors. Yet most of the effects are thought to be on cognitive processes, whereas depression is an emotional disorder. A decline in estrogen is also known to stimulate the production of gonadotropins. These hormones are thought to be linked, in turn, to the pathway that produces serotonin which, when deficient, may contribute to depression. But Harlow emphasizes that how all this adds up is not clear.     "At this point, how exactly estrogen works in the development of depression is an unanswered question," Harlow says. The Pattern of Attraction Harlow has long been intrigued by such mysteries. "I tend to pounce on any area that has a relationship between a reproductive or endocrine problem and something that's psychiatric," he says. In the early 1990s, he and Dan Cramer, associate professor of obstetrics and gynecology and co-author on the current paper, conducted a study exploring the impact of gonadotropin production on risk for ovarian cancer. They noticed among the controls a curious association: women who had never taken oral contraceptives, become pregnant, or breast fed and who had shorter cycles and earlier menarche tended to enter menopause at an earlier age—and tended to become depressed more frequently.     Intrigued, they undertook a survey of women 45 to 54 years of age. They found that those who said they entered menopause before the age of 47 were two to three times more likely to report that they were previously or currently depressed for a period of a year or longer. Wondering whether the early menopause had triggered the depression or the other way around, they embarked on the current project, the Harvard Study of Moods and Cycles.     Unlike the previous study, this one is limited to women who have not yet entered menopause. Using standardized questionnaires, the researchers produced a snapshot of the reproductive and psychiatric history of 5,000 women aged 36 to 44 drawn from communities in and around Boston. In this initial pool, they found 929 cases of women with current depression, 1,153 women with a past history of depression and 2,079 never-depressed women.     Through telephone and in-person interviews, Harlow and his colleagues will keep track of changes in the psychiatric status of a subset of these women. Using blood samples taken every six months, they will monitor hormone levels that signal whether a woman's ovaries are declining in activity.     In fact, their psychiatric and endocrinological measurements are so refined that Harlow expects to be able to see gradations in the associations between depression and risk factors such as years of cigarette smoking, age at first menstruation, number of births, and premenstrual symptoms. "Even in the current study you can see a kind of dose response in relation to severity of depression," he says.     Ultimately, Harlow hopes to see the interaction between ovarian decline and depression as it is happening. "Do women with depression go through menopause earlier than those without depression? Are women without depression but with declining ovarian function—as reflected in their hormone levels—more likely to develop depression?" he asks.     Of course, factors other than ovarian decline may cause depression in these women. "We have tremendous information on psychiatric measures—information about anxiety, neuroticism, social support, life events. So we can tease out hormonal associations from the psychiatric factors," Harlow says. "Clearly, the current paper is just the tip of the iceberg of what we want to look at." —Misia Landau Back to Top