News flash: Men and women are different. OK, so that’s not really news — except in some corners of the world of medicine. Researchers are developing a growing understanding of how sex plays a role in many diseases, including depression.

It has long been known, at least statistically, that women are nearly twice as likely as men to be diagnosed with depression. Now, science is beginning to uncover why. It may start with brain structure. “Male and female brains have differences,” says Dr. Jerrold Rosenbaum, professor of psychiatry at Harvard Medical School and psychiatrist-in-chief at Massachusetts General Hospital. “Some psychiatric disorders are more prevalent in men, like autism and schizophrenia, while depression and anxiety are more common in women. This is presumed to reflect biological differences in brain organization.”

Those differences are likely triggered by the hormones that generate sex, specifically estrogen and testosterone. Sex differences begin in the earliest months of life — during gestation. Studies have found differences in vulnerability to stress, which is known to play a role in depression, between male and female fetuses, Rosenbaum says. “Females are more vulnerable to stress in utero, and more vulnerable to depression post-puberty,” he says.

Hormones are further implicated by the fact that the rates of depression are roughly equal among males and females both before puberty and after menopause. It is during the hormonally charged years of puberty, childbearing and menopause that women are more likely to develop depression.

“There is a different hormonal milieu for women, and those fluctuations in sex hormones appear to confer some risk,” says Dr. Steven C. Schlozman, assistant professor of psychiatry at Harvard Medical School and associate director of The Clay Center for Young Healthy Minds.

“The fact that the ratio seems to lessen around menopause provides more evidence for a hormonal explanation.”

[See: 11 Changes Women Go Through in Menopause.]

The Risks of Being Female

Hormones can’t take all the blame. Other biological factors, such as a family history of mental illness and exposure to traumatic events, are other risk factors for developing depression. Males also have hormone surges in puberty and may go through “manopause” later in life as testosterone levels naturally drop. But female hormones fluctuate more, and more often.

The onset of puberty brings with it the potential for premenstrual syndrome, or PMS. The Mayo Clinic says that PMS symptoms such as bloating, breast tenderness, headache, anxiety and irritability also may include a short-lived bout of “the blues.” However, PMS can worsen into premenstrual dysphoric disorder, a form of depression that needs to be treated.

Pregnancy and its related hormonal changes also can have an impact on mood. So can other pregnancy-related stresses, such as changes in lifestyle or work, relationship difficulties, a pre-pregnancy history of depression and an unintended or unwanted pregnancy. Fertility problems present another set of challenges.

Risk for depression rises after the baby is born. Postpartum depression — which is more than the “baby blues” that many new mothers experience — is a serious medical condition that occurs in about 10 to 15 percent of women, the Mayo Clinic reports. Along with the typical depression symptoms, postpartum depression may cause the following:

— Low self-esteem.

— Feeling like you’re a “bad mother.”

— Anxiety.

— Feeling “numb.”

— Sleep problems beyond the normal newborn disruptions.

— Inability or lack of desire to care for the baby.

— Thoughts of harming your baby or yourself.

At menopause, the lowering of estrogen levels puts women at risk for depression. Paradoxically, there is some evidence that, although estrogen fluctuations may be a risk factor, estrogen itself offers a protective effect against depression, Rosenbaum says. “As women go through menopause, the risk of depression increases as they lose those protective effects of estrogen,” he says. “That is also true when women stop estrogen replacement therapy.” Once hormone levels stabilize, women and men exhibit comparable rates of depression.

[See: Coping With Depression at Work.]

Different Triggers, Different Responses

According to a study in the Journal of Psychiatry & Neuroscience, triggers for depression also appear to present themselves differently in men and women. A study of fraternal twins, for instance, found that women were more sensitive to interpersonal relationships, while men were more sensitive to external factors such as careers and goals.

Along with hormones, there are other differences in how depression may be triggered in men and women. “There are more social determinants, like different pressures and expectations, on women,” Rosenbaum says. “There is also a greater risk of exposure to emotional trauma, particularly sexual abuse.” Other social stresses, including domestic violence, economic vulnerabilities and family pressures weigh more heavily on women. “While we are evolving to be more balanced in terms of expectations and support, society still obviously has some gender bias,” he says.

Other factors in sex difference include thyroid disease, which carries a risk of depression and is more common in women. In addition, females metabolize medications differently than men, Rosenbaum says. “Dosages need to be adjusted for certain drugs. That is something to pay attention to,” he says.

Men and women also differ in the most dangerous fallout from untreated depression. Women attempt suicide more often than men, but men are more likely to complete the act, he says.

[See: 9 Things to Do or Say When a Loved One Talks About Taking Their Life.]

Despite these obvious differences in causes, both men and women are treated in similar ways. “By and large, treatment approaches are the same for both sexes, though we may learn that we can do better than that,” Rosenbaum says. It may be that women respond more to treatments that include interpersonal therapy that emphasizes social connectedness, while men are better suited to other forms of psychotherapy, he says, “but there is not a lot of evidence to support that.”

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Depression Risk: How It Differs for Men and Women originally appeared on usnews.com