Marianne Legato may not quite shout out “Vive la Difference!” at work every day, but she has done well by examining why it is that gender difference makes a difference in the way men and women live, love, and labor.

“It’s a cliche to say that men and women are built differently,” the Columbia University professor of medicine said yesterday. “But beyond reproductive biology, just how significantly different are they? And why does it matter that they are different?”

Dr. Legato, a cardiologist and internist, has sought to come up with answers to such questions during a long and distinguished career of research, teaching, and writing. She helped to set up Columbia’s acclaimed Partnership for Gender-Specific Medicine, edited a widely used textbook on gender-specific medicine, and launched a professional journal on the subject.

The New Jersey-born Dr. Legato recently formed a foundation to further her research, and she is teaming with Johns Hopkins University in a new enterprise that will once again bring her together with her former Columbia mentor, Dr. Myron Weisfeldt. The affiliation will enable Dr. Legato and her colleagues to train young physicians in what she called “a new view” of gender-specific medicine.

Encouraging young physicians is a special concern for her in part because she was the beneficiary of special tutelage at a tender age, Dr. Legato said.

How tender?

“Four years!” she said. “My father, Samuel Legato, was a physician – the only doctor, in fact, in Cliffside Park, where we lived. He would frequently take me to St. Mary’s Hospital in Hoboken, where he practiced, and also on house calls. I remember saying to myself, ‘This is not a bad way to lead life – healing people, helping their families.’ I decided early that I was going to be a doctor.”

That decision took her to Manhattanville College, and then to New York University, where she obtained a medical degree.

How did she get interested in gender-specific medicine?

Well, she pretty much invented the field in cooperation with titans such as Dr. Weisfeldt, transforming what had been a scattershot system of studies into a discipline that’s now recognized internationally. Along the way, Dr. Legato has written several books with alluring titles like “Why Men Never Remember and Women Never Forget.” Such titles suggest a transmutation of her specialized research on the biology of gender differences into a study of the psychology of gender differences.

“The information about how gender modifies normal human function is sparse and scattered haphazardly throughout the medical literature – because few, if any, thought it was important,” Dr. Legato said.

Her discoveries flowed out of her early work in the research lab.

“It all began when I was looking at heart tissues under an electron microscope,” Dr. Legato said. “I found that hearts are not only adaptable, they also have memories.”

That finding led to other research. She studied the fact that men have larger brains than women but women have more intricate and extensive connections between nerve cells in the brain, particularly in the frontal cortex. This is the area involved in judgment and decision making – the “executive center” of the brain.

“Ounce for ounce, women may have more brain bang for the buck because of the greater degree of connectivity between cells,” Dr. Legato said. “Men have 52% higher levels of serotonin, a chemical that’s important in maintaining mood, than women. This is postulated to be one of the reasons depression is twice as frequent in women compared to men.”

Dr. Legato concluded that the risk factors, symptoms, cures, optimal diagnostic techniques, and responses to treatment for coronary-artery disease are different for men and women.

“Recently, we have discovered that there is a subset of women who have constriction of their coronary arteries that is severe enough to result in death of a portion of the heart muscle – a myocardial infarction – without any evidence of arteriosclerotic plaque obstructing their arteries,” she said. “This is not the case for men, and we now believe that for some women, at least, the road to a heart attack is very different for women than for men.”

The paramount value of understanding the biology of gender differences lies in the fact that it can offer clues to better treatment of diseases.

“The medicines we take into our body have to be broken down or ‘metabolized’ so that they can be eliminated from the body by the kidneys or, less frequently, by the lungs,” Dr. Legato said. “The place most of this is done is in the liver, by a system of enzymes that slice and dice the medication and pre pare it for elimination. The enzymes are quite different in the sexes, and women metabolize some medicines differently than men.

“Hormones also influence drug metabolism: Just before their menstrual periods, for example, dilantin [which controls seizures in epileptic women] is broken down faster in women than at other times in their cycle. So ‘catamenial epilepsy,’ or a seizure just before the menstrual period, is unique to women. Other unique biological characteristics of women’s hearts make them sensitive to developing arrhythmias in response to drugs that control arrhythmias or help to maintain a normal heart rhythm in men.”

The biological difference between women and men is so extensive that modern medicine hasn’t fully grasped it, Dr. Legato said.

“Take the gastrointestinal tract – women have different flow rates of saliva from men; men have twice ours,” she said. “The sodium, potassium, and sugar content of our saliva varies with the menstrual cycle. At mid-cycle, the time of ovulation, the enzymes that help to digest our food are more active than at other times, presumably to ensure maximal nutrition for any fertilized ovum.

“Moreover, food leaves the stomach more rapidly in men than in women, and women are less tolerant to alcohol because they have much less of the enzyme that breaks down alcohol in the stomach compared to men,” Dr. Legato said. “Ounce for ounce, women experience a greater impact from alcohol than men.”

She’s working on a book, “Why Men Die First,” that will incorporate her new research. “You’ve only to visit Florida to see for yourself how many lonely women there are in retirement communities,” Dr. Legato said. “Perhaps if we understood biological gender differences better, men would live longer. We would be able to change the length and quality of human life.”