Text: Julie Zaugg
Photo: Boston Globe via Getty images

Paula Johnson: “We need a better understanding of the differences between the sexes”

“Women are not included enough in clinical trials.” Paula Johnson, an internationally renowned women’s health specialist, believes that this negatively affects their care.

Disease does not affect men and women in the same way. Some diseases are even “women-only”. Paula Johnson, Professor of Medicine at Harvard Medical School (USA) and Executive Director of the Connors Center for Women’s Health and Gender Biology, explains why women’s health can’t wait.

IN VIVO Why are men and women not equal when it comes to disease?

PAULA JOHNSON Gender is a genetic construction. There are fundamental differences between men and women in their genes. When these differences are combined with the influence of our hormones, environment and gender – i.e. the roles, behaviour and attitudes that society attributes to each sex – the disease is experienced differently in men and women.

IV Can you give us an example of a disease that affects the two sexes differently?

PJ Women with diabetes have a higher risk than men with the same condition of developing high blood pressure. Cardiovascular disease has the same symptom of chest pain in both sexes, but women are significantly more likely to experience shortness of breath or discomfort in the upper abdomen. Since this disease has been less studied in women, the latter symptom is often confused with gallbladder pain, which can lead to misdiagnosis.

IV Apart from genetic differences, do men and women also react differently to their environment?

PJ Of course. Stress affects women much more than men. There is a condition called the “broken heart” syndrome. It can be triggered by a traumatic event, like the sudden loss of a loved one or a major change in one’s physical environment following an earthquake. It can cause the heart dysfunction. The vast majority of patients afflicted by the syndrome are middle-aged women, whereas men are almost unaffected.

Nor are the two sexes equal in terms of obesity. The areas of the brain associated with regulating the desire for food are not the same in men and women. A study recently showed that when women live in a violent situation, their risk of obesity increases. This is not the case in men.

IV Are there actually “women-only” diseases?

PJ Yes, lymphangioleiomyomatosis (LAM) is a rare disease that causes abnormal growth in lung cells and ends up destroying the organ. It only affects women. It is often diagnosed very late, once it’s already too late, because doctors don’t think of testing their female patients for the condition. Similarly, most of the auto-immune disorders, such as multiple sclerosis, lupus and rheumatoid arthritis, are much more prevalent in women. However, the rate of mortality for men with these diseases is far higher.

“Including different factors in research allows for personalised healthcare.”

IV If they’re so different, should there be distinct methods used to diagnose men and women?

PJ For certain diseases, yes. The standard test used in cardiac catheterisation to detect a heart condition in women often comes out negative. The procedure involves inserting a tube (catheter) into a vessel and injecting dye into the bloodstream. By measuring pressure and blood flow in the heart and vessels, doctors can detect any blockage in the arteries. This is often easily visible in men, but in women this method does not always show the plaque because it is lies more evenly along the blood vessels. Women are even frequently told that they’re in good health and sent home, while they’re actually suffering from a heart condition.

IV So what can we do about it?

PJ We have solutions that are better suited to diagnosing heart conditions in women. An intravascular ultrasound or FFR (fractional flow reserve), used to measure blood flow in arteries, is better at detecting a less conspicuous build-up of plaques in the blood vessels. But then again, it has to occur to doctors to use these methods. They have to remember that there are differences between the sexes.

IV And when a doctor is treating a patient, do they have to think of prescribing a different treatment depending on the sex?

PJ It’s worth considering. Remember the study that came out in the early 1990s that recommended taking one aspirin per day to prevent heart attacks. Well, it was based on a group of exclusively male patients. When the hypothesis was finally tested on women just over eight years ago, the findings showed that aspirin only had the effect on patients over age 55. It helped prevent strokes, but not heart attacks.

Another example came a few years ago during tests on a new lung cancer therapy involving genetic mutations found on the surface of cancer cells. The initial findings looked promising. But by taking a closer look, they found that the treatment was more successful in women (82%). In fact, the genetic mutations targeted by the drug occurred almost exclusively in women. It was a crucial discovery, which encourages a more personalised treatment approach based on the sex of the patient.

IV What can we do to make sure that this type of success does not remain an isolated case?

PJ We need to improve the understanding of the differences between men and women. We had to wait for a law to be passed in 1993 to include women in clinical studies in the United States. The oldest data that we have on women’s reactions to disease only date back about 20 years. We know that women often experience illness differently, for example in heart conditions, but we don’t know why. We have to make sure that women are systematically included in clinical trials – and the same for female animals in pre-clinical testing – and that gender is factored in when results are reported. This is not always the case. Still today, only 33% of participants in studies on cardiovascular diseases are women. Similarly, in neuroscience, 66% of pre-clinical studies are conducted only on male animals or do not report the gender.

IV How do you explain these shortcomings?

PJ Following tragic scandals such as Thalidomide (Editor’s note: a drug used in the 1950s and 1960s to prevent morning sickness in pregnant women which caused serious congenital defects), clinical testing wanted to avoid including people who might be pregnant. But that’s not the only reason. We live in a male-dominated world. A greater diversity in profiles, especially more women, in the medical profession and among researchers would certainly make a difference.

IV Does this inequality exist in terms of funding?

PJ Yes. Research on women’s diseases or those that affect more women are often under-funded. Lung cancer gets very little money, but kills more women in the United States than breast cancer, ovarian cancer, and uterine cancer combined. Women who are non-smokers are also three times more likely to develop the disease than men who are non-smokers.

“Doctors have to remember that there are differences between the sexes.”

IV What concrete steps can we take to change things?

PJ Scientific journals, which have huge power in the academic world, could require researchers to systematically mention gender when reporting their findings. We could also develop labels, similar to the nutritional labels on food packaging, that would clearly say whether a medical drug or device has been adequately tested on both men and women. Lastly, we must teach doctors what we know so far. That will help break the cycle.

IV Can patients do something about it?

PJ Female patients must always ask their doctor about how things affect their gender. When they’re prescribed a treatment, they should ask, “Will it affect me differently because I’m a woman?” or “Has it been tested on women?”. This will require practitioners to examine the issue and seek out answers, which can move things in the right direction.

IV Is this disregard limited to women?

PJ No, we see the same thing with racial minorities. They are also affected differently by disease and often excluded from clinical trials. For example, we know that African-American smokers develop lung cancer more quickly than whites, but we don’t know why. There is also a cumulative effect. African-American women are the population group with the highest risk of developing a cardiovascular disease and dying from it young. There are social and environmental explanations. They are often poorer, more obese and have less access to healthcare. But there are also biological factors that we do not yet understand.

IV Isn’t this driving us towards increasingly personalised medicine?

PJ Definitely. The more these different parameters, such as sex and ethnicity, are factored into medical research, the more we can develop diagnosis solutions, therapies and prevention methods that are adapted to a patient’s individual characteristics. This would not only benefit women and minorities. Men would also benefit from medical care based more on their biological features.




A pioneer in women’s health, particularly in cardiovascular diseases, Paula Johnson has many strings to her bow. She teaches medicine at Harvard, heads the Connors Center for Women’s Health and Gender Biology and is Chief of the Division of Women’s Health at Brigham and the Women’s Hospital in Boston. The 54-year old researcher has spent 25 years working in a number of different departments at the hospital, such as the heart transplant and quality control departments.