Sex Matters

Researchers are discovering more ways than ever in which men and women are different — in the way we develop disease and respond to medications.

At Rhode Island Hospital, one doctor is using that knowledge to change the way emergency medicine is practiced.

Angela Samayoa arrives in the emergency department at Rhode Island Hospital, complaining of chest pain. She’s admitted to an exam room on Urgent A, where Dr. Alyson McGregor is the supervising physician on the three-to-eleven shift that day.

McGregor has seen many patients over the years with symptoms of heart disease. But Samayoa is a special case. She’s also seven weeks pregnant.

After consulting with the chief resident, McGregor pulls aside the curtain to Samayoa’s room, walks over to her bedside and introduces herself to the thirty-two-year-old mother of two and her husband.

“So I understand that you came from Women and Infants?” asks McGregor, who is forty-one, tall and thin with curly brown hair. “Tell me what’s going on.”

“Ever since yesterday at three o’clock, I started feeling this pain,” Samayoa replies. “I kept checking my blood pressure. 170 over 96, 170 over 100. So I thought everything was because they switched my pills.”

“I see,” says McGregor.

“But then it got worse through the night, so I called today to see if they could check me,” Samayoa says. “They did send me to a midwife, but she said go to Women and Infants because there is nothing I can do here. So when I got there, the doctor checked me and said we’re going to send you to Rhode Island Hospital, because we need to get your blood pressure controlled, but we need to find out what’s going on first.”

“Okay. So what medical problems do you have?”

“Only high blood pressure.”

“And you take medications for that?”

“They just switched it to a new one since they found out I was pregnant,” Samayoa says. She rummages through her purse and pulls out two prescription bottles.

“This is the new one that I’m taking. I was taking Lisinopril until Wednesday, then I started taking this.” That medication can cause birth defects, so Samayoa’s doctor switched after she learned she was pregnant.

McGregor asks what other medication she’s on now, then reaches for exam gloves from a dispenser on the wall and pulls them on. Had she ever experienced chest pain before?

“I had it when I had my son, so I thought it was the high blood pressure that was causing all this,” Samayoa replies.

“You’ve had how many children?” McGregor asks as she listens with her stethoscope.

“Two and one miscarriage.”

“…And one miscarriage. Any problems with the births?”

“Just my little one,” Samayoa says. “He’s two years old, but he was a preemie, because my blood pressure went up. He was seven months.”

“So did they induce you?”

“Yes.”

McGregor says she’d like to order some tests and consult with an obstetric specialist about her case.

“My main concern is, is the baby going to be okay, too?” Samayoa says.

Typically when a patient comes into the emergency department and is at risk for a blood clot, McGregor will order a blood test that is known as a D-Dimer. But pregnancy can falsely elevate the test, so doctors go right to a CT scan if they think the possibility of a clot is high enough in a pregnant woman.

The low amount of radiation from the CT scan is also a risk, as McGregor instructed residents earlier in her shift. In 2007, the number of CT scans in emergency departments increased by 17 percent, and the majority were performed on women. Researchers projected that the additional tests could lead to more than 30,000 future malignancies from the radiation.

As McGregor will be the first to tell you, when it comes to caring for patients, sex matters. Because of that, she’s working to change how emergency medicine is practiced. For too long, she says, the scientific community believed that aside from men and women’s reproductive organs, they were physiologically the same. It’s what McGregor describes as “bikini medicine.”

“The science that we know now is men’s health,” McGregor says. “We are just discovering now that we are different in every single way.”

Over the past few decades, in a range of medical specialties, from cardiology to neurology to sports medicine, researchers have learned that important differences exist in the physiology of men and women. It goes right down to our DNA: in what diseases we develop and how they should be treated. And yet until recently, medical testing has been performed mostly on men — something McGregor is working to change.

“Women are not just men with boobs and tubes,” says McGregor, who cofounded a national organization called the Sex and Gender Women’s Health Collaborative that collects data on the differences between men and women. “They have their own anatomy and physiology that deserves to be studied with the same intensity.”

While chest pain is the number-one symptom of heart disease in both women and men, women are more likely to complain of shortness of breath, fatigue and just not feeling right. They may not recognize the signs. Men often experience a clot in a large blood vessel, while women develop heart disease more diffusely in vessels that are smaller, McGregor says. Some standard tests may not pick up heart disease as well in women.

Taking aspirin can help prevent heart attacks in men, but can cause gastrointestinal bleeding in women. If a woman is having a stroke, she might experience head pain and not just a facial droop. Autism is more common in boys, while more women develop Alzheimer’s disease. And women attempt to commit suicide more than men, though men are more often successful.

Meanwhile, the longtime absence of roughly half the population in clinical trials for drugs and medical devices has had some serious implications. In 2013, the Food and Drug Administration took the rare step of recommending that clinicians cut the dose of the sleep aid Ambien in half for women.

The drug was introduced more than twenty years ago, and the prescriptions for it have primarily been written for women, who suffer more sleep disorders than men. The agency took the step in response to receiving hundreds of complaints from women who were waking up drowsy, still under the influence of the sleep aid. Of the drugs that have been removed from the market, 80 percent of those were due to their side effects on women, a government accountability study found.  

“From the moment someone ingests a pill, women and men are totally different in the way that we metabolize it, in the way that we break it down, everything,” McGregor says. “Because we’ve only been studying men, most of our dosing recommendations have been based on them.”

And the latest scientific research suggests that the sex-determining chromosomes in our cells remain active throughout our lives. They may be responsible for how men and women respond differently to medical dosages or develop autoimmune diseases such as multiple sclerosis, which mainly affects women, McGregor says.

Changing the way medicine is practiced to account for the differences between men and women is no small task. But McGregor, who is also an assistant professor at Brown’s medical school and co-created the Division of Sex and Gender in Emergency Medicine there, says there’s no turning back.

“All of these things have to happen at the same time: the scientists have to start doing research on men and women. We have to start taking that science, whatever we know right now, and start teaching it in the medical schools. And then we have to start translating it to the bedside, to patient care.”
 
McGregor didn’t grow up in a town where many kids had parents who were doctors. But often when she left her pediatrician’s office, she told her mother that’s what she was going to be.

The youngest child of a state police captain who worked sixteen-hour days and a medical assistant, McGregor learned discipline from her parents growing up in Coventry, and was insatiably curious.

When McGregor was about nine, her parents took her to visit cousins in New Hampshire who lived on a farm. While she was there, she saw a calf getting born. It was a breech birth, and McGregor’s relatives had to do a lot to make sure the calf was born alive, her father, Peter, says.

“It was just so amazing to her,” Peter McGregor says. “It really took hold, the idea of caring. Incidentally, from that point on, she would never eat meat again.” But blood never bothered her. As a teenager, she loved watching horror movies.

In Catholic school and later at LaSalle Academy, McGregor strived to be first in everything she did. “It was always, if I’m going to do this, I’m going to be the best at it,” her father recalls. Many times, if she got one wrong on a test, she’d go back to the teacher and want to talk about why it was wrong.

McGregor’s family supported her ambition to be a doctor, but as the first person in her family to go to college, she had to figure out how to get there herself. In middle school, McGregor wrote in the yearbook that she was going to be a doctor, her longtime friend, Erin Sarris, recalls. But in high school, she was quieter about her ambitions and didn’t mention wanting to go into medicine in her senior yearbook.

But McGregor continued to pursue her interest in health care. During summers in high school and college, she worked as a certified nurse’s assistant in a nursing home, where she cared for patients who were incapacitated.

“I was a lifeguard,” Sarris says. “And she’s been cleaning feces. To her, it was really building up her education caring for people.”

The friends both attended the University of New Hampshire. It was early in McGregor’s first year that she realized if she was going to pursue medicine, there was no room for error. Advisers were telling her it was almost impossible.

“From that moment on, she was done,” Sarris recalls. “If it meant writing a final paper in the first week, she had the discipline to do that. But she didn’t by any means miss out on the fun college experience.” It was also at UNH where McGregor first started taking classes in women’s studies, which were relatively new at the time and which she loved.

After graduation, McGregor volunteered at what was then the emergency department at Boston City Hospital, biding her time to apply to medical school. It was there that she met a paramedic named Eric Goedecke. He knew of her and made his way over to the area where she worked.

“They met and then she called and said she was going on a ride-along with him,” McGregor’s mother, Joanne, recalls. “And there was an accident and she calls and says, ‘put the TV on, he’s on the news.’ We got to see him on the news. They’ve been together ever since.”

Once McGregor got into medical school at Boston University, she studied all the time. Her parents drove up to Quincy every week and filled her refrigerator, her mother says. “We gave her kisses, heated up a pizza or something for her and said goodbye. She never even got up from her chair.”

“I didn’t have a plan B,” McGregor says. “I needed to be a doctor. It was never, ‘if that doesn’t work out, what else am I going to do?’ I always needed to be doing what I am doing now.”

McGregor graduated from medical school in 2003 and secured a residency in the emergency department at Rhode Island Hospital in Providence, the region’s only Level One Trauma Center. She had always wanted to come back to Rhode Island to practice and be closer to her family. Her older sister, Robyn, works in health care as well as a medical assistant at Women and Infants. And the fast pace and crisis mode of emergency medicine appealed to someone who sometimes joins her brother, a sergeant in the Providence police department, on ride-alongs when she finishes a shift at midnight.

Since then, McGregor has worked at Rhode Island Hospital. A shift in the emergency department there can include anything from stubbed toes and runny noses to overdoses and missing fingers to migraines and chest pains to gunshots and third-degree burns.

During the last year of her residency, McGregor read a book that changed her life, called Principles of Gender Specific Medicine. “A light bulb went off: that women’s health is more than obstetrics and gynecology. That women’s health is about the entire body. I have been a fanatic about it since.”

The history of research on humans “has been fraught with danger and suffering,” according to the National Institutes of Health. “The ancient Hippocratic Oath specified a duty from a physician to avoid harming the patient, but that oath, highly honored today, was not even subscribed to by a majority of doctors at the time.”

That began to change in the 1940s, after the horrors of medical experiments by the Nazis came to light. The Nuremberg Code of Ethics was drafted and required that human subjects must give informed consent to testing.

Over the next few decades, fallout from testing of the experimental drug Thalidomide and the revelation in the 1970s of the Tuskegee Experiment, in which unknowing subjects were infected with and allowed to suffer from syphilis, led to more protections for human subjects.

In part to make sure medical testing would not be performed on women, Congress passed the National Research Act of 1974.

“They thought they were doing a good job,” McGregor says. “They said we shouldn’t be doing research on women. We need to protect them — especially women in the reproductive span of their lives.”

It was also easier and less expensive to leave women out of medical studies, McGregor says. With men, scientists didn’t have to worry about the cycling of women’s hormones, which could mess up the data.

“It turns out that the cells used in that laboratory, they were male cells,” McGregor says. “And the animals used in animal studies were male animals. And the clinical trials were performed almost exclusively on men.”

It wasn’t until the 1980s that the scientific community started to question whether there were physiological differences between the sexes beyond their reproductive organs, McGregor says. In 1990, NIH created the Office of Women’s Health Research and found that it knew little about the unique medical needs of women.

In 1993, the NIH encouraged the study of women, but didn’t make it a rule, McGregor says, so many research studies are still incorporating mostly men. Then last year, the NIH said it was going to give researchers $10 million to include women in pre-clinical research at the cellular level and they must start testing on female animals and cells.

“What’s been wonderful is over the past ten years it’s finally catching on,” McGregor says. “For some reason, this has been such a resistant change in the concept of health and science. It’s inconvenient to study both men and women. Women’s menstrual cycle is inconvenient. But it’s really important.”

When McGregor presented about sex and gender at a national conference in 2007 that was attended by about 5,000 people, just three people showed up, recalls her husband, Eric, who also went on to become an emergency doctor.

“She could have taken that as defeating, and she was upset about that, of course, but she said this is an opportunity for me, I’m going to make sure that my message gets out, because she thought it was an important one,” he says.

Within a few years, McGregor and a colleague, Dr. Esther Choo, founded what would become the Division of Sex and Gender within the Department of Emergency Medicine of Brown University’s medical school. Researchers there are studying differences between the sexes and applying their findings to patient care at Rhode Island Hospital.

“What better place than the emergency department, where we see everything,” McGregor says.

She is also working to change the curriculum in medical schools to include training on the physiological differences between men and women. And a conference they had on sex and gender last year in Providence attracted more than 100 top emergency medicine researchers.

Women now make up half the number of people in NIH-funded studies, but they still don’t participate in nearly as high a percentage of trials conducted by drug companies and medical device manufacturers, according to The New York Times.

After seeing several more patients, McGregor returns to the fishbowl, the central area on Urgent A filled with work stations where supervising doctors, residents and nurses confer and input patients’ information electronically.

So far, Samayoa’s tests have come back normal, and her blood pressure has gone down to about 140 over 80. But she’s still got chest pain, and McGregor wants to make sure she doesn’t have a blood clot. She calls the obstetric specialist, discusses Samayoa’s case with her and circles back to her patient’s room.

“Your chest X-ray looks normal, your EKG looks normal and, so far, your blood work looks okay,” McGregor says. “She and I both agree that it’s worth doing that next test, which is the CT scan of your chest. That’s to rule out a blood clot. Pregnancy is a risk factor for getting a blood clot.”

She describes the test and informs Samayoa of the risks.

“The fact that you’re pregnant, we try and limit the amount of radiation, but this amount is still at a low enough level that it should not cause any birth defects,” McGregor tells her. “I can’t say zero. Nothing is zero percent. There’s always a small risk, and a small risk of childhood cancer, because the radiation may last. But the risks are still low enough.”

Samayoa gives her consent. Hours later, in between the bustle of seeing about ten other patients, McGregor is still waiting for the results from the CT scan. She crosses over to the other side of the emergency department to check the results with the radiologists and returns to Samayoa’s room.

She and her husband are eating French fries he’s brought in from Wendy’s, which McGregor sees as a good sign.

“Feeling any better?” McGregor asks. She’s ruled out anything serious.

“I just reviewed your CT scan with the radiologist and it was normal. No blood clots, no pneumonia. So that’s very, very good. When I spoke with the specialist, she would like you to follow up with her on Tuesday to get an echocardiogram of your heart, which is an ultrasound. Especially since the high blood pressure — you had preeclampsia before — it could mean that your heart is not functioning properly. She wants to make sure that it is,” McGregor says.

She gives Samayoa the specialist’s contact information and says the doctor will follow up with her as well.

“So I’m going home?” Samayoa asks.

“Yeah. You think you’re okay to go home now?” McGregor asks.

“Like I said, I’m just a little bit dizzy.” And she still has pain in her chest.

“It’s tough because you’re pregnant, you have limited options for medications,” McGregor tells her. “Tylenol is very safe in pregnancy. Just keep taking some Tylenol at home and then see how you do over the weekend and follow up with the specialist.”

Then McGregor wishes her well and heads off to another exam room to meet her next patient.