Announcer: From the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health, welcome to another installment of NICHD Research Perspectives. Your host is the Director of the NICHD, Dr. Alan Guttmacher.
Dr. Alan Guttmacher: Hello, I’m Alan Guttmacher and happy to be with you for this podcast.
Dr. Janine Clayton: And I’m Janine Clayton, the Director of the NIH Office of Research on Women’s Health. Happy to be here as well, especially in the month of May.
Dr. Guttmacher: And what’s so special about the month of May?
Dr. Clayton: In May each year, we celebrate National Women’s Health Week, the week right before Mother’s Day—something that we all have in common, I would say. And it’s a week that we talk about how far we’ve come in terms of women’s health, so I’m excited that we’re approaching that special month and that special week.
Dr. Guttmacher: Yeah, I agree. I’m thankful to my mother as I’m sure you are to yours, but also in terms of marking National Women’s Health Week in May . It’s a chance, I think, to look back at how much medicine’s changed, certainly over my lifetime. It’s kind of astonishing how much it has changed, and that may be particularly true, I think, in areas of women’s health. Is that right?
Dr. Clayton: Yes, we certainly have come a long way, and I think it is particularly true in the area of women’s health. For example, back in medical school, I remember being taught about the 70 kilogram man. I don’t know, Alan, if you have that experience as well.
Dr. Guttmacher: He was also in our medical school curriculum—that same guy, yeah.
Dr. Clayton: And you know that’s a little over 150 pounds and the so-called average man . And I’m happy to say that increasingly today we’re able to practice medicine for more than that 70 kg man and really address the 100-pound woman, the 5 foot 6 tall woman, the African American man, the Asian American woman, and the list goes on. Because of research and our understanding about how each of us vary as individuals, we’re able to treat and design therapies for unique individuals rather than the average man.
Dr. Guttmacher: You’re absolutely right, and I know that your office specifically supports research in a number of diseases and conditions that affect women’s health, but you also have a strong focus and I think an increasing one on sex differences in research. Can you tell us a little bit about what sex differences are all about?
Dr. Clayton: Sure. When I say “women’s health,” I think a lot of our listeners may think about diseases that overwhelmingly affect women, and those are often those related to reproduction like breast cancer, cervical cancer, the reproductive system rather. Those are extremely important areas of research. But there is even more at stake for women’s health because women’s health goes beyond what we call “bikini medicine,” caring for the parts of the body covered by a bikini. In fact, women’s health is important from head to toe, and that’s how we think about it as we’ve moved forward. Being female or male is a fundamental biological issue and I think it’s probably the most basic difference that each of us walk around with every day . And we like to say any 5-year-old could tell you that boys and girls are different. In fact, every single cell in your body has a sex—it’s either male or female—and because sex is such an integral, really innate part of our physiology, it can affect our health in many ways. In the Office of Research on Women’s Health, we’re dedicated to investigating the role of sex : being male or female and what that plays, how that plays out in diseases, treatments, and prevention. I’d like to give you a couple of examples of how we see that playing out.
Dr. Guttmacher: Yeah! I’d like to. Yeah, what are those?
Dr. Clayton: So, one is that women can experience the symptoms of a heart attack differently than a man. The classic symptoms are crushing chest pain, feeling like an elephant sitting on your chest, and that can certainly happen in women; but more often than not, women often present with different symptoms: overwhelming fatigue, difficulty sleeping, indigestion, nausea, vomiting, even just kind of unusual sensations like that that can be very nonspecific. Women’s bones and joints are different from a man’s. For example, women can suffer a particular type of knee injury—injured cruciate, the so-called ACL tears—more often than men do and suffer from arthritis, all the forms of arthritis, at higher rates than men.
Another important area is chronic pain disorders. Things like migraine headache and temporomandibular joint disease are more common in women than men . And then certain medications affect men and women differently. For example, aspirin is helpful in preventing primary, primarily preventing heart attacks in men, and in women it works better to prevent strokes in the primary of pattern. And an area that’s near and dear to my heart: pretty much every vision issue is more prevalent in women than men. In fact, two-thirds of those that are visually impaired or blind worldwide are women, and that holds true in the United States as well. So in order to really expand our knowledge base, we need to take advantage of understanding those differences so that we can care for men and women better. It’s a really exciting area of discovery.
Dr. Guttmacher: It certainly sounds like that, and I know obviously, your office, the Office of Research on Women’s Health, you can tell from the name, is very much involved in this area, as you well know personally because you’ve been so helpful to us. And strangely enough, in some people’s eyes, we at the National Institute of Child Health and Human Development—besides doing a lot of child health and human development research—we actually do a lot of research in women’s health and have for decades. In many ways, we’re the primary home at NIH for certainly research involving pregnancy, but also issues of infertility, contraception research, for many women’s gynecologic issues. In fact, we’ve just established within our extramural program, that’s the part of our institute that funds research all over the country and all over the world, a new branch called Gynecologic Health and Disease to really intensify our efforts, which as I’ve said have been there for decades, in the areas of gynecologic health and disease clearly, things like fibroids, endometriosis, pelvic floor disorders. But you know, even without that, our research has led to a lot of advances over the years in women’s health that we’re quite proud of.
Dr. Clayton: Would you like to tell us about a few good examples of those advances?
Dr. Guttmacher: Sure. I guess you always like to brag about some of things that the institute you’re connected with has done well, and certainly women’s health is one of them for us. For instance, the home pregnancy test, which we talked about how things have changed since we were in medical school ; for instance, while I was in medical school anyways, there was no such thing as a home pregnancy test. That was really developed in our intramural program. The intramural programs at NIH, as Janine well knows, are programs that we do basically on the campus where we employ a lot of scientists full-time. It’s a small part of our budget, but we think it has great impact, and in this situation, the woman who first developed the home pregnancy test was working at our intramural programs, so it really grew out of that. And clearly that’s something that you know is used so frequently, not just in the United States, but across the world these days. It’s made a real change, I would suggest, in women’s health.
A very different area that really grew out of our extramural program, the area where we support, as I said before, researchers all over the world is mother-to-child transmission of HIV. Twenty years ago, HIV-positive moms in the U.S. had about a 25 percent chance of passing the virus on to their children when they were born. Now the rates in the United States are less than 1 percent, and while the U.S. is doing particularly well, we’re seeing transmission rates falling around the globe, and a lot of that is based upon research which our Institute has been important in supporting and really leading.
A more recent example of the kinds of areas that we’ve been involved in was one in which we had intramural investigators here at NICHD working with extramural researchers at other institutions, who did an interesting study in which they found that women’s cholesterol levels varied with the stage of the menstrual cycle. This is really a new concept, largely, and if more studies bear this out and show us exactly how to utilize this kind of information, it could really help doctors down the road to develop standardized procedures for measuring cholesterol in premenopausal woman and determining what their individual heart disease risks are.
You know, as we talk about women’s health research, and I think we’ve been doing so far in this podcast, we tend to focus on the researcher, on what the researchers are doing, and that’s obviously incredibly important work, but they couldn’t do it without patients. I’d be interested in your view of that. I know that you’re a real champion around the NIH for the importance of involving women in clinical trials. Can you tell us something about that?
Dr. Clayton: Sure. When we’re able to study a disease or treatment or an intervention in both women and men and people of different racial and ethnic backgrounds, it allows us to have more information, have that information be generalizable to a broader swath of the public, and it helps to give us a more accurate and nuanced understanding of whatever we’re studying. Why that’s important is because our clinicians have that information at their disposal when they’re treating their patients, and obviously we come in different sizes and shapes and backgrounds, and that allows them to have information that will help them to move closer toward delivering personalized care. And we now know that personalized care encompasses prevention, more accurate diagnostics, really delivering individualized treatments, and hopefully these all lead to improved outcomes for everyone.
Dr. Guttmacher: Yeah, it really is important. As I think you know, I’m actually participating in a research trial myself . So, I know how something about both the value that can provide to others, but also the sort of the good feelings one can get in participating in trials, both you get the benefit being in the trial . And that benefit will vary from clinical trial to clinical trial, but what doesn’t vary is the feeling that you’re doing something for others, and by participating in research as a patient participant, you’re helping other people who might develop that disease later , who might have it now—that’s something that even a man can be proud of doing, but I think women as well particularly enjoy being able to do.
You know another aspect of this we haven’t talked about yet really is the question about training and career development, and I know again that the Office of Research on Women’s Health here at the NIH has made significant investments in this, thinks a lot about it. What advice do you have for students, for so-called early-stage investigators, researchers early in their career, who might be interested in pursuing a career studying women’s health or sex differences?
Dr. Clayton: Great question, Alan. My best advice is that studying sex and gender and the similarities and differences in sex and gender is a fundamental aspect to conducting good science and to practicing good medicine. I think that we all realize that. Ultimately, sex and gender analyses, looking at the differences comparing males and females, contrasting the findings, can provide critical insights about both biologic processes and our understanding of health in women’s health and in men’s health. It really is not just a women’s issue, it’s a human health issue. For example, if we were to combine the findings for men and women in a single group and not look at them separately, we’re really looking at an average neuter, non-gender person, and that’s just not how things work.
We really need to make sure that we’re tailoring our understanding and our treatments to men or women. Otherwise, both of us can suffer, and we can be disturbingly coming up with erroneous findings, and that’s really of a concern. So we like to think about analyzing sex differences as an aspect that enhances rigor, reproducibility, and the relevance of studies to males and females, and we like to call those the 3 Rs of good science: rigor, reproducibility, and relevance. And reporting those results, which could be the fourth R, is just as important as conducting the research; and we know that reporting is lower than it should be in pretty much all scientific fields. There’s a gap there that really is an opportunity for, and a promising area for, researchers looking for ways to stand out among their peers: getting that sex-specific information, those results in their publication is really important.
We really focus on early-stage investigators and young scientists and those that are starting out, and we’re hoping to get them launched in several programs at the Office of Research on Women’s Health. One of those is the Building Interdisciplinary Research Careers in Women’s Health program, or BIRCH for short. BIRCH is a mentored career development program, and it connects junior faculty, known as BIRCH scholars, to senior faculty with shared research interests in women’s health and sex differences research. And NICHD has been a longstanding supporter in many of the BIRCH grants, so we are indebted to NICHD for their longstanding support there. The main goal of the BIRCH program is to support the transition to research independence, and that’s where we know we really need to make sure that our trainees, our students, our junior faculty get launched into a research career, an independent research career. A side product, and it’s really important to us, is that the BIRCH aims to reduce fragmentation and women’s health issues, where a woman might be cared for by several different clinicians for different aspects of health, but that care is not coordinated. So the interdisciplinarity of the BIRCH program seeks to address that fragmentation. To date, we’ve trained 542 scholars, 80 percent of them are women; and nearly 80 percent of those BIRCH scholars who’ve completed their training have submitted at least one competitive application for an NIH grant and two-thirds of those received at least one funded grant, and we’re particular proud of that.
Dr. Guttmacher: I know it’s a great program. Part of what I’ve gotten to enjoy in my job is to hear some of the BIRCH scholars present their science, and it really is both stimulating and also gives you hope about the future to see the wonderful level of science in women’s health specifically that these scholars are involved in . And it really does give me great faith that the advances that we’ve seen in recent decades will probably pale in comparison, compared to the advances we’re going to see over the next few decades.
Dr. Clayton: Absolutely. Tell me, Alan, what do you think about some of the future’s most promising research directions in women’s health? What would your thoughts be?
Dr. Guttmacher: Well, I think there really are incredible opportunities. It’s not just this generation of young scientists who we’re helping to nourish who I think are promising, but the research possibilities are really promising right now; there are a lot of things that I think one could think of. One that we’re particularly excited about at NICHD, and your office is certainly involved with us in, is something that we’re going to be launching this year called the Human Placenta Project. Now it really, obviously the name suggests, focuses on the human placenta, which is arguably the least understood human organ and one which has incredible importance for health. We’ve known for a long time that obviously how the placenta develops and functions is very important to how the fetus develops during pregnancy. We’ve also known that it’s very important for the woman’s health during pregnancy. But as you know, in recent years, we’ve gotten more and more evidence that how the placenta functions, and sometimes misfunctions, is very important for the lifelong health of both the woman and the child that comes out of the pregnancy.
So, what we’re hoping to do is to coordinate more effectively a lot of research that’s been going on in placental biology, but also to stimulate it and to really advance it, to accelerate it, with an ultimate goal of being able to monitor placental function development in the human during the pregnancy itself, so that we can see early signs of maybe problems in the pregnancy that we might not otherwise be aware of so that we can intervene and make things better during the pregnancy, but also so that we’ll have a better understanding how it is that this placenta, which does such incredible things in terms of both, for instance, in terms of the immune system. How do you have these two distinct biological beings, the fetus and the mother, who coexist in terms of fighting off various infections, other kinds of things, and sharing nourishment in terms of the development of blood vessels? How is it that the placenta knows, when it’s an important part of the placental development, is that some parts of the placenta die off, disappear in a regulated kind of fashion? We don’t understand all of that. So, if we could understand how that happens in pregnancy, we would know more about how it is that the placenta has this impact upon later health of both mother and child ; for instance, in ways that we could begin to design interventions, even in pregnancy, that would make a difference in lifelong health. So we’re very excited about that one for instance. But let me turn that question on you. Let me ask you, Janine, from your position, what do you think are the most promising research directions?
Dr. Clayton: There’s so many promising areas right now and it’s really, at the National Institutes of Health, it’s delightful to be able to hear from all of our partners in the institutes and centers about all the areas upon which they’re working, but one those that has piqued our interest and is related to the continued study of pregnancy is understanding how women respond to pregnancy afterwards and how a woman’s body during pregnancy, you know, could be thought of as a living laboratory.
Cardiovascular health is one of our major areas of concern. It remains the leading cause of death for both men and women and cardiovascular health during pregnancy we know portends future health of the mother, for example, and this can provide opportunities for us to learn more about how women’s bodies prevent, how women’s bodies respond to pregnancy, and how we can prevent development of cardiovascular disease later in life. For example, preeclampsia, or high blood pressure that occurs during pregnancy, not only poses a risk during the pregnancy itself, but even after delivery and then even subsequent years later. Studies have shown that women who have had preeclampsia are in fact four times more likely to develop hypertension, or high blood pressure, and twice as likely to develop ischemic heart disease, and that can lead to very, very serious problems. So, we think that’s a really critical area, and stress in pregnancy is almost like a stress test that could give us some information about the future.
Gestational diabetes is also an area of interest, and it raises the women’s risk for type 2 diabetes later in life. So, you mentioned the placenta, Alan, how it’s a critically important organ, and I would agree with you, probably the least understood and most understudied organ at this point. We know that the placenta can cause insulin resistance in pregnant women, and we often see that after the placenta is delivered, a woman who had developed gestational diabetes, diabetes during pregnancy, that those high blood sugar and numbers will become normal, and certainly there’s much that we can learn from the placenta, as you mentioned, not only to benefit the children, but also to have large implications for women’s health in the future.
And one other area we’re really interested in is fetal programming, and we find extremely fascinating that we could understand that, despite having the same sequence of DNA, identical twins ; for example, there are these epigenetic changes and other changes that can occur in response to the environment and other insults that can affect us over a lifetime. And the role of sex differences there, we think, is really wide open for exploration.
Dr. Guttmacher: Yeah, I would agree with you. I think that’s something that we’ll understand much better in the next 10 -20 years kind of thing . It really does play a role in terms of sex differences, other kinds of parts of life, and health that would be incredibly interesting to explore, but also more importantly than just the interest, I think, make a real difference in terms of people’s health. Well, it’s really, I have to say, it’s been fun to chat with you today and to, I guess in some way, celebrate National’s Woman’s Health Week together. I thank you for joining us for this discussion, and I also really institutionally need to thank the NIH Office of Research on Women’s Health for what a wonderful partner you’ve been with NICHD to explore a lot of the areas that we’ve talked about during this podcast, along with a number of other institutes/offices at NIH that share our interests in women’s health, but the Office of Research on Women’s Health plays a particularly important role in that. So, we really salute your efforts—not just in May, but around the year—in this.
Dr. Clayton: Thank you, Alan, and we consider that partnership a two-way street, so we appreciate your collaboration as well—the Eunice Kennedy Shriver National Institute of Child Health and Human Development—as a long-term partner of the ORWH. So, thanks so much for having me, and thanks to our listeners out there. For more information on the NIH Office of Research on Women’s Health, you can visit us at www.nih.gov/women and follow us on Twitter @NIH_ORWH .
Dr. Guttmacher: And you can find, as you mentioned, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the only institute at the NIH with a woman’s name in it, you can find us online, too. You can check out our Facebook page or find us on Twitter @NICHD_NIH . Thanks for joining us.
Dr. Clayton: Thank you.
Announcer: This has been NICHD Research Perspectives. To listen to previous installments, visit nichd.nih.gov/researchperspectives. If you have any questions or comments, please email NICHDInformationResourceCenter@mail.nih.gov.