NICHD research offers new routes for diagnosis, addressing pain and infertility
Endometriosis is a condition in which tissue similar to the lining of a woman's uterus grows outside—on the ovaries, fallopian tubes, and in other places in the pelvic cavity.
This misplaced tissue responds to a woman's monthly hormonal cycle and can become inflamed, cause pain and scarring, and lead to infertility. It is one of the most common causes of unexplained infertility in women.
Esther Eisenberg, M.D., M.P.H., a medical officer in the NICHD's Fertility and Infertility Branch and an obstetrician-gynecologist by training, spearheads the NICHD's efforts in support of research advancing endometriosis diagnosis and treatment, including the work of the Reproductive Medicine Network (RMN). Dr. Eisenberg's area of expertise is in the role of hormones in human reproduction.
In this interview, conducted in advance of Endometriosis Awareness Month , Dr. Eisenberg discusses what researchers currently know about the condition and its causes, explains how endometriosis can affect women's daily lives, and highlights recent research findings that offer promising avenues for diagnosing and perhaps ultimately treating endometriosis.
Follow the links below to read Dr. Eisenberg's extended comments.
Q: What is endometriosis?
The exact cause or causes of endometriosis remain unknown. Normally, a woman's menstrual flow removes the tissue lining the inside of the uterus from the body. Sometimes, some of the menstrual blood flows backward—a process called retrograde menstruation—and carries endometrial tissue up through the fallopian tubes and into the pelvic cavity, where it can implant on organs. This tissue continues to respond to the hormones of the menstrual cycle and can bleed and cause inflammation, leading to pelvic pain, scarring, and infertility. Current evidence suggests that retrograde menstruation may play a role in the development of initial lesions, but it is not the cause of endometriosis.
Women with endometriosis often have painful menstrual periods and pain with intercourse. Painful periods may start even when the woman is an adolescent, but at that point, she doesn't know that her periods are different from other women's menstrual periods. The endometriosis may go undiagnosed for quite a while and only be diagnosed once the woman experiences infertility or has severe pelvic pain.
Q: Is it a common cause of infertility?
It is one of the most common causes of unexplained infertility. It's estimated that 40% of women who have unexplained infertility have endometriosis.
Q: How does endometriosis lead to infertility?
We have some ideas, but we don't know the entire picture. Endometriosis actually can have different grades and stages, so you could have minimal or mild endometriosis with just a little bit of the implants in the peritoneal cavity. And you could have moderate and severe endometriosis. With severe endometriosis, this affects the ovaries; there are blood-filled cysts called endometriomas that are present on the ovaries. There can be scar tissue. The reproductive organs can be scarred to the back wall of the uterus, and there may be other endometriotic nodules in the pelvic cavity.
Depending on the stage of the endometriosis, one can really understand that if everything is scarred and there are adhesions around the tubes, that could be an anatomic reason for infertility. On the other hand, even women with minimal endometriosis can experience infertility.
Q: Do we know anything about causes?
We know some things about the cause, but there is much more to learn. The menstrual backflow, what we call retrograde menstruation, may be a part of the cause. But with the advent of laparoscopy—a surgical procedure used to diagnose endometriosis—we found out that most women have retrograde menstruation.
Why do some women develop endometriosis and others not? Women who have endometriosis may have some differences in their hormones or in their immune systems that react differently to the tissue fragments that get deposited in the pelvic cavity. Other women may be able to clear the endometrial tissue more effectively.
There is evidence that there are environmental toxicants that may play a role in the development of endometriosis. There is some evidence that dioxin and other environmental toxins may have an impact on hormones or the immune system, and that may be playing a role in the development of endometriosis.
Q: And would genetics play a role?
There seems to be a genetic component. Women who have endometriosis are more likely to be related to other women with endometriosis.
Q: What would you do to treat a woman who has endometriosis?
It really depends on the woman's goals and her desires, and also her symptoms. A large number of women with endometriosis don't have symptoms, and the condition comes to light when they are being evaluated for infertility. So if infertility is the result or related to the endometriosis, then we do have treatments for those women: We can induce ovulation and sometimes add intrauterine insemination. Sometimes, these women need to undergo in vitro fertilization (IVF). IVF is a very effective treatment, if the goal is to have a baby.
If the problem is pelvic pain, then sometimes treatments with laparoscopy can remove adhesions, can obliterate the endometriosis, and that may resolve the pain for a period of time. Unfortunately, oftentimes the endometriosis recurs, and these treatments need to be done again.
If the problem is painful menstruation, sometimes a treatment as simple as going on birth control pills continuously so that you don't have a period may solve that problem. So there are treatments, and they need to be directed at the symptoms.
When endometriosis is intractable and causes severe pain and none of the medical or surgical treatments are effective, then the ultimate treatment is to have a hysterectomy. Of course, that precludes a woman from having children in the future, and so that is not treatment that we take lightly.
Q: How does pain affect the woman's everyday life?
Endometriosis can have an impact on a woman's quality of life. There can be pain with intercourse, and that can cause depression; it can cause major issues in her relationships. I think that those are the areas that physicians tend not to address that readily. We go for the medical treatment, and I think the behavioral and social components are sometimes overlooked. When a physician talks to a woman about how the pain is affecting her relationships, how she is coping with her daily living, it gets the issue out on the table and allows the physician to help.
Q: What are some of the unanswered questions about endometriosis?
Right now we have treatments that are effective for endometriosis that has progressed to a certain stage. But if we could identify how endometriosis develops, then we could intervene at those levels and perhaps prevent the later-stage adhesions and endometriomas that cause the pain and the infertility.
Q: Can you mention some of the NICHD-funded studies that could help?
One study found that letrozole, a drug that blocks estrogen, may help inhibit the growth of the endometrial patches. That study was done using an animal model.
There are other groups that are looking at enzymes, such as metalloproteinases, and hormones, such as progesterone, that may help to explain why infertility occurs. If we can identify the reasons, then we can work on new treatments, and that would be really helpful.
Researchers at the University of California, San Francisco, are working on a way to diagnose endometriosis that doesn't involve a laparoscopy. They are looking at genetic markers that provide a "fingerprint" of endometriosis that allows the diagnosis.
This diagnostic method has been tested on a small number of endometrial biopsy samples, but it needs to be validated in a larger sample. The RMN is working with the researchers to validate the endometrial biomarkers and to look for other biomarkers that might serve as noninvasive diagnostic markers of endometriosis.
Q: And the advantage is that no surgery is needed?
Yes. Right now, the diagnosis of endometriosis requires a laparoscopy; that's the gold standard. Not everyone has the ability to have surgery. Even if you have medical insurance, it's costly to undergo a laparoscopy. It involves a general anesthetic and an operating room and recovery. If we could identify a way to do an in-office biopsy or just take a tube of blood and then test it, then we could make the diagnosis earlier.
Q: Which area of research is the most promising?
I think that endometriosis is such a broad field that we need to chip at it in many directions. It's almost like having a large jigsaw puzzle, and you have certain parts of it where you have put together the different shapes, but you still don't know what the whole picture is. And so I think we just need to keep working at it piece by piece until we have a better understanding.