Unlikely Help for Uterine Fibroids -- In-Depth Doctor's Interview

Ivanhoe Broadcast Interview with

 Kevin Fiscella, M.D., M.P.H., Family Medicine

 University of Rochester Medical Center

 Rochester, NY

 TOPIC: Unlikely Help for Uterine Fibroids

What are uterine fibroids?

Dr. Fiscella: They are non-cancerous growths in the women’s womb that cause pain and bleeding.

How serious can they be?

Dr. Fiscella: Well, they continue to grow all the time, and as they grow, they often will produce increasing pain and heavy, very unpredictable bleeding that can really disrupt women’s lives.

What are some of the typical treatments to try to stop them from growing?

Dr. Fiscella: There are two main treatments that have been used over the years and one is hysterectomy, which, of course, is a major surgical procedure, and the woman is out of work usually for anywhere from four to six weeks. Another surgical procedure is simply removing the fibroids. With a hysterectomy, the entire uterus is removed. There is another procedure called myomectomy where only the fibroids are removed. That is also a major surgical procedure. The main disadvantages that the fibroids may re-grow, and the woman may require a second surgery.

Are there any other options that are easier?

Dr. Fiscella: The other major option that is developed, but is still widely underused, uterine artery embolization, which is where the blood flow to the uterus is blocked off and essentially strangles the fibroids so that they begin to shrink down. That also requires a shorter hospitalization.

How big is the need for another way to treat these?

Dr. Fiscella: There are a lot of women who would prefer not to have any sort of surgical procedure, who do not want to go into the hospital, who don’t want to take time off from work, so there is a huge need. As many as 70 percent of women have fibroids by ultrasound, that is a way of viewing the uterus, non-invasively. But probably of those maybe 10 to15 percent may have symptoms to some degree.

What is the risk of anemia and how severe can that be and how serious is it?

Dr. Fiscella: It can be very serious because of the very heavy bleeding that can sometimes occur, so the anemia can be very severe, severe enough to require transfusions, severe enough to cause loss of energy and fatigue, interfering with a daily activities.

The fatigue that people have with uterine fibroids is always related to the anemia that they may have?

Dr. Fiscella: That is a great question and one that I don’t think we completely know the answer to. It may be that there are other factors related to the fibroid but also contributed to the fatigue in addition to the bleeding. Certainly in our study, we know that even women who didn’t have significant anemia also experienced quite a bit of fatigue.

Tell me a little bit about your study.

Dr. Fiscella: We studied a drug that blocks the effect of one of two hormones that women produce. Women have two hormones, one is called estrogen, and, of course, that has been in the news quite a bit, and the other twin hormone is called progesterone, and it seems that when either one of these hormones is blocked, fibroids begin to shrink. The problem with blocking the estrogen hormone is that is produces a menopausal-like state, and women begin to lose bone, they become osteoporotic. So there is a drug out that does block estrogen, but it can only be used for six months, after that the bone loss is so severe that it is simply not safe to use. The drug we studied blocks the action of progesterone.

What is the drug you studied?

Dr. Fiscella: The drug’s name is mifepristone.

Commonly known as?

Dr. Fiscella: R-U 486.

And what is it typically used for, this drug?

Dr. Fiscella: Right now, it's only approved for one indication and that is termination of early pregnancy.

So it's FDA approved for that?

Dr. Fiscella: It is.

What is it about this drug that you made you think want to study its effect on fibroids?

Dr. Fiscella:  We have known for a long time that fibroids require the presence of both hormones to continue to grow and, in fact, when women do reach menopause the fibroids often begin to shrink. So, it makes sense that if you block the effect of those hormones that perhaps you might be able to shrink down those fibroids.

And how does the drug block progesterone?

Dr. Fiscella: The fibroids themselves have little receptors on the outside and in order to continue to grow they require an interaction; it's like a lock and key between the hormone progesterone and the receptor, and what the drug does is that it occupies that receptor and blocks the effect of progesterone.

How many women are in your study first and then what did the results show?

Dr. Fiscella: Forty-two women met the final eligibility criteria for the study.

And did they have varying degrees of fibroids?

Dr. Fiscella: They did, but we only enrolled women who had at least moderately severe symptoms because we were interested in the effect on symptoms, so we did not want to enroll women who only had mild symptoms.

What did your results show?

Dr. Fiscella: Our results showed dramatic improvement in women’s quality of life. Pain went down. Bleeding, actually any bleeding, stopped in 40 percent of women, but it dramatically decreased in virtually all the subjects. And the fibroids, which I mentioned earlier, are non-cancerous tumors, shrunk down in size nearly 50 percent.

Did that happen across the board in all women?

Dr. Fiscella: That was the average, right, and there was variability. For some women the shrinkage was greater, 60 or 70 percent, but for other women the shrinkage was smaller.

Did the improvement symptoms correlate with how much they shrank?

Dr. Fiscella: That is another excellent question. Not really. There really was not a correlation, that a women could get shrinkage quite a bit, quite a bit of shrinkage and not as great improvement, although nearly all the women did experience some improvement. But there were also women who experienced dramatic improvement in quality of life. You know the bleeding got better, the pain got better, they had improved energy, but yet they may have only had a 20 or 30 percent shrinkage in the size of the fibroids.

How is that you notice it shrinks 20 percent, it's still there, how is it not causing symptoms?

Dr. Fiscella: We don’t know the answer to that question fully but part of it may be the effect on bleeding. We know that bleeding has a huge effect on women’s quality of life, so if you can improve the bleeding right there, even if the fibroid does not shrink that much, you are going to get a lot of benefit. It may also have other effects that we don’t fully understand in terms of the effect on fatigue. It may be for example that fibroids generate factors that may also contribute to fatigue and by blocking some of these effects as the fibroids begin to shrink may also improve quality of life. Also, the positions of the fibroid within the uterus may also have an effect on how much pain a woman experiences. So, if it is in a particular sensitive area, you might have more pain if it's in a different area, you may have less pain.

What was the dosage?

Dr. Fiscella:  It was one pill a day, one dose, which was 5 milligrams.

And that's much lower than the dose used to terminate a pregnancy.

Dr. Fiscella: The pregnancy terminate that is approved is 600 milligrams.

Did you have any skepticism from any of the women?

Dr. Fiscella: By and large, there really was not that much skepticism. I think most women were really interested in a pill that would help their symptoms and medications have lots of uses and that is true in general. There are many medications on the market that are used for many different things and I think the women who enrolled in this study were really interested in will this pill help me?

We talked to Jean who said, though she stopped taking it a few months ago, she still has no symptoms. Is that typical?

Dr. Fiscella: We are collecting data on that question now. It does appear that their fibroids grow back but quite slowly, and the symptoms do not return immediately. Now, whether they will or how quickly it will take for the symptoms to return to the level they were before women enrolled in the study, we really don’t know yet, but we think that its going to be slowly.

Were there side effects seen with the drug?

Dr. Fiscella:  No, it was a small study, so we cannot exclude the possibility that there may be side effects that just did not occur in this study. But in this study, the drug was very well tolerated, and there really were no side effects reported. We compared it against placebo and that is the best way to determine effectiveness, particularly when you are looking at something like quality of life. We blinded the women so that they women did not know whether they were getting the drug or placebo, basically a sugar pill. And there were no differences in side effects between women getting the drug and those getting placebo.

A lot of women are faced with the option of a hysterectomy. If this medication becomes a real option for women, what could this do for them?

Dr. Fiscella: This could allow women to avoid hysterectomies, and it would probably mean taking the drug up until menopause at which point their hormones naturally drop to a low enough level that the fibroids would begin to shrink on their own. So this really could prevent, you know, thousands of women from having surgery.

What is the potential of an off label use of this drug?

Dr. Fiscella:  That is not going to be possible with this drug because this drug is still considered phase 4 by the FDA. In other words, it is restricted to termination of pregnancy. And it won’t be possible for physicians to prescribe it in an off label way unlike most medications.

Do you get it from your doctor?

Dr. Fiscella:  You would, you wouldn’t get it from a pharmacy. You would get it from your own physician, and they would administer it to you.

What is the next step for this line of research?

Dr. Fiscella: In order to get FDA approval a much larger multi-center involving more women in different centers across the country would be needed particularly to look at the long term benefits and risks associated with the use of the drug.

Are you in the process of doing that?

Dr. Fiscella: We are in the process of looking around for funding for that sort of study.

Are there other people across the country studying this on their own?

Dr. Fiscella: No one else is studying this particular drug for fibroids that I am aware of, but there are a number of companies studying essentially look alikes. So drugs in the same class, anti-progesterones, as they are called, for the same indication.

How surprised were you at the findings of your study when you saw the effect on women?

Dr. Fiscella:  Well, we had done some earlier pilot work that had shown dramatic effects, so we were expecting that women were going to benefit, but we were quite pleased at how dramatic the effects were.

What were the study participants saying to you?

Dr. Fiscella: "How can I continue? How I can get the drug when the study ends? I cannot imagine stopping this drug. It's changed my life."

Are there any risks associated with blocking progesterone?

Dr. Fiscella: None that we know of at this point, but that is exactly why we would need a longer term study with more women and we studied it for six months, but, say a woman was 40 when she started the drug, potentially it could mean taking it for 10 to 15 years. So I think it's important that we learn more about what the effect of this drug as well as the look-a-likes because we don’t fully understand what all the effects might be.

It is restricted by the FDA, if it wasn’t, what would you think would happen?

Dr. Fiscella:  I think given the dramatic effects of the drug I think it's quite likely that obstetricians and family doctors across the country would begin prescribing it off label for women. And word would get around and patients would come in asking for it. So I think it would become widely prescribed off label if it were not restricted.

How simple is this solution?

Dr. Fiscella: Women who have very busy lives, family responsibilities often times feel like they cannot take time out for either, any kind of surgical procedure or even arterial embolization. So taking a medication, particularly one that appears, at least on the surface from our own data, to be well tolerated and free of side effects, would be very attractive to thousands of women. You know, if you read the papers, you saw that Condoleeza Rice had fibroids and given her busy schedule I would imagine she did not have time to be able to go in for surgery. She opted for the arterial embolization but I am sure that an arterial embolization was disruptive to her schedule. So if there were safe, effective medications on the market, there is no question that there will be thousands of women requesting it.

Tell me how exciting this is from your position for women out there who hear this story, how exciting is the potential of this?

Dr. Fiscella:  I think it's very exciting. I think that this is potentially a real breakthrough in the treatment of fibroids, to be able to offer women a pill that they can take once a day, it's well tolerated, free of side effects and has dramatic effects on how women feel. I think that this is, I really hope that this comes to market and that we are able to get the funding to get it approved by the FDA and be able to offer to women.

END OF INTERVIEW

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