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Friday, May 17, 2013

Perspectives: Dr. Ronald T. Burkman, Jr., on IUDs

My guest today is Dr. Ronald T. Burkman, Jr., Professor of Obstetrics and Gynecology in the Tufts University School of Medicine at Baystate Medical Center in Springfield, MA.  He is the past Chair of the Department of Obstetrics and Gynecology at Baystate and was the last Editor-in-Chief of the journal, The Female Patient.  One of Dr. Burkman’s areas of concentration is contraception, in which he has published for almost 40 years.  Recently I had the privilege of speaking with Dr. Burkman about three papers on IUDs published in the Green Journal in May, 2013.

Dr Burkman, I want you to take us back to the 1970s, to the early years of your career.  You were at Johns Hopkins.  What types of IUDs were available at that time?

RTB: I guess one of the slight advantages of growing old is that it sort of puts you in perspective after roughly 40 years of being an obstetrician/gynecologist.  Certainly, I think, many people of my era or age would recognize that around 1960 was when probably the first IUDs came into play primarily in this country (although there were others that predated those) with the introduction of the Lippes loop by Jack Lippes who was then in Buffalo.  At that time I think it was the IUD that was in greatest use up into the 1970s.  Then roughly around the early 1970s through late 1970s was the introduction of other IUDs.  The one that was probably the most notorious in a sense, was the Dalkon shield.  The Dalkon shield differed from other IUDs.  It was crab-shaped and had what I call spicules coming off the side so the retention was excellent with the IUD, but there was one flaw in its manufacture in that the string that was attached to it was braided.  As it turned out this may have led to an increased risk of infection with this particular IUD.  Now, when all of these were in more wide-spread use in the 1970s I think most people did not recognize the role that infection would play in some of the complications that would ensue.  Further, I think that in the 1970s we did not have wide-spread screening programs to screen individuals for gonorrhea, for chlamydia, and the like.  Unfortunately, the IUD seemed to be an ideal device for individuals who could not remember to take pills, who had issues particularly with higher dose pills at that time, and so in a sense they were utilized by a group of women who probably were not the most appropriate, at least in the setting at that time.  This led to a whole host of series of studies documenting that around the time of insertion there was an increased risk of pelvic inflammatory disease, the Dalkon shield’s risk seemed to be much higher than the other IUDs, such that very rapidly people started to have concerns about the use of these in general.  In our country, accompanying this concern about the use of these in general were substantial lawsuits particularly against A.H. Robins, the manufacturer of the Dalkon shield because they basically had not taken any action because of the reports coming in showing possibly an increased risk of infection.  The bottom line is, starting roughly around the late 1970s through early 1980s IUD use in this country virtually disappeared.  The Europeans were a lot smarter than we were.  They recognized the problem, they fixed the problem by screening women prior to insertion, and lo and behold, throughout the 1980s and into the 1990s there were some countries, for example, in Europe that continued to have IUD use rates approaching 30% among contracepting women, where ours were <1%.  Around the mid-1980s there was certainly interest trying to bring back IUDs such that the copper T380A, which had been developed by the Population Council, was introduced, again with all kinds of provisos to protect the users as well as those prescribing it, and very quickly it seemed to be indicated that the sort of problems we had in the 1970s were not occurring with this particular IUD.  In the early 1990s, if I recall, the levonorgestrel-releasing IUD was inserted.  There were others as well.  There was the progestasert IUD that had a fairly short-lived period of time in use.  There was also a copper-7 IUD that also was used in this particular interval.  But as we look at where we stand today, basically the two IUDs we use are the copper T380A (Paragard, as the manufacturer in this country calls their IUD) and the levonorgestrel-releasing IUD or system, known as the Mirena.

blO+G: For a time it looked like we were in the Dark Ages of IUD use in the US, but now it seems that there is a renaissance.  Coincident with that are three papers that are appearing in the May, 2013, issue of the Green Journal.  The first is a paper by Berenson and co-authors on the risks of complications, failure, and early discontinuation of IUDs in teenagers. The authors found that those risks were not greater for teenagers than for older women and that the levonorgestrel-releasing intrauterine system had lower risks than the copper IUD.  Imagine for us, Dr. Burkman, that you’re counseling a teenager about contraception with an IUD.  Are there special considerations for teenagers that are different from those for older women?

RTB: There are some, but I think the important thing is to recognize that the so-called LARC systems, of which the IUD is one of them, appear to have the best property relative to efficacy in general use.  One of the real issues with teenagers when you discuss contraception with them is that their ability to successfully utilize a contraceptive product that requires either a daily use, such as a pill, or even weekly or monthly, is highly variable.  The advantage of the IUD, of course, is once it’s inserted it stays until they want it removed.  Certainly, we do still counsel teenagers, who often are single and not yet in an absolutely stable relationship, that, again, they should continue to use condoms and practice safe sex with the use of condoms.  We do point out that if they develop any positive screening tests for GC or chlamydia, for example, the IUD can be left in but it should be treated.  If they have recurrent episodes it’s worth counseling the advisability of continuing this particular device.  The reality is that in my experience this has not been a substantial issue.  Fortunately, along with the increase in IUD use in this country there’s also an increased use of condoms, so I think people are certainly getting the message about safe sex in addition to using effective contraception. 

blO+G: In this paper the normal pregnancy rate in teenagers in the first year of IUD use was 1.8% for the levonorgestrel-releasing intrauterine system and 3.6% for the copper IUD.  That seems fairly high to me.  Is that what we should expect?

RTB: I’m not sure and again, we have to keep in mind that there are perhaps some issues that you do have with a claims database study.  First, you don’t really have all the factors about each patient and again there’s always the possibility that there is some type of bias that creeps in as to who actually gets which IUD based on some factor that is not part of the claims database.  They would have the age, obviously, but they would not have socioeconomic or behavioral factors in this type of database.  The other issue is, do they capture all the pregnancies? Sometimes there is under-reporting or even over-reporting, depending on how actually the claims come through.  Ideally you would like to have chart review but of course in a study that involves roughly 90,000 women that’s probably something that you really can’t expect.  It’s certain that the copper T380 increase in pregnancy rate does seem a little high, but again, it’s unclear to me why that is so.  I think there is nothing we can discern clearly from this database study that would explain it. 

blO+G: In their paper the authors cite studies that showed reluctance on the part of providers to offer an IUD to teenagers.  Why are providers reluctant and is that reluctance justified?  Is this a legacy of the Women’s Health Study?

RTB: First, you have older practitioners in my age group who remember all the things that went on in the late 1970s and early 1980s.  I would say there is a whole group of those practitioners who will not put it in any patient.  They fear lawsuits and the like when in reality with the newer IUDs that we briefly discussed a few minutes ago the lawsuits against practitioners are minimal compared to what they were many years ago.  Secondly, there’s always a concern that a teenager who has never been pregnant that the IUD may in some way increase the risk of infection when in fact that is not the case.  For example, there is a well-done study a number of years ago in the 1990s, if I recall, where they looked at about 900 women who got prophylactic antibiotics vs. 900 women who did not and the rate of infection was about 1 case out of each group of 900.  Very, very low.  So the risk or concern about infection in reproductive age women has declined and I think because of some of the safe-sex practices and improved pre-screening.  The other issue where some people are reluctant is the theory that maybe the uterus is not well-defined enough or is smaller; therefore there will be a great deal of difficulty in insertions.  This has not been my experience.  I certainly insert a significant number of these in young women who have never borne children and, in general, do not have any great difficulty. 

blO+G: There’s a new IUD on the market.  Its name is Skyla.  What does this one offer over the IUDs already available?

RTB: I’m not sure.  It’s a shorter duration IUD.  I personally would say it really comes down to cost.  It does have a different insertion device that is maybe slightly better than the other levonorgestrel releasing IUD.  At this point the jury is out as to how much an advantage, if any, this will have over what we already have currently.

blO+G: One of the reasons why women discontinue using an IUD is for troublesome vaginal bleeding after placement.  The second paper by Sørdal and co-authors outlines a placebo-controlled randomized trial of mefenamic acid or tranexamic acid for initial bleeding or spotting after levonorgestrel intrauterine system placement.  The authors found that using these treatments in the first 90 days did not help.  What causes what the authors call “nuisance bleeding” after insertion of an IUD and how do you counsel women about it before insertion?

RTB: Remember, this is a progestin-only device that we’re talking about.  The reality is that with any progestin-only contraception, you do get changes of the endometrium.  It tends to become somewhat more atrophic and has less of an estrogen effect such that irregular bleeding is fairly common, particularly initially.  Again, after 90 days, in many women who use the medicated or levonorgestrel-releasing systems, they will start getting still some irregular bleeding but they tend to get very infrequent bleeding.  Doing a 90 day trial is OK except that a lot of this will resolve on its own.  I was curious why just 90 days were picked.  I guess it’s a matter of how you could keep people in the study for this period of time. 

blO+G: The treatments didn’t help but satisfaction and continuation with the IUD was very high.  Did that surprise you?

RTB: Not really.  It’s a counseling issue and anytime you do a randomized trial folks are extensively counseled—more so than most likely we can do in our practice with each and every patient we see and that’s part of getting the informed consent and so forth.  I think they understood as time went by probably near the end of the 90 days that in fact the bleeding was becoming less of an issue for most people and that’s why I think most of them felt that this was OK, there is some irregular bleeding but I think the number of bleeding days, if I recall, also started decreasing at that period of time, and probably more likely to be light bleeding. 

blO+G: From a public health perspective, is post-insertion bleeding an important problem?

RTB: It’s a problem that you have to point out to patients that they’re going to have.  All of this is that if you counsel people as to the likelihood of something occurring they are more readily able to accept that this is likely to get better, which is true with most of the bleeding that occurs with the levonorgestrel-releasing device, and it’s a matter of waiting it out.  It’s similar to what we do with individuals who go on birth control pills.  We point out to most of them that breakthrough bleeding may become an issue and if they can last it out for 3 months or perhaps a little longer it tends to settle down in the vast majority of patients.  I think that’s true also with hormone-releasing intrauterine systems. 

blO+G: The third and final paper is by Wong and co-authors.  In this randomized, controlled trial the authors used the levonorgestrel-releasing intrauterine system to prevent endometrial pathology in women with breast cancer receiving tamoxifen therapy.  Non-contraceptive benefit of IUDs is a relatively recent concept.  The only non-contraceptive benefit I can remember from the 1980s IUDs was adhesion prevention after operative hysteroscopy for Asherman syndrome.  Now we’re using IUDs for more reasons than contraception.  Has this helped with acceptance of IUDs by women and their providers?

RTB: Particularly when you look at the levonorgestrel-releasing system clearly there are studies that show that when you compare this system to procedures such as endometrial ablation, resection, and the like, that it actually performs quite well.  It does provide for patients, particularly with abnormal bleeding, another option and an option that is non-surgical.  I must admit that in my practice this is something also that I have seen increasingly being utilized, particularly in patients who might be perimenopausal with some irregular bleeding it seems to work quite well for them. 

blO+G: How much benefit did these patients in this study get out of the treatment with the levonorgestrel-releasing IUDs?     

RTB: This is an interesting study just from the standpoint of the degree of manipulation that went on.  You have to realize that these patients underwent hysteroscopy at the start and a biopsy and then had this repeated a year out, two years out, 45, and 60 months out, so that’s a lot of procedures which obviously allows you to examine the endometrium extensively.  But when they look at whether or not having treatment with tamoxifen plus the IUD vs. tamoxifen alone they saw no difference in the frequency of occurrence of submucus myomas or of hyperplasia.  The one big difference they saw was a substantial reduction in the number of polyps which was roughly a 5-fold decrease.  This is nothing that is overly new.  There were these types of results reported in a Cochrane database study a number of years ago.  The other issue is, of course, this degree of following patients—is that necessary for patients on tamoxifen?  I think our current standards still hold that in general we don’t screen with ultrasound or hysteroscopy on a regular basis and tend to only do hysteroscopy or biopsy when patients bleed on tamoxifen for the most part. 

blO+G: The levonorgestrel-releasing IUD is listed as a category 4 in the US Medical Eligibility Criteria for breast cancer.  Would you use the device for this purpose?

RTB: This is the one issue that sort of stands out.  The number of patients in this study to fully interpret the safety of this device in this setting—breast cancer survivors—who again some had ongoing disease because there were cancer-related deaths in the study: roughly 6 in the treated group and 5 in the untreated group.  You’re looking at a total of around 100 subjects in this study.  The concern that led to this classification was the occurrence, potentially, of sarcomas and the occurrence, obviously, of other cancers.  You have to remember that this is a progestin and there is concern that there are progestin receptors in some of these cancers, even though the amount that’s being released into the bloodstream is roughly one-fourth of what you would get in a birth control pill that contains the same progestin.  It still may be enough to stimulate cancer that otherwise has been quiescent. 

blO+G: So, your answer to the question is…

RTB: No!

blO+G: Where do we go from here with our research portfolio?  What information would be valuable to have to improve a woman’s experience with IUDs?

RTB: We have to recognize that there is no perfect contraceptive method for all concerned.  We have come a long way.  I’m not sure that going back to the so-called inert devices is the way to go and clearly, because of the abnormal bleeding that those folks had, that’s certainly off the table.  Whether changing the shapes and utilizing the copper in different configurations—this is done in a number of countries and it’s unclear from reviewing the data some years ago whether this makes a substantial difference.  Certainly the hormone-releasing IUDs—there may be additional medications that come to mind that may in fact play a role but I’m not sure where we stand in that.  You can think of other progestins, other potential hormonal preparations—how much of that is under some development or study right now, unfortunately I am not privy to.  But we have come a long way from when I started out in the business about 40 years ago. 

blO+G:  Dr. Burkman, do you have any final thoughts for our listeners about this topic?

RTB: From the perspective of someone who has gone through the early era of IUDs through what I call the Dark Ages of IUDs, the lawsuits, to where we are currently, most practitioners should recognize that these are exceedingly safe and effective forms of contraception.  They should certainly continue to be more widely used and again, the point I would make is we have seen a resurgence in use from <1% up to 5.5% and maybe 8% in this country.  It has significant advantages because it takes the need to have a daily or frequent action to use a contraceptive out of the hands of a user.  It makes it far more convenient for them.  We need to point that out.

blO+G: Dr. Burkman, thank you very much for your perspectives.