NIH-funded study identifies ways to overcome the pill’s failure in obese women
Wednesday, January 14, 2015
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Meredith Carlson Daly: Birth control pills are less effective for obese women. Studies have shown that obesity brings with it hormonal changes that can reduce the pill’s effectiveness. Now, researchers funded by the National Institutes of Health have found two ways to boost the pill’s effectiveness for obese women—either a stronger dose or continuous use without a break during the week of the menstrual cycle.
From the NIH, I am Meredith Carlson Daly, and this is Research Developments, a podcast from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the NICHD. With me today is Dr. Alison Edelman, an associate professor of obstetrics and gynecology at Oregon Health and Science University, to speak about a recent study on the effectiveness of contraceptives in obese women. Thank you for joining us today, Dr. Edelman.
Dr. Edelman: It’s a pleasure. Thanks for having me.
Ms. Daly: Before we get to the findings of your study, can you tell us who this affects in terms of weight limits and the pill’s effectiveness?
Dr. Edelman: Well, it’s been interesting over the years that birth control pills were originally developed when the population was much thinner, so it was kind of a one-size-fits-all model. So, as the population has been growing and we’ve had this epidemic of obesity, we’ve been interested in studying how obese women, or women of varying weights, are affected by birth control and if it’s still effective for them or if it prevents pregnancy.
So, there are several different birth control methods. And oral contraceptives, in particular, are difficult to study because they have failure rates just from day-to-day use in not taking it or not adhering to the regimen, because it’s very hard to take a pill every single day.
So, there’s not really necessarily a cutoff, and actually the studies that we’ve done are mostly drug-level studies, so population-based studies have shown slightly controversial outcomes—some studies showing that obese women have a slightly higher rate of failure and other studies not showing that there’s a slightly higher rate of failure. And really where the cutoff is for birth control pills looks like about a body mass index of 30, which is an obese body mass index. However, the overweight group hasn’t been studied that extensively.
Ms. Daly: Why is it less effective? What is it about hormone levels that interfere with the pill’s effectiveness?
Dr. Edelman: Well, what’s interesting is probably it’s most affected just by day-to-day compliance because all adults, or all people, have trouble being perfect with taking pills, and that doesn’t matter if it’s a birth control pill or any other pill. And so really where probably the effectiveness is affected the most is just by daily adherence of taking something every single day because that’s just hard to do. However, it does look like in obese subjects, or women, that the birth control pill, the clearance of it, has changed.
And it’s interesting, because obesity affects almost every aspect of the body, but for drugs it may affect things a little bit differently in how your body sees drugs and deals with drugs. And what we’ve found for birth control pills in particular is that there’s an altered clearance, which changes the half-life of the drug, which means that the drug level that you get doesn’t happen as fast. So, there is kind of this window where the drug levels are lower, which may increase the risk of having a failure in obese women.
Ms. Daly: Well, aren’t there other forms of contraceptives that obese women could use? Couldn’t they just switch to something that is easier?
Dr. Edelman: So, that’s true of any woman, and I want to reassure people that there are so many types of birth control, and we really have some particularly good types of birth control, whether you’re normal or obese weight, and those continue to be the really highly effective methods, like IUDs and implants. And really, even for obese women, we feel like those are just great forms of birth control, and for normal-weight women, because not only do they have really high levels of effectiveness, but you also don’t have that day-to-day compliance issue that we have with shorter term methods like the birth control pill. Because, really, we think that failure rate happens because of those kind of day-to-day adherence issues.
Ms. Daly: Adherence.
Dr. Edelman: It’s just hard to be perfect. And I don’t even want to call it compliance, because it’s one of those things that it’s just hard to take something every day.
Ms. Daly: Yeah.
Dr. Edelman: You may have taken it or you may have thought you took it. And I talk to patients about the fact that you have these routines every single day—you lock the door, you turn on the iron, you turn it off, and when you leave the house, you thought you did all of those things, right? And then you get to work and you think, did I turn off the iron? Did I lock the door? And it just becomes so inherent in your routine that you may have forgotten to do it, but you thought you did it. And I think that’s what happens with taking pills every single day.
Ms. Daly: So, does lack of adherence affect women with a higher body mass index more so than women who are normal to average weight? Does it affect them more critically?
Dr. Edelman: Yeah, there was a study by Dr. Westhoff in New York, who looked at compliance and weight. And what’s hard is weight issues are confounded by poverty and access and barriers to health care. And also health care may deal with people of different weights in a different way. They may have more chronic medical problems, so they never get to the preventative health care issues. So, there’s so much confounding that information.
So, this one study did show that there were some lower adherence rates in women of higher body mass index. However, it was confounded by this poverty/socio-demographic issue. So, really, I think, and we know that this affects women of all weights, not just women who are obese, and we’ve seen that in the studies coming out of St. Louis, which are the CHOICE studies, where we see that women just have trouble with day-to-day adherence. And I would say that that has been shown in studies outside of birth control pills and in men. So, this isn’t isolated to women, it’s not isolated to body mass index. It’s just one of those things that’s hard to do.
Ms. Daly: In your study you’ve given us kind of the range of the body mass index, I think you said it’s over 30. How long did you observe the women?
Dr. Edelman: Right. So, this study, we had done an original study looking at, is there a difference in how the body deals with birth control pills, whether you’re a normal BMI or obese BMI, and we saw that there was a difference. And so we wanted to say, okay, so whether or not there’s a change in how well your body deals with a birth control pill and how that affects how well it works for you, because we really think this adherence issue really trumps the obesity factor. So, it’s kind of hard to study because it masks the effect somewhat. But we wanted to see, can we make things better for women who are obese and is there an option for them? Because we want all options available to women no matter what their weight, because that just helps improve options.
So, what we did is we took women who were over a body mass index of 30, which is an obese body mass index, and we randomized them to doing continuous use, which is just taking a pill every single day instead of having that period week versus taking a slightly higher dose of birth control pill, which is still a low-dose pill. Almost all of the methods or the options on the market are low, so we had them on a very low dose pill taken continuously, or a slightly higher dose but still low taken cyclically, which is how a lot of people know how to take the pill, which they take almost a month’s worth of active pills and then they have a period week. And so we wanted to see if we could offset these drug-level changes.
What we found is in both groups we were able to offset the changes, but with the slightly higher dose, there was still this delayed study state, so we don’t know if that opens women to this window of opportunity during this period week if they were late taking their pills with the next pack or things like that. But we know that we don’t have that with the continuous use method of taking a pill.
Ms. Daly: How did you monitor the women?
Dr. Edelman: Well, these women were really, they’re paid research subjects when they come into our research studies, and they are just wonderful, wonderful people. They undergo very frequent monitoring with drug levels and pharmacokinetic studies. And pharmacokinetic studies are really difficult to perform because women have to come into our research unit for several days at a time and have multiple blood levels taken from them every couple of hours, and so they have an IV in place to do that. And then afterwards, we follow them several times a week to be able to monitor their blood levels. And also we did ultrasound, so they got vaginal probe ultrasound to look at ovulation and what their ovaries were doing.
Ms. Daly: And just explain what pharmacokinetic is.
Dr. Edelman: Pharmacokinetics are basically drug-level studies, and drug-level studies look at kind of how the body deals with drugs. And there are certain parts of these calculations that kind of can relate to how well a drug works, but it doesn’t 100% tell you what happens in real life. So, we can see these drug-level differences, but does that mean that actually that an outcome in real life when a real person takes it is going to show that it’s going to be 100% correlation? No, that’s not the case. However, we do have pretty extreme differences in drug-level differences between obese and normal women. And I think what our studies show is that probably obese women, because of their obesity, are at slightly increased risk for failure. And then if you add in the compliance issue, probably that really increases things.
Ms. Daly: That was my next question. What did you and the team find?
Dr. Edelman: In our other studies, we found that there is a difference in clearance and difference in half-life, which basically affects the time that you get to the drug level that you need, or that we’re looking for, for effect or contraceptive efficacy. And so what we were doing is trying to kind of offset that or change it. And with the continuous use you don’t even have to deal with that once you’re up and going. You don’t have to go back down again. But with cyclic use, which is how most people take pills, you’re every month having to kind of get back up to your study state, and a lot of times when people miss is at the end of that period week, and that puts you at the greatest risk, whether you have obesity or not, just because of being off the hormones for a while and then needing to suppress your body again in that next month. So, being late at the end of the period week is probably the worst time to miss pills no matter what your weight.
Ms. Daly: So let me get this straight. A woman who is on the pill continuously would never have her period.
Dr. Edelman: Correct. So, the birth control pills were originally designed to kind of mimic a normal menstrual period, which is only—a normal menstrual period of 21 days of no bleeding and then 5 to 7 days of bleeding, which is only about 20 percent of the population. So, even though it’s meant to mimic that, it doesn’t actually mimic most people’s cycles. However, it was meant to mimic that, and so what’s been interesting is it wasn’t really designed to be scientific. There’s no medical reason that you need a cycle like that. And actually a lot of birth control that’s hormonal, you don’t really have a period, or you have a period kind of when your body ends up wanting to bleed and not on a monthly basis, and that’s totally fine if you’re on hormonal birth control.
So, doing continuous use, you can do just as safely as cyclic use. It’s just socially how we’re used to taking the pills having that period week. But that’s gotten less and less as there have been more products out there that have kind of gotten rid of that period week because a lot of women don’t like their period week, you know. Mimicking the period isn’t the best thing to do because it’s not the best thing for them—especially for women with some medical disorders, like menstrual migraines, heavy menstrual bleeding, polycystic ovarian disease, and endometriosis. You really don’t want that period week in there because you don’t want the body to reactivate and cause you problems during the week.
So, we’ve been doing continuous use for women for years who had medical problems, and now it’s becoming more kind of just socially acceptable to skip your period if you’re taking hormonal birth control. And what’s been interesting is there have been studies of just general population, not specifically obese women, showing that continuous use pills have slightly higher effectiveness than cyclic pills. And it’s probably because you don’t have a lot of time period where if you missed, you wouldn’t be taking an active pill the next day. And that’s one of the reasons that we chose that method to try.
Ms. Daly: Based on your study, can doctors definitively kind of recommend a higher or continuous dose for obese women, or do you feel like more research is needed?
Dr. Edelman: Well, what’s interesting is that these are pharmacokinetic studies, they’re small studies; these are drug-level studies, they’re not population studies. And, like I said, there are big population studies, one very large population study showed that there’s a slightly increased risk of contraceptive birth control failure in obese women. Another study didn’t show that, probably because they were using a couple different forms of birth control and grouping women together, so, they weren’t really powered to show that. However, I think, again, the huge rates of adherence issues that happen with shorter term methods, like the pill, really mask probably the smaller effect that obesity has on birth control. So I think providers can use continuous use. We’re already using continuous use. I think obese women are a good group to do that. I think to do one-to-one correlation of our study with a population is difficult because it is a drug-level study. But we are seeing more and more effects of obesity in contraceptive hormones, and probably people have heard about the emergency contraceptive issue that has come out recently.
Ms. Daly: Where do you go next?
Dr. Edelman: [laughs] Well, you know, it’s always about funding, right? But where we’d like to study is actually we’re switching gears a little bit, and I keep on harping on this adherence issue, because it does, I think, make the issue complicated when studying birth control pills. Because even though we’ve proven compliance and adherence in our study groups so that we know that our data are true, it does make it harder to study in populations and to do this correlation as, do you see what we’re seeing in drug-level studies in the population? And so it’s a little bit cleaner to do these studies actually in emergency contraception because women take one dose at one time for one specific reason.
And so we’re switching over, or we’d like to switch over a little bit, to study emergency contraception because there have been population studies showing that these similar hormones in the birth control pill are also in emergency contraceptives. And we have seen a significant decrease in effectiveness of emergency contraception with obesity. And so we would like to study that and see how we can enhance the effect in emergency contraceptives so that we have an emergency contraceptive that can be orally taken by anyone of any weight and to have a good result with that. So, that’s where we’re kind of focusing our attention next.
Ms. Daly: Very interesting. Thank you so much for speaking with us.
Dr. Edelman: Oh, you’re very welcome. It’s been a pleasure.
Ms. Daly: I’ve been speaking with Dr. Alison Edelman, co-author of the study “Correcting Oral Contraceptive Pharmacokinetic Alterations Due to Obesity,” a randomized controlled trial, which was published recently in the Journal of Contraception. Thanks again for joining us, Dr. Edelman.
Dr. Edelman: Thank you.
About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute's website at http://www.nichd.nih.gov/.