Contraception During and After Cancer

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a Medical Oncologist and Co-Director of the Sarcoma Program at Cleveland Clinic. Today, I'm happy to be joined by Dr. Pelin Batur, Professor of OB/GYN and Reproductive Biology at Cleveland Clinic. She's here today to discuss considerations for contraceptive care during and after cancer. So welcome.

Pelin Batur, MD: I'm glad to be here. Thank you for inviting me.

Dale Shepard, MD, PhD: So, tell us a little bit about what you do here at Cleveland Clinic.

Pelin Batur, MD: Yeah, so I've been here since 1998. Did both my residency and fellowship training here in women's health. So I work in the OB/GYN department. I take care of the complex hormonal concerns for women who have complex medical histories. So this includes contraceptive concerns and also menopause. And I also helped lead the sexual health program here that focused on after cancer concerns. And currently, I am the Medical Director of our Women's Comprehensive Health and Research Center that really looks to put it all together for women so that they don't fall through the cracks.

Dale Shepard, MD, PhD: Excellent. Nice you mentioned that because one of the things I'm going to talk to you about is how we keep you from falling through the cracks because we are going to focus on cancer, patients with cancer, contraceptives, how we manage contraceptive care in those settings. The guidelines have been recently updated. Is that correct?

Pelin Batur, MD: Correct. So, the Society of Family Planning led this committee statement. I was the lead joined by several colleagues, including colleagues from the Cleveland Clinic. And this was in collaboration with the Society of Gynecologic Oncology. And we did a review of all the science and then put together guidance on patients with various cancers, history of cancer, diagnosed with cancer, newly diagnosed or past history to guide which contraceptives are safe and which are not.

Dale Shepard, MD, PhD: One of the things about podcasts like this, you sometimes get to see behind the scenes, right? So you led this effort. What kind of specialists are involved in terms of developing guidelines like this? Who do we pull in to put together these guidelines?

Pelin Batur, MD: Yeah, so it took gynecologic oncologists, gynecologists. I'm a women's health internist, so I have a medical training and then I fellowship trained in women's health. So it really was a multidisciplinary effort. And it was so much data to review. We had to put it into three chunks. So the first part was key considerations in general, and then a second section that was a second paper that was on reproductive and breast malignancies, and then a third paper on all other malignancies.

Dale Shepard, MD, PhD: And so I guess before we get into some more specifics about these, what was the biggest surprise in terms of how things had changed since the old guidelines?

Pelin Batur, MD: I think to be honest, the biggest surprise is to me how little has changed in terms of the quality of data. So when we went to look at the data, there were 16,000 studies that we pulled, but we really wanted to focus on the hormonal contraceptives because that's where people get the most fearful about potential risks. And there were about 5,500 studies that had come up in the last decade.

Seems like a good number, but all four authors, we reviewed every single one of these studies. And when you looked at them, it's just not good enough quality. So that just really is very disheartening. It's a lot of population studies. It's a lot of conjecture. It's a lot of associations. And so we just really need more science, and I think that's the biggest surprise for me.

Dale Shepard, MD, PhD: All right, makes sense. And so thinking about hormonal therapies, you said it causes people the most fear and concern. A lot of different people, a lot of backgrounds might be listening in. Why is that? What's the biggest concern most people have and is that founded?

Pelin Batur, MD: Yeah. The biggest thing I think is that people worry about how the hormones are going to impact cancer recurrence rates. And then we also worry about how a cancer treatment might impact a contraceptive's effectiveness and how a contraceptive may affect the treatments that are being used for cancer. And so the guidelines try to look at it from all angles.

So what we did is when we looked, we looked at any kind of hormone exposure for that cancer. We didn't limit our search just to contraceptives. Even though postmenopausal hormone regimens are less potent to lower doses, we looked at that data too to see if we could pull any of that information into clinical decision-making. So that's the nice thing about the guidelines.

There's a recommendation based on the science of what we recommend, but then there's several paragraphs underneath it explaining what the science says and the references for people who want to look at it themselves.

Dale Shepard, MD, PhD: And we think about risks of hormonal therapies. What are the primary risks that you guys found?

Pelin Batur, MD: Well, that doesn't change for the cancer survivor. It is thrombotic risks in general. That's what most people worry about. I think we can dive into estrogen sensitive cancers in a minute, but thrombotic risks, if there's one thing to ever take away from a discussion about contraception is that the risks of an unintended pregnancy is always greater than the risks of any contraceptive. So by denying patients appropriate contraceptives, we may actually be putting them in more harm's way.

Dale Shepard, MD, PhD: Yeah.

Pelin Batur, MD: And I think we need to also talk about the number of people this affects, because sometimes people think this is just a niche audience, but there's a huge number of women that's impacted by this.

Dale Shepard, MD, PhD: Yeah. I guess I was asking risk because cancers themselves can increase risk for things like thrombosis. And then we worry about hormonal therapies doing that the same. And I think I'm guessing that's one of the things people are worried about.

Pelin Batur, MD: Correct. And that's why the first part of it really goes into that thrombotic risk category. There are ways to minimize the risks of thrombosis. In general, it's the estrogen that contributes to that risk. When we're talking about contraceptives, progestins do not increase the risk of a blood clot. And if you're really worried about hormone exposure, there are IUDs that give essentially 1-15th of what's in a birth control pill and it's only the progestin. So there are ways to minimize clots for sure. And we do touch on that in the document.

Dale Shepard, MD, PhD: You talked about estrogen positive cancers. How does contraception fit in with... What do we think about the patients?

Pelin Batur, MD: Yeah, let's talk about that. Again, I want to take one step back if you don't mind.

Dale Shepard, MD, PhD: Sure.

Pelin Batur, MD: You mentioned the thrombotic risk, because that is usually number one on people's mind. Keep in mind, pregnancy is an independent risk factor, so is cancer. So when you combine those two, if somebody has that unintended pregnancy, you actually increase their risk of thrombosis by six, and sixfold is a huge increase.

Dale Shepard, MD, PhD: Back to your point about the contraceptive risk being lower than the risk of an unintended pregnancy.

Pelin Batur, MD: Yeah. So we have nice tables in the documents so that people can do a quick snapshot of different cancers and whether they are estrogen sensitive, but the big ones would be an estrogen positive breast cancer. Most ovarian cancers are safe. In fact, if anything, data shows that hormone exposure can be beneficial, and we can dive more deep into that if you want.

But there's a handful of them that we call out in the article of the granulosa type tumors, low grade serous, endometriosis. So only a handful of the ovarian cancers where we have to worry because they might express the hormone receptors. And then meningiomas is another one. There are some that, for example, melanomas and also lung cancer where the data doesn't match the fear in clinical practice. So the guidelines go into all of that too.

Dale Shepard, MD, PhD: Yeah. Excellent. You broke guidelines into breast cancers and other tumors. And what are the big takeaways in terms of how we approach patients?

Pelin Batur, MD: So first of all, just to remember how many patients there are. So when we look... I mean, not to just go into epidemiology and all that, but I think it's important. We have about 5% of the US is a cancer survivor. That's more than 18 million people. And when you look at reproductive age women, 15 to 40, there is an increasing number of patients that are being diagnosed with cancer, the bad news, but the good news is less and less dying.

And that means that in that reproductive age group, we're seeing a lot of people with pregnancy potential that needs contraceptive. And we know half of pregnancies in the United States are unintended, and that's true for cancer survivors too. So this is an area that we are really neglecting. So I want just to emphasize that to the audience first. But then yeah, we can divide the conversation up into all other cancers and then a little bit more complicated, the breast versus the reproductive.

So if we're going to just talk about all other cancers, really there are very few that really there's any kind of contraindication for. So the big ones, like I mentioned, would be the meningioma that I would worry about. So for example, for meningiomas, we know a lot of them are benign, but they do express receptors to hormones. So about 75% put progesterone receptors on there in the meningioma.

There are about 50% that have androgen receptors like testosterone and only about 10% are estrogen receptor-positive. So the data, for example, even with meningioma is pretty mixed. It's not really clear that hormones egg it on. There's a lot of conversation about injectable Depo-Medroxyprogesterone Acetate, but that one is a very high dose of progestin. It's very unique as compared to the other contraceptives. So that one I think it's shared decision-making.

Outside of that, for example, gliomas, if anything, female hormones are protective, because it's a more male dominant tumor. And then for blood tumors, for example, for myeloproliferative neoplasms like polycythemia vera, it's overall neutral. For your lymphatic or hematopoietic cancers like AML, non-Hodgkin's, you're talking about typically protective effect from hormones. Most gastrointestinal cancers, the studies show either neutral or protective effect from hormones.

So there's no reason to restrict in those situations. For melanoma, the data is quite mixed. When you look at the science, birth control pill use is associated with less parity, is associated with more sunburns, more tanning. So you have to really look at that data. So you would be amazed how many people I see in clinic that had just an atypical mold removed and somebody scared them in that office saying, "Make sure nobody ever gives you any estrogen."

And then the patient walks around for another 30, 40 years thinking that's the way they have to continue it when the science does not support that at all. So we do recommend shared decision-making for melanoma, but really if they have had a low stage, they have a clear indication for it. And similarly, lung cancer, people tell... they restrict. But when you really look at the data, the data is terrible.

It's mixed. It's all over the place. So if the data isn't good, we can't tell people that you need to stay away from hormones. And when it comes to things like bladder cancer, kidney, thyroid, all of those, there's absolutely no restrictions.

Dale Shepard, MD, PhD: Yeah. And then we'll talk about the more complex ones with breast cancer, but I guess a big picture as we think about how you manage all of these, how many people do you suspect actually get good counseling at all about contraception?

Pelin Batur, MD: Very few. And what we see are either unintended pregnancies or people walking around with a lot of untreated premature ovarian insufficiency. That's another big one. So for example, for people who get stem cell transplant, there's a huge rate of POI, premature ovarian insufficiency. We used to call it premature menopause or premature ovarian failure. There's a reason they stopped calling it this because really there can be a five to 10% unintended pregnancy rate.

So I always say that all it takes is one egg and one sperm, right? So I've had patients referred to me, they had three years of amenorrhea, no periods, multiple FSHs that are high in the menopause range in the blood tests, and then they come back pregnant. They hadn't had any bleeding. So these patients are walking around with POI, which means that you're essentially having low estrogen production before the age of 40.

These patients we know have increased risk of neurological disorders, Parkinson's, dementia, increased risk of cardiovascular disease, not to mention the obvious things like bone deterioration, sexual health, et cetera. So estrogen containing contraceptives can be a great way to actually support bone health. So we're not really thinking about the whole picture.

Dale Shepard, MD, PhD: Yeah. I mean, it seems like we don't really do a good job oftentimes in getting people to talk about, say, fertility preservation. But then on the other side, we're also not doing well on contraception.

Pelin Batur, MD: Correct. And so there's something called the one key question in the reproductive health world, and it's very simple, it's would you like to be pregnant in the next year? Recognize if that patient has pregnancy potential, just recognizing that that should be something, counseling that should happen, right? And I used to think, okay, perfect. They say, "Oh no, I don't want to be pregnant."

And then I'm like, "Okay, we've got IUDs. We've got this." I'm ready with my list. And then I listened to an interesting presentation of a paper that said that when you ask a second question, "Well, how would you feel about an unintended pregnancy?" Well, it turns out the whole world is not as OCD as doctors and nurse practitioners are. We're ready with the plan, but the second you just pause and you say, "Well, what would you think about an unintended pregnancy?"

And some people are like, "Oh, well, they would be a blessing." So with those two questions, would you like to be pregnant in the next year and what would you think about an unintended pregnancy, you can have a good idea of what that person's intention is and drive the conversation accordingly.

Dale Shepard, MD, PhD: Yeah. Perfect. I guess just as a very practical question, if I ask those two questions and I do a better job, because I know I don't currently, what's the best way to get support for patients?

Pelin Batur, MD: Well, we all could do better in our busy clinics, right? So don't beat yourself up too much. So these conversations, I mean, this is why we've developed a whole program. We have a complex contraception clinic for here for our Cleveland patients. However, it all starts with conversation. If you're listening to this from another institution or if you're a patient trying to drive this kind of care locally, because too many times, if nobody's even bringing it up, then nobody's taking next steps.

So really when we say shared decision, we're really talking about a conversation between the oncology team, the patient, and the gynecologic primary care, whoever's handling the reproductive concerns for that patient. And it just starts with a conversation.

Dale Shepard, MD, PhD: Tell us a little bit about emergency contraception in these patients.

Pelin Batur, MD: Yeah. I'm so glad you asked because there's a lot of confusion surrounding it. First of all, let's clarify that emergency contraception is not abortion. So there's a few different methods of emergency contraception. They can all be used within five days of intercourse. There are two pills. One is over the counter, it's Levonorgestrel-based, Plan B, and multiple different generics, and then ulipristal acetate, which is a prescription. And these work by delaying ovulation.

So if you have a patient who is about to undergo cancer treatment in cancer and there's a chance of unintended pregnancy, all clinicians, not just OB/GYN, should be aware that these are available. The most effective is actually to put an IUD in within five days. However, the ulipristal acetate since it's a prescription and it is more effective than the over-the-counter products, it'd be good if our clinicians wrote a prescription. So that if a patient has an uh-oh moment, they're not running around from pharmacy to pharmacy. Because the earlier you take it, the more effective it is.

Dale Shepard, MD, PhD: We talked about contraceptive considerations in all other tumors. Let's double back real quick about estrogen receptor-positive breast cancer.

Pelin Batur, MD: Yeah. And actually one thing I did forget to mention to you, if you don't mind me backtracking one more time, for liver, that's a big one. So I talked about gastrointestinal tumors in general are completely safe. Liver is a little bit of an exception. For those who have primary hepatocellular carcinoma, if they have normal liver function, it's fine. But going back to the worries about thrombosis, if they have altered liver function, that's a group in the guideline where we said cautious about the use of hormones.

And we also did include some things such as hepatocellular adenoma. Even though that's not a tumor, there's oftentimes a lot of confusion and that one is something that you would hold off on hormones because those are more hormonally driven than the cancer itself. So I just wanted to put that out there too in case that applies to our audience.

Dale Shepard, MD, PhD: Yeah. I get a lot of patients with desmoid tumors that this comes up as a big concern because of the female predominance and we've actually had some therapies that limit hormonal exposures that have been not in great studies, but anecdotally helpful.

Pelin Batur, MD: Yeah. And you bring up an important point. So anybody where there are data to suggest that an anti-estrogen treatment, anti-hormone treatment would benefit them for their cancer, that's the group that we would be cautious. But we just have to be careful because there are studies sometimes of only 10 patients where we gave them anti-cancer and they seem to do okay, and then that leads to these big blanket statements about do not use hormones.

So we really have to look at what the strength of the data is, especially when we know things like premature ovarian insufficiency has such detrimental effects. So going back to your question about breast and reproductive, let's do breast first because breast is a complicated one. There are not good studies about contraceptive hormones in breast cancer survivors. So we had to look really where there is more study with the postmenopausal hormone replacement.

And believe it or not, there are some good studies that were done, RCTs out of Europe, randomized control trials, and they looked at those with hormone receptor-positive cancers, what happens if you give them postmenopausal hormones? And in one study, there was no increased recurrence rate. The patients did great. And in another, there was a small increased risk of recurrence, but none of these studies have shown increase in death rates.

So that's where it gets a little bit more controversial because obviously we do use anti-estrogen treatments to benefit patients. So if it's a hormone positive, estrogen positive, progesterone positive tumor, then in general we do recommend non-hormonal treatments. One big caveat is that sometimes we're using these hormones to treat a condition. So they're having really heavy menstrual bleeding.

They are extremely young. They're only in their 20s right now and they're having a lot of hot flashes. Or tamoxifen causes a lot of polyps and we know the use of an IUD locally minimizes systemic absorption, but can actually help with the prevention of polyps. So even in the case of an estrogen positive tumor, we recommend shared decision-making. But in general, it's prudent to minimize hormone exposure.

When it comes to breast cancer that's hormone receptor-negative, then in those situations, we really don't have any data suggesting that they shouldn't take hormones, but understandably people are a little bit nervous about it. So that's completely gray zone where we need more studies and shared decision-making has to happen. What we do have the science showing is if I don't have a breast cancer history myself, but if I decide to take contraceptive hormones, is that going to increase my risk of breast cancer?

Because for somebody who's estrogen receptor-negative, that's essentially what you're looking at. I mean, if I take this birth control pill, is it going to increase my risk of a new estrogen positive cancer? And actually if you look at the study, most of the studies show that you do not have a clinically meaningful increased risk in your breast cancer, except for the formulations that were used in the old days in the 1970s, those were higher doses.

If you look at the studies that show increased risk of breast cancer with contraceptives, it's important on a population scale, but for the patient sitting in front of you, the risk is so small that it oftentimes is not a clinically meaningful meaning. It's about one additional breast cancer risk in about 7,700 patients. So yes, it's a risk, but for that individual woman, it might be a small risk.

So this is where I think the shared decision-making is appropriate. And do you mind if I do a side branch for those who carry the genes for the breast cancer?

Dale Shepard, MD, PhD: I think you should.

Pelin Batur, MD: Yeah. Because even though those individuals that carry the hereditary breast and ovarian cancer genes, such as the BRCA positive mutations, we did a carve out for them, even though they're not a breast cancer survivor most of the time, there's a lot of confusion about the safety. And I think the word is out for most people now that most clinicians know that these mutation carriers, that hormone therapy is safe for them, but I'm not sure.

Maybe the word isn't so out. And so we do talk about that science because even in this highest risk group, when you add contraceptive hormones, there's no clinically meaningful increase in the breast cancer risk for a patient, but there's a very clinically meaningful drop in their ovarian cancer risk. So we have a pretty large group of these patients that we follow at Cleveland Clinic. And in general, they are being offered birth control pills to suppress ovulation.

Because the more you suppress ovulation, the more you're going to reduce their ovarian cancer risk until they decide to go to their preventative surgeries. And after their preventative surgeries, if they're young, they're 40, they're 39, whatever, we will oftentimes offer them postmenopausal doses of hormones so that they're not feeling miserable and they have some quality of life.

Dale Shepard, MD, PhD: Makes sense. One thing that's been a theme throughout is not having enough trial data. Are we ever going to get to a point where we get that? It sounds like it'll be tough.

Pelin Batur, MD: We are hoping. The Women's Comprehensive Health and Research Center that I mentioned, we have four pillars, connectivity, meaning clinicians are talking to each other. Access, getting the patients the care that they need with the right person. Research, that's the R, and education, the education of patients and our colleagues. So for the research, we really are working on creating a data, a patient registry so that we can follow patients, that we can use AI tools to connect a patient with the type of research they want. So there's a lot of exciting things to come. Stay tuned.

Dale Shepard, MD, PhD: All right. Well, great insights today. It sounds like we have a launching pad for your next visit.

Pelin Batur, MD: I hope so. Yeah.

Dale Shepard, MD, PhD: All right. Thank you.

Pelin Batur, MD: Yeah, you're very welcome.

Dale Shepard, MD, PhD: To make a direct online referral to our Cancer Institute, complete our online cancer patient referral form by visiting clevelandclinic.org/cancerpatientreferrals. You will receive confirmation once the appointment is scheduled.

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