Is Vaginal Estrogen Safe? Considerations for Special Patient Populations

[Dr. Suzette Sutherland]
I wanted to go back to something that you already mentioned, the boxed warning. What's wrong with the boxed warning? Why should they not believe what's in there? Then tie that into the WHI studies, the Women's Health Initiative studies that came out a number of years ago and caused a generation of women to stop all of their post-menopausal hormones and then the fallout from that, the problems we had and we're trying to make up from that. So many, even well-meaning providers are telling patients, well, you don't want to use that estrogen because it's going to cause a lot of problems with stroke, heart attacks. All these studies show that. Can you debunk that myth as well, please?

[Dr. Rachel Rubin]
This is where the AUA absolutely needs to get involved from an advocacy position and I'm going to flex and get them involved as soon as possible because we must change the box labeling on vaginal estrogen because almost nothing that the box says is true. If you look at a box of vaginal estrogen, it says it causes stroke, blood clots, heart attacks, dementia, and must be used with progestin. None of that is true. All of that is based on systemic hormone therapy. Most of it is not true, but it is no data for local vaginal hormones to need any of those things and there's no data to show that vaginal hormones causes stroke, blood clots, cancer, dementia and we know that you don't need to use a progestin with vaginal hormones. The FDA is actually killing women. I'm going to say it. They're killing women by having that box labeling on there because women are dying from urinary tract infections. Medicare is spending between $6 and $22 billion a year on urinary tract infections that they wouldn't have to spend if women were given vaginal hormones. By trying to overprotect women, we're actually killing them and we have to change that. I'm going to put it to you, Dr. Sutherland, because me, I get lots of time with patients and I go into all the data of the Women's Health Initiative and I say, wait a minute, with systemic estrogen, there was a decreased risk of getting and dying from breast cancer so how is local estrogen going to cause this? I go really into it, but you don't have all the time in the world with your patients so what is your spiel? What do you tell patients about the black box? Because I believe we have to educate patients before they leave that office. Because I don't know what it is about vaginal estrogen but women read the box. They all read the box and nothing else. Nobody reads the box of anything else except vaginal estrogen, so what do you tell them in your shorter visits?

[Dr. Suzette Sutherland]
Yes, basically the same thing you just did but I try to do it a little bit in an elevator speech-type mode. Mostly the take-home message is that the black box warning information is based on systemic estrogen and that's not what I'm advocating for you. We're talking about a small dose that goes locally. Sometimes they talk to another provider and the provider says, but it can be absorbed systemically if you put it into the vagina, and I say, yes, if I tell you to take the applicator and fill it up six times and put it in and do that every night, well, that's a huge dose.

The vagina is a very vascular space and it will definitely get absorbed but that's not what we're advocating. We're talking about a low dose, very small, low dose that stays vaginally and there are a number of studies that have looked at systemic estrogen. You know this very well. Looked at systemic estrogen after low-dose vaginal use and no change, no bumps in the estrogen levels systemically. It does take a lot of education on our parts. I liked what you said. The patients then are labeled noncompliant and the way I would say that is that the responsibility falls on us. They are undereducated, but that's my job, my job to educate them so if they don't understand it, I didn't do it well enough. I do have women who come even after that big spiel. I find out when they follow up at their three months to see how things are going and they stopped using it after two weeks because, "I don't think it was really helping. I was worried about it and I was worried about the estrogen." I said, we had this conversation, so we have the conversation again. Sometimes it takes two conversations. People are really nervous about it and so, I totally agree with you. We need to get out there and advocate against this black box warning because we are hurting patients and it's an uphill battle when other providers are telling their patients the harms, what they think the harms of the estrogen are and it's not based on contemporary data.

[Dr. Rachel Rubin]
You know what's so fascinating? I think we went wrong in a lot of ways trying to understand this. I think we went wrong with calling this a little vaginal dryness, right? A little vaginal dryness means it's okay, lady, suck it up, use a lubricant, use a moisturizer. It's no big deal. You're okay. GSM, genitourinary syndrome of menopause is not a little vaginal dryness. It's pain with sitting. It's pain with pants. It's urinary frequency and urgency. It's bladder pain. It's opioid use. It's literally not being able to be intimate with your partner who you love so very much because it feels like shards of glass. It's recurrent urinary tract infections, which can get you with a PICC line needing IV antibiotics because you have resistance, and so this idea of, oh, well, we don't know the dangers of vaginal estrogen.

There is no data showing danger to vaginal estrogen, but there is a lot of data showing how dangerous genitourinary syndrome of menopause can be. Take a medicine like Tamoxifen, okay? We use Tamoxifen. It's another CIRM for breast cancer prevention. It can cause uterine cancer. It can cause blood clots. It can cause osteoporosis and what do we say? Well, it's going to prevent your risk of getting a breast cancer recurrence, so the benefits outweigh the risk. How can we say that about Tamoxifen, but then say that vaginal hormones, the benefits don't outweigh the risk? Oh my God, the benefits outweigh the risk time and time again because no one can show me a paper that shows actual risk, right? That's the part that I can't understand is how this is so obvious. It's so easy. It's so available and has been since the 1970s, but the reason we're not pushing it and doing it, it's because we're not selling it. We don't even find it important enough. That's where the advocacy must come in.

[Dr. Suzette Sutherland]
Another controversial area, of course, is in the area of cancer so we always think about breast cancer, we see a lot of those patients, but also endometrial cancer or cervical cancer and survivors. What kind of advice are you able to give there from the contemporary data that we have today?

[Dr. Rachel Rubin]
This is why I love spending time getting to know my patients, customizing their care to their specific problem. Again, there is data that shows there's no risk of vaginal hormones in endometrial cancer survivors, in cervical cancers, or ovarian cancer survivors. There's actually data on the breast cancer side that shows no risk of recurrence with Tamoxifen use, whereas there is still some pause in the Anastrozole patients. The purpose of Anastrozole is to block every type of estrogen ever to make there be no estrogen in the body. A lot of oncologists were concerned about using local vaginal hormones with the purpose being that we don't want any estrogen in the body. There's one recent paper that shows a mild blip of a concern with those women on Anastrozole and using vaginal estrogen but that data hasn't been replicated, and even that data was wrought with many problems and older data, even, honestly, before HER2Neu status and some of the new breast cancer therapies so it wasn't really a good study. We don't have any good studies to show real harm with vaginal hormones and breast cancer and we have a lot of studies that show no issues and no harm.

What I tell patients is, again, what are the benefits? What are we trying to treat here? Alcohol is a perfect example. A lot of breast cancer patients will still drink alcohol every now and then, and that's a much higher measurable risk of harm and carcinogen. You have to understand, is this inhibiting you from being intimate with your partner? Do you have frequency and urgency and you're getting up all night because you're leaking and you have to urinate? Do you have an overactive bladder? Can you not sit or wear jeans? Again, with a cancer patient, it's, we treated you so we could keep you alive, but how are you living? Can we make you live better? Do we have all the information in the world? No, but we make the best decisions that we can with the information that we have in 2023. The problem is a lot of your doctors are not updated to 2023. Their brains are back in 2001 and so you have to find the right medical community to give you good advice and to have what we call shared decision-making. Dr. Sutherland and I, we treat men all the time and we do shared decision-making, right? Where it's your body, your choice, and we have to really understand what those decisions are.

[Dr. Suzette Sutherland]
Yes, so how about the patient who, you mentioned it a bit in maybe somebody who's actively being treated, but just on Tamoxifen, the estrogen blocker, and maybe not such a situation where they're trying to block every little thing because they are high risk with all the receptors and all that. We see a lot of patients on Tamoxifen and they're maybe four and five years out towards the end of their Tamoxifen use. The use of some local estrogen in those situations, many of them say, well, the providers will say, well, it won't work because you're going to block that local estrogen. Can you speak to that?

[Dr. Rachel Rubin]
I think we need more data of will it work or not work, but we certainly don't have any data that shows major harm, especially in the Tamoxifen patients. That actually is a place where DHEA may come to the rescue and where certainly the menopause society and the cancer societies have said, DHEA is quite interesting here and we need more studies, but we even have a study with DHEA that shows that even patients on Anastrozole who took DHEA had persistent decrease in recurrence of urinary tract infections so it still worked. It worked quite well and so we need more data. If we cared about women, we would do the data, right? Oncologists should want to answer these questions because they're the ones, patients are going off their Tamoxifen, they're going off their anastrozole because they're having wildly unpleasant sexual side effects and one of those big side effects is genital urinary syndrome of menopause.