Genitourinary Syndrome of Menopause (GSM): Definitions & Management

[Dr. Rachel Rubin]
We've had products since the 1970s. Premarin was the first to the market but since then, we have many more tools in our toolbox and I want to urge doctors to sometimes move away from things like Premarin. The reason is a lot of women don't like goopy creams in their vaginas. It can leak out, mess up their sheets and underwear, but also, Premarin is made from pregnant horse urine, which has some issues with animal cruelty and there's also some chemicals within it that can be irritating or burning.

Now, that being said, if it's the only product available to your patients, it's the best product available, but often, it's not even the cheapest product available. We have estradiol creams, that's your Estrace creams, which you can get on GoodRx or Mark Cuban's pharmacy for $20 a tube, which can last two and a half months. We also have generic estradiol inserts that are 10 micrograms that are fabulous to use every day for two weeks and then twice a week forever. We have branded vaginal estradiol inserts, so they're called Invexi. We have Intrarosa, which is vaginal DHEA, which is a nightly suppository that is fabulous because it's the only FDA-proof product that has androgen. DHEA is an androgen, which is really great. We also have vaginal rings. The ESTRING is a slowly producing estrogen ring that stays in for three months at a time. Now, those are the local therapies. There is one oral therapy called Ospemiphene, which has more systemic properties, and so I tend to use more of the local therapies, but it's approved and quite effective for genitourinary syndrome of menopause.

[Dr. Suzette Sutherland]
Great. You mentioned already some, too, that aren't specific estrogen supplementation, but of course, the downstream effect is still the same. Can you explain that a little bit more, go into detail how the DHEA and the SERMs, how that actually is beneficial in the estrogen side of things?

[Dr. Rachel Rubin]
Yes, I'll start with the DHEA. Now, this product is called Intrarosa. It's a once-nightly vaginal suppository. There's two ingredients, palm oil, and DHEAs, so there's not a lot of stuff in it. It comes with applicators that do get thrown away and they don't have to be reused. It's really important to know that the urethra, the bladder, the vulvar, and the vulvar vestibule tissue has lots of testosterone receptors in it, not just estrogen receptors, but testosterone receptors as well. Often that estrogen-only is often enough, but sometimes it's not. Sometimes that tissue at the opening of the vulva or the urethra is still irritated. What research is finding is that there is a lot of androgen story that we're not talking about because we don't have a lot of products. Well, DHEA is an FDA-approved product that adds androgen locally. The way it works is once you put it in, the body's own enzymes take the DHEA and turn it into both estrogen and testosterone. We presented data at the AUA this year, which won an award, which was very exciting, but that showed that you can decrease urinary tract infections by up to half. This goes into women in their 70s, 80s, and so on. Vaginal estrogen does that as well. It also reduces urinary tract infections and so this is a real preventative strategy that you can give to women.

We also have data that DHEA helps with urinary urgency and urinary frequency and so it's really a lovely product that I see is in your toolbox. Now, often first line is vaginal estrogen because it's often more affordable and better covered by insurance, but we certainly do get prior authorizations for our DHEA and they sample quite well. In terms of the aspemiphene or the CIRM, CIRMs like Tamoxifen is a CIRM, raloxifene is a CIRM. Well, aspemiphene is a CIRM that acts quite well on the vulvar tissue and so there are possibilities of other systemic effects. There is a very small risk of blood clots and things like that. In my older, older patients, I tend to stay away from that product. However, if you have a patient who really does not want to put anything vaginally, we all know we have those patients who it is a barrier. Aspemiphene can be a very great choice.

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[Dr. Suzette Sutherland]
What's your experience with the suppositories? There are two that are on the market, the Vagifem, the Uvifem, are the estrogen suppositories. You also mentioned the Imvexi, but when I prescribe the Vagifem, you already mentioned it's 10 micrograms. It used to be 25 micrograms, and then they brought it down to 10 micrograms. What I find is oftentimes three times a week is really necessary to keep the woman where she needs to be. Do you have that same experience?

[Dr. Rachel Rubin]
Yes. Again, I'm not afraid of it, right? I think this is really the misnomers is so many people are messaging me on Instagram, Dr. Rubin, I'm perimenopausal. Is it safe for me to use this? Dr. Rubin, I'm breastfeeding, is it safe for me to use this? You sit there and you think, wait a minute. When you're breastfeeding, people give you birth control pills, which is like a nuclear bomb amount of hormones. Of course, a 10-microgram insert is totally safe for you to use. If you're perimenopausal, your own estrogen levels can get up to 600. Of course, it's okay to use 10 micrograms of estrogen and so, yes, I think three times a week is totally within reasonable limits.

Again, the worry is if you get very high with estrogen, which you don't with a 10-microgram insert, it's like the equivalent of 1 milligram per year of estrogen in your body. Whereas if I'm giving oral estrogen, which I hardly ever do, I usually do transdermal, but we give 2 milligrams a day of estrogen, right? It really becomes understanding the dose. This is such a low dose. If you wanted to use the insert, but you wanted to have them rub some cream on the opening, that's safe too, right? There's ways around it. Say they have some urethral or vestibule symptoms, well, you can do two things so that you don't have to do all creams. It's $20 a tube. That's kind of some of the workarounds that I use.

[Dr. Suzette Sutherland]
Well, and as you already mentioned, Mark Cuban's pharmacy has made it readily available to some. I've had some who've had some trouble with it, but most of the time these estrogens are pretty expensive on the patient's insurance plans and so if they're not using it appropriately, then they might as well just be flushing it down the toilet because they're not getting the benefit that they need. That's how I talk to patients. If you're using it one day a week, that's not enough to keep you where you need to be so don't even spend the money then.

[Dr. Rachel Rubin]
Letting them know that it's two to three months to start working. Mrs. Jones, if I gave you an acne treatment, it's not going to work tomorrow. It's going to take three months to start to see effects. The tissue has to regenerate, it has to heal, it has to plump up. Give me two to three months and then keep going. Two to three months. They really have to understand in that two to three months, their symptoms might not be immediately better. They may even get a yeast infection in which I say treat it with a Diflucan or whatever you use to treat yeast infections, but keep going with the vaginal hormones. Oh, this is a new one. Patients who say they feel itching with it. If it's not a yeast infection, has anyone ever had itching when a sunburn starts to heal? Your tissue's starting to heal and so it might be a little itchy. That's where I sometimes like the inserts as opposed to the creams because sometimes the ingredients in the creams can be itchy. The key is work with your patients to get the foundational product that really works for them and sometimes you've got to pivot a little bit, but don't give up. Don't go straight to your third-line OAB therapies. Get a foundational hormone product and then after two to three months, if they're still having symptoms, then of course go to your third-line therapies.

[Dr. Suzette Sutherland]
That's great advice. I think another practical piece is if the vaginal tissue is really not healthy. You have an older woman and it already looks to that almost reddish and angry stage, right? No wonder they're having a lot of burning and local irritation. They put the cream on and they say it stings and it burns so they stop. The analogy I give is if your hands are chapped, so dry and cracky, what are you going to do to fix it? You put on some cream. You know when you put it on and it burns, but you don't not put the cream on. You know I have to put on some more until it gets better. It's the same thing here. It might get a little uncomfortable until it gets to a stage where it's okay and then you won't have that burning anymore.