Genitourinary Syndrome of Menopause

The Hormone Menoverse Basics

We’ve spent quite some time on systemic menopausal hormone therapy, meaning estrogen that gets into the blood and travels through the body to different tissues. The main reasons for starting systemic hormones were covered earlier in the Menoverse series and include symptoms (this post) and prevention of osteoporosis (this post), and you can find the full Table of Contents for all the content thus far here. In this section of the series, we will focus on genitourinary syndrome of menopause (GSM), with topics such as what it is, the different therapies, how to choose the right one for you, and how to troubleshoot if there are issues.

It’s easy to write a short post and say, “Here, use vaginal estrogen,” but I think that approach is dismissive because people deserve to know more about what is happening to their body. Also, when people don't know enough about their therapy, they may not even start it, or they might stop it prematurely. For example, it’s important to explain that it can take 4-6 weeks to see an effect, and if you stop, the symptoms will return fairly quickly (which can lead some people to think the treatment hadn’t worked when it worked as expected). Also, I specialize in complex issues related to genitourinary syndrome of menopause, and I want to give you all the advantage of my cumulative years of expertise. This post will cover the basics of GSM and provide an introduction to the therapies to prepare for some more in-depth posts. 

What is GSM?

Genitourinary syndrome of menopause affects up to 84% of women, and it is the name that we use for a collection of symptoms and physical changes to the vulva, vagina, bladder, and urethra that happen with menopause. While most people think of pain with sexual activity, which is definitely seen with GSM, there are a myriad of other symptoms, including vaginal and vulvar dryness, irritation, burning, and a sandpaper-like feeling; vaginal discharge; vaginal odor; and it is a risk factor for urinary tract infections. Looking at women in the Study of Women’s Health Across the Nation 9SWAN), who were aged 42-52 at enrollment, of those who had no pain with sex at baseline, over 13 years of follow-up, almost 50% (48.4% to be exact) developed pain with sex, at least sometimes. Now, this doesn’t mean that pain was all GSM-related for every woman, but it does tell us that pain with sexual activity is a significant issue for many women who are in their 40s and older, and figuring out how much of that is GSM or something else (and sometimes it is both) is very important. Pain with sex is often sadly and inexcusably under-treated. 

With menopause, there are some key changes related to the decrease in estrogen. The blood flow to the genital tissues (including the bladder) decreases, as does the production of collagen (the protein that provides support and strength to tissues and helps maintain elasticity or stretch). The decrease in collagen is likely related to both menopause and age-related changes.

The vagina is lined with layers of skin cells, which are shed regularly and become part of the vaginal discharge. Estrogen is also key for depositing a storage sugar called glycogen into these cells, keeping them plump (for lack of a better word), and when the cells are shed and die, the storage sugar is released into the vagina, feeding the good bacteria. Without estrogen, the cells get thin and fragile and can bleed easily when touched. In addition, the vaginal microbiome shifts causing inflammation and a rise in the vaginal pH. Mucus production decreases, making the tissue more fragile as there is no longer a protective, slippery coating, and the change in mucus may also contribute to changes in the microbiome. The ability to increase secretions or wetness in response to sexual stimulation, something medically known as a vaginal transudate, decreases, so people notice decreased or even absent lubrication with sexual activity. Both the changes in the vaginal microbiome and a direct effect on the bladder and urethra from lack of estrogen increase the risk of bladder infections.

Here is an illustration from The Vagina Bible to show some of these changes at the cellular level: 

The tissues of the vulva and vagina can become thinner and lose stretch due to the loss of collagen, and there is loss of fat in the labia majora (these are both a menopause and an age-related change), and there can even be a shortening and narrowing of the vagina that occurs over many years. Rarely, there is so much inflammation that scarring in the vagina can occur. However, in this situation, it is very important to rule out inflammatory skin conditions, most commonly lichen sclerosus and lichen planus, as those are more likely to cause scar tissue or dramatic physical changes in the appearance of the skin and vagina than menopause. 

The onset of symptoms of GSM varies significantly, and it seems unrelated to estrogen levels in the blood. I’ve seen 46-year-olds skipping a period or two with significant GSM, and I’ve seen a woman in her 80s whose vagina looked like she was 35 (I am not exaggerating). Genetic variations in estrogen receptors, collagen, and other factors likely play a role in the spectrum of how GSM presents. However, if you are 45 or older and your menstrual periods have started to space out, or they have stopped, and you have any of the symptoms mentioned above, then GSM should be considered. People with primary ovarian insufficiency (menstruation stopping before age 40) and premature menopause (menopause between ages 40 and 44) will also get GSM. 

These changes in the vagina, vulva, and bladder have nothing to do with having sex. In other words, the phrase “use it or lose it” in this context is a trash misogynistic concept (yes, I will always tell you how I really feel). The original study that is the basis for the claim should never have been given a second thought. The real conclusion from that study is that when sex hurts, people often avoid it. Several studies have put this ridiculous hypothesis to rest. 

Another important cofactor for symptoms of irritation is incontinence, the risk of which increases with age and also with menopause. With leaking, if urine stays on the vulva, for example, via wet underwear or using menstrual pads for incontinence instead of incontinence products, the skin becomes more susceptible to damage from friction (think wiping or a pad against the skin), and ammonia in the urine raises the pH of the vulvar skin. Both of these phenomena adversely impact the skin's acid mantle, which is a protective coating, increasing the risk of skin irritation and even allergic reactions. Over wiping and using soaps, which people often do when they have incontinence to be extra clean, can further damage the skin barrier. With fecal incontinence, enzymes from the stool can also damage the integrity of the skin. Many women have untreated or under-treated incontinence, so this is a very important consideration. First, they deserve to have their incontinence treated, but also it’s important to know that while estrogen at the vaginal opening can help make the skin more resilient, it is no match for incontinence, and estrogen won’t help irritation around the anus. 

If you want to know more about taking care of your skin with incontinence, check out this post. Also, I am working on a more detailed post about vulvar moisturizers. Many conditions can also masquerade or be misdiagnosed as GSM, and we’ll address those in a later post about troubleshooting when therapy isn’t working.

Non Prescription Options

Nonprescription vaginal lubricants and moisturizers are often offered as first-line therapy. Lubricants are an on-demand product to be used for sexual activity, and vaginal moisturizers are to be used every three days (typically) whether you are sexually active or not. Vaginal moisturizers are bioadhesive, so the products stick to the vaginal tissues and provide ongoing symptom control. If you look under the microscope, moisturizers don’t improve the appearance of tissues, but they can be very effective in managing some symptoms. They typically perform best when there is only one bothersome symptom, think just dryness or just irritation or just pain with sex. It is important to point out that the ability of these products to help symptoms of GSM is often underestimated, as in some studies (all short-term), vaginal moisturizers can perform as well as the lowest doses of estrogen. 

Moisturizers can be water-based (glycerin is a common ingredient), silicone, oil, hyaluronic acid-based, or a combination. You can read more about hyaluronic-based options here. 

If you try one of these products and don’t see the benefit, switching to a different base, for example, from silicone to hyaluronic acid, is something to consider for women who want to avoid a prescription product. I will work on a post looking at all the moisturizers so all the information is in one place for those who are interested.   

Should you try a moisturizer first? 

We have no studies that randomize women to using a vaginal moisturizer or estrogen and then follow them over the long term and compare their outcomes head-to-head (or perhaps vagina-to-vagina?). We know that over time, changes to the vaginal tissues with menopause will occur for many women, but how people will feel long-term on a moisturizer versus estrogen hasn’t been studied. Many guidelines recommend moisturizers as the first line, but we don’t have data to support or refute that approach. The one exception is for someone with estrogen-receptor-positive breast cancer who is taking aromatase inhibitors; the consensus is still to recommend a moisturizer as the first option (we’ll get into the data about vaginal estrogen for people with this kind of cancer in a later post).  

It is important to know that moisturizers will not prevent the physical changes to the tissues seen with menopause or prevent bladder infections. The tissues will still be dry, but the moisturizer may coat them well enough so the symptom isn’t bothersome. The vaginal moisturizers may also rehydrate the tissues enough so sex isn’t painful. 

My approach is to explain what both vaginal moisturizers and prescription products can and can’t do and then discuss the goals of therapy. I’m supportive of people who want to try a vaginal moisturizer first, keeping in mind that moisturizers are most helpful when there is only one bothersome symptom, think dryness or irritation. For someone with recurrent bladder infections or significant tissue changes from low estrogen, I wouldn’t recommend a moisturizer, but if someone wanted to go that route, I would be supportive. The vaginal prescription products for GSM and very effective and safe, so medically, there is really no reason to try a moisturizer first, but I recognize that not everyone wants to use hormones or a prescription product. Also, if a moisturizer hasn’t helped the issue in a few weeks, it’s time to move on. This isn't something you need to try for months to see if it will help.

Some people end up using a vaginal moisturizer because they have been scared by the black box warning on vaginal estrogen products. I tell people to ignore that black box warning; it’s an absurd FDA regulation, and I’ll get into that more in the next post. 

Does Systemic Hormone Therapy Treat GSM?

System hormone therapy, such as a patch or a pill, often treats GSM, although guidelines don’t recommend systemic hormones for the sole purpose of treating the bladder, vulva, or vagina. But for those who are being prescribed estrogen for other reasons, for example, hot flashes, many times, they get enough treatment for GSM. In the Women’s Health Initiative, 75% of people had relief in vaginal dryness with Premarin 0.625 mg taken orally, which we think of as a moderate dose and about equivalent to a 50 mcg estradiol patch or a 1 mg oral estradiol tablet.  

If you consider that a 100 mcg patch delivers the average estradiol that the body makes during a typical menstrual cycle, for those on a higher dose of estrogen (meaning a 75-100 mcg estradiol patch or oral equivalent), their systemic hormone therapy will almost always be enough. Many people on a 50 mcg patch or equivalent will do well, but some will need a vaginal boost, and when you get to a 25 mcg patch equivalent, more people may need a vaginal boost. Typically, if I am starting a patient on systemic hormones, I recommend waiting six weeks or so to see if there is enough improvement in vaginal symptoms and then repeat the exam and go from there. There are always exceptions to the rule, especially for those starting on lower doses of systemic hormones, but those are nuanced in-office discussions and don’t really lend themselves to a general discussion in a format like this. 

One caveat about systemic estrogen is that it can make incontinence worse for some people, and vaginal estrogen does not. Also, while risks with systemic hormones are low, they are not zero. With vaginal estrogen, as long as it is dosed correctly, the risks are as close to zero as we can get with any medical intervention. 

Specific Therapies for GSM

Pharmaceuticals for GSM include vaginal estrogen, vaginal dehydroepiandrosterone, and ospemifene, an oral medication that is a selective estrogen receptor modulator or SERM. These evidence-based prescription medications are very effective, and there are, unfortunately, a variety of reasons why they are under-prescribed, including an underappreciation amongst providers of the serious impact of GSM on quality of life, discomfort discussing sexual health, and a lack of education about the therapies. There is also a perverse and outdated idea that GSM is a “natural” part of aging or being a woman (no one ever says that about erectile dysfunction and men, do they?). Also, sadly, many people with GSM don’t seek help for symptoms as they may have been previously dismissed by their provider, or they don’t know how safe and effective these therapies really are. The cost of prescription therapies can also be a barrier, and some people don’t like vaginal therapies. 

Vaginal estrogen therapy is considered the gold standard and is by far the most well-studied. It works by increasing glycogen in the vaginal tissues nourishing the lactobacilli, which then produce lactic acid lowering the pH. It also increases blood flow, collagen production, lubrication, and tissue elasticity. In the United States, vaginal estrogen products are either estradiol or conjugated equine estrogens (CEE), but in many other countries, vaginal estriol is also an option. 

Vaginal dehydroepiandrosterone is converted by the cells into estradiol, estrone, and testosterone and likely has its effect via the estrogen. It is not as well-studied as vaginal estrogen and has not been compared head-to-head.

The oral option is ospemifene, which acts like estrogen in the vaginal tissues but does not act like estrogen in the breast or endometrium. I’ll just put in a plug here for the wonders of synthetic hormones because this is a fantastic example of how a hormone can be created that does more of what you want and less of what you don’t want. (Science for the win!) The advantage of oral ospemifene is that it doesn’t require vaginal application, which is especially helpful for people with arthritis or who have pain from vulvodynia, and there is no mess, but the main side effect is hot flashes. There has been a concern about an increased risk of blood clots, but post-marketing surveillance (the kind of monitoring that happens after a drug is released to identify rare risks) doesn’t seem to indicate a major concern, although blood clots are still listed as a potential issue on the packaging. Ospemifene is not approved in the United States for breast cancer survivors, but in Europe, there is no contraindication to its use for this population. 

What Therapy to Use?

Most people recommend vaginal estrogen as, unlike vaginal DHEA, daily use long-term isn’t needed (most estrogen products are used for 2 weeks initially, then twice a week thereafter, but the ring is obviously daily). Ospemifene is generally something we use for people who have difficulties with vaginal therapies. 

Here is a chart summarizing the different products, and in the next few post, I’ll take a deeper dive into the different vaginal estrogens, DHEA, and ospemifene.

Coming Up Next

A deeper dive into the different vaginal estrogens, and then we’ll get to the other products.

As always, the information here is not direct medical advice. If you have questions, leave them below. I try to reply to the easier ones directly in the comments (obviously, again, not individual medical advice). For those questions that are more complex, I tuck them away to try to incorporate them in future posts.

References

The NAMS 2020 GSM Position Statement Editorial Panel. The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause. 2020 Sep;27(9):976-992.

Mili N, Paschou SA, Armeni A, Georgopoulos N, Goulis DG, Lambrinoudaki I. Genitourinary syndrome of menopause: a systematic review on prevalence and treatment. Menopause. 2021 Mar 15;28(6):706-716.

Phillips NA, Bachmann GA. The genitourinary syndrome of menopause. Menopause. 2021 Feb 1;28(5):579-588.

Drugs for Menopausal Symptoms. Med Lett Drugs Ther. 2020;62:124-8.

Long CY, Liu CM, Hsu SC, Wu CH, Wang CL, Tsai EM. A randomized comparative study of the effects of oral and topical estrogen therapy on the vaginal vascularization and sexual function in hysterectomized postmenopausal women. Menopause. 2006 Sep-Oct;13(5):737-43. 

Barnabei VM, Cochrane BB, Aragaki AK, Nygaard I, Williams RS, McGovern PG, Young RL, Wells EC, O'Sullivan MJ, Chen B, Schenken R, Johnson SR; Women's Health Initiative Investigators. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative. Obstet Gynecol. 2005 May;105(5 Pt 1):1063-73.

Nordstrom BL, Cai B, De Gregorio F, Ban L, Fraeman KH, Yoshida Y, Gibbs T. Risk of venous thromboembolism among women receiving ospemifene: a comparative observational study. Ther Adv Drug Saf. 2022 Nov 19;13:20420986221135931.

Ospemifene (Osphena) for dyspareunia. Med Lett Drugs Ther 2013; 55:55.

Prasterone (Intrarosa) for dyspareunia. Med Lett Drugs Ther 2017; 59:149.