Your pleasure matters.

Perhaps the most common complaint of women* in my office is of pain with sex.  When I am meeting with a woman around the time of menopause or after, far too often the conversations goes something like this…

Me: “Did this pain start in menopause?”

Client: “Yes, I was fine before that?”

Me: “Did your doctor or nurse practitioner ever prescribe vaginal estrogen?” Client: “Oh yeah, a long time ago but I never used it.  I saw that warning about cancer in the papers that came with the prescription and it just didn’t seem like it was safe.  Do you think it is ok to use?”

And almost universally, I think, “Oh no! Another woman who didn’t get what they needed for an easily treated condition because of this black box warning!”

Could vaginal estrogen really be safe?  

Let’s see what the prescribing information that comes with all estrogen products says….

(https://www.nap.edu/read/25791/chapter/19#310)

This is some fine print for sure…here is some of the text: 

The Women’s Health Initiative (WHI) reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women during 5 years of treatment with conjugated equine estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo (see CLINICAL PHARMACOLOGY, Clinical Studies). Other doses of conjugated estrogens and medroxyprogesterone acetate and other combinations of estrogens and progestins were not studied in the WHI, and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

That is a pretty dramatic statement! MI, Stroke, PE, CANCER – Oh my!  No wonder women are so frightened!

Since 1976 the FDA has required a package insert about the potential adverse health effects of all estrogen containing products.   In fact, oral contraceptive pills were the first medication to ever have a direct to patient package insert.  

The right for patients to have direct access to information about the safety of medications, rather than relying on the good will of physicians and other health care providers, was won after a hard-fought, contentious battle. You can read more about that in the excellent book The Estrogen Elixir by Elizabeth Siegel Watkins.  To me, this is  a straightforward positive development for patient autonomy, informed consent, and a powerful blow to the patriarcho-pharmaceutical system!  Go, ladies!  

But estrogens don’t just have a package insert; they have a large black box warning.  A black box warning is reserved for the most dangerous of medications that have adverse reactions that may be life-threatening, fatal or disabling.  Since 2003, all estrogen products have required a black box warning.  

How is it that estrogen came to be thought of as a life-threatening medication?

THE WOMEN’S HEALTH INITIATIVE, ESTROGEN & THE FDA

Prior to 2001I, it was thought that estrogen had numerous health benefits and minimal risks.  For example, it was believed that estrogen had minimal to no effect on breast cancer risk.  It was also thought that estrogen protected women from cardiovascular disease.  These beliefs were based on multiple large observational trials – but no randomized control trial (the gold standard for knowledge in the science of medicine) had been done.  

Because of this high degree of safety, the numerous supposed benefits of HT, and advertising that promised that HT could keep women “forever young,” HT (in the form of Prempro) was the number one prescribed medication in America in the 1990s. I think that’s shocking! Hormone therapy was number one prescribed medication. Wow.

Enter the WHI, the first large randomized control trial to study the effect of HT on women’s health.  

The Women’s Health Initiative was a landmark study in menopausal hormone therapy (HT). Over 15,000 women were recruited to study the effects of hormone therapy on cardiovascular disease, though other health effects were also monitored including breast cancer, pulmonary embolism, and gallbladder disease.  The study was stopped early in 2001 due to the surprising finding that there seemed to be an increased risk of breast cancer and cardiovascular disease for women on HT.  

When researchers pulled the plug on the study early and announced to the world that HT could actually increase the risk of heart attacks, strokes and breast cancer, it set off a media firestorm.  It was front page news on the NY Times and the morning news.  Women all over the world stopped HT.   Doctors stopped discussing menopause with women, because there no longer was an effective treatment for the often-debilitating symptoms it could cause. 

Of course, the FDA also noted these findings and this is how a black box warning as we know it today became mandatory on all estrogen products in the US. 

SYSTEMIC HORMONE THERAPY VS LOW DOSE VAGINAL HORMONAL THERAPY

If we take it for granted that the findings from the WHI were true and indisputable (for reasons why this isn’t an easy thing to do, click here),  this research only applies to the safety of systemic hormonal therapy (HT).  Systemic HT refers to the use of hormones (applied directly to the skin in the form of a patch or taken orally) with the intention for the medication to enter the circulation and raise the overall body level of estrogen (and potentially progesterone).

What about using hormones just on the vagina and vulva to treat local symptoms there?

This is called low dose vaginal estrogen therapy.  Unlike systemic HT, the intention is to use hormones (in the form of creams, tablets, ovules, suppositories or rings) only on the tissues of the vagina and vulva (and the urinary system, but more on that later).  

Low dose vaginal hormonal therapy is therefore prescribed at much lower doses than systemic hormonal therapy – hence the name “low dose.”  After all, it’s only meant to affect the area where it is applied.

For instance, the average dose of vaginal estrogen is 10mcg of estradiol (a form of bio-identical estrogen) most often used twice per week.  This means that an entire year’s supply of local vaginal estrogen is equal to taking 1mg of estradiol per year.  This is less than half the dose of one oral contraceptive pill. One mg of estradiol  is equal to 0.01mg ethinyl estradiol found in an oral contraceptive pill.

This is low dose, real low dose.  There are even versions of estradiol that go lower – down to 4 mcg.

But, medications are absorbed through the skin of the vagina, right?  Even low doses of a medication could get into the systemic circulation, right?  

Yes, absolutely.  

But how much of the medication becomes systemic and does it matter?

As to the first question, we know that estrogen levels in the blood stream do rise transiently when local vaginal hormone therapy is applied.  Research has confirmed, however, that these levels are not sustained in a range above post-menopausal levels.    

Does this matter?  Namely, does this transient slight increase in the level of estrogen in the systemic circulation cause life-threatening disease- as the FDA’s black box warning states in such dire terms?

IS LOW DOSE VAGINAL ESTROGEN SAFE?

Fortunately, we have excellent data available to offer a begin to offer a reliable answer to this question. 

In addition to the large randomized control trial of HT described above, the WHI also had a component that was an observational trial that tracked the health outcomes for women using of systemic HT or local vaginal estrogen therapy . 

This study was a doozy.  Between 1992 and 2005, it enrolled 93,676 post-menopausal women.  Of these, about 4,200 used vaginal estrogen alone, without systemic HT.  These women were followed for on average 6-7 years. 

The study found that the use of low dose vaginal estrogens did not increase the rates of cardiovascular disease, cancer or blood clots.

In 2020, researchers tallied up all of the research about low dose vaginal estrogens is compared, the finding is the same – it is effective and it is safe.

BUT WHAT ABOUT WOMEN WHO HAVE HAD BREAST CANCER?

Women who have had breast cancer often undergo treatments that seek to decrease estrogen levels in order to reduce the risk of cancer recurrence.  These treatments can lead to profound vaginal dryness and discomfort. 

Can women with breast cancer or with a high risk of breast cancer consider low dose vaginal hormones?

The answer to this question used to be a resounding and definitive, “NO!”

However, in recent years, the medical community has begun to reconsider this.

Several studies have suggested that there is no increased risk for breast cancer for women with or at high risk for breast cancer.  The WHI Observational study found no connection.  Neither did this large Finnish study.  Neither did this small study from 2012.

There was enough data that in 2016, the American College of Obstetricians and Gynecologists (ACOG), stated that “The data do not show an increased recurrence among women currently undergoing treatment for breast cancer or those with a personal history of breast cancer who use vaginal estrogen to relieve urogenital symptoms.”  

So, ACOG says that women with or at high risk for breast cancer can consider using low dose vaginal hormones if non-hormonal options are ineffective. 

In 2020, the North American Menopause Society (NAMS) and the International Society for the Study of Women’s Sexual Health (ISSWSH) issued their updated statement.  They agree that the first line treatments for GSM are non-hormonal moisturizers, lubricants and sometimes vaginal dilators.  These treatments can be effective; but what if these treatments don’t work?  Then the use of local vaginal estrogen can be considered.

ATTEMPTS TO CHANGE THE BLACK BOX WARNING

Based on the currently available evidence about low dose vaginal estrogens, the black box warning currently required on these products not only doesn’t protect women, but it is actually a danger to them. 

Women deserve information about the safety of all medications; this is not in dispute.  The problem comes when the information provided is either misleading or downright false.

False information frightens women unnecessarily and encourages them to avoid safe and effective treatments for no reason.  

This is simply unacceptable.

For these reasons, the North American Menopause Society (NAMS), the international society specializing in menopause in America, submitted a petition to the FDA in 2008 requesting that the black box warning be removed from low-dose vaginal estrogen products.

Unfortunately, the FDA summarily rejected this petition, holding to their position that all estrogens are a danger despite the evidence to the contrary.  

The FDA is simply misreading the meaning of the literature on the subject and refusing to heed any advice from gynecologists, menopause specialists or even oncologists.  They also refuse to acknowledge the damage that their incorrect information has done to countless women’s lives.  

Why has the FDA let women down in this regard?  Well,  it cannot be argued that the FDA has a good track record with women’s health. Whether it be with medical devices.  Or excluding women from drug research trials. 

I am not a willy-nilly critique of the FDA.  They serve an important role in healthcare, I simply demand that they fulfill that role more effectively.  Help every woman have access to safe and effective treatments for debilitating medical conditions like genitourinary syndrome of menopause (GSM). 

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If you are considering low dose vaginal hormones, check out this article to learn more about the type of products that are available.

But do risks associated with systemic hormonal therapy apply to low-dose vaginal creams or inserts that are used to treat GSM. 

*In this article, the term “woman” or “women” will refer to people that are born with a vulva and vagina. As we know, there are women who are not born with this genitalia and other genders who do have a vulva and vagina. Language is somewhat inept in its ability to elegantly capture this beautiful complexity. I encourage you to use the information in this article as it applies to you or your loved ones.

It turns out that sex hurts way more often than you would think.

In fact, pain is probably the single most common concern of women* who come to talk to me about their sex lives.

It may surprise you to know that menopause is the culprit for a lot of this pain (though there are many other causes). As is breastfeeding. As is anything else that decreases estrogen levels.

This pain can feel like burning, tearing, ripping, or stabbing with any attempt at vaginal penetration. One woman poetically described it as feeling, “like there are razor blades in there any time we try to have sex.”

That creates quite a mental image.

To make matters worse, the vulvovaginal tissue may not just be painful during sex, but can feel irritated and create mild misery all the time. Every time you wipe with toilet paper or a wash cloth. Every time you put on jeans or even underwear.

But wait there’s more! You can also feel have irritation or burning in the urethra that feels like a UTI. But there’s no infection. It’s just menopause.

Or maybe you are one of the unlucky women who will actually get more frequent UTIs when estrogen drops.

YOUR VULVA, CLITORIS & VAGINA AT PUBERTY

Why does not having a period any more have such a profound effect on the vulva and vagina?

To answer this, let’s first think back to what happens to vulva and vagina when they were first exposed to estrogen at puberty.

If you check out a textbook of human development, you will see the Tanner Stages described. These stages outline the stereotypical development of so-called secondary sexual characteristics in boys and girls.

As sex hormones come online, girls are described as developing breasts, pubic hairs, and periods. The observers of human development noticed that boys get pubic hairs too, but surprisingly (not surprised) their genitals are also a point of interest, as much attention is paid to the growth of the testicles and penis.

But the fine Mr. Tanner and his colleagues do not describe what happens to the vulva, clitoris and vagina at puberty. Surprised? Not surprised.

And since your textbooks and your doctors never thought about this much, you likely haven’t considered it either.

So, what does happen?

Well, it turns out that the vulva, vagina and clitoris are just as sensitive to the onset of puberty and sex steroid hormones as is the penis.

{https://www.researchgate.net/profile/Miranda-Farage/publication/7557975_Lifetime_changes_in_the_vulva_and_vagina/links/569e7ffa08ae2c638eb56d29/Lifetime-changes-in-the-vulva-and-vagina.pdf}

The lovely labia thicken and grow in length. The skin of the vulva may shift to darker shades of pink and brown.

The wondrous clitoris lengthens and expands, becoming more visible especially during arousal (for more on the real anatomy and physiology of the clitoris).

The marvelous vagina lengthens and becomes more flexible. The introitus or opening of the vagina widens. Secretions from the cervix and vagina increase, which helps with lubrication and fertility.

Inside the vagina, the friendly microbiome, which is essential to vaginal health, matures and stabilizes to fight off infection.

In short, the development of the vulva, vagina, and clitoris is a major event in puberty. It should be recognized and celebrated! So here is my belated congratulations!

PUBERTY IS DRIVEN BY ESTROGEN…MOSTLY

The changes that happen to the body at puberty are orchestrated by a wide array of hormones.

In general, we think of this being primarily about rising estrogen levels for vulva owners and dictated by testosterone for penis owners. When it comes to genital development, this is largely true as it is estrogen that turns on the cellular machinery that causes the vulva, clitoris and vagina to mature.

Other hormones are relevant, though. These hormones likely play a more subtle, but essential role. However, because researchers have seemed mentally wedded to the idea that “women = estrogen” and “men = testosterone,” our knowledge of this is limited.

But women make also make a slew of other hormones, including testosterone and progesterone.

We have rather recently discovered that testosterone is essential to vulvovaginal health. Testosterone is an important contributor to the vulvovaginal tissues ability to produce lubrication. In addition, the opening of the vagina (called the vestibule) can be very sensitive to testosterone levels. In fact, without enough testosterone, you may get the same kind of pain that you get without enough estrogen. Testosterone is also vital to clitoral health, helping to maintain good blood flow which supports pleasure and arousal. (https://pubmed.ncbi.nlm.nih.gov/27914563/).

So, vulvas, clitorises and vaginas love estrogen. No doubt about it. But they also wouldn’t mind a little testosterone, too.

Though I love progesterone for many things and think it is an underrated hormone for women’s health and wellness, it doesn’t seem to play an important role in vulvovaginal health.

Ok, so we have reviewed that estrogen is necessary to get the ball rolling “down there” at puberty. But the cellular machinery that is turned on at puberty doesn’t just need a one-time hit of estrogen. It needs at least a minimal amount of estrogen at all times to keep going. At that is just what they get as estrogen rises and falls with the menstrual cycle.

YOUR VULVA AND VAGINA OFF ESTROGEN

The vulva, clitoris and vagina are exposed to estrogen throughout the waxing and waning phases of the menstrual cycle. Estrogen levels rise and fall in relatively predictable patterns when you bleed or ovulate. When this cycle slows or stops, estrogen levels drop to nothing.

This can be a normal process of aging. This is what happens in menopause.

But it doesn’t just happen at menopause. Breastfeeding women can also lose their period for months to years.

It can happen to people born with vulvas but who are on estrogen blockers and testosterone as part of gender transition.

Women under extreme stress can stop having cycles. So can women who are enduring treatment for cancer or who are suffering from other illnesses.

If estrogen is essential to the development and health of the vulva, vagina and clitoris, what happens when it goes away?

What happens is that the same cellular machinery that was turned on at puberty when estrogen came on board, is now turned off. Every person will experience this differently but the underlying process is the same.

It is important that every woman understand what can happen so that if symptoms develop they know why and what can be done about it. What follows is a list of potential changes that can happen. This is not meant to make you worry but rather it is meant to empower! Here is general process that happens:

• Loss of cushion. The layer of tissue that provides cushioning under the skin of the vulva and vagina shrinks.
• Loss of flexibility. Before menopause there is a layer of tissue under the skin that is pleated like…well like a pleated skirt. This allows it to stretch easily. Without estrogen, this tissue becomes flat and rigid.

• Loss of lubrication. Estrogen (and testosterone) supports the cervix and the vagina to secrete lubrication. No estrogen equals a drop in lubrication.
• Changes to the microbiome and increased pH. Estrogen helps the vagina produce glycogen – the food source for your bacterial friends in the vagina – lactobacillus. Without lactobacillus, the microbiome shifts and the pH goes up. This can change the odor of the vagina – which can be really distressing.
• Decreased strength of pelvic floor muscles. Decreased strength in these muscles contributes to urinary incontinence.
• Smaller labia. Not an earth-shattering problem for most people, but interesting nonetheless.
• Smaller introitus (opening to the vagina). No, the vagina isn’t going to close up. But even subtle changes in the opening which make it smaller and less flexible can lead to significant pain.
• Urethral changes. The urethra becomes larger and more prominent. It can also undergo other benign changes that lead to pain with urination. For some women, this combined with the changes to the vaginal microbiome can lead to increased UTIs.
• Potentially smaller, less sensitive clitoris. This is can affect arousal and orgasm, obviously. Women describe feeling like it takes a really, really long time to get to orgasm or that orgasm is kind of…meh.

These changes affect every person differently. However, studies suggest up to 87% of women will have some symptoms of low estrogen after menopause.
{https://pubmed.ncbi.nlm.nih.gov/33739315/}

This is called GENITOURINARY SYNDROME OF MENOPAUSE or GSM when it happens after the permanent loss of the menstrual cycle.

Given all of these changes, it’s pretty easy to see why sex can become so painful. Less cushion, less flexibility, less lubrication, a smaller introitus? Ouch, indeed! This is why women describe burning, ripping, tearing sensations with sex.

Again, some women may have few or no symptoms; others may find sex intolerable or have other symptoms of general irritation or urethral irritation.

But every woman should know about how estrogen affects their genitals and what can happen when it goes away. This simple information is basic to women’s ability to maintain their health and advocate for themselves as needed.

But maybe this is news to you? Or maybe you knew a little something but not all the details?

Well you are not alone.

THE PATRIARCHY STRIKES AGAIN!

How is it that a syndrome that will affect every single woman who goes through menopause and countless others is not better known?

Why is it that less than half of women have ever heard of this condition and even fewer than that have tried a tried treatment for it? { https://pubmed.ncbi.nlm.nih.gov/33739315/}

How is it that the medical establishment doesn’t provide “anticipatory guidance”? You know…could you give women a heads up about what happens and let them know what they can do about it?

Well…anybody?

Clearly, the reverberations of the patriarchy still echo throughout healthcare. The most annoying thing is that this sort of treatment of women’s issues is still so common place that we aren’t even surprised any more.

In fact, I am no longer surprised when yet another woman tells me that she has never heard of this. I am not surprised when she tells me she hasn’t had sex in several years and that she has been suffering in resigned silence.

I’m not surprised, I am just straight up angry!

From a medical standpoint, this is a very well-understood part of a woman’s life. There are clearly developed and easily accessible guidelines for how to diagnose it and how to treat it. In case you are looking for them, here they are. (https://www.menopause.org/docs/default-source/default-document-library/2020-gsm-ps.pdf)

And yet women are not taught about this and are left to suffer in silence far too often. This is quite simply totally and completely unacceptable. Women deserve better.

Women deserve information about how their body works, information about what to expect as they age or have health changes that affect their hormone levels, and accurate information about SAFE, SIMPLE, AND EFFECTIVE TREATMENTS.

Yes, that’s right. Loss of estrogen is a real problem for vulvovaginal tissue, but there are SAFE, SIMPLE, and EFFECTIVE TREATMENTS!

The medical establishment has let women down when it comes to this issue. It’s a bummer. It’s unacceptable. Though, lots of work (www.menopause.org) is being done to sensitize providers to the importance of this conversation, women are still not adequately supported.

So, let’s support each other.

I encourage you to pass this information along. It’s likely that there are people in your life who know little or nothing about this issue. Please share this with a friend, a wife, a mother, a loved one.

We can close this knowledge gap! One slightly awkward conversation about vulvovaginal health at a time! ☺

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To learn more about safe treatments, check out Five Things to Know About Treating Painful Sex After Menopause.

*In this article, the term “woman” or “women” will refer to people that are born with a vulva and vagina. As we know, there are women who are not born with this genitalia and other genders who do have a vulva and vagina. Language is somewhat inept in its ability to elegantly capture this beautiful complexity. I encourage you to use the information in this article as it applies to you or your loved ones.