Disclaimer:  I am not a doctor or a hormone specialist.  I am nearing completion of my Menopause Support Practitioner Certification and am post-menopause myself.  I follow the evidence and look to vocal advocates for female sexual health and wellness like Dr Kelly Casperson and Dr Rachel Rubin.  This is a summary of some, not all, of the research as it pertains to vaginal health post menopause, namely genitourinary syndrome of menopause, and how it can be treated with estrogen and other products.  Please consult your health care provider to determine which is the best option for you.

Vaginas love estrogen!  Estrogen is our juicy supple hormone and as we approach and move beyond menopause, our estrogen production comes to a halt leaving our vaginas and the tissues around the labia, clitoris, urethra and bladder in a less than supple state shall we say. 

Vaginal dryness affects over 80% of women and it is not something that improves with time.  Vaginal dryness is also a common occurrence postpartum, with the use of birth control pills and other medications as well as various cancer treatments.  Vaginal estrogen and vaginal moisturizers can help overcome this and may even prevent it from happening in the first place but unfortunately many women are either not aware of what GSM is, don’t know how to treat it, are afraid of estrogen or they denied access by their care provider.  Let’s set the record straight.

How Do The Vagina and Vulva Change With Age and When Estrogen Decreases?

The vagina, lower urinary tract (including the bladder and urethra), and pelvic floor all contain estrogen receptors.  When estrogen declines, the tissues become thin and dry and they can atrophy (shrink).  This can contribute to a host of symptoms that fall under the term Genitourinary Syndrome of Menopause or GSM.  Recently a new sister term has been proposed - GSL or Genitourinary Syndrome of Lactation which identifies another similar low estrogen state postpartum.

As we age and move beyond menopause, we also experience age- related muscle loss (especially of the type 2 muscle fibers which are the ones associated with speed and power), collagen loss (see my collagen and the pelvic floor article here) and hyaluronic acid loss that can also contribute to the signs and symptoms of GSM.

What Are The Common Symptoms Associated With Low Estrogen and GSM?

GSM is defined as a collection of signs and symptoms that affect the labia majora/minora, clitoris, vestibule/introitus, vagina, urethra, and bladder.

Genital symptoms:

• dryness
• burning
• itching
• irritation
• stenosis or vaginal opening or vaginal walls
• pelvic pain/pressure
• prolapse

Sexual symptoms:

• lack of lubrication
• pain (dyspareunia)
• bleeding during/after intercourse
• burning
• decreased arousal, orgasm, desire

Urinary symptoms:

• urgency
• frequency
• nocturia
• recurrent urinary tract infections 

GSM is very common with upwards of 80% of women post menopause experiencing these symptoms. Women may present with some or all of the signs and symptoms and most don’t know they can be as a result of low estrogen either because they have never been taught, never been asked about any symptoms and because they are many years post-menopause and think it doesn’t apply to them anymore.

Unlike other symptoms associated with the menopause transition, vaginal dryness and the other signs and symptoms do not get better with time and many women have progressive symptoms that become most bothersome 5-10 years AFTER the onset of menopause, which in North America has an average age of 51.

How Is GSM Treated?

There are several options available to women suffering with symptoms associated with GSM including moisturizers, lasers, lubricants for sexual activity, ospemifene, testosterone, vaginal dhea, sea buckthorn oil and vaginal estrogen with vaginal estrogen being considered the gold standard.

Vaginal Estrogen

Estrogens delivered locally to the vagina by tablets, pessaries, and creams are the most common and highly recommended platforms to treat the genitourinary syndrome of menopause (GSM). Dryness, burning, irritation, painful sex (dyspareunia), frequent UTI’s, urinary frequency and urgency are the most common symptoms of GSM and estrogen products have been found to be clinically effective for the treatment of GSM with doses as low as 4 μg.

This study showed that topical estrogen therapy ameliorates OAB (overactive bladder) in female patients.  Another study showed that all commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy-related complaints and have additional utility in patients with urinary urgency, frequency or nocturia, SUI and UUI, and recurrent UTIs. 

The cost of UTI’s is calculated at $1222 per UTI, and the reduction in UTI spending can range between $3670 and $5499 per beneficiary per year.  Topical estrogens are a cost-conscious way to improve the burden of UTI on postmenopausal women with the potential for billions of dollars in Medicare savings. The other important factor to consider is the risks of chronic UTI’s to kidney function and also the potential of sepsis.  Reducing the risk of UTI’s is one of the major reasons (in my opinion) for vaginal estrogen as a preventive therapy.

Multiple randomized clinical trials have successfully been completed to show the efficacy of local estrogen preparations for the treatment of UTIs and if you need more convincing about the need to reduce the risk of UTI's this article shared that “Up to one-third of elderly patients hospitalized with UTIs can experience some degree of confusion and reduced awareness of their surroundings,” said Shouri Lahiri, MD, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai and senior author of the study. “Delirium affects millions of patients a year in the U.S., contributing to longer hospital stays, long-term cognitive problems and increased mortality. Delirium can be a tipping point from which patients never fully recover. 

Prevention of painful sex (dyspareunia) is another reason for using vaginal estrogen.  So many women are missing out on pleasure and intimacy because of pain associated with vulvovaginal atrophy (VVA).  Very low-dose estradiol vaginal cream dosed twice weekly is an effective and well-tolerated treatment for VVA symptoms and dryness associated with menopause. The REJOICE trial was a RCT evaluating the safety and efficacy of a novel vaginal estradiol soft-gel capsule for symptomatic VVA and found that 4, 10, and 25 μg) was safe, well-tolerated, and effective for treating moderate-to-severe dyspareunia within 2 weeks with minimal systemic estrogen exposure.

When looking at moisturizers and estrogen this study demonstrated that treatment with low-dose vaginal estradiol, but not vaginal moisturizer, modestly improved menopause-related quality of life and sexual function domain scores in post-menopause women with moderate to severe vulvovaginal symptoms. This study highlighted that the recently FDA-approved Estradiol softgel vaginal insert (4 µg and 10 µg) was safe and effective over 12 weeks for treating moderate to severe dyspareunia due to menopausal VVA with minimal systemic Estradiol levels. 

Estrogen helps maintain the pH of the vagina.  When estrogen is low the vagina becomes less acidic and more prone to infection. Further, lactobacilli is a group of bacteria shown to produce antimicrobial and anti-inflammatory factors and that also metabolize glycogen-derived polymers into lactic acid.  The production of lactic acid in turn lowers the pH of the vagina and helps maintain its optimal acidic state.  Women receiving vaginal estradiol experienced a greater abundance of lactobacilli and lower vaginal pH at the end of treatment.  This study demonstrated that vaginal estradiol tablets resulted in substantial changes in the vaginal microbiota and metabolome with a lowering in pH, particularly in women with high-diversity bacterial communities at baseline. Low pH moisturizer or placebo did not significantly impact the vaginal microbiota or metabolome despite lowering the vaginal pH. Estradiol use may offer additional genitourinary health benefits to postmenopausal women.  

Vaginal Moisturizers

It is well established that vaginal moisturizers containing hyaluronic acid are effective in alleviating vaginal dryness from any cause. Hyaluronic acid is naturally occurring in the body and has the capacity to retain moisture.  We produce less HA as we age, and this plays a role in less hydration and plumpness in our tissues. 

One study found that hyaluronic acid vaginal gel was not inferior to estriol vaginal cream in women presenting with vaginal dryness and this study found that Hyaluronic acid and estrogen (estradiol) were equally effective in vulvovaginal atrophy treatment.

A systematic review of 5 primary studies involving 335 women published between the years 2011 and 2017 suggest that treatment with hyaluronic acid, when compared with the use of estrogens, does not present a significant difference in the results obtained for the outcomes: epithelial atrophy, vaginal pH, dyspareunia, and cell maturation.

A RCT trial compared the ladylift vaginal laser with hyaluronic acid suppositories and found no difference between the 2 regimens. It was a small study with just over 20 women in each group and it was observed that both intravaginal laser therapy and hyaluronic acid suppositories are effective treatment options for women after Breast Cancer suffering from urogenital atrophy.

To add on here, A Systematic Review and Meta-analysis looked at the severity of GSM symptoms after Carbon Dioxide Laser vs Vaginal Estrogen Therapy and found that vaginal laser treatment is associated with similar improvement in genitourinary symptoms as vaginal estrogen therapy. 

I love that we have new therapies and technologies coming out all the time.  I think there is huge potential for lasers and radio frequency and energy techniques but they are costly and not accessible to everyone.

Estrogen and moisturizers are much more affordable and accessible to most. I recommend women moisturize their vagina daily with a hyaluronic acid based vaginal moisturizer.

Sea Buckthorn Oil

Sea buckthorn and its bioactive ingredients may have potential in the management of gynecological problems such as uterine inflammation, endometriosis, and easing symptoms of vulvovaginal atrophy in postmenopausal women by targeting inflammatory cytokines and vascular endothelial growth factor. In a double blind placebo controlled trial looking at the Effects of oral sea buckthorn oil intake on vaginal atrophy in postmenopausal women it was found that compared to placebo, there was a significantly better rate of improvement in the integrity of vaginal epithelium in the sea buckthorn oil group.

A double-blind randomized placebo-controlled study looked at the efficacy and safety of a new vaginal gel for the treatment of symptoms associated with vulvovaginal atrophy in postmenopausal women and found that the vaginal gel was effective in reducing vaginal pain, dyspareunia and vaginal pH, with the Vaginal Health Index showing significant improvement at day 90.  It was also effective in reducing vaginal dryness, vaginal itching, and burning sensation at weeks 2 and 4, and the end of the study. The analysis also showed, after the end of treatment, an improvement of sexual function in the active-treatment group.  The gel contained sea buckthorn oil, aloe vera, 18β-Glycyrrhetinic acid (one of the main constituents of licorice), hyaluronic acid and glycogen. 

Ospemifene

Ospemifene (Osphena™) was approved by the US Food and Drug Administration in 2013 after 20+ years in development.  It has been approved for the treatment of moderate-to-severe dyspareunia (painful sex) associated with vulvovaginal atrophy (now called GSM) due to menopause. Ospemifene is an oral, non-steroidal estrogen receptor agonist/antagonist, also known as a selective estrogen receptor modulator (SERM).  It is from the same chemical class as the breast cancer drugs tamoxifen and toremifene but unlike other selective estrogen receptor modulators, ospemifene exerts a strong, nearly full estrogen agonist effect in the vaginal epithelium, making it well suited for the treatment of painful sex in postmenopausal women. This is an important point in that it is indicated for the treatment of painful sex, not urinary symptoms or UTI prevention/treatment. 

Vaginal DHEA

DHEA (dehydroepiandrosterone, also known as prasterone) is an androgen, like testosterone and Androgens contribute to the maintenance of genitourinary tissue structure and function. Similar to estrogen, DHEA plays a role in the integrity of skin, muscle and bone and plays a role in libido. DHEA is produced in the adrenal glands and is a precursor to the production of estrogen and testosterone.  As we approach and move beyond menopause our ovaries stop producing estrogen and we begin to source our hormones from our adrenals. DHEA is a major source of our estrogen production but like our other hormones, our production slows as we move beyond menopause.  If DHEA is delivered directly to the vagina, the tissues convert the DHEA to estrogen, (estradiol).

In this study, daily intravaginal administration of DHEA caused highly statistically significant improvements in four measurements of vaginal atrophy. At gynecological evaluation, vaginal secretions, epithelial integrity, epithelial surface thickness, and color all improved by 86% to 121% over the placebo effect and vaginal pH decreased by 0.66 pH unit over placebo.

Daily 6.5mg (0.50%) of prasterone appears to be at least as efficacious as 0.3mg Conjugated Equine Estrogen or 10μg E₂ for treatment of vulvovaginal atrophy symptoms. Intrarosa is an FDA and Health Canada approved vaginal DHEA

An OTC option is Julva made by my friend Dr Anna Cabeca and is a personal fave of mine.  Unfortunately it is not available in Canada so Canadians will need to ask their doctor for a prescription for Intrarosa.

Personally, I use vaginal estrogen (vagifem tablet) and a compounded estriol cream twice a week and Julva on the alternate nights.  Vaginal estrogen must be prescribed by your physician and they will determine the dosing.

Testosterone

We often don’t think of testosterone being helpful for women.  This double-blind, randomized, placebo-controlled trial wanted to investigate the effects of intravaginal testosterone (IVT) on sexual satisfaction, vaginal symptoms, and urinary incontinence (UI) associated with aromatase inhibitor (AI) use. IVT cream (300 μg per dose) or identical placebo, self-administered daily for 2 weeks and then thrice weekly for 24 weeks.  IVT significantly improved sexual satisfaction and reduced dyspareunia in postmenopausal women on AI therapy. 

Another study wanted to evaluate safety of intravaginal testosterone cream (IVT) or an estradiol-releasing vaginal ring (7.5 μg/d) in patients with early-stage breast cancer (BC) receiving an AI.  Postmenopausal (PM) women with hormone receptor (HR)-positive stage I to III BC taking AIs with self-reported vaginal dryness, dyspareunia, or decreased libido were randomized to 12 weeks of IVT or an estradiol vaginal ring.  Vaginal atrophy, sexual interest, and sexual dysfunction were improved. 

To note a cross-sectional study found that low serum testosterone is associated with an increased likelihood of OAB in women. This supports the potential therapeutic role of testosterone supplementation in women with OAB. Another study found that low serum testosterone is associated with an increased likelihood of stress and mixed incontinence in women.

A recent review found that levator ani and other muscles of the pelvic floor and lower urinary tract are sensitive to the anabolic effects of testosterone. Androgen receptors are also expressed in the pelvic floor and lower urinary tract of both animals and humans. Anabolic effects of androgens may play an important role in the female pelvic-floor and lower-urinary-tract disorders. Furthermore, the interactions between androgen and nitric oxide synthase and arginase have been demonstrated, suggesting that androgens may also participate in modulating the physiological functions of lower urinary tract through nitric oxide.

Given the direct and indirect effects of testosterone on the pelvic floor and lower urinary tract, a potential mechanism for this relationship can be further explored in other studies. I am excited that testosterone therapy is being more researched and it is my hope that it will become more accessible to women for pelvic health and overall health benefits.

Pelvic Floor Muscle Training

I can’t write an article without mentioning pelvic floor muscle training.  It is well established as an effective intervention for improving Health Related Quality of Life (HRQoL)-related urinary symptoms in postmenopausal women. However, there remains insufficient evidence to assess the effectiveness of Kegel's exercise on HRQoL-related genital symptoms in this population. The results support using Kegel's exercise as a useful intervention to manage urinary symptoms in postmenopausal women. Optimizing pelvic floor muscle function will also ensure proper blood flow and circulation which can aid help with lubrication, insertive sex and sexual pleasure.

What is the Best Mode of Delivery of Vaginal Estrogen?

Based on a Cochrane Review, all forms of vaginal estrogen are similarly effective. It is personal preference as to which is best for you.

Before we explore the different options, it is important to understand the term bioidentical.  This is often said to be a ‘marketing claim’ however it is important to know when it comes to hormone therapy.  Bioidentical, sometimes referred to as body identical means that the estrogen is the same chemical structure as our own body makes. 

Non-bioidentical is NOT the same chemical structure as our body. Conjugated Equine Estrogen is a pharmaceutical with hormone-like effects sourced from pregnant horse’s urine (commonly known as Premarin) and is not bioidentical.

All prescription vaginal estrogen therapy is synthetic meaning it is manufactured in a lab regardless of if it is bioidenitical or not. 

It is also important to understand the different types of estrogen;

Estrone (E1) when the ovaries are no longer producing eggs (menopause) estrone is the dominant form of estrogen produced primarily in fat tissue and by converting DHEA and does much of the same thing as estradiol but is considered weaker and more inflammatory.

Estradiol (E2) Produced by the developing eggs in the ovaries during the reproductive years

Estriol (E3) the weakest form of estrogen and produced primarily in pregnancy

Common Brand Names of Estrogen in North America

Vagifem is a tablet form of bioidentical estradiol that is inserted into the vagina with a pre-loaded applicator. IT is available in Canada and the US.

Estrace is a bioidentical estradiol cream available in the US.

Estragyn is an estrone cream.

Estring is a small pessary that is inserted into the vagina and left in for 90 days and then replaced.

 Imvexxy is a vaginal estradiol insert.

Compounded options are great options for those who have sensitivities to the filler ingredients or who do not want certain ingredients in/on their body such as parabens.

How Often and How Long?

The typical dose for vaginal estrogen is twice a week, however, you will work with your care provider to determine the best delivery mode and the best dose for you.  Some may start with a loading dose of once daily for 2 weeks and then twice a week thereafter.  Some find the loading dose too strong and experience some irritation.  Irritation can be from too much too soon or it may be irritation from some of the filler ingredients.  Getting your vaginal estrogen compounded (a compounding pharmacist adds the estrogen to a base free from additives) can be a great option.

For those who have been in a low estrogen state for awhile, when you first start taking vaginal estrogen you may experience a yeast overgrowth/infection as the vaginal microbiome adjusts to the beneficial estrogen.

With regards to how long you will use vaginal estrogen, the answer is until you die.  As I shared earlier, the signs and symptoms of GSM do not improve with time so if you stop using your vaginal estrogen, the signs and symptoms will return.

Finally, you want to make sure you use it away from intercourse.  This study found that men absorb vaginal estradiol during intercourse, whereas intercourse reduces estradiol absorption in women.  YOU need the estrogen, not your partner so use your estrogen away from intercourse.

Are There Risks With Vaginal Estrogen?

Contrary to what the pamphlet tells you, vaginal estrogen is not dangerous or harmful. Vaginal estrogen is incredibly low-dose and little to no estrogen makes it into the blood stream.  I have heard Dr Kelly Casperson share that one year’s worth of typical vaginal estrogen dosing is the equivalent to one oral estrogen pill.

Vaginal estrogen is also remarkably safe, even for individuals with a history of breast cancer or cardiovascular disease and this study showed no evidence of increased early breast cancer-specific mortality in patients who used vaginal estrogen compared with patients who did not us HRT.

This real-world Nationwide Danish population study found that increasing duration and intensity of use of vaginal oestradiol tablets was not found to be associated with an increased risk of breast cancer.

While this study is not referencing vaginal estrogen but rather systemic estrogen, which is much higher dose.  It is interesting to note that there were lower risks of recurrence and mortality in women who used HRT after breast cancer diagnosis than in women who did not.

Another study showed that HRT use in women with a family history of breast cancer is not associated with a significantly increased incidence of breast cancer but is associated with a significantly reduced total mortality rate.

Do I Have To Take Progesterone Too?

When using systemic estrogen (not vaginal) and you have a uterus you do need to take progesterone to prevent the lining of the uterus from becoming too thick.  When taking vaginal estrogen and you have a uterus you do not NEED to take progesterone although you may absolutely still want to for all of the amazing benefits for our bones, our breasts, our mood and our sleep to name a few.

Healthy aging and longevity are keen interests of mine right now.  I want to age gracefully and powerfully and am not interested in suffering.  Bioidentical vaginal estrogen and systemic hormone therapy (transdermal estrogen and micronized oral progesterone) are choices I have made based on all the evidence to their benefits and little to no risks.

Some of my favorite resources for evidence-based information about all things menopause and hormones are as follows;

Books

Estrogen Matters – Dr Avrum Bluming and Dr Carol Tavris

The Hormone Cure – Dr Sarah Gottfried

Roar and Next Level – Dr Stacy Sims

You Are Not Broken – Dr Kelly Casperson

Podcasts

The Hormone Solution – Karen Martel

Everyday Wellness – Cynthia Thurlow

The Thyroid Fixer – Dr Amie Hornaman

Websites

Menopause.org

Menopausechicks.com

sigmamenopause.com

Social Media

Wise and Well

Dr Corine Menn

Dr Rachel Rubin

Dr Kelly Casperson

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