Hormones and Menopause

Today, we talk about the best way to manage the symptoms of menopause – starting with the management of genitourinary syndromes. 

Typically starting about four to five years after their last period, about half of postmenopausal women suffer what we used to call vulvovaginal atrophy, now referred to by the name GSM (genitourinary syndrome of menopause), thanks to the Vulvovaginal Atrophy Terminology Consensus Conference, who needed a more “publicly acceptable term.” After all, the word atrophy had “negative connotations,” and the word vagina “is not a generally accepted term for public discourse.” They liken it to the shift from the “pejorative” impotence to “erectile dysfunction.”

Whatever you call it, it involves changes to the vulva (the external genitalia), the vagina (the birth canal), and bladder, caused by menopausal changes in hormone levels. Vaginal symptoms include vaginal dryness, burning, itchiness, and irritation, pain during penetrative sex, and post-coital bleeding from the thinning of the vaginal lining. Urinary symptoms can include recurrent bladder infections and incontinence. Some women with mild GSM remain asymptomatic. For others, symptom severity can preclude intercourse altogether and result in discomfort even with just sitting or wiping. In a survey of thousands of women with GSM, 59 percent said their symptoms “considerably decreased their enjoyment of sexual activity,” and 23 percent reported it having an adverse effect on their “general enjoyment of life.”

While other menopausal symptoms, like hot flashes, tend to improve over time, GSM symptoms tend to get progressively worse. Unfortunately, women rarely seek medical help, even though there are safe and simple treatments available. The first-line treatment for mild to moderate vaginal dryness are lubricants and moisturizers.

Lubricants are designed to reduce friction during sexual activity, whereas vaginal moisturizers are used on a regular basis (daily or every two to three days as needed) to provide day-to-day comfort by mimicking normal vaginal secretions, regardless of sexual activity. Water-based lubricants have the advantage of being non-staining and are associated with fewer genital symptoms such as discomfort or burning, compared to silicone-based lubricants.

What’s the best vaginal moisturizer? This head-to-head study pitted vaginal estrogen versus Replens, an expensive vaginal moisturizer claiming special “bioadhesive” ingredients, versus a placebo gel of hydroxyethylcellulose, which is found in products 15 times cheaper, like K-Y Jelly. After 12 weeks, the researchers found no difference between any of them—they all worked the same. This “striking double-negative finding” led to an accompanying commentary in the American Medical Association journal to conclude that until there is evidence to suggest otherwise, “postmenopausal women experiencing vulvovaginal symptoms should choose the cheapest moisturizer or lubricant available over the counter” instead of wasting your money. That was for efficacy, though. What about safety?

The World Health Organization recommends, based on the SMI test, that personal lubricants and vaginal moisturizers not exceed an osmolality of 380. That’s a measure of how concentrated the dissolved components are. How did they come up with that number? By lubing up slugs. SMI stands for slug mucosal irritation. They cover slugs with lubricant over a five-day period and measure how much mucosal irritation and tissue damage the slug experiences. No adverse effects below the 380 cut-off, but something like K-Y Jelly at over 2,000 induced mild to moderate irritation, and something off the charts, like Astroglide at 5,000+, caused severe irritation and tissue damage.

Dozens of commonly-used lubricants and moisturizers available world-wide have been put to the test, and the only two vaginal moisturizers that met the WHO criteria were the Yes brand aloe vera gel-based moisturizer and the Balance Activ brand hyaluronic acid-based one. The only lubricants that made the cut were those made by brands Yes, Good Clean Love, System Jo, and one product by Durex, their Sensilube gel, but not their Play Feel lubricant.

In our next story, we find out if vaginal estrogen carries the same risk as oral estrogen?

The first-line treatment for mild to moderate vaginal dryness due to menopause are lubricants and moisturizers. If over-the-counter lubricants and moisturizers are insufficient to control the genitourinary symptoms of menopause, low-dose, local estrogen therapy is recommended, unless women have a history of hormone-dependent cancers like endometrial or breast. Local, meaning applied vaginally, as opposed to taken orally. Vaginal application is considered safer and more effective than systemic hormone therapy. A meta-analysis of 58 studies comparing vaginal to systemic estrogens found that vaginal estrogen therapy offered better symptom relief than estrogen pills, patches, or implants. In fact, many women who are on systemic menopausal hormone therapy have to add on supplemental vaginal estrogens to control symptoms.

Vaginal estrogens are available as a variety of creams, suppositories, and rings. Thirty randomized, controlled comparative trials have been performed, and there appears to be no difference in efficacy between the various preparations. However, they may take weeks before a noticeable alleviation of symptoms is detected, and two to three months before the full effect is achieved. Although year-long studies can clearly demonstrate vaginal estrogen’s benefit, studies as long as 12 weeks have failed to manifest superiority to placebo.

Some of the estrogen applied to the vulva or vagina is systemically absorbed, and therefore conveys the same black-box FDA notice that oral estrogens carry, an all-caps warning of increased risk of “endometrial cancer, cardiovascular disorders, breast cancer and probable dementia.” Vaginal estrogen is considered safer, though, since it can be used at a much lower dose (as low as one-hundredth the oral dose). The Harvard Nurse’s Health Study did not find any increased risks associated with vaginal estrogen use over 18 years of follow-up. Randomized controlled trials lasting up to a year appear to confirm its safety, but there have been observational studies linking vaginal use to about a doubling of odds for endometrial cancer. But this was done back in the 1970s, when higher estrogen doses were used. And a more recent study out of Denmark that found the same thing may have been confounded by concurrent oral estrogen exposure. Out of an abundance of caution, though, even low-dose localized estrogen may be contraindicated in hormone-dependent cancer survivors, to be on the safe side.

Breast cancer survivors suffering from GSM may want to consider vaginal DHEA instead. Oral DHEA doesn’t appear to offer any benefit, but in 2016, the FDA approved vaginal DHEA suppositories for pain during intercourse due to menopause. It’s converted locally into estrogen and does not significantly affect systemic hormone levels. A downside is that it has to be administered nightly, whereas estrogen preparations are typically twice a week, or even every few months with the vaginal rings. For those who would rather an oral treatment, there’s ospemifene, a tamoxifen-type drug that has pro-estrogenic effects on the vaginal lining. However, it can actually double the rate of hot flashes and urinary tract infections in the short-term, and insufficient data are available for long-term safety.

Did you know that soy foods may explain why Japanese-American women not only have the lowest rates of hot flashes in the United States but also have the lowest rates of vaginal dryness. Here’s the story.

One consensus panel of experts concluded that soy can be considered a first-line treatment for menopausal hot flash and night sweat symptoms. What about for vaginal dryness?

There have been a few studies on the topical application of soy isoflavone vaginal gels, which in general have shown beneficial effects––for example, showing a significant improvement in dryness and pain-with-intercourse over placebo gels. In fact, they’re roughly on par with estrogen cream in a head-to-head test. But what about just eating soy? Soy isoflavones improve female sexual dysfunction of mice, significantly increasing vaginal blood flow, but what about in people?

The data using isolated soy supplements are mixed. Some studies totally flopped, showing no benefit over placebo, all the way up to studies showing comparable efficacy when pitted head-to-head against hormone therapy for both hot flashes and muscle pain––as well as vaginal dryness, with no significant differences between the two. And, of course, soy has the benefit of “no increased risk of breast and uterine cancer or cardiovascular disease,” unlike systemic hormonal menopause therapy.

What about soy foods, though, rather than soy supplements? Well, there was a muffin study. Women randomized to daily muffins containing soy flour or ground flaxseeds saw no difference in menopausal sexual symptoms compared to wheat flour placebo muffins. Similarly, women randomized to 12 weeks of a daily scoop of soy protein powder experienced a significant improvement in sexual quality of life symptoms, but not compared to the milk protein control group.

What about soy milk? There have been three studies. Compared to women randomized to drink about two cups of dairy milk a day for eight months, those randomized to soy milk ended up with significantly fewer menopausal sexual symptoms, though this appeared to be more due to symptoms getting worse on the dairy than getting better on the soy. That reminds me of a study in Thailand where women randomized to a soy-free diet experienced a worsening of vaginal dryness and overactive bladder-type symptoms, but adding extra soy didn’t seem to make them better.

The second soy milk study found about two cups a day over two months appeared to drop vaginal and sexual symptoms by a whopping 60 to 70 percent, compared to the do-nothing control group. But since the control group didn’t drink anything special, it’s impossible to rule out placebo effects. The latest study found significant improvements in sexual symptoms after just six weeks of less than a cup of soy milk a day, but again, the control group did nothing. So, does soy milk work? We really don’t know, but it can’t hurt to give it a try—unless you overdo it.

A 44-year-old New Yorker presented to her gynecologist with an “increase in desire that required her to self-stimulate to orgasm approximately 15 times daily.” It turns out a month before, she started eating in excess of four pounds of soy foods a day. Thankfully, within three months of cutting back, her desire cooled to the point that she was able to “engage in satisfying sexual activity only twice daily.”