Review Provides Look at Treatments for Menopause Symptoms

A more definitive picture of how some hormones and moisturizers can offer relief to women experiencing vaginal dryness or painful intercourse during menopause was published in a recent systematic review in Annals of Internal Medicine. However, researchers noted scant long-term data on the safety of these products.

Vaginal dryness and challenges with intercourse and urination are among the symptoms of genitourinary syndrome of menopause (GSM). Hormones such as vaginal estrogen, vaginal dehydroepiandrosterone (DHEA), or oral ospemifene are common treatments, along with moisturizers.

“The main finding is that commonly used therapies are likely to be effective for the common symptoms people have for GSM,” particularly vaginal dryness and painful intercourse, said Elisheva Danan, MD, MPH, a primary care physician and health services researcher at the Minneapolis VA Health Care System and assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, who was the lead study author.

Many women might recognize hot flashes as connected to menopause, Danan said, as these tend to occur with the cessation of the menstrual cycle. However, genitourinary effects may not manifest until a few years later and worsen over time, when the connection to menopause is less clear.

“Women might not bring it up or think there’s a treatment that can work,” Danan said.

The systematic review may provide clinicians with more evidence of specific treatments to recommend. However, most of the trials included in the analysis studied treatment periods of 12 weeks or less, so the safety of long-term use is unclear.

“One question that hasn’t been answered yet in clinical trials is whether there could be a risk of uterine cancer with extended use of any of these treatments,” Danan said, because vaginal estrogen or ospemifene could stimulate growth of the uterine lining.

The studies Danan and colleagues found showed no increased risk for uterine cancer, but Danan noted that the maximum follow-up was 1 year, and study participants had a low risk for cancer to begin with. She advised that clinicians closely monitor women with risk factors if they use hormones to treat GSM indefinitely.

Forty-Six Randomized Controlled Trials, Many Open Questions

Danan and her colleagues conducted a systematic review of 46 randomized controlled trials, meant to inform an upcoming clinical practice guideline from the American Urological Association on treatment of GSM. Danan’s work was funded by the Patient-Centered Outcomes Research Institute.

Studies evaluated vaginal estrogen (22), other hormones such as vaginal oxytocin or vaginal testosterone (16), vaginal moisturizers (4), and multiple interventions (4).

Included trials lasted at least 8 weeks and included at least 20 postmenopausal women; most treatments lasted 12 weeks or less. Studies used varying definitions of GSM, and no head-to-head trials of different treatments were found.

Researchers used the Core Outcomes in Menopause (COMMA) framework, developed in 2021 to standardize outcomes research in menopause care and to understand treatment effectiveness. They applied this framework retroactively, as almost all the studies in the review were written before the COMMA framework existed.

Hormonal treatments were associated with reduced pain during intercourse and decreased vaginal dryness; moisturizers were linked to reduced dryness.

Vaginal estrogen did not reduce pain during intercourse as consistently as DHEA or oral ospemifene, per the review. Danan and her coauthors said this could be because the DHEA and ospemifene trials were larger and more uniformly conducted than those for vaginal estrogen. Even so, vaginal estrogen outperformed placebo at reducing painful intercourse.

But given the short timeframe of most studies and the differing definitions of GSM symptoms, Danan cautioned that all their conclusions have low certainty.

Few studies examined whether these treatments reduced vaginal itchiness or difficulties with urination. And the authors found no evidence for the benefit of oral DHEA, raloxifene, bazedoxifene, vaginal oxytocin, or vaginal testosterone for GSM treatment.

In an accompanying report, the researchers found no evidence for the benefits of treatments such as vaginal testosterone or vaginal laser therapy.

Stephanie Faubion, MD, MBA, medical director for the North American Menopause Society and director of the Mayo Clinic Center for Women’s Health, Rochester, Minnesota, wrote an accompanying editorial noting that the patients represented in the GSM treatment clinical trials were not diverse and that the exclusion criteria generally meant that women with cardiovascular challenges of cancer were not included.

“That’s one of the biggest questions — what is the safety in women with cardiovascular risk factors or history of a blood clot or history of a cancer? The data is just completely absent there,” Faubion said.

The Connection Between GSM and Urinary Tract Infections (UTIs)

“Genitourinary syndrome of menopause is not just a little bit of vaginal dryness that can be cured with moisturizers and lubricants, but the syndrome can lead to recurrent urinary tract infections, which are extremely harmful and dangerous to our patients and cost the healthcare system a lot of money,” said Rachel Rubin, MD, a urologist and sexual medicine specialist in Bethesda, Maryland.

Lubricants and moisturizers can all help with the symptoms of GSM, at least in the short term, Rubin noted. But only hormones can get to the root of the problem and reduce the risk for a recurrent UTI (rUTI), Rubin added, noting that the American Urological Association recommends the use of vaginal estrogen to reduce the risk for rUTIs and is developing the clinical practice guidelines for GSM.

Danan’s review did not address the association between UTIs and GSM, but Rubin said she sees the link in clinical practice.

“Recurrent urinary tract infections occur because of GSM, because of the lack of hormones to the tissue,” sometimes when a woman is in her 60s or 70s and thinks menopause is long over, Rubin said.

The reality is that women may need to take hormones for decades to reduce the risk for UTIs, another reason longer-term safety data are needed, Rubin said.

Danan, Faubion, and Rubin reported no relevant financial relationships.

Marcus A. Banks, MA, is a journalist based in New York City who covers health news with a focus on new cancer research. His work appears in Medscape Medical News, Cancer Today, The Scientist, Gastroenterology & Endoscopy News, Slate, TCTMD, and Spectrum.