Data show short-term benefit of certain hormonal treatments for GSM

A recently published systematic review indicates that certain hormonal therapies such as vaginal estrogen, vaginal dehydroepiandrosterone (DHEA), and oral ospemifene, as well as vaginal moisturizers may improve some genitourinary syndrome of menopause (GSM) symptoms in the short-term.^1,2

Serious treatment-related adverse events were uncommon across all trials.

However, the authors note that long-term data on these treatments are lacking.

“Long-term follow-up for efficacy, tolerability, and endometrial safety represents a critical gap to guide treatment longer than 1 year,” they write.¹

For the study, the investigators assessed 46 randomized controlled trials (RCTs) that were at least 8 weeks in duration and enrolled at least 20 postmenopausal women with at least 1 symptom of GSM per treatment group. This included 22 RCTs evaluating vaginal estrogen, 16 evaluating non-estrogen hormones, 4 evaluating vaginal moisturizers, and 4 evaluating multiple interventions.

Meta-analysis for this review was limited by variability in populations, interventions, comparators, and outcomes. The authors utilized the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework to assess the overall certainty of evidence (COE).

Overall, 4 treatments were identified as having potential benefit in the management of symptoms related to GSM, including vaginal estrogen, vaginal DHEA, oral ospemifene, and vaginal moisturizers.

Specifically, data showed that vaginal estrogen may improve vulvovaginal dryness, dyspareunia, most bothersome symptom, and treatment satisfaction compared with placebo or no treatment. Additionally, vaginal DHEA may improve dryness, dyspareunia, and distress, bother, or interference from GSM compared with placebo or no treatment, and oral ospemifene may improve dryness, dyspareunia, and treatment satisfaction. Vaginal moisturizers may improve dryness.

However, the data suggested that 2 patient-reported outcomes––dysuria or vulvovaginal discomfort or irritation––may not improve with any of these treatments.

The review also indicated that 5 treatments––vaginal testosterone, systemic DHEA, vaginal oxytocin, oral raloxifene, or oral bazedoxifene––may not offer benefit (low COE) or have insufficient evidence to determine treatment effects (very low COE). These findings are consistent with prior recommendations as none of these treatments are approved by the FDA for the treatment of patients with GSM.

Regarding safety, serious treatment-related adverse events (AEs) were uncommon across all trials. Notable serious AEs included 1 instance of breast cancer each among patients who received vaginal estrogen or bazedoxifene plus oral estrogen, as well as 1 instance of deep venous thrombosis in a patient who received ospemifene.

Less serious AEs were infrequent and varied across treatments. Specifically, vaginal estrogen was associated with vaginal bleeding, discharge, and breast tenderness; vaginal DHEA was associated with increased facial hair, voice changes, and headaches; and oral ospemifene was associated with hot flushes and vaginal candidiasis.

However, the authors again emphasized that their data was limited by the lack of long-term follow-up; the majority of studies were 12 weeks or less in duration. Additionally, they note that only 4 of the studies enrolled patients with a history of cancer, which according to the authors, “leav[es] patients and clinicians with little evidence to guide treatment decisions.”

Overall, the authors concluded, “Future studies would be strengthened by standard definitions of symptoms and uniform diagnostic criteria for GSM, a common set of validated outcome measures and reporting standards, and attention to clinically relevant patient populations and intervention comparisons.”¹

References

1. Danan ER, Sowerby C, Ullman KE, et al. Hormonal treatments and vaginal moisturizers for genitourinary syndrome of menopause: A systematic review. Ann Intern Med. 2024. doi:10.7326/ANNALS-24-00610

2. Systematic review finds 3 medications with potential to treat vaginal symptoms of GSM in menopause. News release. American College of Physicians (ACP). September 3, 2024. Accessed September 10, 2024. https://www.newswise.com/articles/systematic-review-finds-3-medications-with-potential-to-treat-vaginal-symptoms-of-gsm-in-menopause