Expert Commentary

Is vaginal estrogen used for GSM associated with a higher risk of CVD or cancer?

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No. Vaginal estrogen use (average duration of use, 37.5 months) for genitourinary symptoms of menopause (GSM) was not associated with a higher risk of cardiovascular disease (CVD) or cancer in nonusers of systemic hormone therapy in the Nurses’ Health Study. During 18 years of follow-up for the almost 900 postmenopausal users of vaginal estrogen, compared with about 53,000 nonusers, the risks of CVD, cancers, and hip fractures were not different between groups. Presence or absence of a uterus did not change the study results.



Expert Commentary

Bhupathiraju SN, Grodstein F, Stampfer MJ, et al. Vaginal estrogen use and chronic disease risk in the Nurses’ Health Study. Menopause. December 17, 2018. doi: 10.1097/GME.0000000000001284.

GSM, a chronic and often progressive condition, occurs in almost 50% of postmenopausal women and has been shown to impair sexual function and quality of life.1 Symptoms include vaginal dryness, vulvar or vaginal itching, dyspareunia, urinary urgency or frequency, and increased urinary tract infections. Although lubricants or vaginal moisturizers may be sufficient to treat GSM, targeted hormonal therapy may be needed to improve the symptoms and resolve the underlying cause, due to vaginal hormone loss.

Despite lack of any observational or clinical trial evidence for chronic health disease risks related to low-dose vaginal estrogen use, there remains an US Food and Drug Administration boxed warning on the package label for low-dose vaginal estrogen related to risks of heart disease, stroke, venous thromboembolism, pdementia, and breast cancer. The objective of the investigation by Bhupathiraju and colleagues was to evaluate associations between vaginal estrogen use and health outcomes, including CVD (myocardial infarction, stroke, and pulmonary embolism/deep vein thrombosis), cancer (total invasive, breast, endometrial, ovarian, and colorectal), and hip fracture.

Details of the study

The prospective analysis included 896 postmenopausal current users of vaginal estrogen in the Nurses’ Health Study (NHS; 1982­­–2012), compared with 52,901 nonusers. Eighteen years of follow-up was evaluated. Users of systemic hormone therapy were excluded from the analysis. For the NHS, self-reported data were collected every 2 years on questionnaires for vaginal estrogen use and health outcomes. Investigators used medical records to confirm health outcomes.

After adjusting for covariates, no significant differences in risks were found for CVD, cancer, and hip fracture between users and nonusers of vaginal estrogen, regardless of hysterectomy status.

Key findings

After adjusting for multiple variables (including age, race, physical activity, age at menopause, hysterectomy, aspirin use, parental history of cancer, etc), health outcomes for CVDs, all cancers, and hip fracture were:

  • myocardial infarction: hazard ratio (HR), 0.73 (95% confidence interval [CI], 0.47–1.13)
  • stroke: HR, 0.85 (95% CI, 0.56–1.29)
  • pulmonary embolism/deep vein thrombosis: HR, 1.06 (95% CI, 0.58–1.93)
  • hip fracture: HR, 0.91 (95% CI, 0.60–1.38)
  • all cancers: HR, 1.05 (95% CI, 0.89–1.25).

Continue to: Health outcomes for specific invasive cancers

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