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Vaginal estrogen not associated with increased risks for CVD, cancer
Postmenopausal women who reported use of vaginal estrogen were not at increased risks for developing cardiovascular disease, cancer or hip fracture over 18 years vs. similar women who did not report taking vaginal estrogen, according to an analysis of the Nurses’ Health Study.
Unlike oral estrogen therapy, vaginal estrogen to treat genitourinary syndrome of menopause is not subject to gastrointestinal conversion of estradiol to estrone, avoiding the first-pass liver metabolism that has been associated with increased risk for thrombosis, JoAnn E. Manson, MD, DrPH, FACE, chief of the division of preventive medicine at Brigham and Women’s Hospital, and professor of medicine and the Michael and Lee Bell Professor of Women’s Health at Harvard Medical School, and colleagues wrote in the study background.
“Despite the availability of strong and generally consistent data to show its effectiveness, low-dose vaginal estrogen therapy remains underutilized owing to perceived risks associated with menopausal hormone therapy,” Manson and colleagues wrote. “In addition, the FDA-issued black box warning on the low-dose vaginal estrogen package label discourages clinicians from prescribing the product and women from using prescribed therapy.”
Manson and colleagues analyzed data from 53,797 postmenopausal women participating in the Nurses’ Health Study (1982-2012) who were not current users of systemic HT at baseline or during 18 years of follow-up. Participants self-reported vaginal estrogen use on biennial questionnaires (n = 896), and incident health outcomes were assessed via self-report and medical records. Researchers used Cox proportional hazard models to estimate risks for any cancer, CV outcomes (total myocardial infarction, stroke and pulmonary embolism/deep vein thrombosis) and hip fracture with vaginal estrogen use.
Women reporting vaginal estrogen use were more likely to be never smokers, have a lower BMI and lower prevalence of hypertension vs. women who did not report vaginal estrogen use. However, users of vaginal estrogen were also more likely to have had a bilateral oophorectomy, hysterectomy or family history of cancer vs. nonusers. Average duration of vaginal estrogen use was 35.7 months.
Researchers found that users of vaginal estrogen had a lower risk for total MI (HR = 0.56; 95% CI, 0.36-0.87) and a lower risk for stroke that did not rise to significance (HR = 0.71; 95% CI, 0.47-1.09) vs. nonusers. There were no between-group differences for pulmonary embolism or deep vein thrombosis, total invasive cancer or hip fracture.
In models adjusted for multiple factors, including race, smoking status, BMI, aspirin use, age at menopause and medical history, there were no between-group differences for all major CV outcomes, cancer outcomes or hip fracture.
“Our data lend support to the safety of vaginal estrogen use because no excess risk of cardiovascular disease or cancer was observed among women who self-reported use of various delivery systems and doses of vaginal estrogen,” the researchers wrote. “Our findings provide a comprehensive summary of the relationship between vaginal estrogen and multiple health outcomes and offer reassurance regarding the safety of low-dose vaginal estrogen to treat [genitourinary syndrome of menopause].” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.
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Bhupathiraju SN, et al. Menopause. 2018;doi:10.1097/GME.0000000000001284.