Low-dose vaginal oestrogen poses no increased risk of endometrial hyperplasia, cancer
Use of low-dose vaginal oestrogen without a concomitant progestogen for treating vulvar and vaginal atrophy in menopausal women appears to be safe and does not contribute to a heightened risk of endometrial hyperplasia or cancer, according to a recent study.
Researchers performed a systematic review of studies evaluating menopausal vaginal oestrogen use in relation to endometrial histology or incidence of endometrial malignancy. They accessed multiple online databases for their literature search and identified 36 articles and two abstracts for critical review and interpretation.
Of the studies included, 20 were randomized controlled trials, eight were prospective interventional studies, two were prospective observational studies, and eight were retrospective observational studies.
Collectively, the studies showed no clear evidence of an increased risk of endometrial hyperplasia or cancer with low-dose vaginal oestrogens, the respective rates of which were 0.03 percent and 0.4 percent from 20 trials (2,983 women).
Endometrial hyperplasia occurred with various doses and durations and seemed random (except conjugated equine oestrogens at 1.25 mg), consistent with endometrial hyperplasia rates in the general population. A Denmark registry study proved to be an exception and reported an association between vaginal oestrogen use and increased endometrial cancer risk (risk ratio, 1.96, 95 percent CI, 1.77–2.17), although the data might have limited applicability to the US.
The most recent US data from the Women's Health Initiative Observational Study, which investigated real-world use of higher-dose vaginal oestrogen products with systemic absorption, reported no increased risk of endometrial cancer (1.3 cases/1,000 women-years with vaginal oestrogens vs 1.0/1,000 women-years for nonuse; hazard ratio, 1.47, 0.75–2.90)
Longer-term data are needed to confirm the endometrial safety profile of vaginal oestrogens, the researchers said.