Vaginal estrogen therapy not associated with increased risk of endometrial cancer recurrence

A cohort study involving more than 2,800 younger endometrial cancer survivors found that the use of local, low-dose, and short-term vaginal estrogen therapy (ET) did not increase the risk of cancer recurrence. The research, published in Menopause, the journal of The Menopause Society, suggests that this form of estrogen may be a safe option for managing menopause symptoms in a population that frequently experiences early onset menopause due to cancer treatments.^1,2

Endometrial cancer incidence in American women aged 50 years and younger has increased steadily from 2.2 to 3.3 per 100,000 women between 2000 and 2019, according to the Menopause Society. Treatment for this malignancy commonly requires hysterectomy with bilateral salpingo-oophorectomy, radiation, or chemotherapy, all of which can induce early menopause. These survivors often experience night sweats, hot flashes, and genitourinary symptoms that are typically more severe than those seen in natural menopause.² Despite the proven benefits of vaginal ET in managing vaginal dryness, urinary problems, and pain during intercourse, many women have historically been deterred from its use because of safety concerns and black-boxed warnings identical to those found on higher-dose systemic therapies.²

Study design and methodology

Researchers conducted a cohort study utilizing the TriNetX database’s US Collaborative Network, which comprises electronic health records and insurance claims data from 68 health care organizations. The study focused on women aged 18 to 51 years who were diagnosed with endometrial cancer between November 1, 2005, and December 31, 2023.^1,2

The investigators identified 1,412 endometrial cancer survivors who utilized vaginal ET and 23,859 who did not. To ensure a rigorous comparison, the researchers used 1:1 propensity score matching to create balanced cohorts. This resulted in a final analysis of 1,412 individuals in the vaginal ET group and 1,412 in the non-ET group.¹ The primary outcome measured was the risk of endometrial cancer recurrence, estimated using hazard ratios (HR) with 95% confidence intervals (CIs).¹

Utilization and recurrence outcomes

The mean duration of vaginal ET treatment among participants was 1.88 years. The study found that the initiation of vaginal ET remains minimal among younger endometrial cancer survivors, estimated at only 5.6%.² Researchers noted that survivors are commonly prescribed nonhormone treatments for menopause symptoms, which often have limited efficacy.

Regarding the primary safety outcome, the risk of endometrial cancer recurrence was not increased among those who used vaginal ET.¹ The estimated hazard ratio was 0.87 (HR, 0.87; 95% CI, 0.60-1.27).¹ Consequently, the authors concluded that survivors with short-term exposure to local, low-dose vaginal ET did not have an elevated risk of cancer recurrence compared with those who did not use the therapy.^1,2

“Early detection and improved targeted therapies have led to more women surviving their endometrial cancer diagnoses,” said Monica Christmas, MD, associate medical director for The Menopause Society, in a statement.

“However,“ she said, “the sequalae from these life-sparing treatments often result in significant impairment to quality of life and sexual function. Genitourinary symptoms associated with menopause rarely improve without treatment and are exacerbated in the context of abrupt, early menopause. Helping survivors of endometrial cancer to make evidence-based decisions about their care is empowering, especially during a vulnerable time.”

The investigators stated that younger survivors of endometrial cancer do not face an elevated risk of recurrence following short-term exposure to vaginal ET.¹

“Expanding treatment options to include local, low-dose vaginal estrogen therapy in this population will have long-lasting benefits,” Christmas stated.

References:

1. Hsu CD, Yu X, Richardson G, et al. Vaginal estrogen therapy utilization and associated outcomes in younger survivors of endometrial cancer. Menopause. doi:10.1097/GME.0000000000000002747.
2. Vaginal estrogen therapy not linked to cancer recurrence in survivors of endometrial cancer. The Menopause Society. Press release. Published March 4, 2026. Accessed March 4, 2026. https://www.eurekalert.org/news-releases/1118552