Does topical estrogen (estrogen replacement therapy) vaginal cream increase the risk of cancer?

From the Guidelines

Topical estrogen vaginal cream does not significantly increase cancer risks when used as prescribed, according to the most recent guidelines. The NCCN guidelines, as outlined in the study from 2024 1, suggest that vaginal estrogen is the most effective treatment for vaginal dryness leading to sexual dysfunction and has been shown to be effective in treating itching, discomfort, and painful intercourse in postmenopausal individuals. A large cohort study of almost 50,000 patients with breast cancer followed for up to 20 years showed no evidence that there was a higher risk of breast cancer–specific mortality in those using vaginal estrogen 1.

Key points to consider when prescribing topical estrogen vaginal cream include:

• Using the lowest effective dose for the shortest duration needed
• Having regular gynecological check-ups
• Individualized risk assessment with a healthcare provider before starting treatment, especially for those with a personal history of estrogen-dependent cancers
• The minimal absorption of vaginal preparations means the actual risk is considered very low, even for women with a history of breast cancer

It is essential to note that the safety of vaginal hormones has not been firmly established in survivors of estrogen-dependent cancers, and therefore, caution should be exercised when prescribing these medications to this population 1. However, for many women, the benefits of topical estrogen vaginal cream in improving vaginal dryness, pain with intercourse, and urinary symptoms may outweigh the potential risks.

From the Research

Topical Estrogen Vaginal Cream and Cancer Risks

• The use of topical estrogen vaginal cream for the treatment of vulvar and vaginal atrophy (VVA) has been studied in various research papers 2, 3, 4, 5, 6.
• According to a systematic review and meta-analysis, low-dose vaginal estrogen showed the smallest changes in serum estradiol levels and had the most evidence, but safety remains unclear, especially for patients on aromatase inhibitors 3.
• A meta-analysis found that local hormonal treatment of VVA in women treated with aromatase inhibitors did not change serum levels of luteinizing hormone and estradiol, suggesting that vaginal estrogen administration may not be associated with systemic absorption of sex hormones 4.
• The International Society for the Study of Vulvovaginal Disease recommends the use of vaginal estrogens, including estradiol and estriol, as a beneficial option for the management of postmenopausal VVA, but notes that limited absorption of low/ultra-low doses of estrogens suggests safety, especially in women under treatment with aromatase inhibitors 5.
• A review of the Women's Health Initiative Hormone Trials and other studies found that the risk of breast cancer does not appear to increase until after 4 to 5 years of use of estrogen plus progestin, and was not increased with estrogen-alone use after 7 years of treatment 6.

Key Findings

• Topical estrogen vaginal cream may not increase the risk of cancer, especially when used at low doses and for short periods of time 3, 4, 5.
• The safety of topical estrogen vaginal cream remains unclear, especially for patients on aromatase inhibitors 3, 4.
• Vaginal estrogen administration may not be associated with systemic absorption of sex hormones, suggesting a potential benefit for women with VVA 4.
• The use of topical estrogen vaginal cream should be individualized and based on a woman's age, symptoms, general health, and treatment preferences 5.