A systematic review of randomised clinical trials – The safety of vaginal hormones and selective estrogen receptor modulators for the treatment of genitourinary menopausal symptoms in breast cancer survivors Original paper

What was studied?

This systematic review focused on the safety of vaginal hormone therapies and selective estrogen receptor modulators (SERMs) for the treatment of genitourinary menopausal symptoms (GMS) in breast cancer survivors. It specifically aimed to evaluate the risks of breast cancer recurrence associated with these treatments, as well as any significant rise in serum estrogen levels following their use. The study assessed randomized clinical trials (RCTs) that tested vaginal estrogen therapies, dehydroepiandrosterone (DHEA), and oral SERMs, all of which are used to manage menopausal symptoms, particularly those affecting the genitourinary system. The review also aimed to clarify the clinical safety of these therapies in the context of breast cancer, where concerns about estrogenic effects potentially increasing the risk of cancer recurrence are prevalent.

Who was studied?

The review included breast cancer survivors who were treated with various forms of hormone therapy to manage genitourinary menopausal symptoms. The studies selected for this review specifically focused on postmenopausal women, ages 18 and older, who had previously been diagnosed with breast cancer and were undergoing treatments such as vaginal estrogen therapies (e.g., estriol and estradiol) and dehydroepiandrosterone (DHEA) gel. Participants in these trials did not have any active breast cancer or recurrence but had been treated for early-stage breast cancer, often receiving tamoxifen or aromatase inhibitors (AIs) as part of their post-cancer endocrine therapy.

Most important findings

The systematic review found that none of the included studies specifically assessed breast cancer recurrence, a critical factor for these patients. However, among the studies observing for serious adverse effects, no increased incidence of breast cancer recurrence was reported. Additionally, studies did not observe a persistent or significant rise in serum estrogen levels following the use of vaginal estrogen products or DHEA gel. The reviewed RCTs demonstrated that while vaginal estrogen may cause transient elevations in estrogen levels, these levels did not remain elevated over time, minimizing the risk of systemic absorption that could impact breast cancer recurrence. One study found transient estrogen rises in serum levels, but no significant long-term effects were noted. The review highlighted the need for larger RCTs with longer follow-up periods to better assess the potential risks of these therapies in breast cancer survivors.

Key implications

The findings suggest that vaginal estrogen and DHEA gel may be viable options for managing genitourinary menopausal symptoms in breast cancer survivors, as long as serum estrogen levels do not rise significantly or persistently. These therapies appear to be relatively safe with regard to breast cancer recurrence, based on current evidence, although more robust clinical trials with longer follow-up are needed. Given the complex relationship between hormonal treatments and cancer recurrence risk, clinicians should consider these findings carefully, especially in patients undergoing aromatase inhibitor therapy. While the review supports the use of vaginal estrogen as a second-line treatment for severe genitourinary symptoms in breast cancer survivors, it calls for more comprehensive trials to provide clearer evidence on long-term safety.