Treating genitourinary syndrome of menopause in breast cancer survivors

Treating genitourinary syndrome of menopause in breast cancer survivors | Image Credit: © SewcreamStudio - © SewcreamStudio - stock.adobe.com.

Larger clinical trials with longer follow-ups are needed for treating genitourinary syndrome of menopause (GSM) in breast cancer survivors (BCS), according to a recent review published in Pharmaceuticals.

Breast cancer has been ranked the most common cancer in women and the second leading cause of cancer-related mortality. Data from GLOBOCAN 2020 has indicated breast cancer incidence is rising, with about 2,261,419 new cases annually. 

Long-term BCS must consider concerns on quality of life and long-lasting side effects. The best treatment option differs based on which subtype of breast cancer impacting an individual.

BCS often develop GSM because of the treatment used against breast cancer, leading to GSM symptoms in an estimated 70% of BCS. Vaginal symptoms include dryness and poor lubrication, burning and irritation, and vaginal discharge. Urinary symptoms include urinary urgency, dysuria, and recurrent urinary infections. Vulvovaginal atrophy is also a key symptom of GSM.

Therapy options for GSM in BCS include physical therapy, non-hormonal topical treatments, and hormonal, systemic, and topical treatments. Current guidelines suggest beginning with non-hormonal therapy, then administering hormonal treatments if no results are found.

To evaluate different methods of treatments for GSM in BCS and determine which are most effective, investigators conducted a systematic review. Literature on GSM management was collected through searches on PubMed, Medline, and the Cochrane Library.

Search terms included breast cancer survivors, genitourinary syndrome of menopause, vulvovaginal atrophy, aromatase inhibitors, vaginal lubricants, vaginal moisturizers, local hormone therapy, and vaginal laser therapy. An initial 648 pieces were found, 38 of which were included in the final analysis. All literature reviewed was in English.

Non-hormonal therapies for treating GSM included moisturizers and lubricants, hyaluronic acid, polynucleotides, phytoestrogens, vasodilators mechanical, vaginal vitamin D and E, vaginal and oral probiotics, and laser radiofrequency. While these methods may slow down evolution of the pathological picture, they do not regenerate vaginal barriers or improve their characteristics.

The greatest advantage non-hormonal therapies have over hormonal therapies is a lack of side effects, allowing them to be used continuously. However, it may take long periods for results to appear.

As vaginal atrophy is associated with drops in estrogen levels, hormonal supplementation such as local estrogen administration has been proven to be the most effective treatment. This method leads to improved tropism of vaginal mucous membranes and tissue regeneration. Estrogen may be administered through cream, vaginal rings, ovules, or gels.

Recent studies have indicated a potential increase in breast cancer recurrence risk from vaginal estrogen therapy. This has led some researchers to recommend estriol over estradiol as it has faster metabolic clearance. However, estriol is not approved by the FDA for any indication, and further research is needed on the safety of hormone therapies.

Promestriene, a synthetic estrogen analog, may also be used for treatment. Investigators have suggested caution when prescribing this treatment, however, as it may stimulate the growth of estrogen receptor-reactive breast cancer cell lines. Endocrine adjuvant systemic treatment was also available for women who received surgery for luminal early breast cancer.

Active drugs on the hypothalamicpituitary-ovarian axis and the estrogen receptors may be used to reduce circulating estrogen levels through hormone therapy. Treatment options may differ between pre- and post-menopausal women.

Adverse events from endocrine therapy are seen in about 95% of patients, and include increased cardiovascular and thromboembolic risk, osteoporosis, and issues attributed to GSM. While new therapies for GSM treatment are being developed with promising safety and efficacy results, further research is needed to confirm this data.

While skepticism still surrounds the use of hormone therapy, investigators found it is the most effective treatment against GSM in BCS, and concluded combination therapies when viable may be most effective.

Reference

Merlino L, D'Ovidio G, Matys V, et al. Therapeutic choices for genitourinary syndrome of menopause (GSM) in breast cancer survivors: A systematic review and update. Pharmaceuticals (Basel). 2023;16(4):550. doi:10.3390/ph16040550