Safety, Efficacy of Vaginal Testosterone Cream, Estradiol Vaginal Ring in Breast Cancer

Both intravaginal testosterone cream and an estradiol-releasing vaginal ring appear to be safe and effective for treating the urogenital symptoms that often accompany treatment with aromatase inhibitors in postmenopausal women with breast cancer, according to a new study published in JAMA Oncology.¹

“Aromatase inhibitors are the preferred adjuvant therapy for postmenopausal women with hormone receptor-positive early-stage breast cancer,” the researchers wrote. However, they noted that urogenital symptoms, such as vaginal dryness and decreased sex drive, may result in poor compliance, early discontinuation of therapy, and worse quality of life.¹ Although vaginal estrogens effectively treat these symptoms, concerns persist about whether they pose a safety risk to women with breast cancer.¹

To learn more about the safety of these treatments, the researchers conducted a randomized clinical trial (Vaginal Testosterone Cream vs ESTRING for Vaginal Dryness or Decreased Libido in Early Stage Breast Cancer Patients [E-String]; ClinicalTrials.gov identifier: NCT00698035) involving postmenopausal women with hormone receptor-positive stage I to III breast cancer taking aromatase inhibitors who self-reported vaginal dryness, dyspareunia, or decreased libido. Women were randomly assigned to 12 weeks of treatment with either intravaginal testosterone cream (n=34) or an estradiol ring (n=35). The researchers measured estradiol at baseline and at 4 and 12 weeks, and follicle-stimulating hormone levels were measured at baseline and 4 weeks. Women completed questionnaires about sexual quality of life and underwent gynecologic examinations at baseline and 12 weeks.

The intervention was deemed unsafe if more than 25% of patients experienced persistent elevation in estradiol levels. Changes in sexual quality of life and vaginal atrophy served as additional end points.

Seventy-six women gave consent for study participation (mean age: 56 years), 75 of whom initiated treatment and 69 of whom completed 12 weeks of treatment.¹ The researchers noted that, surprisingly, estradiol was elevated in 28 of 76 women (37%) at baseline.¹

Persistent estradiol elevation was defined as levels greater than 10 pg/mL and at least 10 pg/mL above baseline after starting treatment on 2 consecutive tests at least 2 weeks apart. Only 3 of 34 (12%) of women using the intravaginal testosterone cream and none of the women using the vaginal ring experienced persistent estradiol elevation.¹ The researchers noted transient estradiol elevation in 4 of 35 (11%) women using the vaginal ring  and 4 of 34 (12%) using intravaginal testosterone.¹

Vaginal atrophy and sexual interest and dysfunction also improved for all patients.¹

In light of their findings, the researchers concluded that both intravaginal testosterone cream and an estradiol-releasing vaginal ring are safe and effective for treating urogenital symptoms in women with breast cancer taking aromatase inhibitors.¹

The study included several limitations, including its small size and high percentage of patients with elevated estradiol levels at baseline.¹

In an accompanying editorial, Katherine Reeder-Hayes, MD, MBA, MSCR, and Hyman B. Muss, MD, both from the University of North Carolina at Chapel Hill School of Medicine and the University of North Carolina Lineberger Comprehensive Cancer Center, placed the findings in context.

“As the absolute risk of recurrence and the absolute benefits of continued treatment diminish over time for many breast cancer survivors while the adverse effects remain essentially constant, we must ask ourselves, ‘How safe is safe enough?’ Evidence on the risks of vaginal hormonal interventions remains extremely limited, although we may hope for additional research to advance this area of supportive care,” they wrote.²

“In the meantime, if nonhormonal approaches are initially considered and found to be unhelpful and after a frank discussion and shared decision making, the interventions such as those proposed by Drs Melisko and colleaguegs that may have a meaningful effect on quality of life, relationship satisfaction, and ability to move beyond breast cancer, appears the best strategy.”

Disclosures: This study was funded by AstraZeneca. The researchers report no relevant financial disclosures. Drs Reeder-Hayes and Muss report no relevant financial disclosures.

References

1. Melisko ME, Goldman ME, Hwang J, et al. Vaginal testosterone cream vs estradiol vaginal ring for vaginal dryness or decreased libido in women receiving aromatase inhibitors for early-stage breast cancer: a randomized clinical trial. JAMA Oncol. 2016 Nov 10. doi:10.1001/jamaoncol.2016.3904 [Epub ahead of print].
2. Reeder-Hayes K, Muss HB. Vaginal estrogens and aromatase inhibitors: How safe is safe enough? JAMA Oncol. 2016 Nov 10. doi:10.1001/jamaoncol.2016.3934 [Epub ahead of print].