For women with early-stage breast cancer receiving an AI, is a vaginal estradiol ring or testosterone cream safe for genital atrophy?
Yes, according to results of a randomized, noncomparative short-term trial that found both agents improved vaginal dryness and sexual dysfunction and had little tendency to persistently elevate serum estradiol levels
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 [published online ahead of print November 10, 2016]. JAMA Oncol. doi: 10.1001/jamaoncol.2016.3904.
Long-term adjuvant AI therapy, which often causes vaginal dryness and sexual dysfunction, is recommended for postmenopausal women with hormone receptor-positive breast cancer. Although use of a vaginally administered low-dose 3-month estradiol ring as well as compounded testosterone cream is known to improve menopausal genital atrophy and sexual symptoms, little data address these agents' impact on serum estradiol levels in women using AIs.
In a safety evaluation study of these treatments performed at an academic US cancer center, Melisko and colleagues randomly assigned postmenopausal women with hormone receptor-positive breast cancer who reported vaginal dryness, sexual pain, or reduced sexual desire to 12 weeks of off-label treatment with an estradiol vaginal ring or intravaginal testosterone cream.
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Details of the study
Among 68 evaluable women (mean age, 56 years), mean baseline estradiol levels were 20 pg/mL (range, <2 to 127 pg/mL); estradiol levels were above the postmenopausal range (>10 pg/mL) in 37% of participants. During the 12-week trial, transient and persistent estradiol levels above this threshold were noted, respectively, in 4 and 0 women treated with the vaginal ring and in 4 and 4 women treated with testosterone cream. Estradiol levels assessed using commercially available (liquid chromatography and mass spectrometry) and research laboratory (radioimmune assay) methodology yielded similar results. In the testosterone cream group, persistent elevations above the normal postmenopausal range were common.
Atrophic vaginal changes, sexual desire, and sexual dysfunction improved in both treatment groups based on gynecologic examinations and sexual quality-of-life questionnaires completed at baseline and week 12.
WHAT THIS EVIDENCE MEANS FOR PRACTICEThe study authors noted the possibility that variable adherence with AI treatment and covert use of estrogen-containing supplements might explain why so many participants had baseline estradiol levels above the postmenopausal range. Despite this observation, however, the study's results provide reassurance that off-label use of the low-dose estradiol vaginal ring does not produce sustained elevations in estradiol serum levels.
The authors indicated that their current practice is to continue the estradiol vaginal ring or testosterone cream in AI users who experience symptomatic improvement with these formulations. They check serum estradiol levels every few months. A future large, long-term trial assessing the impact of off-label use of the estradiol vaginal ring on the incidence of recurrent disease in breast cancer survivors would provide definitive evidence of this treatment's safety.
--Andrew M. Kaunitz, MD
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