November 14, 2016
By Marilynn Larkin
NEW YORK (Reuters Health) - Both an estradiol-releasing vaginal ring and intravaginal testosterone (IVT) cream effectively treat vaginal atrophy and sexual dysfunction due to aromatase inhibitor treatment in women with early-stage breast cancer, researchers say.
Dr. Michelle Melisko of the University of California, San Francisco told Reuters Health in an interview, "The take-home message is that with careful supervision and monitoring of estradiol levels, a vaginally-delivered, hormonally-based intervention is a reasonable option for patients with hormone receptor-positive breast cancer and won't increase their risk of raising systemic estrogen levels."
As reported in JAMA Oncology, online November 10, Dr. Melisko and colleagues assessed the safety of a compounded intravaginal testosterone cream and a 2 mg estradiol vaginal ring, marketed by Pfizer as Estring, that releases 7.5 micrograms of estradiol every 24 hours for 90 days.
Participants were postmenopausal women with hormone receptor-positive stage I to III breast cancer with self-reported vaginal dryness, painful intercourse or decreased libido during treatment with an aromatase inhibitor. They were randomized to three months of the vaginal ring or IVT.
At baseline, estradiol levels and follicle-stimulating hormone levels were measured and the women underwent gynecological exams and completed sexual quality-of-life questionnaires. At one month, estradiol levels and follicle-stimulating hormone levels were measured. At the end of the study, estradiol levels were measured, and the women underwent another gynecological exam and completed the same questionnaire.
The intervention was considered unsafe if more than 25% of patients had persistent elevation in estradiol, defined as >10 pg/mL and at least 10 pg/mL above baseline after treatment initiation on two consecutive tests at least two weeks apart.
A total of 69 women completed the study. Baseline estradiol was 20 pg/mL on average, and above the postmenopausal range (>10 pg/mL) in 37% of participants. No persistent elevation in estradiol was observed with the vaginal ring, whereas 12% of women using IVT had persistently elevated estradiol.
Transient elevation in estradiol was seen in 11% of those using a vaginal ring and in 12% of those using IVT. All participants experienced improvements in vaginal atrophy and sexual interest and dysfunction.
Dr. Melisko said, "Finding that many women had a higher baseline estradiol level was interesting because it raises questions about the use of various estrogen-containing products. Here on the West Coast, many patients use supplemental herbal products and topical skin products. So before initiating any vaginal intervention, the physician should get a baseline estradiol level and assess what products the patients are using. Most don't think they're using something that will elevate estradiol levels, but clearly there's a surprising amount of that out there."
She continued, "In my practice, I favor the Estring because there's some quality control to it. For the cream, even if a women went to a compounding pharmacy that followed the exact same instructions for the one we used in the study, they could end up with a different product."
Dr. Melisko said either product is an option for women who have tried non-hormonal options without success. She suggested that physicians assess estradiol at baseline "and perhaps intervals of every four to eight weeks when they first start the product and perhaps every six months or so after."
Despite the encouraging findings, she noted, "the black box warning that says the product should not be used in breast cancer patients won't go away because of this small study."
Dr. Hyman Muss of the University of North Carolina, Chapel Hill, coauthor of an accompanying editorial, told Reuters Health, "Sexual dysfunction is among the least talked about and reported side effects of endocrine treatment for early breast cancer."
"Non-hormonal treatments to improve sexual symptoms should be tried first, but if unsuccessful, the interventions proposed in this trial can be considered," he said. "Since these sexually related symptoms are so common and can have such a profound effect on quality of life, larger trials focusing on long-term safety, notably breast cancer recurrence, are needed."
Dr. Steve Vasilev, medical director of Integrative Gynecologic Oncology at Providence Saint John's Health Center, commented, "This is a small but important study . . . Symptoms such as vaginal dryness or atrophy . . . can lead to non-compliance and discontinuation of aromatase inhibitors, which is the preferred therapy in such cases."
Although the study offers women another option to consider beyond non-hormonal remedies, he told Reuters Health by email, "caution should still be exercised in that this was a small study and the safety was only demonstrated in terms of stability of estradiol blood levels. Thus, the study indirectly demonstrated relative safety based on a proxy assumption."
Dr. Vasilev concluded, "More research is necessary to definitively prove safety in terms of potential impact of any estradiol elevation due to these treatments on actual recurrence rates."
The study was funded by Astra Zeneca. No conflicts of interest were reported.
SOURCE: http://bit.ly/2eK7N0n and http://bit.ly/2g8wlpx
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