Trial Suggests Potential Role for DHEA in Relieving Vaginal Symptoms

Debra L. Barton, RN, PhD

Professor

Mary Lou Willard French Professor of Nursing

University of Michigan School of Nursing

Ann Arbor, MI

A randomized multi-center trial examining the efficacy of adding the prohormone dehydroepiandosterone (DHEA) to a vaginal bioadhesive moisturizer in postmenopausal survivors of breast or gynecologic cancer has found that daily rather than as-needed use of such a moisturizer significantly relieves symptoms of vaginal atrophy in these women, and that when DHEA is added, survivors report significant improvements in sexual desire, arousal, pain, and overall sexual function. Abstract 9507

Debra L. Barton, RN, PhD, AOCN, FAAN, a professor at the University of Michigan School of Nursing, presented the findings at the 2014 ASCO meeting. She noted that very few longitudinal studies have examined predictors of sexual health in cancer survivors, despite the distress this symptom is known to cause them.

Current treatment for vaginal dryness due to estrogen depletion has focused on local approaches, such as water-soluble or silicone-based lubricants for use during intercourse, moisturizers to hydrate the vaginal tissues— which many patients find ineffective, noted Barton— and topical estrogen. Barton said the latter represents the “gold standard” for treatment, but it is likely a last resort, particularly in breast cancer survivors due to safety concerns. “There is still a need to find effective treatments that don’t have estrogenic effects outside the vagina,” said Barton

Investigators sought to find out whether a possible solution to these treatment challenges might be found in DHEA. Previous research on the compound has supported the hypothesis that when used vaginally, DHEA is turned into active forms of estrogen or androgen in the target tissue but is not systemically active.

The study, under the auspices of the Alliance for Clinical Trials in Oncology, enrolled 411 postmenopausal women from 82 institutions across the United States and Canada. Eligible women had finished treatment for breast or gynecologic cancer with no evidence of disease and reported having at least moderate vaginal dryness or dyspareunia over the previous 2 months. Women receiving adjuvant endocrine therapy were eligible to participate if the therapy had been initiated at least 8 weeks prior, and no changes in the treatment regimen were expected during the 12 weeks of the study.

Patients were randomized equally (n = 147) to one of three arms: 3.25 mg or 6.5 mg of DHEA (both provided in a bioadhesive moisturizer base) or the base alone. Each treatment was applied daily via a small, prefilled syringe which participants were directed to administer at bedtime, after any sexual activity. Importantly, Barton noted, the bioadhesive moisturizer used in each of the cohorts is not inactive but rather, represents a current standard of care.

Patient characteristics were similar across all three arms. The majority of participants had been treated for breast cancer (97% in each arm), very few (15%-16%) were on tamoxifen therapy, and more than half (55%-56%) were taking aromatase inhibitors (AIs). The most bothersome symptom across all three groups was dyspareunia, experienced by 60%, 59%, and 51% of patients receiving 3.25 mg of DHEA, 6.25 mg, or none, respectively. Dryness was experienced by 40%, 41%, and 49% of patients in each respective arm.

As the study’s primary endpoint, researchers looked to see what effect the intervention had on change from baseline in dryness or dyspareunia. As secondary outcomes, the study elicited side effect reports and survivor assessments of sexual function and quality of life.

At 12 weeks, there was not a statistically significant difference in the two symptoms between the control and the two DHEA arms, said Barton, but there was a trend that DHEA was decreasing symptoms, with the 6.5 mg dose significant at 8 weeks.

Sexual function, as measured by change from baseline on the Female Sexual Function Index (FSFI), was improved in both DHEA cohorts. The higher dose yielded statistically significant improvements on the full FSFI scale, as well as on most domain subscales (desire, arousal, lubrication, satisfaction, and pain), with the exception of orgasm. Barton added that overall quality of life decreased slightly in the control arm and improved in both DHEA arms, a statistically significant finding.

When women were asked how much their symptoms had changed as a result of this treatment, “more women in the DHEA arms perceived a ‘moderate to very much better’ change than did controls,” Barton said—with 55% of patients in the 3.25-mg arm, 58% in the 6.25 mg group, and 40% in the control arm indicating such improvement.

The grade and frequency of adverse events did not differ significantly between the experimental and control arms; however, hirsutism was reported only in the 6.5-mg arm. Two self-reported side effects of headache (in the 3.2-mg arm) and slight voice change (in both DHEA arms), were worse compared with controls.

Laboratory analysis did not detect evidence of clinically important systemic estrogenic activity, and no changes in estradiol occurred in women receiving AI therapy; both AI- and non-AI—users benefited from the treatment.

“Daily bioadhesive moisturizers used as we prescribed in this study did improve symptoms of vaginal pain and dryness over 12 weeks,” concluded Barton, adding that “DHEA improved symptoms perhaps a bit quicker with the 6.5 mg dose, significantly improving several aspects of sexual function.”

Nurse Perspective

A. Nicole Spray, APRN

Hays Med Breast Center

Hays, KS

The magnitude of sexual dysfunction among postmenopausal women and cancer survivors is underestimated. Healthcare providers may not include questions in a review of systems to address sexual dysfunction. Additionally, many patients feel embarrassed to bring this issue to the attention of their primary care provider or treating oncologist. Sexual dysfunction in this population may encompass many different symptoms, including painful intercourse (dyspareunia), vaginal dryness or decrease in lubrication, and decreased arousal, desire, or satisfaction, all of which can lead to a reduction in quality of life.

These results of a randomized trial using a vaginal bioadhesive moisturizer with DHEA in postmenopausal, cancer-surviving women are encouraging. Women used bioadhesive moisturizer with DHEA daily for 12 weeks. Although there was not a statistically significant difference between the control group and the two DHEA arms of the study that varied by dose, women treated with the DHEA were noted to have decreasing sexual dysfunction symptoms.

Moreover, the higher dose of DHEA showed statistically significant improvements in the Female Sexual Function Index and domain subscales including desire, arousal, lubrication, satisfaction, and pain. Of concern to breast cancer survivors, is the risk of using a vaginal cream that may contain unwanted estrogen exposure. The use of DHEA in a bioadhesive moisturizer, in this trial, did not show any evidence of systemic estrogenic activity.

Perhaps some of the benefit of this treatment was due to daily use. I find in clinical practice that the compliance rate with over-the-counter (OTC) vaginal moisturizer is very low. Patient feedback with use of OTC vaginal moisturizers is that they don’t work very well and the intravaginal administration is unpleasant. Perhaps compliance with prescription bioadhesive moisturizer with DHEA would be perceived as a “prescription,” and women would be more likely to be compliant with instructed use as prescribed.

Additionally, in clinical practice, I find many women get discouraged with the lack of immediate results and they give up treatment with vaginal moisturizers. This trial had women use the intravaginal preparation daily for 12 weeks which supports the idea that postmenopausal vaginal changes, with any treatment, take time to improve

As providers and nurses, we should find a way to assess for sexual dysfunction among cancer survivors consistently and offer viable solutions to help with this problem. Incorporating this treatment may help to address sexual dysfunction in postmenopausal, cancer-surviving women.