Vaginal dehydroepiandrosterone (DHEA) may improve sexual function, without negative systemic effects, in women with breast and gynecologic cancer with vaginal and sexual-related complaints.
Breast and gynecologic cancer patients can experience a range of symptoms associated with sexual dysfunction, among them vaginal dryness and dyspareunia. According to findings presented by Debra Barton, RN, PhD, AOCN, at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology 2014 annual meeting, effective treatment is needed for female sexual dysfunction associated with breast and gynecologic cancer, and vaginal DHEA has proven beneficial.
The vagina is highly regulated by estrogen. “When estrogen is depleted it leads to changes in vaginal tissues, resulting in a vagina that is dry, uncomfortable, and susceptible to infections,” said Barton, professor and the Mary Lou Willard French Endowed Chair in Oncology at the University of Michigan School of Nursing in Ann Arbor.
The focus of treatment for vaginal symptoms is local, noted Barton. Current evidence-based interventions include lubricants, which are used solely for the purpose of reducing friction during intercourse, and vaginal moisturizers, which are used several times a week and for the purpose of hydrating vaginal tissue. Vaginal estrogen is the gold standard for treatment, but it is a last resort in women with cancer due to safety concerns. “There is a need for effective treatment without systemic estrogenic effects,” Barton said.
DHEA—A Possible Solution
“One possible solution is DHEA,” said Barton. DHEA is a prohormone made by the adrenal gland. A prohormone has no known activity in and of itself but has to be converted, mostly in target tissue, to either estrogens or androgens. Previous work with DHEA has supported the hypothesis that when used vaginally it does not produce systemic effects.
Barton and her colleagues conducted a study on postmenopausal women with a history of breast/gynecologic cancer who had completed chemotherapy and radiation and had no evidence of disease. Women were eligible if they reported at least moderately severe vaginal complaints present for no less than 2 months. This analysis of secondary physiological end points examined the impact of vaginal DHEA on vaginal health, hormone concentrations, bone turnover, and sexual function.
A total of 464 women were accrued from 82 sites; 21 withdrew prior to randomization and 2 could not classify worst symptom. The remaining women were randomized to study arms of 3.25 versus 6.5 mg of DHEA versus plain moisturizer (PM). DHEA was compounded into a bioadhesive vaginal moisturizer gel, which was designed to adhere to the vaginal wall. Women inserted the DHEA using a prefilled syringe nightly for 12 weeks, just before sleep and subsequent to any sexual activity. Laboratory tests, maturation index, and vaginal pH were evaluated at baseline and again at 12 weeks.
Safety and Physiological Effects
Blood samples were taken from the 147 women on each of the 3 study arms; a total of 47 women provided pre- and postvaginal tissue samples. Women in all arms experienced a decrease in pH, which is the desired direction, with a greater decrease in the DHEA arms. While none in the control arm (who had levels >5 at baseline) achieved a pH 5, this lower level was achieved by 9% with DHEA 3.25 mg and 7% with DHEA 6.5 mg.
Vaginal cell maturation (no intermediate superficial cells vs some/any) was observed in 100% receiving DHEA 3.25 mg, 86% with DHEA 6.5 mg, and 64% with PM.
Regarding systemic hormone concentrations, DHEA levels increased in each DHEA arm, significantly different from the PM group. However, while the increases were considered to be significant, these values at 12 weeks were not out of line with the normal range for women in that age group, Barton explained.
Bone biomarkers were essentially unchanged. “Based on our data, there is no evidence that vaginal DHEA was having effects on the bones,” she added. A lack of effect on bone markers indicates the absence of estrogenic activity.
DHEA—Did It Work?
In all arms, a significant reduction in the primary symptom was observed compared with baseline, with severity reduced by almost half, and there were no significant differences between the study arms.
“However, the 2 doses of DHEA did significantly improve sexual function, with the 6.5-mg dose improving every single subscale of sexual function except for orgasm,” Barton noted (Table).
Self-reported adverse effects included vaginal discharge, which was experienced by women in all 3 arms, as well as voice change experienced by women in the DHEA arms. “In concert possibly with the testosterone levels, we did see some evidence of androgenic side effects, with voice change being statistically different in the DHEA arms compared to moisturizer, although these differences are quite small,” added Barton.
This study provided evidence of some systemic absorption of DHEA accompanied by hormone changes, although these changes were small and concentrations for all hormones still stayed in the lower normal ranges. Based on the bone biomarker data, there was no indication of extravaginal effects of the DHEA. The adverse and physiological effects led to the hypothesis that vaginal DHEA is working through androgenic means at the site of the vagina, with only minor systemic androgenic effects.
Based on these data, Barton and her colleagues concluded that DHEA improved physiological vaginal health and overall female sexual function more than did PM alone.
Barton D, Sloan JA, Shuster LT, et al. Physiologic effects of vaginal dehydroepiandrosterone (DHEA): Alliance Trial N10C1. Presented at: 2014 Annual Meeting of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology; June 26-28, 2014; Miami, FL.