Question
What is the current evidence on the use of intravaginal dehydroepiandrosterone (DHEA) in urogenital atrophy and sexual function?
Commentary from Susan R. Davis, MBBS, FRACP, PhD
Sex steroids are vital for the integrity of the urogenital tract (vagina, vulva, lower urinary tract, and supporting pelvic structures). These tissues are rich in estrogen and androgen receptors.[1] In addition, estrogen and testosterone enhance blood flow to the genital tract,[2] which is fundamental for genital sexual arousal and lubrication.[3]
;The fall in estrogen at menopause and the gradual decline in androgen levels with age[4] result in what is now described as genitourinary syndrome of menopause (GSM). This includes vulvovaginal atrophy (VVA) and an increase in vaginal pH.[3] At a cellular level, there is a reduction in healthy vaginal epithelial superficial cells and an increase in parabasal cells. The increase in vaginal pH changes the vaginal microflora. Lactobacilli disappear, and as a consequence there is increased vulnerability to vaginal infection. Symptoms of VVA include vaginal dryness, irritation, itching, infection, and dyspareunia.[5] This in turn leads to diminished sexual desire, arousal difficulties, diminished physical and emotional sexual satisfaction, and relationship issues.[6]
Most postmenopausal women will experience some GSM symptoms.[7] Symptoms of VVA can be effectively treated with either vaginal or systemic estrogen therapy.[8] Estrogenization will thicken and revascularize the vaginal epithelium, lower vaginal pH, and normalize vaginal flora. The number of vaginal epithelial superficial cells will increase.[8,9] Although data show that vaginal estrogen acts locally, thus minimizing systemic exposure to estrogen, some studies have shown blood estradiol levels increase with vaginal application.[10,11,12] A two- to fivefold increase in serum estradiol has been reported after one week of vaginal administration of a 25 µg estradiol vaginal tablet or 1g of 0.625 mg conjugated estrogen cream.[10] After 24 weeks of treatment, only 2% of women have estradiol levels outside the postmenopausal range.[13]
Researchers have looked for alternative approaches for GSM management. In postmenopausal women, adrenal dehydro-epiandrosterone (DHEA) is an important precursor for extra-gonadal biosynthesis of estrone (by aromatization) and testosterone (by 5-alpha reduction). Casson and colleagues first studied the effects of a vaginal DHEA 150 mg pessary versus placebo in five premenopausal women as a mode of hormone delivery and reported an increase in blood levels of DHEA with this approach.[14] The daily vaginal application of three different doses of DHEA cream (6.5 mg, 13 mg, and 23.5 mg) was studied for one week in postmenopausal women.[15] Labrie and colleagues reported a decrease in vaginal pH, an improvement in the vaginal cell maturation index, and restoration of DHEA levels to the range for premenopausal women at the highest dose.[15] The circulating levels of other sex steroids remained within the normal range for postmenopausal women.
A randomized controlled trial of the daily application of three different doses of vaginal DHEA ovules (3.25 mg, 6.5 mg, or 13 mg) was studied over 12 weeks in 218 postmenopausal women who met the entry criterion of dyspareunia. This single study has resulted in a number of publications to support the efficacy of this treatment for VVA.[16,17,18,19,20,21] In these various publications, the investigators have reported an improvement in vaginal cytology and a reduction in pH. An analysis restricted to the women who fulfilled investigational criteria for a low percentage of vaginal epithelial cells and vaginal pH greater than 5 reported an increase in superficial cells and a reduction in pH with an associated improvement in dyspareunia compared with placebo.[21] Sexual function was assessed by three questions in the Menopause Quality of Life Questionnaire (sexual desire, vaginal dryness during intercourse, or avoiding intimacy) and by the Abbreviated Sexual Function Questionnaire. At 12 weeks the total Menopause Quality of Life Questionnaire sexual domain score showed a significantly greater response for each treatment group versus placebo, with more mixed findings in the Abbreviated Sexual Function Question-naire.[17]
DHEA Benefits Include Helping To Relieve Vaginal Pain Caused By Menopausal Dryness, Atrophy
New research suggests a DHEA vaginal suppository for treating vaginal dryness may be one step closer to government approval. The DHEA formulation could provide an effective alternative for women hoping to ease their symptoms of menopause — without resorting to estrogen.
During perimenopause, vaginal tissues begin to atrophy, the lining thins and secretes less and less fluid, and the pH becomes more alkaline, explain the researchers. Not only do these signs of age lead to discomfort during sex, they also increase a woman’s susceptibility to infections and urinary problems. While hormonal treatments may help alleviate such symptoms, many women have a past history of cancer or higher genetic risk for reproductive cancers rendering such medicines unsafe.
As an alternatives to estrogen treatments, some women resort to non-hormonal lubricants. While these products may temporarily provide moisture and even ease sexual pains, they do not correct the physical problems producing the symptoms. By comparison, DHEA (dehydroepiandrosterone) is a precursor of estrogens and androgens and so can induce physical changes that protect the vagina, according to the researchers. That said, the DHEA product in this study is still considered “hormonal” by regulatory authorities, such as the Food and Drug Administration.
Safety Testing a New Product
For the study, a research team from EndoCeutics, a private bio-pharm company, recruited nearly 500 women to participate in a randomized, double-blind, placebo-controlled trial of its DHEA suppository product. The majority of the women, 84 percent, complained of moderate to severe vaginal dryness. The researchers divided the women, ranging in age from 40 to 80, into two groups: 325 women in the DHEA-treatment group and 157 in a placebo group. After a baseline gynecological test, the women used a daily suppository of either the DHEA or placebo, depending on their group, for 12 weeks.
Compared with the women using a placebo, the women who used the DHEA ovules experienced improvements. Their scores on a scale of 0 to 3 for pain during sex dropped 0.36 points more than the women using placebo and their scores improved by 0.27 points with regard to vaginal dryness. Importantly, the gynecologists who examined them saw 86 percent to 121 percent better improvements in vaginal secretions, integrity of the vaginal lining, lining thickness, and tissue color in the women who used DHEA, while their vaginal pH shifted 0.66 points toward acidity (a positive direction).
“The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at body temperature and this was reported in about 6 percent of the participants,” noted the researchers in their study.
Importantly, this therapy has not been tested in patient at risk or with a history of breast cancer.
“Although this medication is considered ‘hormonal,’ the mechanism appears to be primarily local with minimal side effects beyond vaginal discharge from the suppository,” Dr. JoAnn V. Pinkerton, executive director of North American Menopause Society, stated in a press release.
Source: Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2016.
Dr Colin Holloway 