Results of a recent Phase III trial suggest that intravaginal dehydroepiandrosterone (DHEA) could provide women who cannot or do not wish to use intravaginal estrogen with an effective vaginal alternative for easing vaginal symptoms and pain with sex after meno-pause.1 The drug, under development as Intrarosa by Endoceutics, a North American biopharma company, is under review by the Food and Drug Administration (FDA).
In menopause, vaginal tissues atrophy, the lining thins and secretes less and less fluid, and the pH becomes more alkaline, which leads to discomfort with sex, as well as increased susceptibility to vaginal infections and urinary problems for many women.2 Providers offer moisturizers and lubricants as nonhormonal alternatives to intravaginal estrogen to temporarily ease pain with sex and provide moisture, but these treatments cannot correct the physical changes that produce the symptoms. These genitourinary syndromes of menopause can be problematic for many women. In a study of 94,000 postmenopausal women ages 50-79, 52% reported that they had been sexually active with a partner in the past year.3
The current study analyzed the local beneficial effects of Intrarosa, Endoceutics’ DHEA product used intravaginally, on moderate to severe dyspareunia, the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause. In the prospective, randomized, double-blind, and placebo-controlled study, the 325 women who used the daily 0.5% DHEA (6.5 mg) ovules enjoyed significant improvements after 12 weeks compared with the 157 women who used a placebo. Their scores on a scale of 0 to 3 for pain with sex dropped 0.36 points more than for the women who used the placebo.
Results suggest that women who used DHEA also had significantly less thinning of the vaginal lining, with them showing an 8.44% greater increase in lining cells called “superficial cells” and a 27.7% greater decrease in parabasal cells, the immature precursors of the superficial cells. The DHEA users’ moderate to severe vaginal dryness also improved by 0.27 points more on a scale of 0 to 3. Researchers saw 86% to 121% better improvements in vaginal secretions, integrity of the vaginal lining, lining thickness, and tissue color in the women who used DHEA.1
Treatment of postmenopausal vaginal dryness is an important topic for providers who care for those in this patient population. Symptoms of vaginal dryness and atrophy can cause vulvar itching, painful sex, or increased risk of vaginal or bladder infections, says JoAnn Pinkerton, MD, NCMP, executive director of the North American Menopause Society in Cleveland.
“The good news is that we do have effective treatments,” observes Pinkerton. “Over-the-counter lubricants and moisturizers, vaginal exercises, or dilators may make sex more comfortable, but don’t ‘fix’ the problem of changes in the vaginal lining due to low estrogen levels.”
Different forms of low-dose vaginal estrogen therapies include the following: Vagifem (vaginal tablet, Novo Nordisk, Plainsboro, NJ); Estrace (cream, Warner Chilcott, Rockaway, NJ); Premarin (cream, Pfizer, New York City,): Estring (low-dose vaginal ring, Pfizer); and an oral estrogen agonist/antagonist pill (ospemifene, Osphena, Shionogi, Florham Park, NJ).
However, not all women choose to take vaginal estrogen, sometimes out of fear raised by the boxed warning of risks from systemic hormones, which don’t apply to the low-dose vaginal products, notes Pinkerton. Sometimes women can’t take estrogen products and prefer not to take the new oral daily pill. These women need non-estrogen containing effective therapy, which “fixes” the problem more than just the improvement seen with vaginal moisturizers, she notes. The biggest need is in women with advanced estrogen-positive breast cancers, who are fearful of any type of estrogen, even low-dose vaginal therapies, says Pinkerton.
Vaginal DHEA suppositories are not yet approved by the FDA but are showing a positive effect in the vagina, she says. However, neither the new estrogen agonist/antagonist ospemifene (Osphena) nor the vaginal DHEA suppositories have been tested in women at high risk of breast cancer or with breast cancer, Pinkerton states. Anyone with an estrogen-sensitive cancer should discuss their problems with vaginal symptoms or painful sex with their gynecologist and their oncologist to determine what product is best and safest for them, says Pinkerton.
In a release accompanying the study results, David Archer, principle investigator of the Intrarosa trial and professor of obstetrics and gynecology and director of the Clinical Research Center at the Eastern Virginia Medical Center in Norfolk, said, “Having a new therapeutic option for menopausal women which is effective in treating painful sex without the possible safety concerns of traditional hormonal treatments should provide more women the ability to stop dealing with the issue on their own and give them a reason to reach out to their obstetrician-gynecologist or women’s healthcare provider to get clinical support they need and discuss this novel solution.”
REFERENCES
- Labrie F, Archer DF, Koltun W, et al. Efficacy of intravaginal on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause 2015; doi: 10.1097/GME.0000000000000571.
- Tan O, Bradshaw K, Carr BR. Management of vulvovaginal atrophy-related sexual dysfunction in postmenopausal women: An up-to-date review. Menopause 2012; 19:109-117.
- McCall-Hosenfeld JS, Jaramillo SA, Legault C, et al. Correlates of sexual satisfaction among sexually active postmenopausal women in the Women’s Health Initiative Observational Study. J Gen Intern Med 2008; 23:2000-2009.
