About 32 million postmenopausal women in the United States are affected by vulvar and vaginal atrophy, which can cause painful sexual activity and urination, as well as vaginal dryness, itching, and irritation.1 Recent data presented at ENDO 2016, the annual meeting of the Endocrine Society, suggests an investigational low-dose vaginal estrogen capsule may help relieve such symptoms.2,3
Vulvar and vaginal atrophy is chronic and progressive. Unlike vasomotor symptoms, it will not resolve with time and without treatment. Left untreated, these symptoms not only can cause discomfort, but also can negatively impact women’s quality of life, including sexual relationships and emotional well-being.4
A recent study recruited women ages 55 and older from primary care offices and senior centers to answer questions about common symptoms after menopause. Results indicate that vulvar and vaginal symptoms such as itching, burning, stinging, pain, irritation, dryness, discharge, or odor, were very common. More than half of the women (51%) said they had one or more of these symptoms; 40% of women with symptoms said the symptoms posed emotional problems, and 33% said they had an impact on their lifestyle.5
There is an “unmet need” for postmenopausal women to have regular gynecologic visits during which questions can be asked about vaginal and urinary health problems and assessment can be made to determine the presence of these symptoms, says JoAnn Pinkerton, MD, NCMP, executive director of the North American Menopause Society.
“Women need to tell their healthcare providers about their genitourinary symptoms, and providers need to ask,” states Pinkerton.
To help providers and patients more comfortably discuss the changes often associated with menopause, the North American Menopause Society and the International Society for the Study of Women’s Sexual Health in 2014 developed the term “genitourinary syndrome of menopause.” The term defines “a collection of symptoms and signs associated with a decrease in estrogen and other sex steroids involving changes to the labia majora/minora, clitoris, vestibule/introitus, vagina, urethra, and bladder,” and includes genital symptoms of dryness, burning, and irritation; sexual symptoms of lack of lubrication, discomfort or pain, and impaired function; and urinary symptoms of urgency, dysuria, and recurrent urinary tract infections.6 The research presented at the ENDO 2016 conference looked at TX-004HR, an investigational drug containing the estrogen 17β-estradiol. The drug, under development by TherapeuticsMD of Boca Raton, FL, is in clinical trials and is not available to the general public.
TherapeuticsMD conducted the double-blind, randomized Phase 3 clinical trial comparing three doses (4, 10, and 25 mcg) of TX-004HR with placebo in 764 postmenopausal women ages 40-75 in 105 medical centers in the United States and Canada. The women in the study received vaginal softgel capsules containing one of the three doses of TX-004HR or placebo, once daily for two weeks, then twice weekly for 10 weeks.
Study results suggest that within two weeks, at all doses, vaginal cells, and vaginal pH improved, compared with placebo. Superficial and parabasal vaginal cell improvement was found at baseline and at two, six, eight, and 12 weeks. Study findings suggest vaginal pH returned to premenopausal levels. Dyspareunia, vaginal dryness, and irritation also showed improvement. Scientists report that TX-004HR did not, on average, increase blood levels of estradiol outside the normal postmenopausal range. The treatment was well-tolerated. No treatment-related serious adverse events were reported, and no clinically significant differences in any adverse events or treatment-related serious adverse events were found between TX-004HR and placebo.2,3
The current treatment for genitourinary syndrome of menopause is low-dose estrogen in the vagina through creams, pills, or rings. TherapeuticsMD says it plans to use its trial data for TX-004HR, conditionally branded as Yuvvexy, as the basis for a New Drug Application to the FDA.
“This study provides a new easy-to-use option for vulvar and vaginal atrophy, for which only about 7% of women are currently treated with a prescription product,” said lead author Ginger Constantine, MD, president and CEO of EndoRheum Consultants in Malvern, PA, in a statement accompanying the study presentation. “Health care providers and their patients may soon have an additional safe and effective product for a very untreated condition.”
- The North American Menopause Society. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause 2013; 20(9):888-902.
- Constantine GD, Simon JA, Pickar JH, et al. The REJOICE trial: A phase 3 randomized controlled trial evaluating the safety and efficacy of a novel vaginal estradiol softgel capsule for symptomatic vulvar and vaginal atrophy (VVA). Presented at the ENDO 2016 annual meeting of the Endocrine Society. Boston; April 2016.
- Archer DA, Constantine GD, Kushner H, et al. TX-004HR vaginal estradiol effectively treats vulvar and vaginal atrophy (VVA) with negligible to low systemic absorption of estradiol. Presented at the ENDO 2016 annual meeting of the Endocrine Society. Boston; April 2016.
- Wysocki S, Kingsberg S, Krychman M. Management of vaginal atrophy: Implications from the REVIVE survey. Clin Med Insights Reprod Health 2014; 8:23-30.
- Erekson EA, Li FY, Martin DK, et al. Vulvovaginal symptoms prevalence in postmenopausal women and relationship to other menopausal symptoms and pelvic floor disorders. Menopause 2016; 23(4):368-375.
- Portman DJ, Gass ML; on behalf of the Vulvovaginal Atrophy Terminology Consensus Conference Panel. Genitourinary syndrome of menopause: New terminology for vulvovaginal atrophy from the International Society for the Study of Women’s Sexual Health and The North American Menopause Society. Menopause 2014; 10:1063-1068.