A recent headline "Costly Menopause Vaginal Treatments No Better Than Placebo" regarding a study published in JAMA Intern Medicine caught my eye. After reading the article and then the study, I am again frustrated with what we call "evidence-based medicine".
The study addressed a very important aspect of menopause: vulvar vaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM). VVA is a common and under reported condition associated with decreased estrogenization of the vaginal tissue. Symptoms include dryness, irritation, soreness, and dyspareunia with urinary frequency, urgency, and urge incontinence.
The study compared a single vaginal estrogen treatment containing very low dose 10 microgram estradiol in hard tablet form and over the counter vaginal moisturizers to placebo tablets and placebo moisturizers. The study found no difference between the treatment arms and placebo. This was in regards to "reported symptoms" by patients.
I believe there exist significant flaws in this study including:
Most critical would be other forms of vaginal hormone treatment exist including higher dose estradiol vaginal creams, vaginal rings, vaginal DHEA suppositories and of course, compounded vaginal combinations. The results of this study ONLY apply to the 10 microgram estradiol tablets (Vagifem) but that is not the information being transmitted to the public.
For one of the placebos they used a gel, which could be considered a vaginal moisturizer on its own. This may have contributed to the significant placebo response in this trial, confusing the results.
The study showed slight changes in the vaginal wall and pH for patients assigned the estradiol tablets but noted this was not associated with reduced symptoms so therefore not considered a positive outcome.
The short duration of the trial at 3 months.
I definitely would not use this study to overrule the current guidelines published by the North American Menopause Society (NAMS) stating estrogen therapy is the most effective treatment for moderate to severe symptoms of VVA.
Compounding gives physicians and patients many other options for vaginal treatment including
Estriol, a weak estrogen shown clinically to improve vaginal symptoms
Combining Estradiol and Estriol, known as Biest
Adding low dose testosterone for low libido and anorgasmia
Adding progesterone to balance the estrogen
Adding DHEA
Or any combination of the above
using hypoallergenic cream bases or gels that adhere to vaginal mucosa
References:
Mitchell et al. Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial. JAMA Intern Med. 2018 Mar 19.
Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause 2013; 20(9) 888-902.
https://www.medscape.com/viewarticle/894376
picture from https://www.shecares.com/symptoms/vaginal-dryness