| Summary by: Dr. Tori Hudson, N.D.
The tissues of the urogenital tract (including the vagina, vulva, lower urinary tract and supporting pelvic floor structures) are rich in estrogen and androgen receptors as well as responsive to the enhanced blood flow to the genital tract that estrogen and testosterone provides, which is vital for genital sexual arousal and lubrication. The decline in estrogen levels at menopause and the gradual age related decline in androgens result in what is now being called genitourinary syndrome of menopause (GSM). GSM includes vulvovaginal atrophy, an increase in vaginal pH, reduced vaginal epithelial superficial cells and an increase in parabasal cells. The change in the vaginal ecosystem includes an increase in vaginal pH, dramatically disappearing lactobacilli and thus a change in the whole organisms that reside in the vagina. Symptoms of vulvovaginal atrophy include diminished sexual arousal, arousal difficulties, diminished orgasm, pain with touch and/or penetration, vaginal dryness, irritation, itching, burning and possibly vaginal or urinary tract infections.
Most postmenopausal women experience some GSM symptoms. Fortunately, topical or systemic estrogen therapy is very effective for symptoms of vulvovaginal atrophy. Estrogen therapy thickens and revascularizes the vaginal epithelium, increases the vaginal epithelial superficial cells, and propagates the proliferation of Lactobacilli thus lowering vaginal pH towards normal and restoring optimal vaginal flora.
The use of intravaginal and/or topical estrogen provides a largely local effect, minimizing the systemic exposure to estrogen, however, some studies have shown an increase in estradiol blood levels with vaginal application. 1,2,3
The delivery method of intravaginal estrogen products appears to effect the serum level of estradiol, with creams 0.625 mg conjugated estrogen cream, resulting in a greater serum level than does the local ring (Estring) or vaginal tablet of a 25 mcg dose (Vagifem ).4 However, after 24 weeks of treatment, only 2% of women have estradiol levels outside the postmenopausal range.5
There are alternative approaches to GSM, which include vaginal moisturizers, vaginal lubricants, hops gel, oral kudzu, and a recent study on oral soy isoflavones.6
What also has emerged are several studies on vaginal DHEA. It was first studied as a vaginal DHEA 150 mg pessary versus placebo in five premenopausal women and resulted in an increase in blood levels of DHEA.7
I started using vaginal DHEA for VVA in my practice after the first study by Labrie and colleagues in 2008. In this initial study, a 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.8 Observations included a decrease in vaginal pH, an improvement in the vaginal cell maturation index, and at the highest dose of 23.5 mg, there was an increase in serum DHEA levels to the range for premenopausal women at the highest dose. None of the other sex steroids changed from the normal postmenopausal reference ranges.
In 2009, Labrie and colleagues published the results of a randomized controlled trial spanning 12 weeks of intravaginal applications of DHEA ovules, at 3 different doses of 3.25 mg, 6.5 mg and 13 mg. That study resulted in several publications by Labrie, et al demonstrating efficacy of this method of treatment for VVA.9-14
Improvements in vaginal cytology, a lowering of vaginal pH, improved vaginal dryness and dyspareunia and an increase in sexual function including arousal and even libido. In addition, this study showed a lack of systemic absorption or change in blood levels of DHEA metabolites. One might think that due to the propensity of drugs that are absorbed through the vaginal mucosa, this is a welcome surprise.
The most recent study, a double blind placebo controlled phase III trial, and now from a different researcher, aims to confirm the local effects of intravaginal DHEA on moderate to severe dyspareunia, as a result of menopause.15 A daily intravaginal DHEA 6.5 mg suppository was examined on the effects of four co-primary objectives: 1) percentage of vaginal parabasal cells, 2) percentage of vaginal superficial cells, 3) vaginal pH and 4) moderate to severe dyspareunia. After a daily vaginal administration for 12 weeks, the % of parabasal cells decreased by 45.8% compared to placebo, the % of superficial cells increased by 4.7% over placebo, vaginal pH decreased by 0.83 units compared with placebo and the severity of dyspareunia decreased by 46% over placebo. In addition, vaginal dryness decreased by 42% compared to placebo. On the physical exam, there was a 14.4% to 21.1% improvement in vaginal secretions, epithelial integrity, epithelial surface thickness, and color, over placebo. Serum levels remained in postmenopausal range and after 12 weeks, endometrial biopsies confirmed atrophy of the endometrial lining.
References:
1. Labrie F, Cusan L, Gomez JL, et al. Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women. Menopause. 2009;16(1):30-36.
2. Kendall A, Dowsett M, Folkerd E, Smith I. Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol. 2006;17(4):584-587.
3. Weisberg E, Ayton R, Darling G, et al. Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet. Climacteric. 2005;8(1):83-92.
4. Labrie F, Cusan L, Gomez JL, et al. Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women. Menopause. 2009;16(1):30-36.
5. Rioux JE, Devlin C, Gelfand MM, Steinberg WM, Hepburn DS. 17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause. 2000;7(3): 156-161.
6. Camfignani L, Pedro A, Montemor E, et al. Effects of a soy-based dietary supplement compared with low-dose hormone therapy on the urogenital system: a randomized, double-blind, controlled clinical trial. Menopause 2015;22(7):741-749
7. Casson PR, Straughn AB, Umstot ES, Abraham GE, Carson SA, Buster JE. Delivery of deyhdroepian-drosterone to premenopausal women: effects of micronization and nonoral administration. Am J Obstet Gynecol. 1996;174(2):649-653.
8. Labrie F, Cusan L, Gomez JL, et al. Effect of intravaginal DHEA on serum DHEA and eleven of its metabolites in postmenopausal women. J Steroid Biochem Mol Biol. 2008;111(3-5):178-194
9. Labrie F, Archer D, Bouchard C, et al. Serum steroid levels during 12-week intravaginal dehydro-epiandrosterone administration. Menopause. 2009; 16(5):897-906.
10. Labrie F, Archer D, Bouchard C, et al. Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women. Menopause. 2009;16(5):923-931.
11. Labrie F, Archer D, Bouchard C, et al. Intravaginal dehydroepiandrosterone (Prasterone), a physiological and highly efficient treatment of vaginal atrophy. Menopause. 2009;16(5):907-922.
12. Labrie F, Archer D, Bouchard C, et al. High internal consistency and efficacy of intravaginal DHEA for vaginal atrophy. Gynecol Endocrinol. 2010;26(7):524-532.
13. Labrie F, Archer D, Bouchard C, et al. Lack of influence of dyspareunia on the beneficial effect of intravaginal prasterone (dehydroepiandrosterone, DHEA) on sexual dysfunction in postmenopausal women. J Sex Med. 2014;11(7):1766-1785.
14. Labrie F, Archer DF, Bouchard C, et al. Intravaginal dehydroepiandrosterone (prasterone), a highly efficient treatment of dyspareunia. Climacteric. 2011;14(2):282-288.
15. Archer D, Labrie F, Bouchard C, et al. Treatment of pain at sexual activity (dyspareunia) with intravaginal dehydroepiandrosterone (prasterone). Menopause 2015;22(9): 950-963. |
