Advances in the Treatment of Vulvovaginal Atrophy

Jill M Krapf; Zoe R Belkin; Andrew T Goldstein


Expert Rev of Obstet Gynecol. 2013;8(5):457-465. 

In This Article

Role of Estrogen in Vulvovaginal Atrophy

The symptoms of vulvovaginal atrophy, such as vaginal dryness, irritation, itching, dysuria and dyspareunia, are caused by loss of estrogen production with menopause.[1] As estrogen levels decrease, the vulvovaginal tissue becomes progressively avascular, collagen fibers fuse and hyalinize, elastic fibers undergo fragmentation, and connective tissue increases. Concurrently, the vaginal epithelium becomes thin and pale and shows loss of rugae, which may result in signs of inflammation, such as erythematous patches with fine petechial hemorrhages. Loss of elasticity leads to shortening and narrowing of the vagina[5–7] and limited blood flow to the tissue causes decreased vaginal secretions, leading to insufficient lubrication.[8] Because the female urethra, bladder and pelvic floor musculature are derived from the same embryologic origin as the distal vagina and possess many estrogen receptors (ERs), atrophic changes may also lead to symptoms of dysuria, urethral discomfort, pelvic organ prolapse and stress urinary incontinence.[9–11]

Decreased estrogen also affects vaginal cytology, quantified by the vaginal maturation index (VMI), a ratio of superficial, intermediate and parabasal cells from the upper third of the vagina. As vulvovaginal atrophy develops, there is an increase in the proportion of parabasal cells with a concurrent decrease in superficial squamous cells.[12] Additionally, a lack of estrogen results in diminished glycogen content in epithelial cells, which in turn inhibits lactobacilli growth, contributing to decreased lactic acid production and elevated vaginal pH. Ultimately, the heightened pH fosters pathological bacterial colonization of the vagina, followed by possible odorous discharge.[5,13]

Like estrogen, serum androgens and dehydroepiandrosterone (DHEA) markedly decrease with age and menopausal status. Approximately 60% of androgens present at age 30 are lost at the time of menopause, with serum DHEA showing a similar decline.[14] Animal studies show that DHEA exerts both androgen and estrogenic effects on vaginal mucosa. Treatment with DHEA affects all three layers of the vaginal wall in the rat model, increasing mucification of the epithelium, thickness of the muscularis, and collagen fiber compactness in the lamina propria.[15] Furthermore, androgen receptors and aromatases have been identified by immunohistochemistry in human vaginal epithelium,[39] supporting the theory that not only estrogen, but also androgens are involved in the pathophysiology of vulvovaginal atrophy.