In the setting of estrogen deprivation, the mucosal and stromal tissues of the vagina, urethra, and trigone of the bladder undergo atrophy, resulting in decreased tissue elasticity and fluid secretion. This may lead to symptomatic vaginal dryness and irritation as well as dyspareunia. Estrogen deprivation also leads to an elevation in vaginal pH which may increase the risk of vaginal and urinary tract infections. Review of the literature on management of vaginal symptoms in post-menopausal women (most without a history of breast cancer) identifies several therapies that appear to be effective in improving vaginal dryness and decreasing dyspareunia.
The twenty-five microgram 17 beta-estradiol vaginal tablet (Vagifem) was compared to 1.25-mg conjugated equine estrogen vaginal cream (Premarin Vaginal Cream) for the relief of atrophic vaginitis in post-menopausal women [20
]. Both treatments provided equivalent relief of the symptoms of atrophic vaginitis based on composite scores of vaginal symptoms (dryness, soreness, and irritation). At weeks 2, 12, and 24, increases in serum estradiol concentrations and suppression of follicle-stimulating hormone (FSH) were observed in significantly more patients who were using the vaginal cream than in those who were using the vaginal tablets (p
0.001). Vaginal tablet therapy resulted in greater patient acceptance and lower withdrawal rates compared with vaginal cream therapy. In a double-blind placebo-controlled, 1612 post-menopausal patients with urogenital complaints were randomized to receive the Vagifem insert or placebo tablet once a day over a period of 2 weeks, and then twice a week for a total of the 12 months [21
]. The overall success rates of Vagifem vs. placebo on subjective and objective symptoms of vaginal atrophy were 85.5%, and 41.4%, respectively. A significant improvement of urinary atrophy symptoms was also seen in the Vagifem treated group as compared with the beginning of the study (51.9% vs. 15.5%, p
0.001). Compared to baseline evaluations, therapy with the Vagifem insert did not raise serum 17β
-estradiol levels or stimulate endometrial growth based on mean endometrial thickness.
A slow release estradiol vaginal ring (Estring) has been compared to a topical estriol cream (Synapause®) in a 12 week treatment study in postmenopausal women. The Estring was found to be well tolerated, produced equivalent results in reducing vaginal symptoms, and was preferred by patients as less messy and easier to use [22
]. Clinical trials with Estring have shown that there is minimal systemic absorption of estradiol and the range of serum estradiol levels measured at various time points fell within the post-menopausal range [23
]. A prospective randomized study compared the Estring to the Vagifem insert for relief of estrogen deficiency symptoms in post menopausal women over a period of 12 months [24
]. The primary endpoint was endometrial safety based on the results of ultrasound measurement of endometrial thickness and the proportion of subjects who experienced vaginal bleeding or spotting after a progestogen challenge test. Efficacy was determined by changes in patient reported urogenital estrogen deficiency symptoms including vaginal dryness, vulvar pruritus, dyspareunia, dysuria, and urinary urgency and frequency. Evaluation of vaginal epithelial atrophy including pallor, petechiae, friability, and vaginal dryness was also performed by the investigators who graded each between 0 and 4. There was no statistical difference between the groups in the alleviation of symptoms and signs of urogenital estrogen deficiency, and after 48 weeks of treatment, there was no statistically significant difference in endometrial thickness between the two groups. Estradiol and total estrone serum levels increased during treatment in both groups but remained within the postmenopausal range.