Nonhormonal treatment options

Management of vaginal atrophy should be tailored to the individual patient’s needs and take into account such factors as any lifestyle concerns, severity of current symptoms, and medical history. Recommended lifestyle modifications for patients with vaginal atrophy should include maintenance of vulvar hygiene, smoking cessation, and increased coital activity.4 In addition, such nonhormonal treatment options as vaginal lubricants and moisturizers can be of benefit to many patients and are recommended as first-line therapies for women with vaginal atrophy, according to the 2007 North American Menopause Society (NAMS) position statement.1 Clinical studies of a suppository containing hyaluronic acid, vitamin A, and vitamin E found significant improvements in vaginal symptoms with no reported treatment-related adverse events.18,19 Botanical supplements have been used by many patients with menopausal symptoms, and one study of menopausal and perimenopausal women found that a variety of botanical supplements were commonly used, including soy (42%), green tea (34.68%), chamomile (20.76%), gingko (20.51%), ginseng (17.97%), echinacea (15.44%), and St. John’s wort (7%).20 (The study did not clearly state what percentage of women were taking the supplements for relief of vaginal symptoms.)Some evidence is available suggesting that vitamins D and E, as well as soy, may be useful in the treatment of vaginal symptoms by providing relief of vaginal dryness and irritation; however, more data are needed to provide firm evidence of these effects.2,4

Role of exogenous local estrogen therapy

Treatment with systemic estrogen will alleviate general symptoms of menopause (e.g., hot flushes) found in addition to vaginal atrophy. However, local administration of estrogen can also effectively alleviate symptoms of vaginal atrophy with fewer adverse effects that may be associated with systemic exposure.1,4 Available vaginal products that deliver a local estrogen dose are conjugated equine estrogen, synthetic estrogen or estradiol creams, an estradiol ring, and an estradiol tablet (Table 2).1,21


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Several key organizations have developed guidelines for the use of exogenous estrogen therapy for vaginal atrophy. The NAMS recommends that first-line therapies for vaginal atrophy include nonhormonal lubricants and moisturizers.1 The currently available creams, rings, and tablets are recommended equally when initiating low-dose local vaginal estrogen therapy, as they have all been found to be effective and well tolerated.1 According to both the American College of Obstetricians and Gynecologists task force and the American Association for Clinical Endocrinologists (AACE) menopause guidelines, hormone therapy is an effective treatment option for women with vaginal atrophy, but the risks associated with treatment need to be assessed individually for each patient.22,23 The AACE menopause guidelines conclude that when estrogen is prescribed solely for relief of symptoms associated with vulvar and vaginal atrophy, local vaginal preparations at the lowest dose necessary to provide relief from symptoms should primarily be considered, as the risks for each preparation are not always clearly understood on the basis of scientific studies.23

There is a significant body of evidence from clinical trials regarding the safety and efficacy of estrogen products when used to treat vaginal atrophy. A Cochrane review of 16 clinical trials concluded that several different local estrogen-delivery systems (i.e., vaginal cream, vaginal tablets, and vaginal rings) were equally effective in relieving symptoms of vaginal atrophy. In this study, the outcome measures assessed included vaginal symptoms, vaginal pH, cytologic changes, safety, and acceptability.24 Some adverse effects were noted with vaginal cream administration (including uterine bleeding, breast pain, and perineal pain [observed in one study]) in addition to endometrial overstimulation (observed in two studies). Cases of hyperplasia and endometrial overstimulation were observed with the ring, cream, and tablets in different studies, although incidence of these observations was not statistically significant.24 Results from several recent clinical studies have included significant improvements in vaginal symptoms (which may include dryness, itching, soreness, dysuria, and/or dyspareunia), positive changes in the vaginal maturation index (as demonstrated by significant increases in superficial and intermediate cells with a matching decrease in parabasal cells), and reduced vaginal pH based on the use of estrogen tablets,25,26 creams,27 gels,28,29 and rings30 compared with placebo.

In reviewing clinical evidence coupled with patient preferences, some comparisons between the different types of estrogen preparations can be made. In the analysis of the Cochrane review, some symptoms were relieved preferentially using different estrogen preparations, although these results may not translate to differences observed in clinical practice.1,24 For example, some advantages were observed regarding vaginal pH when using vaginal rings as compared with tablets. In different studies, vaginal tablets were found to be more effective in reducing symptoms of dyspareunia, urinary frequency, and dryness when compared with the vaginal ring.24 However, in a study directly comparing the vaginal ring with the tablet, the same efficacy and safety were observed as measured by comparing endometrial thickness, relief of vaginal symptoms, and cytologic changes.31 The majority of patients in this study found both the vaginal tablet and ring to be acceptable forms of treatment.31 However, an earlier study demonstrated a clear patient preference for the vaginal ring compared with vaginal cream.32 Predilection of tablet use was demonstrated in one study with significantly improved adherence to treatment with tablets compared with vaginal cream33 and another in which significantly more patients using vaginal tablets rated their medication as easy and comfortable to use compared with patients who were using vaginal cream (P ≤0.001).34 Patient preference should be an important consideration when deciding the type of vaginal estrogen preparation to use.

While exogenous estrogen therapy has been utilized for many years in clinical practice, potential concerns with use of this therapy have been raised over time. Traditionally, estrogen-replacement therapy is associated with an increased risk for thromboembolic disease, stroke, endometrial cancer, breast cancer, and coronary events.22,23 The use of exogenous estrogen therapy is currently contraindicated for breast cancer survivors; however, use of nonhormonal alternatives to relieve symptoms of vaginal atrophy have not demonstrated complete effectiveness. Preliminary data suggest that very low doses (≤10 μg/day) of vaginal estrogen preparations may be useful to relieve vaginal atrophy symptoms in patients with breast cancer.35 Although local estrogen therapy is generally recommended as treatment for vaginal atrophy to reduce systemic exposure to exogenous hormones, relatively high systemic levels of estradiol have still been observed in association with some vaginal estrogen preparations.36 For example, treatment with a 25-μg estradiol tablet or 1 g (0.625 mg) of a conjugated estrogen vaginal cream was found to increase serum estradiol by an average of 5.4-fold from 3 to 17 pg/mL during the period 24 hours post-administration.36 However, previous pharmacokinetic studies demonstrated that the initial absorption of vaginal estrogen was dose-dependent, but after maturation of the vaginal epithelium, the amount of absorption decreased significantly by day 14 as measured by plasma concentrations of estrogen.37 Additional long-term research is needed to more fully understand the risks and potential consequences associated with the use of local estrogen therapy, especially in patients with hormone-related cancer.

Conclusions

Vaginal atrophy is a condition that can negatively impact the quality of life of many postmenopausal women. Local exogenous estrogen therapy can effectively alter the anatomic and pathophysiologic effects associated with vaginal atrophy, resulting in relief of symptoms with manageable adverse effects. n

Dr. Freeman is the director of the Women’s Health Nurse Practitioner Program and a combined Women’s Health Nurse Practitioner and Adult Nurse Practitioner Program at the Emory University School of Nursing in Atlanta. The author wishes to thank Jennifer R. Kent, PhD, of DesignWrite, LLC, for providing writing and editorial assistance. Funding to support this activity was provided by Novo Nordisk, Inc.


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References

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