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
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.
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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1. North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of The North American Menopause Society. Menopause. 2007;14(3 Pt 1):355-369.
2. Castelo-Branco C, Cancelo MJ, Villero J, et al. Management of post-menopausal vaginal atrophy and atrophic vaginitis. Maturitas. 2005;52(Suppl 1):S46-S52.
3. Pastore LM, Carter RA, Hulka BS, et al. Self-reported urogenital symptoms in postmenopausal women: Women’s Health Initiative. Maturitas. 2004;49:292-303.
4. Mehta A, Bachmann G. Vulvovaginal complaints. Clin Obstet Gynecol. 2008;51:549-555.
5. Goldstein I, Alexander JL. Practical aspects in the management of vaginal atrophy and sexual dysfunction in perimenopausal and postmenopausal women. J Sex Med. 2005;2(Suppl 3):154-165.
6. Alexander JL, Kotz K, Dennerstein L, et al. The effects of postmenopausal hormone therapies on female sexual functioning: a review of double-blind, randomized controlled trials. Menopause. 2004;11(6 Pt 2):749-765.
7. Bachmann GA, Ebert GA, Burd ID. Vulvovaginal complaints. In: Lobo RA, ed. Treatment of the Postmenopausal Woman: Basic and Clinical Aspects. 2nd ed. Philadelphia, Pa.: Lippincott Williams & Wilkins; 1999:195-201.
8. Ballagh SA. Vaginal hormone therapy for urogenital and menopausal symptoms. Semin Reprod Med. 2005;23:126-140.
9. Farage M, Maibach H. Lifetime changes in the vulva and vagina. Arch Gynecol Obstet. 2006;273:195-202.
10. Gorodeski GI. Effects of estrogen on proton secretion via the apical membrane in vaginal-ectocervical epithelial cells of postmenopausal women. Menopause. 2005;12:679-684. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC2373250/.
11. Gorodeski GI, Hopfer U, Liu CC, et al. Estrogen acidifies vaginal pH by up-regulation of proton secretion via the apical membrane of vaginal-ectocervical epithelial cells. Endocrinology. 2005;146:816-824. Available at endo.endojournals.org/cgi/content/full/146/2/816.
12. Levine KB, Williams RE, Hartmann KE. Vulvovaginal atrophy is strongly associated with female sexual dysfunction among sexually active postmenopausal women. Menopause. 2008;15:661-666.
13. Kao A, Binik YM, Kapuscinski A, et al. Dyspareunia in postmenopausal women: a critical review. Pain Res Manag. 2008;13:243-254. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC2671314/.
14. Cardozo L, Lose G, McClish D, et al. A systematic review of estrogens for recurrent urinary tract infections: third report of the Hormones and Urogenital Therapy (HUT) committee. Int Urogynecol J Pelvic Floor Dysfunct. 2001;12:15-20.
15. Gupta S, Kumar N, Singhal N, et al. Cytohormonal and morphological alterations in cervicovaginal smears of postmenopausal women on hormone replacement therapy. Diagnostic Cytopathology. 2006;34:676-681.
16. Galhardo CL, Soares JM Jr, Simões RS, et al. Estrogen effects on the vaginal pH, flora and cytology in late postmenopause after a long period without hormone therapy. Clin Exp Obstet Gynecol. 2006;33:85-89.
17. Bachmann GA, Nevadunsky NS. Diagnosis and treatment of atrophic vaginitis. Am Fam Physician. 2000;61:3090-3096.
18. Costantino D, Guaraldi C. Effectiveness and safety of vaginal suppositories for the treatment of the vaginal atrophy in postmenopausal women: an open, non-controlled clinical trial. Eur Rev Med Pharmacol Sci. 2008;12:411-416.
19. Morali G, Polatti F, Metelitsa EN, et al. Open, non-controlled clinical studies to assess the efficacy and safety of a medical device in form of gel topically and intravaginally used in postmenopausal women with genital atrophy. Arzneimittelforschung. 2006;56:230-238.
20. Mahady GB, Parrot J, Lee C, et al. Botanical dietary supplement use in peri- and postmenopausal women. Menopause. 2003;10:65-72.
21. Facts and Comparisons: Estrogens. In: Kastrup EK, ed. Drug Facts and Comparisons. St. Louis, Mo.: Wolters Kluwer Health; 2009:217-224D.
22. American College of Obstetricians and Gynecologists Women’s Health Care Physicians. Executive summary. Hormone therapy. Obstet Gynecol. 2004; 104(4 Suppl):1S-4S.
23. Cobin RH, Futterweit W, Ginzburg SB, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of menopause. Endocr Pract. 2006;12:315-337.
24. Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women (review). Cochrane Database Syst Rev. 2006;4:CD001500.
25. Simon J, Nachtigall L, Gut R, et al. Effective treatment of vaginal atrophy with an ultra-low-dose estradiol vaginal tablet. Obstet Gynecol. 2008;112:1053-1060.
26. Bachmann G, Lobo RA, Gut R, et al. Efficacy of low-dose estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Obstet Gynecol. 2008;111:67-76.
27. Freedman M, Kaunitz AM, Reape KZ, et al. Twice-weekly synthetic conjugated estrogens vaginal cream for the treatment of vaginal atrophy. Menopause. 2009;16:735-741.
28. Hedrick RE, Ackerman RT, Koltun WD, et al. Transdermal estradiol gel 0.1% for the treatment of vasomotor symptoms in postmenopausal women. Menopause. 2009;16:132-140.
29. Simon JA, Bouchard C, Waldbaum A, et al. Low dose of transdermal estradiol gel for treatment of symptomatic postmenopausal women: a randomized controlled trial. Obstet Gynecol. 2007;109:588-596.
30. Speroff L. Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms. Obstet Gynecol. 2003;102:823-834.
31. 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;8:83-92.
32. Barentsen R, van de Weijer PH, Schram JH. Continuous low dose estradiol released from a vaginal ring versus estriol vaginal cream for urogenital atrophy. Eur J Obstet Gynecol Reprod Biol. 1997;71:73-80.
33. Shulman LP, Portman DJ, Lee WC, et al. A retrospective managed care claims data analysis of medication adherence to vaginal estrogen therapy: implications for clinical practice. J Womens Health (Larchmt). 2008;17:569-578.
34. Rioux JE, Devlin C, Gelfand MM, et al. 17beta-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause. 2000;7:156-161.
35. Ponzone R, Biglia N, Jacomuzzi ME, et al. Vaginal oestrogen therapy after breast cancer: is it safe? Eur J Cancer. 2005;41:2673-2681.
36. 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;16:30-36.
37. Nilsson K, Heimer G. Low-dose oestradiol in the treatment of urogenital oestrogen deficiency-a pharmacokinetic and pharmacodynamic study. Maturitas. 1992;15:121-127.
All electronic documents accessed August 15, 2010.
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