An estimated 43% of postmenopausal women in the United States experience symptoms related to vaginal atrophy, including vaginal dryness, irritation, itching, burning and abnormal discharge.1,2 Other symptoms include dyspareunia and urinary problems such as increased frequency, nocturia, urgency, dysuria, hematuria or frequent urinary tract infections.3-5 Often, the underlying cause of these symptoms is a lack of estrogen. A decrease in ovarian estrogen production at menopause causes thinning of the vaginal epithelium, reduced vaginal blood flow and diminished vaginal secretions.6
Although vaginal symptoms often interfere with quality of life, many women do not feel comfortable expressing urogenital health concerns, making recognition and diagnosis a challenge in clinical settings.2
Presentation and Diagnosis
Vaginal atrophy typically presents with the following symptoms: vulvar tenderness, dryness, irritation or itching; discomfort during speculum examinations and during intercourse; brownish yellow or clear discharge; and burning with urination.4,5
Examination usually reveals pale, shiny, dry vulvar and vaginal mucosae that exhibit reduced elasticity and may appear inflamed.5 Clusters of petechiae or larger purpura may be present; in some cases, ecchymoses may also occur. The vagina may appear narrowed and shortened, while the rugal folds may be diminished or absent, resulting in a much smoother vaginal epithelium. The cervix may be flush with the vaginal wall.5 A loss of architecture may be observed; more specifically, the subcutaneous fat pad of the mons pubis and labia majora may be reduced, and the labia minora may have receded (Figure 1).4 These symptoms and characteristics may affect a woman's quality of life, regardless of her sexual activity.
Typically, vaginal atrophy is diagnosed on the basis of an examination and patient-reported symptoms. Confirmatory tests of pH and vaginal maturation index (VMI) may be performed. Vaginal pH may be measured prior to the speculum examination by holding a strip of pH paper against the lateral wall of the vagina.5
Figure 1. Vaginal atrophy. Typical physical aspects of vaginal atrophy include hypopigmentation, reduced labia minora, vaginal dryness and decreased elasticity and turgor of the vulvovaginal tissue. Photo courtesy Aron Schuftan, MD. Appears with permission.
Figure 2. Normal and atrophic vaginal smears. Photomicrographs of normal (top) and atrophic (bottom) vaginal smears. Superficial and intermediate cells predominate in a well-estrogenized vagina. (Papanicolaou stain; original magnification X 20). Reproduced from Vulvovaginal atrophy. Mayo Clinic Proceedings. 2010;85(1):87-94. Copyright Quadrant HealthCom, Inc. Appears with permission.
Before menopause, estrogen stimulates the vaginal epithelium to produce glycogen, which is broken down into glucose and metabolized into lactic acid by Lactobacillus to maintain a pH of 3.5 to 4.5.6 At menopause, lower estrogen levels lead to an increase in pH to 5.0 or higher, which predisposes women to vaginal or urinary tract infections.
The VMI describes the relative proportions of immature parabasal cells, intermediate cells and mature superficial cells in a smear taken from the posterior lateral walls of the vagina. Although the VMI is not typically evaluated in the office, it may be reported by the cytopathologist at the time of a routine Papanicolaou smear (Figure 2).
Premenopausal women typically have at least 15% superficial cells, while postmenopausal women with vaginal atrophy typically have less than 5% superficial cells, which is indicative of a low-estrogen state.5 The VMI assessment is more reliable for determining the extent of estrogen deprivation than patient-reported symptoms.7
No matter which diagnostic approach is used, a differential diagnosis must be considered because vaginal atrophy may be complicated by or confused with several other conditions, including infection, skin disease or contact dermatitis.
Treatment of Vaginal Atrophy
The North American Menopause Society (NAMS) states that first-line treatment for vaginal atrophy should include use of nonhormonal vaginal moisturizers and lubricants and continued sexual activity.6 With regular use, vaginal moisturizers can improve vaginal moisture, fluid volume, elasticity and pH.8 Lubricants are recommended for use during sexual activity. For patients whose symptoms do not respond to over-the-counter (OTC) products, NAMS has declared that low-dose, local vaginal estrogen delivery is effective and well tolerated.6
All forms of local vaginal estrogen (e.g., Premarin9, Estrace10, Estring11 and Vagifem12; Table 1) are considered equally effective at the recommended doses. Therefore, choice of therapy should reflect clinical experience and the practical concerns of the patient (e.g., ease of administration and frequency of dosage).6
Local vaginal estrogen therapies avoid systemic adverse effects such as bleeding, breast tenderness and endometrial stimulation; they also address estrogen deficiency in the vagina.13 Therefore, in the absence of other menopausal symptoms that must be addressed (e.g., hot flashes and night sweats), vaginal estrogen is the recommended treatment for vaginal atrophy.
Systemic estrogen prescribed for vasomotor symptoms is also effective for treating vaginal atrophy, but some women who take systemic estrogen may require additional local treatment. A higher-dose vaginal ring that treats vasomotor symptoms and vaginal atrophy (Femring)14 is also available.
Safety of Local Vaginal Estrogen
The safety of local vaginal estrogen preparations may be largely attributed to low systemic absorption. While premenopausal serum estradiol levels fluctuate between 30 pg/mL and 600 pg/mL during the menstrual cycle, postmenopausal levels are much lower (mean ± SD = 5.6 ± 3.8 pg/mL; n = 374 normal postmenopausal women).3,15 Studies show that low-dose local products keep systemic estradiol within the normal range of menopause.13,16,17
For example, the vaginal ring, which releases 7.5 mcg estradiol every 24 hours, results in a steady state estradiol level of only 6 pg/mL to 8 pg/mL, which is extremely low.16 Estradiol levels may transiently reach 63 pg/mL after insertion of the first ring, since a small initial burst release occurs prior to sustained release. Normal postmenopausal levels are restored within 48 hours.16 This burst effect decreases with the second ring.16
The lowest dose vaginal estrogen regimen available, the 10-mcg vaginal tablet, has a smaller burst effect and a mean peak plasma estradiol concentration of < 25 pg/mL approximately 7 hours after initial administration.17 By day 14 of treatment in a recent study (the last day of daily dosing before biweekly dosing), no peak was evident.17
Additionally, the average plasma estradiol concentration over 24 hours varied from 3.15 pg/mL at baseline to 9.39 pg/mL on day 1, 6.56 pg/mL on day 14, 1.87 pg/mL on day 82 (immediately before last biweekly dose), and 4.64 pg/mL on day 83 (immediately after last biweekly dose).17 These values indicate extremely low systemic exposure.
Depending on dosing, creams may result in somewhat higher serum estradiol levels than rings. After 1 week of daily administration of conjugated estrogen (CE) cream (1 g), serum estradiol levels averaged 17 pg/mL over a 24-hour period.18 The lowest recommended dosage regimen (0.5 g cream, biweekly) would be expected to produce lower average serum levels, but this has not been studied. After treatment with estradiol cream (2 g daily), mean serum estradiol levels were approximately 62 pg/mL after both 12 hours and 15 days.19 Lower dosages would be expected to result in lower average serum levels.
Recent clinical trials support endometrial safety of the 10-mcg vaginal tablet (0.52% incidence of endometrial hyperplasia or carcinoma in 386 evaluable biopsy samples, similar to background incidence20), the ring (endometrial thickening to > 7 mm in 2 of 126 women, neither of whom had evidence of proliferation upon biopsy21), and low doses of the CE cream (no incidence of endometrial hyperplasia or carcinoma in 155 evaluable biopsy samples22).
Total annual exposure with these therapies is low (1.14 mg estradiol from the tablet,12 2.74 mg estradiol from the ring,11 or a variable amount of CE from the CE cream, depending on the regimen9).
NAMS recommends that women with a history of hormone-dependent cancer be treated according to their preferences, in consultation with their oncologists. Women with a history of nonhormone-dependent cancer can be treated the same as women who have never been diagnosed with cancer.6
Breast cancer survivors are disproportionally affected by vaginal atrophy because surgical, endocrine and chemotherapeutic cancer treatments may precipitate or exacerbate vaginal atrophy.5,6,23 For some of these women, low-dose vaginal estrogen therapy may be more acceptable than living with severe symptoms.
Role of NPs & PAs
Nurse practitioners and physician assistants play an essential role in identifying patients with vaginal atrophy who might benefit from treatment. Patients typically do not report vaginal issues without prompting, usually because of embarrassment or the mistaken belief that safe and effective treatments aren't available.
In a recent international survey,2 43% of American women ages 55 to 65 said they had recently experienced "vaginal discomfort," defined as dryness, smarting pain, itching, involuntary urination, or pain in the vagina with touching or intercourse.
This discomfort had multiple negative effects on quality of life, including negative consequences on sex life (41%), self-esteem (17%), marriage/relationship (15%), and social life (5%).2
Of all women experiencing vaginal discomfort, only 34% had spoken to a gynecologist and only 22% to a general practitioner.2 Thirty-three percent had not discussed their vaginal discomfort with anyone, citing reasons such as embarrassment (60%) and their preference for a healthcare provider to initiate the conversation (20%).2
With these findings in mind, NPs and PAs should make broaching the subject a priority, even under tight time constraints. To help make women feel more comfortable about discussing vaginal health, NPs and PAs might first mention that many menopausal women experience vaginal dryness and then ask the patient whether she has experienced this. If so, an examination of the vulva should be performed and the course of treatment should be based on the results of this examination.
It is essential for the patient to understand that vaginal atrophy results from a lack of estrogen and that local vaginal estrogen therapy restores estrogen to the vagina. The vagina is a highly estrogen-dependent organ at every stage in life.
Furthermore, it is easier to rehabilitate a vagina in the earlier stages of atrophy than it is with severe atrophy. Many patients with moderate to severe vaginal atrophy have tried OTC moisturizers and/or lubricants on their own, without adequate relief, and require estrogen to improve bothersome symptoms.
It is important to clarify the difference between systemic estrogen therapy, which affects the whole body, and local vaginal estrogen therapy, which almost exclusively affects the vaginal tissue. Patients might be reassured to hear that the latter causes only a minimal increase in systemic estrogen level, which generally remains within the postmenopausal range.13
Because all available formulations (creams, ring and tablet) have been proven safe and effective, the patient should be presented with the advantages and limitations of each method of delivery (Table 2) and allowed to choose the one she finds most acceptable.
Because vaginal atrophy is a chronic condition, patients must continue treatment to prevent the return of symptoms, regardless of sexual activity.24
The duration of therapy depends on how long the patient wants to maintain optimal vaginal health. The two main reasons patients sometimes stop using prescribed therapy are cost and concern about using estrogen therapy.
To address the former issue, patients may be directed toward a less expensive regimen or given information about cost-assistance programs.
On the latter issue, it might be useful to mention that a year's supply of ultra-low-dose vaginal tablets has roughly as much estradiol as a single dose of systemic oral estradiol.
Then reiterate the benefits, safety and low systemic absorption of low-dose vaginal estrogen while supplying information about various OTC treatments (vaginal moisturizers, lubricants for intercourse, and external application of olive oil for mild irritation).
Encourage patients to return for routine follow-up because long-term management is usually necessary.
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1. Santoro N, Komi J. Prevalence and impact of vaginal symptoms among postmenopausal women. J Sex Med. 2009;6(8):2133-2142.
2. Nappi RE, Kokot-Kierepa M. Women's voices in the menopause: results from an international survey on vaginal atrophy. Maturitas. 2010;67(3):233-238.
3. Bachmann G, Santen RJ. Clinical manifestations and diagnosis of vaginal atrophy. http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-vaginal-atrophy
4. Stika CS. Atrophic vaginitis. Dermatol Ther. 2010;23(5):514-522.
5. Mac Bride MB, et al. Vulvovaginal atrophy. Mayo Clin Proc. 2010;85(1):87-94.
6. The 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):357-369.
7. Greendale GA, et al. Development and validation of a physical examination scale to assess vaginal atrophy and inflammation. Climacteric. 1999;2(3):197-204.
8. Nachtigall LE. Comparative study: Replens versus local estrogen in menopausal women. Fertil Steril. 1994;61(1):178-180.
9. Premarin (conjugated estrogens) vaginal cream pprescribing information. http://labeling.pfizer.com/showlabeling.aspx?id=131
10. Estrace (estradiol vaginal cream, USP, 0.01%) prescribing information. http://www.wcrx.com/pdfs/pi/pi_ppi_estrace_cream.pdf
11. Estring (estradiol vaginal ring) prescribing information. http://labeling.pfizer.com/showlabeling.aspx?id=131
12. Vagifem (estradiol vaginal tablets) [prescribing information]. Princeton, N.J.: Novo Nordisk Inc; Nov 25, 2009.
13. Suckling J, et al. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2006(4):CD001500.
14. Femring (estradiol acetate vaginal ring) [prescribing information]. Rockaway, NJ: Warner Chilcott (US), LLC; April 2010.
15. Lee JS, et al. Comparison of methods to measure low serum estradiol levels in postmenopausal women. J Clin Endocrinol Metab. 2006;91(10):3791-3797.
16. Bachmann G. The estradiol vaginal ring - a study of existing clinical data. Maturitas. 1995;22(suppl):S21-S29.
17. Eugster-Hausmann M, et al. Minimized estradiol absorption with ultra-low-dose 10 microg 17beta-estradiol vaginal tablets. Climacteric. 2010;13(3):219-227.
18. Labrie F, et al. Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women. Menopause. 2009;16(1):30-36.
19. Martin PL, et al. Systemic absorption and sustained effects of vaginal estrogen creams. JAMA. 1979;242(24):2699-2700.
20. Simon J, et al. Endometrial safety of ultra-low-dose estradiol vaginal tablets. Obstet Gynecol. 2010;116(4):876-883.
21. Weisberg E, et al. Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet. Climacteric. 2005;8(1):83-92.
22. Bachmann G, et al. Efficacy and safety of low-dose regimens of conjugated estrogens cream administered vaginally. Menopause. 2009;16(4):719-727.
23. Pruthi S, et al. Current overview of the management of urogenital atrophy in women with breast cancer. Breast J. 2011;17(4):403-408.
24. Palacios S. Managing urogenital atrophy. Maturitas. 2009;63(4):315-318.
Linda Burdette is a physician assistant at Premier Women's Health of Yakima in Yakima, Wash. Barbara Clark is a physician assistant at Knox OB/GYN Ltd. in Galesburg, Ill. They have completed disclosure statements and report no relationships related to this article. The authors received writing support from Pamela Barendt, PhD, of ETHOS Health Communications in Newtown, Pa., with financial assistance from Novo Nordisk, Inc., in compliance with international guidelines for Good Publication Practice. The authors received no remuneration for the development of this manuscript.