Recognizing and Treating Urogenital Atrophy in Postmenopausal Women

Abstract

Urogenital atrophy resulting from postmenopausal estrogen deficiency has numerous clinical effects, including vaginal dryness, sexual dysfunction, urinary incontinence, and recurrent urinary tract infections (UTIs), all of which can cause significant distress and reduction in quality of life. Although nearly one third to one half of postmenopausal women experience these symptoms, they are often overlooked because patients may be reluctant to discuss them and clinicians fail to screen for them. As these symptoms are unlikely to resolve without treatment, the prompt diagnosis and treatment of urogenital atrophy is essential. Estrogen therapy, administered either locally or systemically, provides significant relief from symptoms related to urogenital atrophy. However, systemic estrogen therapy is contraindicated in some women and may not be accepted in women without other menopausal symptoms. Local low-dose vaginal estrogen therapy, in the form of vaginal estrogen tablets, creams, or rings, has been shown to reduce dyspareunia and vaginal dryness, restore vaginal pH, and restore normal vaginal cytology. All forms of vaginal estrogen therapy are effective and well tolerated, although vaginal tablets and rings may have fewer adverse effects and have higher rates of adherence than creams.

Introduction

Postmenopausal estrogen deficiency has numerous physiological consequences, including hot flushes, bone loss, and an increased risk of cardiovascular disease (CVD), all of which deserve clinical attention. Other signs of estrogen deficiency, however, such as urogenital atrophy, sexual dysfunction, and lower urinary tract dysfunction, may be even more prevalent and are among the most underrecognized and undertreated features of menopause.¹ Whereas such menopausal symptoms as hot flushes resolve within 4–5 years in many women, urogenital symptoms, sexual dysfunction, and lower urinary tract dysfunction usually persist or may worsen in the absence of treatment. Because the average life expectancy has increased to nearly 80, women may be bothered by these often untreated urogenital symptoms for more than one third of their lives. Urogenital atrophy, sexual dysfunction, and urinary symptoms have been reported to cause significant emotional distress and reduced quality of life in women.^2
–4

Urogenital atrophy associated with estrogen decline can lead to vulvovaginal symptoms and sexual dysfunction. Common vulvovaginal symptoms, which can range in intensity from annoying to debilitating, include dyspareunia and vaginal discomfort, dryness, itching, and burning. Inadequate lubrication and consequent dyspareunia, vaginitis, and vaginismus also affect sexual desire,^5,6 responsiveness, and satisfaction.⁷ Thus, vulvovaginal symptoms can directly affect all the dimensions of women's sexual function, such as diminished desire, arousal, and orgasm and increased sexual pain. As a result, vaginal atrophy can be a significant problem in sexually active women who may find sexual activity uncomfortable because of their symptoms.³

Urogenital atrophy associated with estrogen decline can also lead to lower urinary tract dysfunction and urinary symptoms, such as increased frequency, urgency, dysuria, and recurrent urinary tract infections (UTIs).^1,8 These symptoms can be troubling and can prompt women to make lifestyle changes, such as restricting activity outside the home, using sanitary protection, and altering fluid intake. Urinary symptoms also worsen sexual function either by such factors as embarrassment or from frank distracting pain.⁹

Urogenital atrophy is often progressive and may cause years of discomfort and urinary and sexual health problems. For many reasons, symptoms associated with urogenital atrophy are often overlooked. Many physicians are uncomfortable or too busy to inquire if their postmenopausal patients are having sexual health, vulvovaginal, or urinary concerns. Many postmenopausal women are also uncomfortable broaching the subject of urogenital health to their healthcare provider. Some women may be unwilling to report their symptoms because of embarrassment or their cultural or religious beliefs; they may also perceive the presence of vaginal atrophy and its symptoms as a link to the aging process and to a loss of attractiveness. A greater focus on understanding urogenital atrophy, eliminating associated embarrassment, and empowering the woman who is bothered or distressed to seek information about treatment is needed.

Prevalence of Urogenital Atrophy, Sexual Dysfunction, and Lower Urinary Tract Dysfunction

A recent survey reported that 57% of sexually active women 40–65 years old experienced vulvovaginal atrophy and 55% experienced sexual dysfunction.¹⁰ This survey reported that women with sexual dysfunction were nearly four times more likely to have vulvovaginal atrophy than women without sexual dysfunction. Other observational studies have reported that 27%–55% of postmenopausal women experience vaginal dryness,^11
–13 32%–41% experience dyspareunia,^11,12,14,15 and 39% report difficulty with vaginal lubrication.¹⁶ For example, in the Women's Health Initiative (WHI) observational study and clinical trials,¹⁷ 27% reported vaginal dryness and 19% reported irritation or itching. According to one study, 32% of women with vaginal dryness had lost interest in sex.^6,11

Urinary symptoms related to urogenital atrophy are also relatively common in postmenopausal women. Bacteriuria has been found in 20% of noninstitutionalized elderly women,¹⁸ recurrent UTI has been noted in 12%–17% of menopausal women,^18,19 and urinary incontinence has been shown to affect 15%–35% of women older than 60 years²⁰ living in the community.²¹ Despite the prevalence and impact of these symptoms, urogenital atrophy is vastly underreported and undertreated. It is estimated that only approximately 20%–25% of postmenopausal women with symptoms of urogenital atrophy will ever seek medical help.^22,23

Causes of Urogenital Atrophy

Role of estrogen deficiency

Urogenital tissues depend on estrogen stimulation to maintain normal structure and function.³ Estrogen receptors in the genitourinary system are found not only in the vagina and vulva but also in the urethra and neck of the bladder.^24,25 A recent study in which investigators performed RNA profiling on vaginal biopsies of postmenopausal women with vaginal atrophy after treatment with estrogen found that more than 3000 genes are regulated by estrogen, including those involved in regulating cell growth and proliferation and defense against pathogens.²⁶

Estrogen causes a thickening of the vaginal epithelium, creating a redundant tissue layer that invaginates into vaginal rugae. The redundancy allows the vaginal surface area to expand greatly and increase in length during sexual arousal. In addition, the thickened estrogen-stimulated vaginal epithelium acts as a physical barrier along with cervical mucus, secretions, and local bacterial flora. The stratified squamous epithelium of the vaginal wall sheds constantly, making it difficult for organisms to invade or access the basement membrane/capillary bed. Further, estrogen stimulates the glycogen content of the epithelial cells. Vaginal epithelial glycogen is metabolized by vaginal organisms to lactic acid by the lactobacilli that proliferate near the epithelium, which acts to maintain the vaginal pH around 3.8–4.2.

Urogenital atrophy induced by estrogen decline is usually progressive in nature and can start as early as the perimenopausal years. The incidence of symptoms related to vaginal atrophy is associated with serum estrogen levels, with higher rates of vaginal dryness and dyspareunia among postmenopausal women with lower serum estradiol levels (<50 pg/mL) compared with those with higher levels (>50 pg/mL).²⁷

Declining estrogen levels cause numerous cytological changes in the vagina and structural changes in the vulva, vagina, and lower urinary tract.²² Vaginal cytological changes include an increase in the proportion of parabasal cells and a substantial decrease in the proportion of intermediate and superficial cells, which predominate in premenopausal women.^22,28 In the vulva, losses in collagen, adipose tissue, and the ability to retain water are common with estrogen deficiency, resulting in thinning of its epithelial surface.²⁹ The clitoral glans also loses its protective covering and can be irritated from contact more easily. The vagina shortens and narrows, and its walls become thinner, less elastic, more smooth, and increasingly pale in color.²² Estrogen deficiency may also decrease vaginal function and interfere with physiological responses associated with sexual arousal, including smooth muscle relaxation, vasocongestion, and vaginal lubrication.³ For example, vaginal blood flow and vaginal secretions decrease, and lubrication after sexual stimulation is decreased and delayed.²² Reduced vestibular sensation and diminished perception of vibratory, hot, and cold stimuli also may occur.³

Estrogen decline causes the vaginal epithelium to thin considerably. Vaginal rugae are lost, and the depth of the vagina shortens. Vessels and lymphatic structures perfusing and draining the vagina undergo attrition. As a result, women experience vaginal dryness during sexual arousal and dyspareunia. The vaginal atrophy, dryness, and dyspareunia that result from estrogen deficiency often prompt women to avoid sexual intercourse because of a fear of painful sex.³ A low frequency of sexual intercourse can cause further atrophy, exacerbating dyspareunia and contributing to a cycle of avoidance, diminished desire, and painful intercourse.³⁰

Another consequence of estrogen decline is alterations in vaginal pH. The presence of estrogen maintains an acidic vaginal pH that discourages the growth of pathogenic bacteria.³ As estrogen levels decline, the conversion of glycogen to glucose is reduced, which decreases the amount of glucose available to nonpathogenic vaginal bacteria for lactic acid production. These changes cause a rise in vaginal pH, leading to a shift in the vaginal pH and increasing the likelihood of vaginal discharge and odor.³ An increase in vaginal pH allows colonization of the vagina by fecal flora and other pathogens, increasing the risk of UTIs.²² Together, these changes increase the risk of urogenital trauma, infection, and pain.

Because estrogen loss is associated with a loss of collagen content and atrophic changes in the tissues of the pelvic floor, estrogen deficiency also may play a role in the development or acceleration of the signs and symptoms of pelvic organ prolapse,³¹ especially in women who sustained damage to their pelvic floor during childbirth.

Other factors that contribute to urogenital atrophy

Because of its association with estrogen loss, vaginal atrophy can also occur in women who take antiestrogenic medications or who have medical or surgical conditions that cause low estrogen levels. Cancer treatments, such as surgery, pelvic radiation, chemotherapy, selective estrogen receptor modulators (SERMs), and aromatase inhibitors, can cause symptomatic vaginal atrophy.²² In addition, the use of agents that dry mucous membranes in patients with vaginal atrophy may significantly worsen dyspareunia as a result of the impact of these agents on lubrication.³² Cigarette smoking also may increase vaginal atrophy because it reduces estrogen bioavailability and diminishes blood perfusion.^33,34

Paradigm for Managing Urogenital Atrophy

Step 1: Identifying urogenital health problems

Clinicians have an opportunity to improve the urogenital health and quality of life of a large number of postmenopausal women by identifying and treating urogenital atrophy, an often overlooked condition. Still, identifying women with bothersome urogenital atrophy can be challenging because women may be unwilling to report symptoms even if their quality of life is affected. A recent survey of women aged 57–85 found that only approximately 1 in 5 women reported having discussed sex with a physician since the age of 50 years.¹⁶ Consequently, healthcare providers should routinely assess postmenopausal women for the signs and symptoms of urogenital atrophy.¹⁵ The first step in managing women with these complaints is to identify relevant symptoms and determine their severity. The following case study illustrates the symptoms and symptomatic management of a postmenopausal woman with urogenital atrophy.

Case study

Patient DB is a 58-year-old woman who has been postmenopausal for 7 years. She is a married mother of 3 adult children and works as an account executive in an advertising agency. She comes to her gynecologist for a routine physical examination. During the examination, the gynecologist inquires: “Many women in menopause have concerns related to sexual health. Do you have any?” DB claims that until relatively recently, her sex life was excellent, but in the past 3–4 years, it has progressively deteriorated.

Initial workup

A complete history and physical examination form the foundation of any evaluation of urogenital problems. To ensure all potential factors related to the symptoms can be characterized, the history should include three components: a medical history, a sexual history, and a psychosocial history if sexual problems are present.³

Healthcare providers should evaluate the patient's current sexual health in terms of interest, arousal, and orgasm in comparison to her time of peak sexual function. In the medical history, symptoms of vaginal dryness, vaginal bleeding with contact, pain, soreness after sexual activity, and the presence of other menopausal symptoms (e.g., hot flushes) should be assessed. An attempt to localize pain on schematic diagrams of female genitalia may be helpful. Medication and drug use should also be part of the evaluation. Psychosocial factors that may affect sexual function, such as emotional concerns, sexual beliefs, interpersonal relationship matters, and psychiatric disorders, should be identified. Patients with psychiatric disorders and those who may benefit from additional care should be referred to an appropriate healthcare professional.

Case study (continued)

DB reports avoiding sex because she often experiences pain during intercourse, a symptom that first occurred about 3 years ago and has been occurring with increasing frequency. She complains of vaginal dryness, difficulty lubricating, and pain during sex, even with the use of a lubricant and a moisturizer. When she does engage in sexual activity, arousal is delayed and orgasm is less intense. She now tends to avoid intercourse because of discomfort. She thinks her avoidance of sex disappoints her husband, but she describes no other difficulties in their marriage. Although she feels that these symptoms are an unavoidable response to aging, her husband has suggested that she talk to you about possible treatments. She is upset by the changes in her sex life but reports no symptoms or history indicative of a psychiatric disorder. She takes no medications.

Physical examination

The cornerstone of evaluating menopausal women with sexual health complaints is the pelvic examination. The pelvic examination of menopausal patients should include an assessment of vaginal atrophy even if the patient has not complained of atrophic symptoms. Although most vulvovaginal complaints in menopausal women result from atrophy, a complete evaluation should be performed to rule out other causes. Because lichen sclerosus, lichen planus, and recurrent vulvovaginal candidiasis also can cause dyspareunia and labial fusion, these conditions should be considered in the differential diagnosis of women experiencing these disorders.

Laboratory markers of vaginal atrophy include an elevated vaginal pH and a greater proportion of basal cells in the vaginal maturation index.¹⁵ Vaginal and urethral pH can be used as a marker of estrogenization of the vaginal vault.³⁵ There is no current consensus on what laboratory testing should be considered for perimenopausal and postmenopausal women with sexual health concerns.³ Obtaining serum follicle-stimulating hormone (FSH) and estradiol levels may be helpful in confirming the diagnosis of postmenopausal vaginal atrophy.

Case study (continued)

Upon examination of DB, it was noted that the labia minora had completely fused with the labia majora, which, along with the introital opening, had decreased in size (Fig. 1).³⁶ There were multiple areas of erythema overlying the ostia of the minor vestibular glands. The vagina was dry and pale with a complete lack of rugae. The vaginal pH was 6.1.

FIG. 1.

Vaginal atrophy. The labia minora revealed complete fusion to the labia majora bilaterally (labial agglutination), and the vagina was dry, with lack of rugae noted. These physical examination findings are consistent with atrophic vaginitis.

Step 2: Patient education

During this step of the clinical assessment, results of the history, physical examination, and laboratory testing should be reviewed. Patient education should focus on the basic facts about women's sexual health, including genital anatomy and the relationship between genital structural health and changes in hormones associated with menopause.⁸ Treatment options, the role of additional diagnostic testing, and a referral, when necessary, should be considered and discussed.

Case study (continued)

DB's gynecologist reviews the results of her physical examination, explaining that vaginal atrophy is likely the cause of her symptoms. The gynecologist then discusses the decline of estrogen after menopause and the role of estrogen loss in the development of vaginal symptoms. Because estrogen deficiency is the primary cause of vaginal atrophy, DB's gynecologist discusses treatments addressing estrogen deficiency that will likely improve her symptoms.

Step 3: Treatment

Treating vulvovaginal complaints should be individualized and depends on the patient's pattern and severity of symptoms, medical history, lifestyle, and preferences.

Lifestyle modifications and nonhormonal treatments

Lifestyle modifications that may ameliorate the symptoms of urogenital atrophy include smoking cessation, regular coital activity, masturbation, and in patients with recurrent UTIs, consumption of cranberry juice.^15,37

Vaginal moisturizers, such as Replens (LDS Consumer Products, Cedar Rapids, IA) have been shown to produce positive changes in the vaginal epithelium and increases in vaginal moisture and fluid.³⁸ Data indicate that Replens improved symptoms of vaginal itching, irritation, and dyspareunia.³⁹ Vaginal lubricants also decrease immediate irritation during sexual activity, but evidence about their long-term therapeutic effects is limited.¹⁵ In contrast, studies of dietary estrogen (e.g., phytoestrogens) or dietary supplements have failed to show any beneficial effect on vaginal atrophy.^40,41 For example, in a recent 1-year randomized, double-blind, placebo-controlled study of 351 women aged 45–55, black cohosh, used alone or with soy dietary changes, did not affect the vaginal epithelium.⁴²

Hormone therapy

Endogenous estrogen has established efficacy in improving the symptoms of vaginal atrophy.¹ Moreover, estrogen restores vaginal pH, thickens the vaginal epithelium, alleviates existing vulvovaginal symptoms, and may prevent the development of symptoms if initiated at menopause.^{24,25,27,35,43
–45} Estrogens can be administered systemically or locally, but the dosage and method of delivery must be individualized.

Systemic estrogen therapy

Systemic oral, vaginal, or transdermal hormone therapy is indicated for women who seek relief from multiple menopausal symptoms (e.g., hot flushes), protection from osteoporosis, and treatment for vulvovaginal symptoms.²² However, systemic therapy requires the concomitant use of a progestin in women with a uterus and is associated with adverse effects, such as endometrial bleeding, breast tenderness, and an increase in the risk of stroke, venous thromboembolism, and breast cancer (when used in combination with a progestin).^46,47 The risk of these effects with systemic estrogen plus progestin therapy may vary with different doses, regimens, and routes of administration. Because of the potential for adverse effects with estrogen plus progestin therapy, systemic hormone use may be contraindicated or unacceptable to some women.²²

Low-dose vaginal estrogen therapy

When estrogen therapy is considered solely for treating vulvovaginal symptoms of urogenital atrophy, low-dose vaginal estrogen therapy is usually recommended, according to the North American Menopause Society (NAMS).²² Low-dose vaginal estrogen therapy also may be useful for women who experience inadequate urogenital symptom relief on low-dose systemic estrogen therapy. Vaginally administered estrogen therapy can provide sufficient estrogen to reverse atrophic changes, with limited systemic absorption.²² According to NAMS, low-dose vaginal estrogen is effective and well tolerated for treating vaginal atrophy and has been shown to reduce vaginal symptoms, including dyspareunia and vaginal dryness; restore vaginal pH and normal vaginal cytology; and prevent frequent UTIs.²² Estrogen therapy, however, is not indicated for the prevention or treatment of urinary symptoms.

Advantages of vaginal estrogen administration include its direct effect on the vagina, its limited systemic exposure, and its reduced risk of adverse effects (e.g., endometrial stimulation, bleeding, breast tenderness, and increased risk of breast cancer) compared with systemic estrogen.⁴⁸ Unlike systemic estrogen therapy, however, vaginal estrogen is not indicated for treating vasomotor symptoms or maintaining bone density.

It should be noted that such drugs as vaginal estradiol are, in fact, rapidly absorbed through the vaginal epithelium, especially if the vaginal epithelium is thin. There is no stratum corneum and no adipose tissue or other cell layers with metabolic enzymes for pharmacological agents to traverse as with the transdermal or oral routes. As vaginal absorption is the rule, the key to safety with vaginal estradiol is to understand that lower dosing of estradiol leads to lower systemic exposure and a lower incidence of side effects. Low-dose vaginal estradiol therapy allows for selective regional therapeutic exposure (the vagina) for the treatment of vaginal atrophic complaints.

Local estrogen formulations include vaginal estradiol tablets, estrogen creams, and estrogen rings (Table 1 ²²). A Cochrane Review concluded that the conjugated estrogen (CE) vaginal cream, estradiol hemihydrate vaginal tablet, and estradiol vaginal ring were equally effective for the relief of symptoms of vaginal atrophy.⁴⁹ Clinical guidelines recommend that vaginal estrogen be titrated to the lowest dose and frequency required for providing the desired effect.²²

Table 1.

Vaginal Estrogen Therapy Approved for Use in the United States

Formulation	Product name	Dosing
Vaginal cream
Estradiol	Estrace,^® Warner Chilcott, Rockaway, NJ	Initial: 2.0–4.0 g/day for 1–2 weeksMaintenance: 1.0 g/day
Conjugated estrogens	Premarin,^® Wyeth Pharmaceuticals, NY, NY	0.5 to 2.0 g/day
Vaginal ring
Estradiol	Estring,^® Pfizer Pharmaceuticals, NY, NY	Device containing 2 mg releases 7.5 μg/day for 90 days
Estradiol acetate	Femring,^® Warner Chilcott Rockaway, NJ	Systemic-dose device containing 12.4 or 24.8 mg releases 0.05 or 0.10 mg/day estradiol for 90 days
Vaginal tablet
Estradiol hemihydrate	Vagifem,^® Novo Nordisk Pharmaceuticals, Princeton, NJ	Initial: 1 tablet/day for 2 weeksMaintenance: 1 tablet twice weekly (tablet containing 25.8 μg estradiol hemihydrate equivalent to 25 μg/day estradiol)

Adapted from the North American Menopause Society.²⁰

Regarding estrogen creams, clinical trials have reported that CE vaginal cream in doses of 0.5–2.0 g (delivering 0.3–1.25 mg CE) is effective in relieving vaginal symptoms.^39,50

–53 Treatment with vaginal estradiol cream has also been shown to be effective.⁵⁴ Vaginal creams containing estriol, which are available in some European countries, are also associated with moderate improvement in symptoms of vaginal atrophy.⁵⁵ It is recommended that the cream be titrated to the lowest effective dose; however, the dose can be variable because the cream is not distributed in prepackaged dosing units.²² Vaginal creams have been reported to cause higher absorption than rings or tablets.^49,56

Among estrogen rings, a sustained-release estradiol ring, which releases 7.5 μg estradiol every 24 hours for 90 days, has been shown to be more effective than placebo and as effective as vaginal cream and vaginal tablets in relieving the symptoms of vaginal atrophy and restoring vaginal pH and cytology.^{52,53,57
–59} Although patient acceptability with the ring is greater than with vaginal cream, insertion can be difficult for women with limited vaginal capacity or manual dexterity. Dislodgment also can occur in women with pelvic organ prolapse. In addition, sexual partners may be aware of the ring during sexual intercourse.¹⁵

Regarding vaginal estradiol tablets, estrogen doses as low as 10 μg estradiol administered by vaginal tablet and applicator are effective in relieving vaginal symptoms, improving vaginal atrophy, decreasing vaginal pH, and increasing maturation of the vaginal and urethral epithelium.^60
–62 Using vaginal tablets allows administration of a consistent dose of estrogen, reduces the potential for leakage, and is associated with greater adherence compared with vaginal creams.^51,63,64 A recent retrospective study demonstrated that women using vaginal tablets were more likely to continue treatment with vaginal therapy for longer periods of time than women using vaginal creams.⁶⁴

Adverse effects of low-dose vaginal estrogen formulations. Adverse events with low-dose vaginal estrogen formulations are infrequent and are less common than those seen with systemic estrogen formulations. In trials of low-dose vaginal estrogen therapy, vaginal bleeding and breast pain are the most commonly reported adverse events, suggesting that systemic absorption of vaginal estrogen can occur.²² It should be noted that there is significantly lower absorption of estradiol in women of fertile age and in women who have had the vaginal epithelium thickened by previous intravaginal estradiol therapy. The degree of maturation of the vaginal epithelium is responsible, in part, for the degree of estradiol absorption from the vagina, although a mature vaginal epithelium does not prevent the absorption of estradiol.

Generally, creams are thought to have more adverse effects than the estrogen ring or tablets, possibly because it is easier for patients to apply higher-than-recommended doses.²² However, the Cochrane Review found no significant differences in the incidence of adverse events among vaginal estrogen delivered by cream, ring, or tablet.⁴⁹

The ability of vaginal estrogen formulations to stimulate the endometrium is a common concern with their use. Studies of unopposed systemic estrogen have demonstrated that the risk of endometrial stimulation with estrogen depends on the dose and duration of therapy. Evidence suggests that fewer patients using vaginal tablets experienced endometrial proliferation or hyperplasia compared with patients using vaginal cream.⁵¹ Although endometrial hyperplasia has been observed with low-dose vaginal estrogen, it is rare, and progestogen is generally not indicated in women using low-dose vaginal estrogen therapy.²²

Low-dose vaginal estrogen therapy may be an appropriate treatment for vaginal atrophy in patients with a history of nonhormone-dependent cancers; for women with hormone-dependent cancers, however, moisturizers and vaginal lubricants are first-line treatment.²² In these women, it is important to consider the physical and psychosocial impact of vaginal atrophy as well as its potential impact on the cancer or its risk of recurrence.²² Some patients who do not respond to first-line treatment might want to discuss the benefits and risks of low-dose vaginal estrogen therapy.

Local dehydroepiandrosterone (DHEA) therapy

A recent randomized, placebo-controlled, double-blind study evaluated the impact of a daily intravaginal application of 1 ovule DHEA (at three different concentrations), a precursor to androgens and estrogens, on vaginal maturation and vaginal pH.⁶⁵ In this study, 7 days of treatment significantly increased vaginal maturation and significantly decreased vaginal pH. However, serum concentrations of estradiol and testosterone remained within the values found in normal postmenopausal women at all doses. Additional research is needed to assess the effects of intravaginal DHEA on symptoms associated with vaginal atrophy.

Case study (continued)

DB chooses to begin estrogen therapy because she has been unsatisfied with vaginal moisturizer and lubricants in the past. As she no longer experiences vasomotor symptoms and she is not at significant risk for osteoporosis, she decides to try low-dose vaginal estrogen therapy.

Step 4: Patient monitoring and follow-up

Approximately 80%–90% of women who use low-dose vaginal estrogen therapy report subjective improvement.^22,66 Although improvement in vaginal symptoms typically occurs within a few weeks of beginning therapy, some patients may require 4–6 weeks to experience adequate relief.²² In women who do not respond to estrogen therapy, additional evaluation and examination are warranted. NAMS recommends that low-dose vaginal estrogen therapy be used as long as discomfort from symptoms continues.²² Because there are few long-term safety data on low-dose vaginal estrogen therapy, no limits for the duration of therapy have been established.

Currently, data are too limited to recommend annual endometrial monitoring in women without endometrial symptoms who are using low-dose vaginal estrogen therapy.²² However, closer endometrial surveillance is required in women who are at high risk of endometrial cancer, who are using a higher dose of vaginal estrogen therapy, or who are experiencing spotting or breakthrough bleeding.

Case study (continued)

Six weeks later, DB reports significant improvement in urogenital atrophy, indicating that she has fewer problems lubricating and that she no longer has pain during sex. On physical examination, her vulva and vagina appear less tender, less pale, and less dry and without erythema. Vaginal pH is 4.5.

Discussion

Postmenopausal urogenital atrophy causes a wide array of symptoms, ranging from vaginal dryness and dyspareunia to recurrent UTIs and urinary incontinence. Although these symptoms are highly prevalent and have a significant impact on quality of life, they are often ignored by women or overlooked by healthcare providers. In the absence of treatment, these symptoms generally persist and may increase in severity. Increasing life expectancies mean that women may have symptoms of urogenital atrophy for more than one third of their life, reinforcing the considerable need for identifying and appropriately managing these symptoms. The first step in diagnosing and managing vaginal atrophy is increased clinical suspicion, which should prompt the initiation of efficacious and safe therapies.

Estrogen therapy, administered either locally or systemically, provides significant relief from symptoms related to vaginal atrophy. Although systemic estrogen therapy offers protection from postmenopausal osteoporosis and hot flushes as well as urogenital atrophy, it is contraindicated in some women and may not be accepted in other women who seek relief from vulvovaginal symptoms. Therefore, low-dose vaginal estrogen therapy, in the form of vaginal estrogen tablets, creams, or rings, may be more appropriate for some women or preferred by others. Low-dose vaginal estrogen therapy has been shown to reduce dyspareunia, improve vaginal dryness, and restore vaginal pH and normal vaginal cytology. All forms of vaginal estrogen therapy are effective and well tolerated, although vaginal tablets and rings may have fewer adverse effects than estrogen creams. In addition, data suggest that patient adherence to the use of vaginal tablets may be higher than of creams. The availability of numerous effective options for treating urogenital atrophy enables clinicians to individualize therapy and, thus, minimize or eliminate its symptoms in most women.

Footnotes

Acknowledgments

I thank Nicole Cooper (DesignWrite, LLC) for writing and editorial assistance, which was supported by funding from Novo Nordisk.

Disclosure Statement

I.G. has served in the following capacities: Alagin Research, LLC, consultant; Auxilium, honoraria; Bayer Schering AG, honoraria; BioSante, honoraria; Boehringer-Ingelheim, consultant; Coloplast, honoraria; Eli Lilly, honoraria; Johnson & Johnson Pharmaceuticals, consultant; Medtronic, consultant; Pfizer Pharmaceuticals Inc., consultant, honoraria; Plethora Solutions, consultant; Slate, consultant; Timm Medical Technologies, honoraria; Vivus, consultant, honoraria; and Wyeth Pharmaceuticals, consultant.

References

American College of Obstetricians and Gynecologists Women's Healthcare Physicians. Genitourinary tract changes. Obstet Gynecol, 2004; 104:56S–61S.

Santoro

, Komi

. Prevalence and impact of vaginal symptoms among postmenopausal women. J Sex Med, 2009Epub ahead of print.

Goldstein

, Alexander

. 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.

Calleja-Agius

, Brincat

. Urogenital atrophy. Climacteric, 2009; 12:279–285.

Avis

, Stellato

, Crawford

, Johannes

, Longcope

. Is there an association between menopause status and sexual functioning? Menopause, 2000; 7:297–309.

Graziottin

. Prevalence and evaluation of sexual health problems—HSDD in Europe. J Sex Med, 2007; 4,Suppl 3:211–219.

Semmens

, Wagner

. Estrogen deprivation and vaginal function in postmenopausal women. JAMA, 1982; 248:445–448.

Schwenkhagen

. Hormonal changes in menopause and implications on sexual health. J Sex Med, 2007; 4,Suppl 3:220–226.

Cohen

, Barboglio

, Gousse

. The impact of lower urinary tract symptoms and urinary incontinence on female sexual dysfunction using a validated instrument. J Sex Med, 2008; 5:1418–1423.

10.

Levine

, Williams

, Hartmann

. Vulvovaginal atrophy is strongly associated with female sexual dysfunction among sexually active postmenopausal women. Menopause, 2008; 15:661–666.

11.

Stenberg

, Heimer

, Ulmsten

, Cnattingius

. Prevalence of genitourinary and other climacteric symptoms in 61-year-old women. Maturitas, 1996; 24:31–36.

12.

Utian

, Schiff

. NAMS-Gallup survey on women's knowledge, information sources, and attitudes to menopause and hormone replacement therapy. Menopause, 1994; 1:39–48.

13.

van Geelen

, van de Weijer

, Arnolds

. Urogenital symptoms and resulting discomfort in non-institutionalized Dutch women aged 50–75 years. Int Urogynecol J Pelvic Floor Dysfunct, 2000; 11:9–14.

14.

Clayton

. Epidemiology and neurobiology of female sexual dysfunction. J Sex Med, 2007; 4,Suppl 4:260–268.

15.

Johnston

, Farrell

, Bouchard

et al. The detection and management of vaginal atrophy. J Obstet Gynaecol Can, 2004; 26:503–515.

16.

Lindau

, Schumm

, Laumann

, Levinson

, O'Muircheartaigh

, Waite

. A study of sexuality and health among older adults in the United States. N Engl J Med, 2007; 357:762–774.

17.

Pastore

, Carter

, Hulka

, Wells

. Self-reported urogenital symptoms in postmenopausal women: Women's Health Initiative. Maturitas, 2004; 49:292–303.

18.

Molander

, Milsom

, Ekelund

, Mellstrom

. An epidemiological study of urinary incontinence and related urogenital symptoms in elderly women. Maturitas, 1990; 12:51–60.

19.

Iosif

, Bekassy

. Prevalence of genito-urinary symptoms in the late menopause. Acta Obstet Gynecol Scand, 1984; 63:257–260.

20.

Pace

, Vicentini

. Female sexual function evaluation of the tension-free vaginal tape (TVT) and transobturator suburethral tape (TOT) incontinence surgery: Results of a prospective study. J Sex Med, 2008; 5:387–393.

21.

Robinson

, Cardozo

. The pathophysiology and management of postmenopausal urogenital oestrogen deficiency. J Br Menopause Soc, 2001; 7:67–73.

22.

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; 14:355–369.

23.

Pandit

, Ouslander

. Postmenopausal vaginal atrophy and atrophic vaginitis. Am J Med Sci, 1997; 314:228–231.

24.

Freedman

. Sexuality in post-menopausal women. Menopausal Med, 2000; 8:1–5.

25.

McCoy

. Female sexuality during aging. Hof

, Mobbs

. Functional neurobiology of aging. New York: Academic Press, 2001; 769–779.

26.

Cotreau

, Chennathukuzhi

, Harris

et al. A study of 17beta-estradiol-regulated genes in the vagina of postmenopausal women with vaginal atrophy. Maturitas, 2007; 58:366–376.

27.

Sarrel

. Effects of hormone replacement therapy on sexual psychophysiology and behavior in postmenopause. J Womens Health Gend Based Med, 2000; 9:S25–S32.

28.

Bachmann

, Ebert

, Burd

. Vulvovaginal complaints. Lobo

. Treatment of the postmenopausal woman: Basic and clinical aspects. Philadelphia, PA: Lippincott Williams & Wilkins, 1999; 195–201.

29.

Ballagh

. Vaginal hormone therapy for urogenital and menopausal symptoms. Semin Reprod Med, 2005; 23:126–140.

30.

Wylie

, Daines

, Jannini

et al. Loss of sexual desire in the postmenopausal woman. J Sex Med, 2007; 4:395–405.

31.

Quinn

, Domoney

. The effects of hormones on urinary incontinence in postmenopausal women. Climacteric, 2009; 12:106–113.

32.

Nappi

, Salonia

, Traish

et al. Clinical biologic pathophysiologies of women's sexual dysfunction. J Sex Med, 2005; 2:4–25.

33.

Castelo-Branco

, Cancelo

, Villero

, Nohales

, Julia

. Management of post-menopausal vaginal atrophy and atrophic vaginitis. Maturitas, 2005; 52,Suppl 1:S46–S52.

34.

Baron

, La

, Levi

. The antiestrogenic effect of cigarette smoking in women. Am J Obstet Gynecol, 1990; 162:502–514.

35.

Bachmann

, Leiblum

. The impact of hormones on menopausal sexuality: A literature review. Menopause, 2004; 11:120–130.

36.

Goldstein

. Current management strategies of the postmenopausal patient with sexual health problems. J Sex Med, 2007; 4,Suppl 3:235–253.

37.

Jepson

, Craig

. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev, 2008; CD001321.

38.

Bygdeman

, Swahn

. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas, 1996; 23:259–263.

39.

Nachtigall

. Comparative study: Replens versus local estrogen in menopausal women. Fertil Steril, 1994; 61:178–180.

40.

Bouchard

. Herbal alternatives as substitutes for hormone therapy in urogenital atrophy: Scientific evidence is needed. Menopause, 2008; 15:12–13.

41.

Manonai

, Songchitsomboon

, Chanda

, Hong

, Komindr

. The effect of a soy-rich diet on urogenital atrophy: A randomized, cross-over trial. Maturitas, 2006; 54:135–140.

42.

Reed

, Newton

, LaCroix

, Grothaus

, Grieco

, Ehrlich

. Vaginal, endometrial, and reproductive hormone findings: Randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: The Herbal Alternatives for Menopause (HALT) Study. Menopause, 2008; 15:51–58.

43.

Berman

, Goldstein

. Female sexual dysfunction. Urol Clin North Am, 2001; 28:405–416.

44.

Dennerstein

, Dudley

, Hopper

, Burger

. Sexuality, hormones and the menopausal transition. Maturitas, 1997; 26:83–93.

45.

Semmens

, Tsai

, Semmens

, Loadholt

. Effects of estrogen therapy on vaginal physiology during menopause. Obstet Gynecol, 1985; 66:15–18.

46.

Anderson

, Limacher

, Assaf

et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA, 2004; 291:1701–1712.

47.

Writing Group for the Women's Health Initiative Randomized Control Trial. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. JAMA, 2002; 288:321–333.

48.

Cicinelli

. Intravaginal oestrogen and progestin administration: Advantages and disadvantages. Best Pract Res Clin Obstet Gynaecol, 2008; 22:391–405.

49.

Suckling

, Lethaby

, Kennedy

. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev, 2003; CD001500.

50.

Nachtigall

. Clinical trial of the estradiol vaginal ring in the U.S. Maturitas, 1995; 22,Suppl:S43–S47.

51.

Rioux

, Devlin

, Gelfand

, Steinberg

, Hepburn

. 17β-Estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis. Menopause, 2000; 7:156–161.

52.

Ayton

, Darling

, Murkies

et al. A comparative study of safety and efficacy of continuous low dose oestradiol released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy. Br J Obstet Gynaecol, 1996; 103:351–358.

53.

Manonai

, Theppisai

, Suthutvoravut

, Udomsubpayakul

, Chittacharoen

. The effect of estradiol vaginal tablet and conjugated estrogen cream on urogenital symptoms in postmenopausal women: A comparative study. J Obstet Gynaecol Res, 2001; 27:255–260.

54.

Santen

, Pinkerton

, Conaway

et al. Treatment of urogenital atrophy with low-dose estradiol: Preliminary results. Menopause, 2002; 9:179–187.

55.

Foidart

, Vervliet

, Buytaert

. Efficacy of sustained-release vaginal oestriol in alleviating urogenital and systemic climacteric complaints. Maturitas, 1991; 13:99–107.

56.

Crandall

. Vaginal estrogen preparations: A review of safety and efficacy for vaginal atrophy. J Womens Health, 2002; 11:857–877.

57.

Casper

, Petri

. Local treatment of urogenital atrophy with an estradiol-releasing vaginal ring: A comparative and a placebo-controlled multicenter study. Vaginal Ring Study Group. Int Urogynecol J Pelvic Floor Dysfunct, 1999; 10:171–176.

58.

Weisberg

, Ayton

, Darling

et al. Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet. Climacteric, 2005; 8:83–93.

59.

Smith

, Heimer

, Lindskog

, Ulmsten

. Oestradiol-releasing vaginal ring for treatment of postmenopausal urogenital atrophy. Maturitas, 1993; 16:145–154.

60.

Mainini

, Scaffa

, Rotondi

, Messalli

, Quirino

, Ragucci

. Local estrogen replacement therapy in postmenopausal atrophic vaginitis: efficacy and safety of low dose 17β-estradiol vaginal tablets. Clin Exp Obstet Gynecol, 2005; 32:111–113.

61.

Bachmann

, Lobo

, Gut

, Nachtigall

, Notelovitz

. Efficacy of low-dose estradiol vaginal tablets in the treatment of atrophic vaginitis: A randomized controlled trial. Obstet Gynecol, 2008; 111:67–76.

62.

Simon

, Nachtigall

, Gut

, Lang

, Archer

, Utian

. Effective treatment of vaginal atrophy with an ultra-low-dose estradiol vaginal tablet. Obstet Gynecol, 2008; 112:1053–1060.

63.

Dugal

, Hesla

, Sordal

, Aase

, Lilleeidet

, Wickstrom

. Comparison of usefulness of estradiol vaginal tablets and estriol vagitories for treatment of vaginal atrophy. Acta Obstet Gynecol Scand, 2000; 79:293–297.

64.

Shulman

, Portman

, Lee

et al. A retrospective managed care claims data analysis of medication adherence to vaginal estrogen therapy: implications for clinical practice. J Womens Health, 2008; 17:569–578.

65.

Labrie

, Cusan

, Gomez

et al. Effect of intravaginal DHEA on serum DHEA and eleven of its metabolites in postmenopausal women. J Steroid Biochem Mol Biol, 2008; 111:178–194.

66.

Willhite

, O'Connell

. Urogenital atrophy: Prevention and treatment. Pharmacotherapy, 2001; 21:464–480.