golden girls dilemma: genitourinary syndrome of menopause p

women’s health

In 2014, the International Society for the Study of Women’s Sexual Health and the Board of Trustees of the North American Menopause Society made an important decision to change the term vulvovaginal atrophy/atrophic vaginitis to genitourinary syndrome of menopause (GSM). The change to a more medically accurate terminology avoided the stigmatizing connotations associated with the old nomenclature.1 Vulvovaginal atrophy/ atrophic vaginitis implies that the condition is limited to the vulvovaginal area, incorrectly assumes that the etiology is infectious and/or inflammatory, and that the patient is responsible for the condition due to underuse or other negative actions. The term vulvovaginal atrophy/atrophic vaginitis fails to include the wide variety of changes in the vulva, vagina, and bladder that are associated with estrogen deficiency in menopause. Negative societal attitudes regarding women’s sexuality, patient’s feeling of embarrassment, shame, and fear, and minimization of sexual problems inhibit discussions about GSM between patients and clinicians.2-5 The VIVA—vaginal health, insights, views, attitudes— study found that among 3,520 participants from 6 countries, only 2% felt comfortable with the term vaginal atrophy.6 The EMPOWER survey of 1,858 women with GSM found that 72% of women had never discussed their symptoms with their clinician and 81% were not aware of the condition.7 The goal of the nomenclature change was to increase awareness and decrease stigmatization of a condition that often goes untreated despite significant quality of life degradation.8,9 This article will define the current terminology, describe the prevalence, physiology, and impact of GSM, and provide an overview of available treatments.

is a collection of symptoms and signs associated

with a decrease in estrogen and other sex steroids with accompanying changes to the vulva, vagina, urethra, and bladder. The syndrome may include but is not limited to genital symptoms of dryness, burning, and irritation; sexual symptoms of lack of lubrication, discomfort or pain, and impaired function; and urinary symptoms of urgency, dysuria, and recurrent urinary tract infections.1 Unlike vasomotor symptoms of menopause that generally improve over time, GSM is a chronic progressive condition with symptoms that persist unless treated. The prevalence of symptoms in early menopause is 4%, rising to 47% three years after menopause.10 About 50% of peri- and postmenopausal women report GSM symptoms; of those, another 50% report moderate to severe symptoms.9,11-13 Symptoms of GSM are not limited to the perimenopausal years but also occur when women experience other hypoestrogenic states including the postpartum and lactation periods, hypothalamic amenorrhea, tobacco usage, premature ovarian insufficiency, or when taking antiestrogen medications such as gonadotropin antagonists/ agonists or aromatase inhibitors.14-17 Symptoms are also associated with nonwhite race, diabetes, lower body mass index, and younger age.18

VULVOVAGINAL SYMPTOMS

Vulvovaginal symptoms are reported by half of midlife and older women.9 The common symptoms are vaginal dryness (55%–75%), itching and irritation (18%–37%), and soreness and pain (18%–29%).6,9,18-20 Women may also experience vaginal spotting from sexual intercourse or even with minimal trauma of daily activity. Because vulvovaginal tissue is estrogen responsive, the loss of estrogen during menopausal transition contributes to the changes seen and experienced by patients. Vulvovaginal tissue becomes thinner and more friable due to multiple physiologic changes including thinning of the vaginal epithelium and lamina propria, smooth muscle atrophy, decreased collagen and glycogen, and reduction of physiologic discharge and vascularization.21,22 On external genital exam, there is decreased pubic hair and vulvar skin elasticity, a narrowed vaginal introitus, fusion or resorption of the labia minora, decreased skin moisture, and loss of the labial fat pad. On internal vaginal exam, reduction in vaginal rugae can be seen. The epithelium appears pale, smooth, and shiny. The result is decreased vaginal length, width, and elasticity. Additionally, the cervix is smaller and may be flush with the vaginal fornices. Sometimes, blood vessels and petechiae are visible through the thinned epithelium. Signs of severe GSM include ulcerations of the labia majora and fissures at the posterior fourchette.16 Occasionally, symptoms do not correlate with exam findings.23 Vulvovaginal changes can cause severe pain and distress at time of vaginal exam. Small or pediatric sized speculums, adequate lubrication, gentle palpation, explaining the reason for the exam, and working with the patient to set the pace or extent of the exam can prevent a physically and emotionally traumatizing experience. Diagnosis of GSM is based on history and physician exam findings. Laboratory studies are not needed to confirm vulvovaginal symptoms of GSM, although other vulvovaginal conditions can present with similar symptoms. Vaginitis cultures may be useful to exclude acute vaginitis, and a vulvar skin punch biopsy may be necessary to diagnose other skin conditions like lichen sclerosis, lichen simplex chronicus, and lichen planus.

SEXUAL DYSFUNCTION

Sexual pain—dyspareunia—is one of the 2 most common symptoms of GSM, affecting 38% of perimenopausal women and 56% of postmenopausal women.24 Dyspareunia is the reason why 58% to 87% of women and 30% of women’s partners stop engaging in sex.13,25 While the exact cause of the increase in pain sensation is not known, it may be related to increased innervation of vaginal mucosa in hypoestrogenic states. Vestibular pain has been reported by postmenopausal women with lower serum estradiol levels.26,27 Vulvovaginal dryness, introital narrowing, fissures, and decreased elasticity may also cause dyspareunia.

72% of women had never 72% of women had never 72% of women had never discussed their symptoms discussed their symptoms discussed their symptoms with their clinician… with their clinician…

Vulvovaginal symptoms of GSM not only result in sexual pain but also emotional distress. Women with vulvovaginal symptoms have a 4-fold higher risk of sexual dysfunction including difficulty with desire, arousal, and orgasm.28 Low libido and dyspareunia in women are strongly associated with unhappiness.29 Among the 500 American women surveyed in the VIVA study, 75% felt adverse effects on sexual intimacy, 64% reported decreased libido, 33% felt their symptoms were preventing them from having a loving relationship, and 26% reported negative self-esteem.25 Women may feel that they have to choose the lesser of 2 evils: experience relationship deterioration or even break-up with their partner due to cessation of sex, or continue to have sex despite the pain. Unfortunately, 72% of perimenopausal women with dyspareunia continue to engage in sexual intercourse at least once a month and 34% at least once weekly.13 Because GSM is chronic and progressive, continued sexual intercourse with dyspareunia and vaginal dryness may lead to persistent or worsened sexual dysfunction. Most women do not discuss dyspareunia and vaginal dryness with their clinicians, leading to needless pain and suffering since improvement of GSM-related vulvovaginal symptoms are associated with improvement in sexual function.30-32

LOWER URINARY TRACT SYMPTOMS

In addition to reductive effects on the vulva and vagina, hypoestrogenization impacts the lower urinary tract. The nomenclature change better reflects the inclusion of these genital areas. The urethra, bladder, vulvar vestibule, and the upper vagina are all embryologically derived from the urogenital sinus tissue.33 Estrogen receptors have been found in the urethra, bladder and pelvic floor muscles, and exogenous estrogen has been shown to increase urethral closure pressure.34,35 After menopause, the vaginal pH becomes elevated (pH > 5) due to the decrease of beneficial vaginal lactobacilli and results in disruption of the vaginal microbiome with subsequent increase in uropathogens.36,37 The shift from a lactobacillus-dominant microbiome could be one of the reasons for frequent vaginal or urinary tract infections. Dysuria and recurrent urinary tract infections affect 13% and 4% of postmenopausal patients, respectively,38,39 and there is a 7-fold greater risk of sexual pain disorders in women with lower urinary tract symptoms.34

QUALITY OF LIFE

In addition to genitourinary symptoms, women with GSM report a significant decrease in quality of life. The ReVIVE study found that among 3,064 postmenopausal American women, 29% reported negative effects on sleep and 27% reported negative effects on enjoyment of life.20 Another study found that for every increment in severity of GSM symptoms, there was a clinically significant incremental decrease in quality of life scores, comparable to other chronic conditions such as chronic obstructive pulmonary disease and irritable bowel syndrome.9

BARRIERS TO CARE

GSM is an underdiagnosed and undertreated condition despite the common occurrence and severity of symptoms. Women and their clinicians are often reluctant to initiate conversations regarding GSM due to social and cultural taboos regarding female genitalia and sexuality.40 Women with GSM may feel embarrassment, shame, and

loss of self-esteem that may further prevent them from seeking care.6 In the ReVIVE study, only 25% of women initiated discussion regarding genitourinary concerns with their clinicians and only 54% of women were willing to respond when their clinicians asked about their symptoms.20 When women do seek treatment, they feel that they are often dismissed by their clinicians.7,25 To overcome these barriers, clinicians should routinely screen for GSM symptoms in perimenopausal and menopausal women in a supportive and nonjudgmental fashion. Clinicians can decrease stigma and assuage feelings of isolation by sharing information such as the high prevalence of GSM. For example, “Women in their 40s or older often experience vaginal dryness, urinary problems, and pain with sex. Are you experiencing any of these symptoms?” Similar to principles of trauma informed care, it is important to foster a compassionate environment that is sensitive and respectful of the patients’ negative experiences thus far with GSM symptoms. Lack of awareness regarding symptoms of GSM is another major barrier. Women often think that the symptoms are a natural part of aging, that prescription treatments are not available, or that there is not enough information available about the safety of medications.13 Women may suffer silently and needlessly. Patient visits with primary care/family physicians, gynecologists, and urologists are all opportunities to improve awareness, destigmatize the condition, facilitate detection, and direct appropriate treatment.

TREATMENT

Symptoms of GSM should be treated given the condition’s chronic and progressive nature. Clinicians should counsel patients on the natural course of the condition, emphasizing that continued treatment is necessary to prevent future recurrences or relapses. Treatment strategy depends on symptom type and severity, and is usually multimodal. Women with mild vulvovaginal symptoms and dyspareunia can apply vaginal moisturizer every 2 to 3 days to relieve vaginal dryness and discomfort. There are a variety of over-the-counter vaginal moisturizers although there is paucity of research on their efficacy. The World Health Organization recommends vaginal moisturizers with osmolarity of less than 1,200 mOsm/kg due to concern for epithelial cell damage.41 Vaginal lubricants for all partners prior to and during sexual activity are essential to decrease tissue trauma from friction, though relief is only temporary and does not address the underlying changes caused by a hypoestrogenic state. Women who use condoms for contraception should avoid oil-based moisturizers and lubricants as oil will damage condoms. Continuation of nonpainful sexual intercourse on a regular basis can help maintain vaginal elasticity.42 Women can also use a vibrator with or without a partner to stimulate vulvovaginal blood flow.43 Pelvic floor physical therapy with dilator therapy can help women with introital narrowing or pelvic floor hypertonicity.44 Mindfulness exercises and topical lidocaine applied to the vaginal introitus prior to sexual activity may decrease dyspareunia.45,46 Women with sexual dysfunction and associated psychosocial effects such as intimacy avoidance, low self-esteem, and body image concerns may also benefit from sex therapy. Couples psychotherapy may facilitate education, communication, and exploration of other ways to achieve satisfying sexual activity.47 Clinicians should discuss starting lowdose vaginal estrogen therapy for women with moderate to severe GSM or those who have persistent symptoms despite nonhormonal treatment. Low-dose vaginal estrogen therapy is preferred over systemic hormone therapy when only GSM symptoms are present.16 Low-dose vaginal estrogen therapy is available in cream, capsule, pill, and ring form, and all are FDA-approved. A 2016 Cochrane review found similar efficacy between the different formulations.48 Low-dose vaginal estrogen has been shown to be effective for reducing urinary incontinence, frequency of urinary tract infections, dysuria, dyspareunia, and vaginal dryness.49,50 It has also been shown to decrease the vaginal pH, increase vaginal lactobacilli counts, and increase blood flow.51,52 Symptom improvement occurs within a few weeks of treatment, although full improvement may not be seen for 8 to 12 weeks.16 Bothersome symptoms will recur with cessation of treatment. Low-dose vaginal estrogen therapy is safer than systemic estrogen therapy, and serum estrogen levels with low-dose vaginal estrogen therapy stay within postmenopausal range.53 Vaginal bleeding, vaginal discharge, breast tenderness, and nausea rarely occur with vaginal estrogen therapy.54 Low-dose vaginal estrogen therapy has not been shown to increase risk of endometrial cancer, thromboembolism, cardiovascular disease, or breast cancer.55,56 However, caution should be exercised for women with history of estrogen-dependent cancers as little data are available regarding the safety of vaginal estrogen therapy in estrogen-dependent cancer survivors. Nonhormonal therapy should be first line for these patients, and the decision to initiate vaginal estrogen therapy should be made in conjunction with the patient and her oncologist. Ospemifene and dehydroepiandrosterone (DHEA) are nonestrogen medications that are FDA-approved for treatment of vaginal dryness and dyspareunia due to GSM. Ospemifene is a selective estrogen receptor modulator that is an estrogen agonist in the vagina. Although ex vivo studies in human breast tissue showed that ospemifene is an estrogen antagonist,57 it has not been studied in women with or at high risk for breast cancer and is not approved by FDA for women with breast cancer. Risks of ospemifene include increased incidence of thromboembolism and hot flushes. DHEA is a sex hormone precursor for estrogen and androgen synthesis. The most common side effects are vaginal discharge and an abnormal pap test result.58DHEA

Symptoms of GSM are not limited to the perimenopausal years…

is not FDA-approved for women with breast cancer due to lack of safety data. The efficacy and safety of vulvovaginal energy-based devices including lasers and radiofrequency devices are still under investigation, and these therapies are not FDA approved for treatment of GSM.

CONCLUSION

GSM is a chronic and progressive condition that is underdiagnosed and undertreated. The effects of GSM are broad and encompass vulvovaginal symptoms, urinary symptoms, sexual dysfunction, psychosocial distress, and decreased quality of life. Barriers to treatment include social and cultural taboo surrounding women’s sexuality, and lack of awareness regarding the condition and available treatments. The shift in terminology from vulvovaginal atrophy/atrophic vaginitis to genitourinary syndrome of menopause provides patients and clinicians a socially acceptable way to discuss and promote more research and education on this condition. Given patients’ reluctance to discuss GSM symptoms, clinicians should screen for GSM in a sensitive and respectful manner. Patient education should emphasize the chronic nature of the condition, the need for continued treatment, and the effects on genitourinary and sexual health. Multimodal therapy should be tailored to the patient’s symptomology. While low-dose estrogen therapy is preferred for moderate to severe symptoms in women without estrogen-dependent cancers, shared therapeutic decision making should include nonhormonal therapies such as moisturizers, lubricants, physical therapy, and individual or couples sex therapy.

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