REVIEW CME CREDIT NANCY A. PHILLIPS, MD GLORIA A. BACHMANN, MD Associate Professor, Department of Obstetrics, Professor of Obstetrics and Gynecology and Professor Gynecology, and Reproductive Sciences, of Medicine, Department of Obstetrics, Gynecology, Rutgers Robert Wood Johnson Medical School, and Reproductive Sciences, Rutgers Robert Wood New Brunswick, NJ Johnson Medical School, New Brunswick, NJ

Genitourinary syndrome of : Common problem, effective treatments

ABSTRACT or many women, the postmenopausal F loss of is associated with uncom- After menopause, about half of all women experience fortable genitourinary symptoms, collectively genital, sexual, and urinary symptoms associated with referred to as the genitourinary syndrome of decreases in estrogen, termed genitourinary syndrome of menopause (GSM). But despite the preva- menopause. First-line therapies are nonhormonal vaginal lence of GSM and the availability of treat- lubricants and moisturizers. For persistent symptoms, ments, most women do not seek relief. prescription estrogen in cream and ring formulations is This article reviews the syndrome and of- effective. fers advice on how to talk about it with pa- tients and what treatment options to consider. KEY POINTS ■ Practitioners can use the patient’s most bothersome A SYNDROME RECENTLY DEFINED symptom and her vaginal pH level to assess clinical The term GSM and its defi nition were ap- responses to therapy. proved by the North American Menopause Society and the International Society for the Study of Women’s Sexual Health in 2014.1 It The diagnosis is based on clinical signs and symptoms replaces older terms such as vulvovaginal atro- from the medical history and physical examination. phy, urogenital atrophy, and atrophic vaginitis. GSM refers collectively to the symptoms If the symptoms are not bothersome to the patient, the associated with estrogen loss after menopause syndrome does not require treatment. that adversely affect the vulvovaginal area and lower urinary tract. The most common symp- toms are vulvovaginal dryness, burning, or ir- ritation; sexual pain from inadequate lubrica- tion; and urinary urgency, dysuria, or recurrent urinary tract infection.1,2 The defi nition notes that symptoms are self- reported as bothersome and are not the result of another disorder. Symptoms may be chronic and progressive, are not likely to resolve without treatment (pharmacologic or nonpharmacolog- ic), and can have a signifi cant negative impact on a woman’s quality of life and sexual health.1,2

■ COMMON BUT UNDERTREATED From 40% to 60% of postmenopausal women experience GSM, but few seek treatment.3 doi:10.3949/ccjm.85a.15081 Nevertheless, most postmenopausal women

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remain sexually active. In a 2008 survey of therapy, radiation, and surgical removal of 94,000 postmenopausal women ages 50 to 79, may also precipitate symptoms. The 52% reported that they had been sexually ac- abrupt onset of menopause that may occur tive with a partner in the past year.4 However, with these treatments is often associated with 45% of postmenopausal women experienced signifi cantly greater sexual dysfunction and unpleasant vaginal symptoms, according to a negative impact on quality of life. Cigarette 2012 international survey of 3,520 postmeno- smoking also leads to lower estrogen levels, pausal women ages 55 to 65.5 In this survey, which may contribute to GSM. most respondents (75%) felt that vaginal symptoms had a negative impact on their life, ■ WHAT CAUSES GSM? but only 4% connected their symptoms to the The genitourinary system develops from com- vulvovaginal atrophy that resulted from loss of mon embryologic tissue, the basis for the estrogen after menopause. Moreover, almost functional and clinical connection. Estrogen half were unaware of management options.5 maintains the of the , , These fi ndings were supported by a 2013 , and bladder trigone via estrogen re- survey of more than 3,000 US women who ceptors present throughout these tissues.9 reported unpleasant vulvar and vaginal symp- toms.6 From 60% to 85% noted negative sexu- Premenopausal changes al consequences from vulvovaginal symptoms, Histologically, the estrogen-exposed vagina of 47% felt their relationship suffered, and 27% a premenopausal woman is lined by glycogen- felt it had a negative impact on their general rich, stratifi ed squamous epithelium, with un- enjoyment of life. In this study, 24% attrib- derlying supportive fi bromuscular layers. The uted their symptoms to menopause and 12% epithelium is composed of superfi cial, inter- to hormonal changes. Although 56% had mediate, and parabasal cellular layers. In the discussed GSM symptoms with a healthcare presence of estrogen, the superfi cial and inter- provider, only 40% were using GSM-specifi c mediate cellular levels predominate, with few topical treatments, mostly over-the-counter parabasal cells. preparations. Glycogen acts as a substrate for lactobacil- About half Male partners of symptomatic women also li, producing organic acids, primarily lactate, of post- note adverse emotional and physical effects.7 that help maintain an acidic pH of 2.8 to 4.0. In an online survey of 4,100 men and 4,100 The low pH helps protect against pathologic menopausal women ages 55 to 65, 52% to 78% of men and shifts in the microbiome. Estrogen also main- women have 58% to 64% of women expressed the negative tains the collagen content of the epithelium, genitourinary effects of vulvovaginal symptoms on intimacy, maintains acid mucopolysaccharides and hy- libido, and sexual pain. aluronic acid, and optimizes vaginal blood symptoms GSM is a progressive disorder. Women may fl ow. These effects result in optimal epithelial note symptoms many years before menopause thickness and elasticity, moisture, vaginal se- or have no symptoms until several years after cretions, and lubrication.10 menopause. One study found the prevalence of GSM to be 4% during perimenopause, ris- Postmenopausal changes ing after menopause to 25% after 1 year and to Low levels of estrogen after menopause result 47% after 3 years.8 in adverse anatomic, physiologic, and clinical Although distressing symptoms occur changes in vaginal tissue. Effects of hypoes- mostly after menopause, they may be seen in trogenism include the loss of collagen and women of any age who experience a hypo- adipose, leading to decreased elasticity and estrogenic state, even if it is transient. Causes vaginal mucosal thinning. Vascular fl ow is de- of this include premature ovarian failure, creased. The epithelial cytology transitions to hypothalamic amenorrhea, and hyperprolac- a predominance of parabasal cells and a de- tinemia. In addition, some treatments such as crease in superfi cial and intermediate cells. gonadotropin-releasing hormone agonists and Eccrine and glands become attenu- aromatase inhibitors may cause vulvovaginal ated. These changes result in decreased vagi- and lower urinary tract symptoms. Chemo- nal secretions, diminished or delayed lubrica-

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TABLE 1 agnostic tools for GSM are lacking, but some tools are available. Genitourinary syndrome of menopause: In 2006, the US Food and Drug Adminis- Clinical symptoms tration (FDA) published guidelines for indus- try to better defi ne patient-reported outcome Vulvovaginal dryness, itching, burning, irritation measures in clinical trials.13 The most signifi - Vaginal discharge cant addition was having the patient defi ne Decreased lubrication or arousal with sexual activity the symptoms and rate how “bothersome” the Pain with introital insertion during sexual activity (dyspareunia) symptoms are. Although this measure does not help diagnose GSM, it can be used effec- Decreased or delayed orgasm tively to follow response to treatment. The Vaginal Symptom Questionnaire14 can Dysuria be useful for assessing symptoms. It is a vali- dated 21-item questionnaire that measures the Urinary frequency or urgency quality-of-life impact of genital, but not uri- Recurrent urinary tract infections nary, symptoms of menopause. Ask patients about symptoms tion with sexual stimulation, friability of the Healthcare providers should ask about GSM , and vaginal dryness.11 symptoms (Table 1) during routine clinical Additionally, without estrogen, glycogen visits with women who are peri- or postmeno- content is diminished, leading to decreased pausal or who have from lactic acid production and a rise in vaginal pH other causes, as many women are reluctant to to greater than 5. As the pH rises, Lactobacil- initiate this discussion. Conversely, in women lus colonization decreases, leading to a further who present with sexual problems, such as decrease in glycogen metabolism and to propa- diffi culty with arousal or dyspareunia, GSM gation of an elevated vaginal pH. The loss of should be considered as a possible cause. Anatomic vaginal acidity makes the vagina more suscep- Specifi cally, ask women if they have any of tible to pathologic bacteria, including those the following symptoms: effects found in the bowel and skin, sexually trans- • Vaginal itching, burning, discomfort, or ir- of estrogen loss mitted infections, and bacterial vaginosis.12 ritation Other affected tissues. Anatomic effects • Malodorous or irritating vaginal discharge are not limited of estrogen loss are not limited to the va- • Urinary frequency, urgency, dysuria, ure- to the vagina gina. The epithelium, connective tissue, and thral discomfort, or recurrent urinary tract smooth muscle of the vulva, vagina, urethra, infections and bladder trigone are also affected. The la- • Sexual symptoms of entry dyspareunia, bia minora become thinner and regress, the vaginal pain, or irritation with sexual ac- introitus retracts, and narrowing and stricture tivity, which may be complicated by post- of the vaginal canal and introitus may result. coital bleeding, spotting, or fi ssuring. In some women, the urethral meatus becomes Vulvovaginal pain or irritation may be con- prominent relative to the introitus and more stant or may be present in the absence of sexu- vulnerable to physical irritation, infection, al activity, such as with exercise, wearing tight and trauma. clothing, or sitting for long periods. Clinically, estrogen-related changes are Physical examination usually responsible for vaginal dryness, irrita- Characteristic physical fi ndings of GSM in- tion, burning, and superfi cial or deep dyspa- clude scarce pubic hair, thinning of the reunia. Urinary frequency, urgency, and in- from loss of labial fat, resorption of the labia continence also may develop. minora, or fusion of the and ma- 15,16 ■ jora (Table 2). The vulvar skin is pale and THE DIAGNOSIS IS CLINICAL thin. The may retract, exposing The diagnosis of GSM is based on the history the glans (which may lead to increased pain and physical examination. Standardized di- with sexual stimulation), or clitoral hood

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fusion may occur. The vagina is pale, dry, TABLE 2 smooth, and shiny with loss of rugae; shorten- ing or stricturing may be present. Vaginal elas- Physical examination fi ndings ticity decreases. Infl ammation and petechiae in genitourinary syndrome of menopause (pinpoint, nonraised, round purple-red spots) may be present. The may be fl ush with Thinning of pubic hair the vaginal fornices. Thinning or fusion of labia Prolonged atrophy may result in introital Vulvovaginal pallor or erythema, petechiae narrowing and friability, which may cause remnants tearing with sexual activity or insertion of a speculum during pelvic examination. In ad- Introital retraction, stricture dition, the epithelium of the lower urinary Loss of vaginal rugae tract thins, and the muscular and fi brous lay- Prominence of urethral meatus, caruncle ers atrophy—changes that may not be obvious during examination. A urethral caruncle may form, presenting as proliferative red tissue at view the use of detergents, soaps, douches, or the entrance of the urethra. Prolapse may be- over-the-counter topical products that could come more prominent. cause genitourinary symptoms secondary to In women with severe genitourinary atro- contact irritation or allergy. phy, pelvic examination may cause signifi cant Any isolated, ulcerated, or nonhealing le- discomfort. Reassuring the patient that she sion should be biopsied. Reevaluate patients can ask the clinician to stop at any time due who have not responded to previous topical to extreme discomfort is the fi rst step in a suc- therapy or consider referral to a specialist. cessful pelvic examination. Assess the personal, interpersonal, social, In some situations, initial examination of and sexual impact of the symptoms: if they the pelvic area may not include insertion of do not cause distress, GSM does not require a speculum. Use of a hand-held mirror so the treatment. Nevertheless, potential treatment patient can observe the examination may help options should be discussed as symptoms may Ask about her relax during the examination. progress, making intervention necessary. GSM symptoms Vaginal pH and cultures, if indicated, may Laboratory tests: Helpful, not essential during visits be obtained by gently inserting a cotton-tipped Laboratory tests are unnecessary for the diag- swab into the vagina without a speculum and nosis of GSM. However, offi ce-based objective with peri- before applying lubricant. Lubricant should be evaluations such as vaginal pH testing and the or post- used generously; in some instances, topical li- maturation index can support the diagnosis. menopausal docaine gel (diluted, as it may burn) may be The pH of the estrogenized vagina ranges placed against the perineum on a gauze pad for from 3.8 to 4.2, whereas in women with GSM, women 3 to 5 minutes before insertion of the specu- the pH may reach 5.5 or higher. The pH can lum. be obtained by placing a pH-sensitive paper When an internal pelvic examination is against the lateral vaginal wall, avoiding any necessary in a timely manner, such as with discharge or cervical mucus. A vaginal pH of postmenopausal bleeding or a history of an 5 or greater in the absence of blood, semen, or abnormal Papanicolaou smear, but is too pain- infection suggests vulvovaginal atrophy.19 ful for the patient, the examination should be The vaginal maturation index is deter- done under anesthesia. mined by a vaginal smear using Rakoff stain- Additional considerations ing, in which 100 cells are counted and the The history should review current medical number of parabasal, intermediate, and super- conditions, medication use, nongenital skin fi cial cells is determined. In general, a well- disorders (eg, eczema), and systemic meno- estrogenized vagina has mostly superfi cial and pausal symptoms, such as hot fl ashes. intermediate cells, which shifts to a predomi- Also, consider other potential causes of nance of parabasal cells as estrogen levels de- GSM during the evaluation (Table 3).17,18 Re- cline.20

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■ TABLE 3 SELECTING A TREATMENT Nonhormonal causes Symptomatic women with GSM who desire intervention should be offered over-the-coun- of genitourinary symptoms ter nonhormonal products as the fi rst line of Conditions Associated symptoms therapy. If nonhormonal products are ineffec- Medical problems tive and there are no contraindications, lo- Sexually transmitted infections Vaginal discharge, odor, irritation cally applied estrogen in cream, tablet, or Candidiasis a ring delivery system may be offered. Local Bacterial vaginosis dehydroepiandrosterone (DHEA) inserts or Trichomoniasis ospemifene, an oral selective estrogen-recep- Lichen sclerosis Hypopigmented, waxy, agglutination, tor modulator, are FDA-approved for moder- loss of labial folds ate to severe dyspareunia secondary to GSM. Lichen planus Red plaques, pain Oral estrogen therapy is not indicated for Lichen simplex chonicus Lichenifi ed skin vulvovaginal symptoms, but some women tak- ing systemic estrogen for vasomotor symptoms Vulvar intraepithelial neoplasm Raised or eroded lesions may need additional local estrogen applica- Vulvar cancer Ulcer with raised edges tion to relieve vaginal symptoms. Paget disease Red, scaly plaque with sharp border Nonhormonal treatments Vulvodynia Dyspareunia Nonhormonal over-the-counter therapies Vaginismus Dyspareunia provide suffi cient relief for most women with Psoriasis, eczema Multiple plaque-like lesions, mild symptoms. There is a plethora of prod- nongenital lesions ucts, so practitioners need to offer guidance to help women with their individual choices. Infl ammatory bowel disease Fissures Vaginal lubricants are intended for use Skin irritants with sexual or penetrative activity (including Perfumes Contact dermatitis, pelvic examination). They provide short-term Powders skin irritation, reactions relief of symptoms, but there is no evidence of Deodorants any impact on histologic changes of atrophy. Soaps They are meant to relieve friction. Lubricants Spermicides may be water-based, oil-based, silicone-based, Lubricants or a combination. Individual products have Hot tub and pool additives Foreign bodies different effects on condom integrity. Per- Panty liners fumed, warming, or stimulating products may Perineal pads be irritating to some women and should be Tight-fi tting or synthetic clothing tried initially in small amounts. Retained foreign body Vaginal moisturizers are intended to treat GSM. They are applied regularly, not just Adapted from references 17 and 18. with vaginal activity, usually once or twice a week. Some vaginal lubricants can maintain A recent review of vaginal atrophy sug- an acidic pH in the vagina and may reverse gests that after a diagnosis of GSM, health- the histologic changes of atrophy. Symptom- care providers can consider the most bother- atic improvement over placebo or estrogen some symptom along with the vaginal pH to has been shown in clinical trials.22–24 assess the response to treatment.21 In general, Women should be advised that trial and schedule a follow-up appointment at 8 to 12 error in choosing products may be necessary weeks to review treatment response. If treat- to establish a successful regimen. Products ment has not resulted in adequate symptom should be tried in succession, not simultane- relief, consider a pelvic examination and fur- ously, with a “wash-out” period between, to be ther testing. able to evaluate response.

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Vaginal dilators and pelvic fl oor Dosing considerations physical therapy The vaginal ring and the vaginal tablet pro- Sexual activity, either by self-stimulation or vide the lowest prefi xed daily dose of estradiol with a partner, helps maintain vaginal health (7.5 and 10 μg daily, respectively). Estrogen by contributing to increased vascularity and creams (estradiol, conjugated equine estro- elasticity of tissue. Women who resume sexual gens) are more readily absorbed, and dosing activity after a long period of inactivity may should be tapered to the lowest, most effective benefi t from the use of vaginal dilators, which dose for symptom relief. aid both in mechanical distention and pro- The FDA-approved doses for vaginal gressive relaxation of the vaginal musculature. creams containing 17-beta estradiol are higher In some women, long-term dyspareunia than the dose found to be effective in clinical may result in vaginismus, an involuntary con- practice (0.5 g twice a week). Most practitio- traction of the vaginal musculature. For these ners start with the lower dose, reserving the women, dilators may be effective. Additional FDA-approved higher doses for patients who options focus on pelvic fl oor physical therapy, do not obtain adequate relief over 6 to 8 weeks which can isolate trigger points, using bio- of treatment. The conjugated-estrogen vaginal feedback to teach relaxation and home exer- cream Premarin is the only locally applied es- cises such as vaginal massage. trogen approved by the FDA to treat dyspareu- nia. It is dosed at 0.5 g intravaginally for 21 days ■ HORMONAL THERAPIES and is then either withdrawn for 7 days or, more commonly, administered at 0.5 g twice a week. If nonhormonal lubricants and moisturizers do Initial treatment with vaginal cream may not achieve satisfactory symptomatic relief, require more frequent vulvovaginal applica- FDA-approved hormonal therapies (Table 4) tion, such as daily for 1 to 2 weeks. Women include estrogen-containing vaginal creams, with vaginal fi ssures or tearing will benefi t rings, and a tablet; a vaginal tablet containing from externally applied creams in addition to DHEA; and an oral tablet containing ospemi- internal applications. Response to therapy is fene. usually seen within 4 to 6 weeks from onset of A vaginal pH ≥ 5 treatment. Once symptom relief is obtained, Estrogen products suggests treatment should continue indefi nitely. Al- For patients whose symptoms do not respond though long-term safety studies are lacking, vulvovaginal to nonhormonal therapies, low-dose, locally risks are believed to be minimal. atrophy applied estrogen therapy is the fi rst treatment 2 Endometrial impact. Women with con- recommended. Locally applied can traindications to systemic estrogen should be reverse the atrophic changes of estrogen depri- counseled about possible small increases in se- vation, resulting in an increase in blood fl ow, rum levels of estradiol associated with locally elasticity, and vaginal wall thickness. This applied estrogens and the potential risks and therapy also can normalize pH levels with benefi ts those increases incur. Endometrial subsequent restoration of a healthy lactoba- surveillance with either transvaginal ultraso- cilli-based fl ora. Locally applied estrogens also nography or endometrial sampling is not re- have been shown to decrease the frequency of quired, even with long-term use, but it should recurrent urinary tract infection.25 be considered with higher doses or more fre- Estrogen-containing vaginal creams, rings, quent applications. and a tablet are available, and each has been Similarly, progesterone replacement for shown to be effective for GSM. Locally ap- endometrial protection is not recommended plied estrogens at recommended dosages tend but can be considered in women with an in- to have fewer adverse events and risks than tact at high risk of endometrial can- systemic estrogens.26 Estradiol levels generally cer, such as obese patients. If a systemic pro- do not exceed levels found in the untreated gestational agent is considered, the risks and menopausal population, although a dose- and benefi ts should be weighed carefully. Even in duration-dependent increase in systemic lev- women at high risk, endometrial surveillance els may occur.27 may be the most appropriate option.28 Uterine

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TABLE 4 FDA-approved preparations for vulvovaginal atrophy

Product Proprietary name Dosing Vaginal creams 17-beta estradiol Estrace vaginal cream Initial: 2–4 g/day for 1–2 weeks 0.1 mg/g Maintenance: 1 g at 1–3 times a weeka Conjugated estrogens Premarin vaginal creamb Vulvovaginal atrophy: 0.5–2 g/d for 21 days, (0.625 mg/g) then off 7 days or twice a weeka Dyspareunia: 0.5 g/day for 21 days, then off 7 days or twice a weeka Vaginal ring 17-beta estradiol Estring (7.5 μg/day) Inserted for 90-day intervals without interruption Estradiol acetate Femring (5 and 10 μg/day) Vaginal tablet inserts Estradiol hemihydrate Vagifem, Yuvafemc Initial: 1 tablet/day for 2 weeks (10 μg/day) Maintenance: 1 tablet twice a week DHEA (prasterone) Intrarosa (6.5 mg insert) 1 insert into vagina, once daily Oral tablet Ospemifene Osphena (60 mg) 1 tablet orally every day

Nonhormonal a Common clinical dosage is 0.5 g twice a week for maintenance. b Premarin vaginal cream is the only locally applied preparation with FDA approval for dyspareunia due to GSM. over-the-counter c Yuvafem is an FDA-approved generic equivalent to Vagifem. therapies provide DHEA = dehydroepiandrosterone; FDA = US Food and Drug Administration relief for most bleeding that occurs should be considered ab- out any signifi cant impact on serum levels of women with normal and should be investigated. DHEA, DHEA-sulfate, estradiol, testosterone, mild symptoms or their metabolites. Importantly, transvaginal DHEA (prasterone) DHEA had negligible endometrial effect. In 2016, the FDA approved intravaginal The breast cancer risk associated with prasterone, a DHEA-containing product for the vaginal DHEA has not been fully evaluated. treatment of dyspareunia secondary to moder- However, labeling lists breast cancer as a ate to severe vulvovaginal atrophy caused by warning, not a contraindication. menopause. DHEA is an endogenous steroid that is converted by aromatase activity into tes- Selective estrogen-receptor modulator tosterone and estradiol. In 2013, the FDA approved ospemifene for the Clinical trials have found that 12 weeks treatment of dyspareunia caused by GSM. Os- of vaginal DHEA supplementation (0.25%, pemifene, an estrogen agonist in the vagina, 0.5%, and 1% DHEA ovules) was more effec- is taken daily as a 60-mg oral dose. Long-term tive than placebo in improving vaginal dryness safety studies suggested no adverse effects on the and dyspareunia in women with GSM.29–31 or breast for at least 52 weeks.32 In these studies, locally applied DHEA de- These studies also noted that ospemifene creased parabasal cells, decreased vaginal pH, improved the vaginal maturation index (de- increased vaginal secretions, and improved creased parabasal cells and increased super- epithelial surface thickness and integrity with- fi cial cells) and decreased vaginal pH. It has

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further been shown to decrease severity of the nal dryness associated with aromatase inhibi- self-identifi ed most bothersome symptom— tor use in breast cancer patients.37 However, dyspareunia or vaginal dryness—compared due to the lack of safety and effi cacy data from with placebo.33 larger, controlled trials, testosterone therapy is Potential increases in hot fl ashes, which not currently recommended. may occur in up to 7% of patients, and the risk of blood clots should be considered. Addition- Isofl avones ally, the safety of ospemifene in women with Isofl avones are phytoestrogens found in soy. In a history of breast cancer has not been estab- a 12-week, double-blind placebo-controlled lished. Although early studies suggest it either study of vaginally applied 4% soy isofl avone has no effect or possibly a protective effect on gel, improvements in vaginal atrophy symp- breast tissue, the FDA does not recommend its toms, maturation values, and vaginal pH were use in women at risk for breast cancer. Long- found in 60 postmenopausal women.38 Addi- term effects on bone are unknown. tional data on effi cacy and safety are needed The labeling for ospemifene includes a boxed before isofl avones should be considered as a warning about the risk of stroke, blood clots, treatment for GSM. and cancer of the lining of the uterus. Patients Bioidentical hormones should be counseled about worrisome signs or symptoms that require medical attention. Bioidentical hormones are plant-derived hor- mones that are chemically similar or identi- ■ ALTERNATIVE THERAPIES cal to those produced by the body. Although there are FDA-approved bioidentical hor- Treatments for GSM not approved by the mones (eg, micronized progesterone, estradiol, FDA include laser and radiofrequency thera- DHEA), the term bioidentical usually refers to pies, testosterone, isofl avones, and bioidenti- non-FDA-approved, commercially available cal hormones. hormones produced and compounded by spe- Laser and radiofrequency therapies cialty pharmacies. Both of these therapies aim to promote tissue Patients often view these substances as be- Some vaginal remodeling with increased collagen and elas- ing better, safer, and more acceptable for use, moisturizers and healthcare practitioners need to be pre- tin production and increased vascularity. This, may reverse in turn, increases muscle support and tone. pared to address these beliefs. The FDA and Laser therapies act by ablating and coagu- the American College of Obstetricians and histologic lating vaginal tissues; radiofrequency thera- Gynecologists consider bioidentical hormones changes pies directly heat the tissue. Both treatments to be a marketing term and not an alternative are offi ce-based, require up to 3 initial treat- treatment based on scientifi c evidence.39 Pa- of atrophy ments, and are followed by retreatment at ap- tients should be informed that bioidentical proximately 1-year intervals. hormones have the same risks as any similar Studies have reported high patient satis- hormone preparation along with additional faction rates (91% to 100%), improved sexual risks related to potential lack of purity and po- functioning, and decreased GSM symptoms of tency. Further, they have not been adequately vaginal dryness, burning, itching, and dyspa- studied in controlled clinical trials. reunia.34–36 Data, however, are from observa- tional studies, not placebo-controlled trials. ■ FOLLOW-UP CARE Although laser and radiofrequency thera- Healthcare providers caring for women should pies are FDA-approved for several indications, assume a proactive role in diagnosing and treat- laser treatment for symptoms of vulvovaginal ing the symptoms of GSM. And once diagnosis atrophy is not currently an approved indica- of GSM is established and treatment is under tion. Patients should be advised of this. way, practitioners can use symptom question- Testosterone naires and vaginal pH testing as easy and re- Locally applied testosterone was shown in a liable means of measuring clinical response to small study to improve dyspareunia and vagi- therapy. ■

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