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Genitourinary Syndrome of Menopause

Key Questions Aug 15, 2022
thoughtful woman sitting with cup of tea

Introduction

The Patient-Centered Outcomes Research Institute (PCORI) is partnering with the Agency for Healthcare Research and Quality (AHRQ) to develop a systematic evidence review on Genitourinary Syndrome of Menopause. The American Urological Association (AUA) plans to use this systematic evidence review to develop related clinical guidelines.

Genitourinary syndrome of menopause (GSM) is a term that describes the spectrum of symptoms and signs caused by hypoestrogenic changes in urogenital tissues typically occurring during menopause, but which can also occur among premenopausal women under certain circumstances.1 The term GSM was introduced in 2014 by the International Society for the Study of Women's Sexual Health (ISSWSH) and the North American Menopause Society (NAMS) to encompass a constellation of conditions including vulvovaginal atrophy, atrophic vaginitis, or urogenital atrophy.1  Symptoms of GSM may include vulvovaginal dryness, burning, and irritation; sexual symptoms of lack of lubrication, discomfort or pain, or impaired function; and urinary symptoms of urgency, dysuria, or recurrent urinary tract infections. Although not all individuals with atrophic changes on examination are symptomatic, it is estimated that over half of postmenopausal women in the United States experience atrophy-related symptoms.2 The negative effect of GSM on quality of life is substantial; as many as 85% of patients over 40 years of age report vaginal dryness, 29-59% report dyspareunia, 26-77% report vaginal itching and irritation and 40-68% report negative consequences on their sex life, including decreased sexual satisfaction and frequency.3 Unlike menopause-associated vasomotor symptoms (e.g. hot flashes, night sweats, heart palpitations, and changes in blood pressure) that tend to decrease over time, GSM symptoms do not spontaneously remit but worsen with age.4

Despite the high prevalence of symptoms, only a small minority of affected women seek help.5 An unfortunate barrier to treatment is that women believe symptoms of GSM are a normal consequence of aging that they must accept. As a result, women rarely discuss symptoms with their healthcare provider and providers do not consistently ask about symptoms.1,5

The primary goal for the treatment of GSM is to relieve symptoms.1 Determining which type of treatment is appropriate for a patient is based on the patient’s medical history (such as GSM symptoms and co-morbidities) and preferences.9 Based on limited evidence, non-hormonal vaginal moisturizers and lubricants have been recommended as first-line therapy for GSM symptoms related to vaginal atrophy (e.g. vaginal dryness, dyspareunia, etc.).1 Other non-hormonal therapies proposed as alternatives include oral vitamin D, vaginal vitamin E, probiotics and phytoestrogens. Prescription hormones are also available for GSM treatment and include vaginal and low-dose oral estrogen, vaginal dehydroepiandrosterone (DHEA), vaginal testosterone, and oral ospemifene.1 A body of evidence has shown that vaginal and low-dose systemic estrogen therapy are effective for treating many symptoms of GSM1,6 and also may ameliorate some urinary tract symptoms of GSM.7 A comprehensive analysis of the benefits and harms of treatments for GSM has not been completed in several years2,4,6 and trial data has subsequently accumulated.

In addition to the need for an updated comprehensive assessment of treatments for GSM that have been around a while, newer treatments need to be incorporated as well. Several novel treatments have recently emerged, including laser and radiofrequency devices (e.g. microablative fractional CO2, non-ablative erbium: YAG [Er:YAG], and temperature-controlled radiofrequency [RF] laser).1 Despite initial excitement, use of these new therapeutic approaches is controversial and an independent review of the evidence on benefits and harms would be valuable.1,8

Although a handful of recent position and consensus statements on the management of GSM exist,1,8-13 a clinical practice guideline based on an independent systematic review of the evidence has yet to be produced.  Consequently, a review that synthesizes the totality of evidence available on the benefits and harms of screening, diagnosis and treatment of GSM is needed to support the development of a clinical practice guideline and to inform decision-making for healthcare professionals, clinicians, patients, and caregivers.

Proposed Revised Key Questions

  1. What is the effectiveness and harms of screening strategies to identify GSM in peri- or postmenopausal women? Does screening reduce patient reported symptoms or improve quality of life?”
  2. What is the efficacy and comparative effectiveness of hormonal, non-hormonal, and energy-based interventions when used alone or in combination for treatment of GSM? Which treatments show improvement for which symptoms?
  3. What are the harms (and comparative harms) of hormonal, non-hormonal, and energy-based interventions for GSM?
  4. What is the appropriate follow-up interval to assess improvement, sustained improvement, or regression of symptoms of GSM in women treated with hormonal, non-hormonal, and energy-based interventions?
  5. What is the effectiveness and harms of endometrial surveillance among women who have a uterus and are using vaginal or low-dose oral estrogen therapy?

For all key questions, how do the findings vary for women with a history of breast cancer or other hormone-related cancers, a high risk of cancer, or conditions such as primary ovarian insufficiency; women experiencing surgical menopause, transmen; and within subgroups defined severity of GSM symptoms, and patient characteristics (i.e., by age, race, socioeconomic status, etc.).

Draft Analytic Framework for Genitourinary Syndrome of Menopause

The analytic framework is a diagram that shows the population (adult women with genitourinary symptoms of menopause) , followed by the three interventions (KQ1: Screening evaluations and/or questionnaires; KQ2,4: Hormonal, non-hormonal and energy-based interventions, and follow up (KQ4); KQ5: Endometrial surveillance with ultrasound or biopsy). An arrow leads downward from KQ1 to Adverse effects (Safety outcomes, adverse events, misdiagnosis, unnecessary diagnostics). An arrow leads downward from KQ2/4  to Adverse effects of treatment: Safety outcomes, adverse events, adverse systemic events. Intermediate outcomes are Increase condition diagnosis (KQ1), and Improvement of certain genitourinary and sexual symptoms (KQ2). Long term outcomes are Improvement of certain urological symptom, Improvement of psychological symptoms (e.g.  depression, anxiety), and Improved quality of life. A box below contains several potential effect modifiers: History of breast cancer or other hormone-related cancer or high risk of cancer, Conditions such as primary ovarian insufficiency, Women experiencing surgical menopause, Transmen, Subgroups defined severity of GSM symptoms, Patient characteristics (i.e., by age, race, socioeconomic status, etc.)

Table 1. PICOTS for Diagnosis and Treatment of Genitourinary Syndrome of Menopause

 

Inclusion

Exclusion

Population

KQ1:

Peri and postmenopausal women

 

KQ2-4:

Peri and postmenopausal women, premenopausal women in hypoestrogenic state, or transmen complaining of one or more vulvovaginal or genitourinary symptoms of GSM

Individuals with genitourinary symptoms for reasons other than GSM

KQ5:

Patients with a uterus using low-dose oral or vaginal estrogen therapy with complaints of GSM symptoms

 

Interventions

KQ1:

Screening evaluations and/or questionnaires, patient or physician-directed education, patient history, physical exam

 

KQ2-4:

Hormonal Interventions: Low-dose oral estrogen, vaginal estrogen therapy, including vaginal cream, tablets, inserts or ring, Ospemifene, intravaginal dehydroepiandrosterone (DHEA), vaginal testosterone
Energy-based interventions: CO2 laser, Erbium: YAG, radio-frequency laser, vaginal rejuvenation
Non-hormonal interventions: Over-the-counter non-hormone vaginal lubricants and moisturizers, hyaluronic acid, herbal therapies/supplemental alternatives [compounded and bioidentical hormonal therapies], phytoestrogens, vitamin D, vitamin E, probiotics, oxytocin vaginal gel, adjuvant, pelvic floor physical therapy to treat vaginal symptoms of GSM.
For KQ4. Assess different durations of follow-up

Hormone replacement therapy
Laser therapy for anatomic areas other than the vagina
Pelvic floor physical therapy for urinary incontinence

KQ5:

Endometrial surveillance with ultrasound or biopsy

 

Comparison

KQ1:

Usual care

 

KQ2-4:

Efficacy: Placebo, inactive control, sham
Comparative Effectiveness: Another hormonal, non-hormonal, or energy-based intervention
For KQ4.Assess different durations of follow up

 

KQ5:

Usual care, or different type or level of surveillance

 

Outcomes

KQ1:

Diagnosis of GSM, potential harms: misdiagnosis as another condition with similar presentation such as inflammatory dermatologic conditions, malignancy, infections, or presence of symptoms prior to menopause.  Progressing to unnecessary diagnostics for the index patient such as vaginal or endometrial biopsy.

 

KQ 1, 2&4

Improvement in symptoms:
Genitourinary symptoms: urinary frequency, urinary urgency, nocturia, dysuria, hesitancy, urethral stricture, urinary tract infections, CAUTI
Other urinary symptoms (outcomes evaluated for interventions other than PFMT): urinary incontinence, overactive bladder
Genital signs and symptoms: urethral caruncle, urethral prolapse, vaginal atrophy, atrophic vaginitis, vaginal dryness, vaginal / vulvar irritation, vaginal soreness, vaginal lubrication, bleeding associated with sexual activity, vaginal pain, pelvic pain
Sexual symptoms: vaginal dryness, dyspareunia, pelvic pain, orgasmic dysfunction, low libido, decreased arousal, sexual desire, sexual function
Psychological symptoms: depression, anxiety, quality of life, partner satisfaction

Systemic hormone levels

KQ3&5:

Safety outcomes: breast cancer, breast cancer recurrence or progression, breast tenderness, cardiovascular risk, endometrial cancer (KQ5), post-menopausal bleeding (KQ5), endometrial hyperplasia (KQ5), endometrial thickness (KQ5)
Adverse events: worsening or onset of urinary, genital, or sexual symptoms: vaginal burning, vaginal bleeding, vaginal discharge, vaginal scarring, vaginal stenosis; pelvic pain; dyspareunia; urethral strictures; meatal stricture/stenosis.
Systemic adverse events: chronic pain, CVA (stroke); VTE (DVT); death; hot flashes; headache; breast pain; cramps; bloating; nausea; vomiting  

 

Timing

All KQ

Intervention: any
Outcomes:  any                                         

 

Setting

All KQ

Physician visit, any publication date

 

Study design

KQ1,3,5:

RCT, prospective studies

 

KQ2&4:

RCT

 

References

  1. Portman DJ, Gass ML; Vulvovaginal Atrophy Terminology Consensus Conference Panel. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and the North American Menopause Society. Menopause. 2014 Oct;21(10):1063-8. doi: 10.1097/GME.0000000000000329. PMID: 25160739.
  2. Crandall CJ, Diamant A, Santoro N. Safety of vaginal estrogens: a systematic review. Menopause. 2020 Mar;27(3):339-360. doi: 10.1097/GME.0000000000001468. PMID: 31913230.
  3. Biehl C, Plotsker O, Mirkin S. A systematic review of the efficacy and safety of vaginal estrogen products for the treatment of genitourinary syndrome of menopause. Menopause. 2019 Apr;26(4):431-453. doi: 10.1097/GME.0000000000001221. PMID: 30363010.
  4. Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, Olivera CK, Abed H, Balk EM, Murphy M; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol. 2014 Dec;124(6):1147-1156. doi: 10.1097/AOG.0000000000000526. PMID: 25415166; PMCID: PMC4855283.
  5. Krychman M, Graham S, Bernick B, Mirkin S, Kingsberg SA. The Women's EMPOWER Survey: Women's Knowledge and Awareness of Treatment Options for Vulvar and Vaginal Atrophy Remains Inadequate. J Sex Med. 2017 Mar;14(3):425-433. doi: 10.1016/j.jsxm.2017.01.011. Epub 2017 Feb 12. PMID: 28202319.
  6. Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2016 Aug 31;2016(8):CD001500. doi: 10.1002/14651858.CD001500.pub3. PMID: 27577677; PMCID: PMC7076628.
  7. Cody JD, Jacobs ML, Richardson K, Moehrer B, Hextall A. Oestrogen therapy for urinary incontinence in post-menopausal women. Cochrane Database Syst Rev. 2012 Oct 17;10(10):CD001405. doi: 10.1002/14651858.CD001405.pub3. PMID: 23076892; PMCID: PMC7086391.
  8. Kagan R, Kellogg-Spadt S, Parish SJ. Practical Treatment Considerations in the Management of Genitourinary Syndrome of Menopause. Drugs Aging. 2019 Oct;36(10):897-908. doi: 10.1007/s40266-019-00700-w. PMID: 31452067; PMCID: PMC6764929.
  9. American College of Obstetricians and Gynecologists’ Committee on Clinical Consensus—Gynecology. Treatment of Urogenital Symptoms in Individuals With a History of Estrogen-dependent Breast Cancer: Clinical Consensus. Obstet Gynecol. 2021 Dec 1;138(6):950-960. doi: 10.1097/AOG.0000000000004601. PMID: 34794166.
  10. Faubion SS, Larkin LC, Stuenkel CA, Bachmann GA, Chism LA, Kagan R, Kaunitz AM, Krychman ML, Parish SJ, Partridge AH, Pinkerton JV, Rowen TS, Shapiro M, Simon JA, Goldfarb SB, Kingsberg SA. Management of genitourinary syndrome of menopause in women with or at high risk for breast cancer: consensus recommendations from The North American Menopause Society and The International Society for the Study of Women's Sexual Health. Menopause. 2018 Jun;25(6):596-608. doi: 10.1097/GME.0000000000001121. PMID: 29762200.
  11. Simon JA, Goldstein I, Kim NN, Davis SR, Kellogg-Spadt S, Lowenstein L, Pinkerton JV, Stuenkel CA, Traish AM, Archer DF, Bachmann G, Goldstein AT, Nappi RE, Vignozzi L. The role of androgens in the treatment of genitourinary syndrome of menopause (GSM): International Society for the Study of Women's Sexual Health (ISSWSH) expert consensus panel review. Menopause. 2018 Jul;25(7):837-847. doi: 10.1097/GME.0000000000001138. PMID: 29870471.
  12. The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017 Jul;24(7):728-753. doi: 10.1097/GME.0000000000000921. PMID: 28650869.
  13. American College of Obstetricians and Gynecologists. Practice Bulletin No. 141: management of menopausal symptoms. Obstet Gynecol. 2014 Jan;123(1):202-216. doi: 10.1097/01.AOG.0000441353.20693.78. Erratum in: Obstet Gynecol. 2016 Jan;127(1):166. Erratum in: Obstet Gynecol. 2018 Mar;131(3):604. PMID: 24463691.

Project Timeline

Genitourinary Syndrome of Menopause

Aug 15, 2022
Topic Initiated
Aug 15, 2022
Key Questions
Page last reviewed August 2022
Page originally created August 2022

Internet Citation: Key Questions: Genitourinary Syndrome of Menopause. Content last reviewed August 2022. Effective Health Care Program, Agency for Healthcare Research and Quality, Rockville, MD.
https://effectivehealthcare.ahrq.gov/products/genitourinary-syndrome/key-questions

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