Endorsed by The International Society for the Study of Women’s Sexual Health (ISSWSH), The Sexual Medicine Society of North America (SMSNA), and The Menopause Society (TMS).

Unabridged version of this Guideline [pdf]

To cite this guideline:

Kaufman MR, Ackerman LA, Amin KA, et al. The AUA/SUFU/AUGS Guideline on Genitourinary Syndrome of Menopause. J Urol. 0(0). doi:10.1097/JU.0000000000004589. https://www.auajournals.org/doi/10.1097/JU.0000000000004589

Melissa R. Kaufman, MD, PhD; A. Lenore Ackerman, MD, PhD; Katherine A. Amin, MD; Marge Coffey, MSW; Stephanie S. Faubion, MD, MBA; Anne Hardart, MD; Irwin Goldstein, MD; Giulia M. Ippolito, MD, MS; Gina M. Northington, MD, PhD; Charles R. Powell, MD; Rachel S. Rubin, MD; O. Lenaine Westney, MD; Tracey S. Wilson, MD; Una J. Lee, MD

Systematic Review prepared by the Minnesota Evidence-based Practice Center, Minneapolis, MN. Investigators: Elisheva R. Danan, MD, MPH; Susan Diem, MD, MPH; Catherine Sowerby, BA; Kristen Ullman, MPH; Kristine Ensrud, MD, MPH; Adrienne Landsteiner, PhD, MPH; Nancy Greer, PhD; Nicholas Zerzan, MPH; Maylen Anthony, MPH; Caleb Kalinowski, MS; Mary Forte, PhD, DC; Hamdi I. Abdi, MPH; Jessica K. Friedman, PhD; Rahel Nardos, MD, MS; Cynthia Fok, MD, MPH; Philipp Dahm, MD, MHSc; Mary Butler, PhD, MBA; Timothy J. Wilt, MD, MPH

Purpose

Genitourinary syndrome of menopause (GSM) describes the spectrum of symptoms and physical changes resulting from declining estrogen and androgen concentrations in the genitourinary tract during the menopausal transition.¹ There has not been a consensus reached about the number or type of symptoms (vulvovaginal, urinary, or sexual) needed to diagnose GSM, nor a requirement for identifying concurrent physical signs.^{2, 3}  Furthermore, the urinary symptoms associated with GSM are also linked with other common urologic conditions in older patients, such as overactive bladder, making identification, evaluation, and treatment complex.⁴ This guideline provides information to clinicians regarding identification, diagnosis, counseling, and treatment for patients with GSM to optimize symptom control and quality of life while minimizing adverse events.  The strategies defined in this document were derived from evidence-based and consensus-based processes; however, shared decision-making is the optimal strategy to individualize level of impact and ultimate interventions. Outreach to the marginalized and underserved GSM population is essential; this guideline will give clinicians across a multitude of disciplines the tools to evaluate, manage, and treat GSM patients.

Methodology

The systematic review utilized in the creation of this guideline is based on research conducted by the Minnesota Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ) and funded by the Patient Centered Outcomes Research Institute (PCORI).⁵ Low and moderate risk of bias studies were synthesized and provided Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty of evidence (COE) ratings for 8 patient-centered outcomes identified by the Core Outcomes in Menopause (COMMA) review¹ as most important to patients and clinicians, including: (1) pain with sex, (2) vulvovaginal dryness, (3) vulvovaginal discomfort/irritation, (4) dysuria, (5) change in Most Bothersome Symptom (MBS), (6) distress, bother, or interference of genitourinary symptoms, (7) satisfaction with treatment, and (8) treatment side effects. 

After assessing 107 publications for risk of bias (RoB), the EPC extracted and synthesized effectiveness and/or harms outcomes from 68 publications that were rated low, some concerns, or moderate RoB (24 estrogen publications, 35 non-estrogen, 11 energy-based, and 4 moisturizers). Of 39 high, serious, or critical RoB publications, the EPC extracted long-term harms from only 15 uncontrolled studies of energy-based interventions (all serious or critical RoB due to confounding). An additional 66 publications evaluating 46 non-hormonal interventions, including natural products, mind/body practices, and educational interventions, were described in an evidence map. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions.

GUIDELINE STATEMENTS

Shared Decision Making

1. Clinicians and patients should engage in shared decision-making, taking into consideration the best available evidence and the patient’s expressed values, preferences, and goals of GSM care. (Clinical Principle)

Screening & Diagnosis

2. Clinicians should screen patients at risk for, or presenting with signs of, GSM for genital, sexual, and/or urinary symptoms using a focused medical, sexual, and psychosocial history. (Clinical Principle)
3. Patients with symptoms of GSM should undergo a genitourinary examination. (Clinical Principle)
4. Clinicians should educate patients with GSM about genitourinary signs and symptoms that result from decreased sex steroid hormones. (Clinical Principle)
5. During evaluation of patients with GSM, clinicians should assess for coexisting genitourinary conditions, utilizing additional testing or referral when appropriate. (Clinical Principle)
6. In patients with GSM and psychosocial and/or sexual health concerns, clinicians may refer to a credentialed therapist. (Expert Opinion)
7. In patients with GSM and pelvic floor dysfunction, clinicians may refer to a physical therapist specializing in pelvic floor conditions. (Expert Opinion)

Hormonal Interventions

8. Clinicians should offer the option of local low-dose vaginal estrogen to patients with GSM to improve vulvovaginal discomfort/irritation, dryness, and/or dyspareunia. (Strong Recommendation; Evidence Level: Grade C)
9. Clinicians should offer the option of vaginal dehydroepiandrosterone (DHEA) to patients with GSM to improve vulvovaginal dryness and/or dyspareunia. (Moderate Recommendation; Evidence Level: Grade C)
10. Clinicians may offer the option of ospemifene to patients with GSM to improve vulvovaginal dryness and/or dyspareunia. (Conditional Recommendation; Evidence Level: Grade C)
11. In patients with GSM who are on systemic estrogen therapy, clinicians should offer the option of local low-dose vaginal estrogen or vaginal dehydroepiandrosterone (DHEA). (Expert Opinion)
12. In patients with GSM and comorbid genitourinary conditions (e.g., overactive bladder), clinicians may offer the option of local low-dose vaginal estrogen to improve genitourinary symptoms. (Expert Opinion)
13. In patients with GSM and recurrent urinary tract infections, clinicians should recommend local low-dose vaginal estrogen to reduce the risk for future urinary tract infections. (Moderate Recommendation; Evidence Level: Grade B)

Non-Hormonal Interventions

14. Clinicians should recommend the use of vaginal moisturizers and/or lubricants, either alone or in combination with other therapies, to improve vaginal dryness and/or dyspareunia in patients with GSM. (Moderate Recommendation; Evidence Level: Grade C)
15. Clinicians should counsel patients that the evidence does not support the use of alternative supplements in the treatment of GSM. (Expert Opinion)
16. Clinicians should counsel patients to avoid vulvovaginal irritants and/or cleansers which may exacerbate the signs and symptoms of GSM. (Expert Opinion)

Energy-Based Interventions

17. Clinicians should counsel patients that the evidence does not support the use of CO₂ laser, ER:YAG laser, or radiofrequency in the treatment of GSM-related vulvovaginal dryness, vulvovaginal discomfort/irritation, dysuria, quality of life, change in bothersome symptoms, satisfaction with treatment, or dyspareunia. (Moderate Recommendation, Evidence Level: Grade C)
18. In the context of shared decision-making, and with the disclosure that these therapies are considered experimental outside of clinical trials, clinicians may consider CO₂ laser treatment in patients who are not candidates for, or prefer alternatives to, FDA-approved treatments for GSM-related vulvovaginal dryness, vulvovaginal discomfort/irritation, dysuria, and/or dyspareunia. (Expert Opinion)

Breast and Endometrial Cancer

19. Clinicians should inform patients of the absence of evidence linking local low-dose vaginal estrogen to the development of breast cancer. (Expert Opinion)
20. For patients with GSM who have a personal history of breast cancer, clinicians may recommend local low-dose vaginal estrogen in the context of multi-disciplinary shared decision-making. (Expert Opinion)
21. Clinicians should counsel patients with GSM that neither vaginal dehydroepiandrosterone (DHEA) nor ospemifene increase the risk for breast cancer. (Expert Opinion)
22. Clinicians should counsel patients with GSM that local low-dose vaginal estrogen, does not increase the risk for endometrial hyperplasia with atypia or endometrial cancer. (Moderate Recommendation; Evidence Level: Grade C)
23. Clinicians should counsel patients with GSM that neither vaginal dehydroepiandrosterone (DHEA) nor ospemifene increase the risk for endometrial hyperplasia with atypia or endometrial cancer. (Moderate Recommendation; Evidence Level: Grade C)

Endometrial Surveillance

24. Clinicians should not perform endometrial surveillance in patients with GSM solely due to their use of local low-dose vaginal estrogen, vaginal dehydroepiandrosterone (DHEA), or ospemifene. (Expert Opinion)

Follow-Up

25. After initiation of treatment, clinicians should reassess patients with GSM to monitor response. (Clinical Principle)
26. Clinicians should counsel patients receiving therapy for GSM that long-term treatment and follow-up may be required to manage signs and symptoms. (Clinical Principle)

The source of the Introduction and Methodology text below, as well as some text summarizing evidence results, is drawn from the evidence report used to create this Guideline, “Genitourinary Syndrome of Menopause: A Systematic Review,” by the Minnesota Evidence-based Practice Center Program at the Agency for Healthcare Research and Quality (AHRQ) and funded by the Patient-Centered Outcomes Research Institute (PCORI®)⁵ The use of this report to derive clinical practice guidelines does not imply endorsement by PCORI®, AHRQ, or U.S. Department of Health and Human Services.

Genitourinary syndrome of menopause (GSM) describes the spectrum of symptoms and physical changes resulting from declining estrogen and androgen concentrations in the genitourinary tract during perimenopause and after menopause.¹ Menopause, which is defined as the phase that begins 12 months after the last menstrual period, is characterized by the natural decline in ovarian function and associated physiological changes that occur in most women in their early 50s.⁶  For some individuals, menopause is associated with vasomotor symptoms (i.e., hot flashes/flushes and/or night sweats) and/or genitourinary symptoms, with wide variability in prevalence, duration, and severity.⁷

Since introduction of the term GSM in 2014,¹ no consensus has been reached about the number or type of symptoms (vulvovaginal, urinary, or sexual) needed to diagnose GSM, nor a requirement for identifying concurrent physical signs.^{2, 3} Vulvovaginal symptoms associated with menopause include dryness, burning, and irritation.⁸ Urinary symptoms include urgency, frequency, dysuria, and recurrent urinary tract infections (UTI).⁹ The vulvovaginal and urinary effects of menopause are often considered the cause of sexual symptoms of GSM, including dyspareunia and bleeding during intercourse, as well as broader impacts on sexual function, such as reduced libido, arousal, and orgasm.^9-11 Physical changes associated with GSM include labial atrophy, reduced moisture, introital stenosis, and clitoral atrophy.¹ The vaginal surface may be friable and hypopigmented, with petechiae, ulcerations, and tears; urethral findings may include caruncles, prolapse, or polyps.⁴ However, presence and severity of physical exam findings do not directly correlate with self-reported GSM symptoms.^{4, 12, 13}

Clinicians generally diagnose GSM based on symptoms, with or without related physical findings, and after ruling out other etiologies or co-occurring pathologies (e.g., infectious vaginitis, vulvar lichen sclerosus, dermatitis, lichen planus, or an active UTI).^{9, 14, 15} Objective measures of postmenopausal vaginal changes include the Vaginal Maturation Index (VMI)¹⁶ and vaginal pH.¹⁷ The VMI demonstrates a shift from superficial cells to parabasal cells as the vaginal epithelium thins, and vaginal pH then rises as fewer superficial epithelial cells exfoliate and break down to release glycogen and glucose, which would typically be broken down into lactic acid by Lactobacilli in an estrogenized vagina.⁸  Trials have sometimes limited inclusion to patients with moderate to severe GSM symptoms, 5% or fewer superficial cells on VMI, and vaginal pH greater than 5, however these measures are neither required nor commonly used for clinical diagnosis and treatment of GSM.¹⁸

GSM prevalence estimates in postmenopausal patients vary widely from 13 to 87 percent.¹⁹ This inconsistency stems from many factors including variation in the symptoms and/or signs assessed and evaluated, the symptom assessment tools used, and the demographics and settings of study populations.¹⁹ Unlike vasomotor symptoms of menopause (i.e., hot flashes and/or night sweats), the prevalence and intensity of some genitourinary symptoms, such as vulvovaginal dryness, increase with advancing age.^{20, 21} GSM may be associated with reduced quality of life (QoL) and sexual functioning, and a higher likelihood of urinary complaints, all of which may interfere with interpersonal relationships.^22-27 Despite the potentially disruptive nature of GSM, only about half of individuals with GSM symptoms report discussing their symptoms with their clinicians, and of those who did, most said the clinician did not initiate the conversation.^{28, 29}

Several organizations recommend identifying GSM through a case-finding approach, by screening patients for symptoms with routine questions.^30-32 However, few tools have been validated for GSM assessment and existing tools are limited to vulvovaginal symptoms.^{10, 33} The urinary symptoms associated with GSM are also linked with other common urologic conditions in older patients, such as overactive bladder (OAB),  making identification, evaluation, and treatment of these symptoms complex.⁴ A causal relationship between reduced hormone levels and urinary symptoms remains controversial.^34-36 Some have even questioned whether GSM meets the definition of a disease syndrome.³⁷  These questions create uncertainty around the optimal approach to screening, identification, evaluation, and management of GSM.

Nonetheless, the range of GSM treatments has increased substantially in recent years.^{32, 38} Traditional therapies, such as vaginal estrogen, moisturizers, and lubricants restore, alleviate symptoms, or avoid friction, respectively.  Estrogen binds to receptors in the vagina, vulva, urethra, bladder, and pelvic floor, shifts the vaginal cytology toward superficial cells, away from parabasal cells, and reduces the vaginal pH. Vaginal moisturizers increase the fluid content in the endothelium and reduce the vaginal pH. Personal lubricants can be water, silicone, or oil-based and are primarily used to provide short-term lubrication during sexual activity; lubricants are often used as a placebo or control treatment in clinical trials. Newer hormonal approaches include vaginal dehydroepiandrosterone (DHEA), vaginal oxytocin, selective estrogen receptor modulators (SERMs), and testosterone. DHEA is a precursor to both androgens and estrogens that is transformed into estradiol and testosterone within vaginal cells. Oxytocin is a pituitary hormone primarily implicated in uterine labor contractions and lactation, but vaginal oxytocin gel has also been shown to reduce vaginal pH and increase the proportion of superficial cells in small studies. SERMs have varied estrogen agonist/antagonist effects throughout the body; among SERMs, ospemifene has unique estrogen receptor agonist activity in vaginal tissue. Complementary therapies, including oral and vaginal natural products (e.g., herbal supplements, phytoestrogens, vitamins, probiotics), mind-body practices, pelvic floor physical therapy (PFPT), and educational interventions, offer various mechanisms of action while appealing to individuals who wish to avoid hormonal treatments. Finally, energy-based treatments such as laser and radiofrequency devices claim to stimulate collagen formation, angiogenesis, and epithelial thickening by causing microtrauma or heating superficial tissue layers.

Some of these treatments aim to improve a broad range of GSM symptoms, while others target a specific bothersome symptom. Randomized controlled trials (RCTs) are typically short term, and lack long-term intervention efficacy, adherence, or harms data. Study populations are often not comparable and confounding variables can impact the validity of the findings.  Consequently, guidance for longer-term follow-up and surveillance as well as treatment in special populations, such as patients with a history of hormonally sensitive breast cancer, has relied on expert consensus in the absence of robust evidence.^{30, 32, 39}

This guideline endeavors to provide information to clinicians regarding identification, diagnosis, counseling and treatment for patients with GSM to optimize symptom control and improve QoL while minimizing adverse effects (AE).  The strategies defined in this document were derived from evidence-based and consensus-based processes.  However, shared decision-making (SDM) is the optimal strategy to individualize level of impact and ultimate interventions. As outreach to this marginalized and underserved population is essential, the Panel trusts this document will guide all types of clinicians who evaluate, manage and treat patients with GSM across a multitude of disciplines.

The systematic review utilized in the creation of this guideline is based on research conducted by the Minnesota Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ) and funded by the Patient Centered Outcomes Research Institute (PCORI).  Searches covered publication dates from database inception through December 11, 2023. To improve applicability of findings to U.S. patients and clinicians, the EPC included only U.S.-available interventions. Where evidence was sufficient without an unacceptable amount of clinical heterogeneity, the EPC conducted pairwise meta-analyses. For studies that evaluated non-hormonal interventions (other than vaginal moisturizers), an evidence map describing study characteristics was created. For hormonal and energy-based interventions, and vaginal moisturizers, low and moderate risk of bias studies were synthesized and the EPC provided Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty of evidence (COE) ratings for 8 patient-centered outcomes identified by the Core Outcomes in Menopause (COMMA) review¹ as most important to patients and clinicians, including: (1) pain with sex, (2) vulvovaginal dryness, (3) vulvovaginal discomfort/irritation, (4) dysuria, (5) change in Most Bothersome Symptom (MBS), (6) distress, bother, or interference of genitourinary symptoms, (7) satisfaction with treatment, and (8) treatment side effects. The EPC derived COE from statistical rather than clinical significance or effect magnitude, in part because validated measures of clinically meaningful differences do not exist for most outcomes.

Results

After assessing 107 publications for risk of bias (RoB), the EPC extracted effectiveness and/or harms outcomes from 68 publications describing trials or prospective, controlled observational studies that were rated low, some concerns, or moderate RoB (24 estrogen publications, 35 non-estrogen, 11 energy-based, and 4 moisturizers). Of 39 high, serious, or critical RoB publications, the EPC only extracted long-term harms from 15 uncontrolled studies of energy-based interventions (all serious or critical RoB due to confounding). Among 19 high RoB randomized controlled trials (RCT), the most common source of bias was missing outcome data. An additional 66 publications evaluating 46 non-hormonal interventions are described in an evidence map. Most non-hormonal interventions in the evidence map were focused on natural products (i.e., herbal or botanical supplements, vitamins) and were small in sample size. Five trials^{1-3, 6, 7} (9 publications) compared active interventions from more than one category with placebo and are counted more than once in the description above. The relevant arms of each trial are described in their respective sections.

Key Questions (Appendix A)

No studies evaluated Key Questions (KQ) related to GSM screening (KQ1) or directly addressed appropriate follow-up intervals (KQ4) or the effectiveness and harms of endometrial surveillance (KQ5).

For efficacy/effectiveness (KQ2) and harms (KQ3), the certainty of evidence for most intervention-comparison-outcome combinations was low or very low; COE was moderate or high for only a few comparisons. Overall, for KQ2 the EPC concluded that vaginal estrogen, vaginal DHEA, vaginal moisturizers, and oral ospemifene, may all improve at least some GSM symptoms, primarily vulvovaginal dryness and, to a lesser extent, dyspareunia. No treatment significantly improved vaginal discomfort/irritation or dysuria. Placebo effect was high, particularly in studies using a lubricating vaginal gel or cream placebo. Evidence does not demonstrate the efficacy of energy-based therapies (carbon dioxide [CO₂] or Erbium-doped yttrium aluminum garnet [Er:YAG] laser), vaginal or systemic testosterone, vaginal oxytocin, oral raloxifene, or bazedoxifene for any GSM symptoms.

Compared with placebo, vaginal estrogen may improve vulvovaginal dryness, MBS, and treatment satisfaction (low COE), but probably results in little to no difference in QoL (moderate COE) and may result in little to no difference in dyspareunia or dysuria (low COE). Compared with no treatment, vaginal estrogen may improve vulvovaginal dryness and dyspareunia and may result in little to no difference in vulvovaginal discomfort/irritation or dysuria (low COE).

Among non-estrogen hormonal interventions, vaginal DHEA compared with placebo may improve vulvovaginal dryness, dyspareunia, and QoL (low COE), but may result in more AEs (low COE). Oxytocin compared with placebo probably results in little to no difference in MBS (moderate COE) and may result in little to no difference in serious AEs (low COE). Ospemifene compared with placebo may improve vulvovaginal dryness and dyspareunia (low COE) and results in higher treatment satisfaction (high COE), but results in little to no difference in vulvovaginal discomfort/irritation (high COE) and may result in little to no difference in AEs (low COE). Raloxifene added to vaginal estrogen or moisturizer compared with vaginal estrogen or moisturizer plus placebo may result in little to no difference in vulvovaginal dryness, discomfort/irritation, dysuria, and dyspareunia (low COE). Bazedoxifene may improve QoL less than placebo (low COE). Oral bazedoxifene or raloxifene compared with placebo may result in higher treatment satisfaction (low COE).

Systemic estrogen plus systemic testosterone compared with systemic estrogen alone may result in little to no difference in vulvovaginal dryness and dyspareunia (low COE). Vaginal moisturizers compared with placebo may improve vulvovaginal dryness (low COE) but may result in little to no difference in MBS (low COE). Vaginal moisturizers compared with placebo probably result in little to no difference in AEs (moderate COE). Among energy-based interventions, CO₂ laser (compared with sham laser) may result in little to no difference in MBS, dysuria, QoL, or serious AEs (low COE). Compared with vaginal estrogen cream, CO₂ laser may result in little to no difference in vulvovaginal dryness, dyspareunia, discomfort/irritation, dysuria, QoL, or serious AEs (low COE). Er:YAG laser compared with sham laser may result in little to no difference in QoL (low COE).

For the eight COMMA outcomes defined above, the evidence was very uncertain (very low COE) for all other studied intervention-comparator-outcome combinations. The full report contains results for additional effectiveness outcomes, including recurrent urinary infections, sexual function, urinary incontinence, physical signs of vulvovaginal atrophy, common AEs, and warnings reported by the U.S. Food and Drug Administration (FDA).

Harms reporting (KQ3) was limited, in part, by studies not being sufficiently powered to evaluate infrequent but serious harms, though most studies did not find evidence of frequent serious harms. Infrequent AEs varied by treatment. For example, vaginal estrogen was associated with vaginal bleeding, discharge, and breast tenderness; vaginal DHEA was associated with increased facial hair, voice changes, and headaches; oral ospemifene was associated with hot flushes and vaginal candidiasis; and CO₂ laser was associated with vaginal bleeding, pain, and discharge. For KQ4, limited evidence within studies of effective treatments, suggests that symptoms begin improving within 1-2 months and continue to improve through 12 weeks (average length of study follow-up). For endometrial outcomes (KQ5), among hormonal interventions, ospemifene was associated with thickened endometrial lining, proliferative endometrial histology, and one case of endometrial hyperplasia. In 6 of 10 studies that evaluated endometrial stimulation up to 36 weeks, vaginal estrogen was associated with cases of vaginal bleeding, a nominal increase in endometrial thickness, proliferative endometrium, and one case of endometrial hyperplasia in a polyp. Limited evidence suggests that vaginal DHEA, vaginal oxytocin, oral bazedoxifene and raloxifene, and vaginal testosterone are not associated with clinically relevant endometrial stimulation as measured by transvaginal ultrasound or endometrial biopsy in primarily short-term studies and 3 year-long studies.

Determining the Evidence Strength

The GRADE⁴⁰ system was used to determine the aggregate evidence quality for each outcome, or group of related outcomes, informing Key Questions. GRADE defines a body of evidence in relation to how confident guideline developers can be that the estimate of effects as reported by that body of evidence is correct.  Evidence is categorized as high, moderate, low and very low, and assessment is based on the aggregate risk of bias for the evidence base, plus limitations introduced as a consequence of inconsistency, indirectness, imprecision and publication bias across the studies.⁴¹ Upgrading of evidence is possible if the body of evidence indicates a large effect or if confounding would suggest either spurious effects or would reduce the demonstrated effect.

The American Urological Association (AUA) employs a 3-tiered strength of evidence system to underpin evidence-based guideline statements. Table 1 summarizes the GRADE categories, definitions and how these categories translate to the AUA strength of evidence categories.  In short, high certainty by GRADE translates to AUA A-category strength of evidence, moderate to B, and both low and very low to C. 

Table 1: Strength of Evidence Definition

AUA Nomenclature: Linking Statement Type to Evidence Strength

The AUA nomenclature system explicitly links statement type to body of evidence strength, level of certainty, magnitude of benefit or risk/burdens, and the Panel’s judgment regarding the balance between benefits and risks/burdens (Table 2). Strong Recommendations are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken because net benefit or net harm is substantial. Moderate Recommendations are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken because net benefit or net harm is moderate. Conditional Recommendations are non-directive statements used when the evidence indicates there is no apparent net benefit or harm or when the balance between benefits and risks/burden is unclear. All three statement types may be supported by any body of evidence strength grade. Body of evidence strength Grade A in support of a Strong or Moderate Recommendation indicates the statement can be applied to most patients in most circumstances and that future research is unlikely to change confidence. Body of evidence strength Grade B in support of a Strong or Moderate Recommendation indicates the statement can be applied to most patients in most circumstances, but better evidence could change confidence. Body of evidence strength Grade C in support of a Strong or Moderate Recommendation indicates the statement can be applied to most patients in most circumstances, but better evidence is likely to change confidence. Body of evidence strength Grade C is only rarely used in support of a Strong Recommendation. Conditional Recommendations can also be supported by any evidence strength. When body of evidence strength is Grade A, the statement indicates benefits and risks/burdens appear balanced, the best action depends on patient circumstances, and future research is unlikely to change confidence. When body of evidence strength Grade B is used, benefits and risks/burdens appear balanced, the best action also depends on individual patient circumstances, and better evidence could change confidence. When body of evidence strength Grade C is used, there is uncertainty regarding the balance between benefits and risks/burdens, alternative strategies may be equally reasonable, and better evidence is likely to change confidence.

Where gaps in the evidence existed, Clinical Principles or Expert Opinions are provided via consensus of the Panel. A Clinical Principle is a statement about a component of clinical care widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature. Expert Opinion refers to a statement based on members' clinical training, experience, knowledge, and judgment for which there may or may not be evidence in the medical literature.

Table 2: AUA Nomenclature Linking Statement Type to Level of Certainty, Magnitude of Benefit or Risk/Burden, and Body of Evidence Strength

Panel Formation

The GSM Guideline Panel was created in 2022 by the American Urological Association Education and Research, Inc and in in collaboration with the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU) and the American Urogynecologic Society (AUGS). The Practice Guidelines Committee (PGC) of the AUA selected the Panel Chairs who in turn appointed the additional panel members based on an open nomination process. SUFU and AUGS each appointed two panelists. Additionally, the Panel included patient representation. Funding of the Guideline was provided by the AUA; panel members received no remuneration for their work. Funding for the AHRQ systematic review was provided by the PCORI.

Peer Review

An integral part of the guideline development process at the AUA is external peer review. The AUA conducted a thorough peer review process to ensure that the document was reviewed by experts in the diagnosis and treatment of Genitourinary Syndrome of Menopause. In addition to reviewers from the AUA PGC, Science and Quality Council (SQC), and Board of Directors (BOD), the document was reviewed by representatives from SUFU and AUGS and external content experts. A call for reviewers was placed on the AUA website from September 27 – October 11, 2024, to allow any additional interested parties to request a copy of the document for review. The guideline was also sent to the Urology Care Foundation and the AUA Public Policy & Advocacy team to open the document further to the patient perspective. The draft guideline document was distributed to 45 nominated peer reviewers, including 8 external reviewers (i.e., peer reviewers who responded to the call for comments), and 5 reviewers nominated by AUGS and SUFU; 40 AUA Committee members (PGC, SQC, BOD) and 16 AUA staff.  All peer review comments were blinded and sent to the Panel for review. In total, 43 reviewers provided comments, including 6 external reviewers. At the end of the peer review process, a total of 594 comments were received. Following comment discussion, the Panel revised the draft as needed. Once finalized, the guideline was submitted for approval to the AUA PGC, SQC, and BOD, the SUFU Executive Committee; and the AUGS Board of Directors for final approval. 

Clinicians and patients should engage in shared decision-making, taking into consideration the best available evidence and the patient’s expressed values, preferences, and goals of GSM care. (Clinical Principle)

Clinicians should screen patients at risk for, or presenting with signs of, GSM for genital, sexual, and/or urinary symptoms using a focused medical, sexual, and psychosocial history. (Clinical Principle)

Patients with symptoms of GSM should undergo a genitourinary examination. (Clinical Principle)

Clinicians should educate patients with GSM about genitourinary signs and symptoms that result from decreased sex steroid hormones. (Clinical Principle)

During evaluation of patients with GSM, clinicians should assess for coexisting  genitourinary conditions, utilizing additional testing or referral when appropriate. (Clinical Principle)

In patients with GSM and psychosocial and/or sexual health concerns, clinicians may refer to a credentialed therapist. (Expert Opinion)

In patients with GSM and pelvic floor dysfunction, clinicians may refer to a physical therapist specializing in pelvic floor conditions. (Expert Opinion)

While there is a large body of evidence that is supportive of both vaginal and systemic hormonal approaches to the management of GSM, there is insufficient evidence to compare the efficacy of these hormonal interventions against one another. Thus, this guideline is not meant to support a stepwise progression through different hormonal approaches, but instead to provide evidence to support a process of SDM between the clinician and patient in choosing an appropriate therapy. While there is insufficient information to recommend one hormonal therapy over another, the greatest amount of evidence and experience exists for vaginal estrogen supplementation. The consensus of the Panel is that the choice of agent should be considered not only using evidence of efficacy and AEs, but also of patient preference, accessibility, and ability to use consistently (i.e., patient dexterity, anatomy, social support).

There was insufficient evidence to support clinical recommendations for vaginal and systemic testosterone and oxytocin. The existing evidence and its limitations are detailed below.

Clinicians should offer the option of local low-dose vaginal estrogen to patients with GSM to improve vulvovaginal discomfort/irritation, dryness, and/or dyspareunia. (Strong Recommendation; Evidence Level: Grade C)

Clinicians should offer the option of vaginal dehydroepiandrosterone (DHEA) to patients with GSM to improve vulvovaginal dryness and/or dyspareunia. (Moderate Recommendation; Evidence Level: Grade C)

Clinicians may offer the option of ospemifene to patients with GSM to improve vulvovaginal dryness and/or dyspareunia. (Conditional Recommendation; Evidence Level: Grade C)

In patients with GSM who are on systemic estrogen therapy, clinicians should offer the option of local low-dose vaginal estrogen or vaginal dehydroepiandrosterone (DHEA). (Expert Opinion)

In patients with GSM and comorbid genitourinary conditions (e.g., overactive bladder), clinicians may offer local low-dose vaginal estrogen to improve genitourinary symptoms. (Expert Opinion)

In patients with GSM and recurrent urinary tract infections, clinicians should recommend local low-dose vaginal estrogen to reduce the risk for future urinary tract infections. (Moderate Recommendation; Evidence Level: Grade B)

Clinicians should recommend the use of vaginal moisturizers and/or lubricants, either alone or in combination with other therapies, to improve vaginal dryness and/or dyspareunia in patients with GSM. (Moderate Recommendation; Evidence Level: Grade C)

Clinicians should counsel patients that the evidence does not support the use of alternative supplements in the treatment of GSM. (Expert Opinion)

Clinicians should counsel patients to avoid vulvovaginal irritants and/or cleansers which may exacerbate the signs and symptoms of GSM. (Expert Opinion)

Clinicians should counsel patients that the evidence does not support the use of CO₂ laser, ER:YAG laser, or radiofrequency in the treatment of GSM-related vulvovaginal dryness, vulvovaginal discomfort/irritation, dysuria, quality of life, change in bothersome symptoms, satisfaction with treatment, or dyspareunia. (Moderate Recommendation, Evidence Level: Grade C)

In the context of shared decision-making, and with the disclosure that these therapies are considered experimental outside of clinical trials, clinicians may consider CO₂ laser treatment in patients who are not candidates for, or prefer alternatives to, FDA-approved treatments for GSM-related vulvovaginal dryness, vulvovaginal discomfort/irritation, dysuria, and/or dyspareunia. (Expert Opinion)

Clinicians should inform patients of the absence of evidence linking local low-dose vaginal estrogen to the development of breast cancer. (Expert Opinion)

For patients with GSM who have a personal history of breast cancer, clinicians may recommend local low-dose vaginal estrogen in the context of multi-disciplinary shared decision-making. (Expert Opinion)

Clinicians should counsel patients with GSM that neither vaginal dehydroepiandrosterone (DHEA) nor ospemifene increase the risk for breast cancer. (Expert Opinion)

Clinicians should counsel patients with GSM that local low-dose vaginal estrogen does not increase the risk for endometrial hyperplasia with atypia or endometrial cancer. (Moderate Recommendation; Evidence Strength: Level C)

Clinicians should counsel patients with GSM that neither vaginal dehydroepiandrosterone (DHEA) nor ospemifene increase the risk for endometrial hyperplasia with atypia or endometrial cancer. (Moderate Recommendation; Evidence Level: Grade C)

Clinicians should not perform endometrial surveillance in patients with GSM solely due to their use of local low-dose vaginal estrogen, vaginal dehydroepiandrosterone (DHEA), or ospemifene. (Expert Opinion)

After initiation of treatment, clinicians should reassess patients with GSM to monitor response.  (Clinical Principle)

Clinicians should counsel patients receiving therapy for GSM that long-term treatment and follow-up may be required to manage signs and symptoms. (Clinical Principle)

Comparable to other functional urologic conditions, GSM is a symptom and sign-based diagnosis made after careful clinical evaluation and at the exclusion of other causes. The hormonal imbalances that drive development of GSM manifest differently in each patient so tailoring individualized management strategies is fundamental for establishing goals of care. Thus, there is no single intervention for GSM which is universally effective or acceptable. Indeed, additional urologic and gynecologic conditions, such as OAB or sexual dysfunction, may co-exist with GSM and may need additional diagnosis-specific targeted treatment to meet the patient’s goals.

Understanding the concept of trauma-informed care for the GSM patient and utilizing language that supports patient choice and safety is important for clinicians during history-taking, performing physical exams, and providing treatment. Defining mechanisms for standardizing clinical training regarding counseling and logistics of examinations to preserve a patient’s dignity and avoiding negative triggers will empower both clinicians and patients. Given the intimate and impactful nature of GSM, patients should be cared for in a wholistic manner where diagnostic and treatment strategies are implemented in a compassionate and patient-centered manner.

In addition to the aforementioned need for standardized diagnostic criteria and outcomes, further exposure across disciplines to the terminology of GSM would assist to demystify the condition and further expand opportunities for access to care, as well as development of future interventions. Mandated within the framework of definitions would be standardized reporting for AE associated with treatments, or lack thereof, for patients with GSM.

Qualitative studies of the patient perspective on GSM¹⁸³ have identified themes including: the need for education on medications including usage instructions, discussion on potential side effects, interest in alternative therapies, and needing support for and validation of GSM and GSM symptoms from health care clinicians. Understanding and overcoming patient-centered barriers to common treatments is critical for driving both compliance and policy.¹⁸⁴ This guideline serves to begin the conversation to increase awareness and establish evidence-based best practices for clinicians. Future studies should continue to explore and include patient’s knowledge, attitudes, and beliefs, so that the medical community can better meet GSM patients’ needs.

With a standard language for GSM, it is important to collaborate and codify across disciplines to be able to accurately express symptoms such that they may be objectively measured. Broadly, phenotyping our patients to describe the manifestations of GSM on vaginal, urinary, and general pelvic health domains is critical to provide clinically meaningful and standardized research outcomes. A future direction may involve differentiation of the symptoms associated with GSM to best define what is implied by a syndrome.

With regards to expanding the relevance of research outcomes, intentional, community-engaged efforts to recruit clinically relevant and racialized, minoritized, and systematically excluded patient populations who have been historically left out of clinical trials and research studies must be implemented to increase the relevance and robustness of research outcomes. Including a broader, more inclusive population to reflect the real-world experience of patients and clinicians is key to increase the generalizability of research findings. Contemporary outreach efforts engaging local organizations and implementing telehealth strategies may facilitate inclusive engagement. Additionally, defining best practices with regards to time of follow up, including more long-term evaluation, is critically important for a condition that typically worsens or is subject to influence of comorbid conditions over time. The panel expressed the need for evaluation of otherwise marginalized populations outside of the traditional postmenopausal patient for inclusion in research to explore and establish best practices. This includes transgender patients, patients on systemic estrogen, young women using oral contraceptives, breast- or chest-feeding patients, individuals with hypothalamic amenorrhea, patient on gonadotropin regulating hormone for endometriosis or uterine fibroids, post-oophorectomy patients, and further analysis of the impact of interventions on cancer survivors. Further understanding of the wide manifestation of sex steroid deficiencies, including low and elevated follicle stimulating hormone impacts^{19, 30} should expand inclusion and drive recruitment in future clinical trials to serve patients with GSM.

Even with commonly accepted treatment strategies that have been outlined in these guidelines, there remain significant gaps in the comparative effectiveness of interventions. As the treatment decisions are individualized, these types of safety and efficacy parameters become a critical aspect of patient counseling. As outlined in earlier sections, the panel appreciates the impact of current boxed warning of estrogen products and advocates for national efforts to update these labels to reflect contemporary literature, particularly regarding low-dose vaginal estrogen. Development of studies defining and standardizing dosing and scheduling of interventions are important to reduce variation and comparison of therapies. Patient engagement and advocacy will help drive research on issues and research questions that matter most to patients with GSM. Comparative effectiveness studies and studies utilizing patient-centered outcome measures are essential to provide patients with information they need to make informed decisions about their health.

A singular limitation of the data interrogated in this guideline is the lack of high-level data detailing GSM treatment on commonly coexistent bladder symptoms and signs including OAB and recurrent UTIs. Future research in this arena is essential to determine best practices for prevention of conditions that negatively affect the QoL of an aging population. Additionally, future research efforts should be directed to understand the influence of local low-dose vaginal estrogen in patients being concurrently treated with systemic estrogen therapies as this represents a substantial population of high-impact.

And with regards to cost and access, this guideline does not address financial impact of either GSM or the treatments thereof. However, the panel acknowledges the potential financial burden for patients and expresses to the need to explore the issues of cost and access in future research.¹⁸²

In conclusion, the GSM is a common and undertreated condition affecting patients across the lifespan. Safe and effective treatments exist that alleviate bothersome symptoms and improve QoL. Increased education and awareness is critical to reach those affected by GSM. While there are evidence-based best practices in the area of GSM, future research is needed to deepen our understanding of this condition.

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Key Questions

KQ1. What are the effectiveness and harms of screening strategies to identify genitourinary syndrome of menopause (GSM) in postmenopausal women? Does screening impact patient reported symptoms or improve quality of life (QoL)?

KQ2. What are the effectiveness and comparative effectiveness of hormonal, non-hormonal, and energy-based interventions when used alone or in combination for treatment of GSM symptoms? Which treatments show improvement for which symptoms?

KQ3. What are the harms (and comparative harms) of hormonal, non- hormonal, and energy-based interventions for GSM symptoms?

KQ4. 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?

KQ5. What are the effectiveness, comparative effectiveness, and harms of endometrial surveillance among women who have a uterus and are using hormonal therapy for GSM?