BJOG · Nov 8, 2026
Comparative Efficacy and Safety of Modern Treatment Modalities for Genitourinary Syndrome of Menopause: A Systematic Review and Network Meta‐Analysis
By Randombage PJS, Akurugodagama MS
Background: Genitourinary syndrome of menopause (GSM) is a chronic consequence of hypoestrogenism affecting vaginal, sexual and lower urinary tract health. Treatments include local vaginal oestrogen, intravaginal prasterone, oral ospemifene, hyaluronic acid preparations, moisturisers/lubricants and energy‐based interventions, but comparative evidence is heterogeneous. Objectives: To compare the relative efficacy and safety of contemporary GSM therapies using a systematic review and class‐level network meta‐analysis (NMA) of randomised controlled trials. Search Strategy: MEDLINE/PubMed, Scopus, Cochrane CENTRAL, Web of Science, Google Scholar, ClinicalTrials.gov and WHO ICTRP were searched from inception to March 2026, with backward and forward citation searching. Selection Criteria: Randomised controlled trials enrolling postmenopausal women with symptomatic GSM or equivalent diagnoses. Data Collection and Analysis: Two reviewers independently screened, extracted and linked reports from the same trial family and assessed RoB 2. The primary outcome was harmonised patient‐reported symptom burden, using a prespecified hierarchy of global symptom score, most bothersome symptom, dyspareunia and vaginal dryness. A frequentist random‐effects consistency NMA generated; Hedges g standardised mean differences (SMDs), 95% confidence intervals (CIs), prediction intervals and P‐scores. Heterogeneity was estimated by REML; node splitting, a design‐by‐treatment interaction decomposition and sensitivity analyses assessed incoherence and influence. Confidence in all 21 network comparisons was evaluated with CINeMA using a validated percentage contribution matrix. Results: Twenty‐six efficacy publications represented 24 unique trial families and 4958 randomised participants after denominator adjudication. The primary symptom NMA included 15 trial families, seven nodes and 3415 participants. Versus placebo/sham/control, local vaginal oestrogen was the only class with a CI excluding the null (SMD 0.34, 95% CI 0.02–0.66). Estimates were imprecise for prasterone (0.37, −0.10 to 0.84), hyaluronic acid (0.31, −0.10 to 0.72), ospemifene (0.24, −0.38 to 0.87), moisturiser/lubricant (0.15, −0.37 to 0.67) and CO ₂ laser (0.03, −0.56 to 0.61). Heterogeneity remained material ( τ ² = 0.097; I ² = 65.6%). Node splitting showed no statistically detectable local incoherence (all p ≥ 0.35) and the global design‐by‐treatment interaction decomposition was also non‐significant (Q = 4.90, df = 3, p = 0.179). P‐scores were similar for local oestrogen (0.704) and prasterone (0.704) and rankings were sensitivity‐dependent. CINeMA confidence was low for local oestrogen versus placebo/sham/control and prasterone versus placebo/sham/control and very low for the remaining 19 network comparisons. Radiofrequency was not included in the primary symptom NMA because a hierarchy‐compatible continuous symptom effect with extractable dispersion was unavailable. Overall RoB 2 was low for 2 trial families, some concerns for 11 and high for 11. Conclusions: Local vaginal oestrogen remains the best‐supported benchmark for symptomatic GSM. Hyaluronic acid, prasterone and ospemifene have clinically relevant evidence, but cross‐class estimates are imprecise and rankings are unstable. CO ₂ laser and radiofrequency should not be positioned as equivalent or superior first‐line treatments on the available evidence. The data support individualised stepped care rather than a definitive treatment hierarchy. Trial Registration: PROSPERO CRD420261332305