Effectiveness and Safety of Emerging Therapies Versus Conventional Treatments or Placebo for Chronic Gynecologic Pelvic Pain in Adult Women: A Systematic Review

Background: Chronic gynecologic pelvic pain (CGPP) is a multifactorial condition associated with functional impairment and heterogeneous treatment responses. Emerging therapies are increasingly being used. However, their comparative effectiveness and safety remain uncertain. Methods: We conducted a systematic review of comparative studies in adult women (≥18 years) with CGPP lasting ≥6 months. Interventions included pelvic floor rehabilitation, botulinum toxin type A (BoNT-A), psychological and behavioral therapies, nutraceuticals, and oral gonadotropin-releasing hormone (GnRH) antagonists. MEDLINE, EMBASE, and CENTRAL were searched from inception without language restrictions. Study selection and data extraction were performed independently by two reviewers. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool. Due to substantial heterogeneity across study populations, interventions, comparators, outcomes, and follow-up durations, a meta-analysis was not performed. Findings were synthesized narratively and stratified according to predefined pain phenotypes based on the primary clinical diagnosis reported in each study, including endometriosis-associated pain, pelvic floor myofascial pain, and vulvodynia. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results: 21 studies were included. Pelvic floor training was associated with modest reductions in current pelvic pain at 4 and 12 months. Evidence for BoNT-A was inconsistent across studies of pelvic floor myalgia and vestibulodynia. Psychological interventions demonstrated more consistent improvements in functional and psychosocial outcomes than in pain intensity. GnRH antagonists produced dose-dependent reductions in endometriosis-associated pain, with higher responder rates than placebo, but were associated with hypoestrogenic adverse effects. Conclusions: Emerging therapies may offer benefits in specific CGPP phenotypes; however, the available evidence remains heterogeneous. A phenotype-informed, multimodal treatment approach may be considered, with careful attention to potential safety trade-offs. Registration: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420261302453. Registration record: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261302453.