Botulinum Toxin and Hyaluronic Acid Fillers in Contemporary Obstetrics and Gynaecology: Mechanisms, Clinical Applications, and Future Directions

 Introduction

Pelvic floor dysfunction and vulvovaginal pain syndromes significantly affect quality of life in women and often persist despite standard therapy (1,2). Standard therapies including physiotherapy, pharmacological treatment, and surgery are effective in many cases but are insufficient in refractory disease (1,20).

Botulinum toxin (BoNT) and hyaluronic acid (HA) fillers have emerged as minimally invasive adjuncts in functional gynaecology (3,10). Their use remains largely off-label and heterogeneous across clinical practice (3,12).

Despite increasing clinical interest, the absence of standardised protocols, variability in patient selection, and limited long-term safety data continue to restrict their integration into routine care.

Pelvic floor disorders encompass a spectrum of conditions including pelvic floor hypertonicity, vaginismus, vulvodynia, dyspareunia, and chronic pelvic pain, often characterised by complex and multifactorial pathophysiology involving neuromuscular dysfunction, central sensitisation, hormonal influences, and psychosocial factors (1,2). These overlapping mechanisms frequently necessitate multidisciplinary management approaches integrating physiotherapy, pain medicine, sexual health, and psychological support. In this context, BoNT offers a targeted neuromodulatory approach through reversible chemodenervation, potentially interrupting maladaptive pain–spasm cycles, while HA fillers provide structural and hydrophilic support to vulvovaginal tissues, with emerging interest in their role as regenerative biomaterials (3,10). The combined functional and structural rationale underlying these therapies reflects a broader shift towards minimally invasive, mechanism-based interventions in gynaecology.

However, current evidence remains fragmented, with substantial heterogeneity in study design, dosing strategies, injection mapping, and outcome measures across published studies (3,12). Furthermore, most applications fall outside established regulatory indications, highlighting the need for rigorous evaluation of safety, efficacy, and reproducibility before widespread adoption.

This review aims to synthesise current evidence on the mechanisms, clinical applications, safety profile, and future directions of BoNT and HA fillers in obstetrics and gynaecology, with emphasis on their role in functional pelvic disorders and emerging regenerative approaches.

Methods

A structured narrative review was conducted in accordance with BJOG expectations for evidence-based reviews. The review methodology was designed to ensure transparency, reproducibility, and alignment with established principles for narrative synthesis of heterogeneous clinical evidence.

MEDLINE, PubMed, EMBASE, Scopus, and the Cochrane Library were searched for studies published between1995 and 2026. Additional hand-searching of reference lists from key systematic reviews and consensus statements was performed to ensure comprehensive capture of relevant literature.

Search terms included combinations of: botulinum toxin, hyaluronic acid, pelvic floor dysfunction, vulvodynia, vaginismus, chronic pelvic pain, urogynecology, and regenerative gynaecology. Search strategies were adapted for each database using appropriate Boolean operators and Medical Subject Headings (MeSH) where applicable.

Inclusion criteria:

• Randomised controlled trials

• Systematic reviews and meta-analyses

• Prospective and retrospective cohort studies

• High-quality observational studies

• Relevant translational studies

Exclusion criteria:

• Non-English publications without translation

• Case reports lacking clinical relevance

• Studies without full-text availability

• Studies with insufficient methodological detail for interpretation

Evidence was categorised according to Oxford Centre for Evidence-Based Medicine (OCEBM) levels:

• Level I: RCTs / meta-analyses

• Level II: Cohort studies

• Level III: Observational studies

• Level IV: Case series / experimental studies

Study quality and relevance were assessed narratively with emphasis on study design, sample size, outcome measures, and risk of bias, given the heterogeneity of available literature in this field.

Mechanisms of Action

Botulinum Toxin

Botulinum toxin (BoNT) exerts its primary pharmacological effect through inhibition of acetylcholine release at the neuromuscular junction via SNAP-25 cleavage, resulting in reversible chemical denervation and muscle relaxation (3,4). This neuromuscular blockade underpins its established clinical utility in conditions characterised by pelvic floor hypertonicity, myofascial spasm, and functional outlet obstruction syndromes. In addition to its motor effects, BoNT has been shown in experimental and translational models to modulate nociceptive signalling pathways. This includes inhibition of neurotransmitters such as substance P and calcitonin gene-related peptide (CGRP), which are involved in peripheral pain transmission and neurogenic inflammation (2,3). These mechanisms provide a theoretical basis for its use in chronic pelvic pain and vulvovaginal pain syndromes, although the extent to which sensory modulation contributes to clinical improvement in gynaecological populations remains incompletely defined.

Further preclinical evidence suggests potential effects on peripheral sensitisation, autonomic dysregulation, and local inflammatory mediators. However, these findings are largely derived from non-gynaecological models, and their translation into consistent, measurable clinical benefit in pelvic pain disorders remains uncertain. As such, BoNT in gynaecology should currently be considered primarily a neuromuscular modulator, with secondary and still investigational analgesic and anti-inflammatory properties.

Clinical indications and injection protocols derived from these mechanisms are summarised in Table 1.

Table 1: Clinical Indications and Injection Protocols

Hyaluronic Acid Fillers

Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan with viscoelastic and hygroscopic properties that enable restoration of tissue volume, hydration, and mechanical cushioning (10,11). In gynaecological applications, these properties are relevant to mucosal integrity, tissue elasticity, and structural support within the vulvovaginal and periurethral environments.

Beyond its mechanical role, HA may influence the extracellular matrix by creating a hydrated scaffold that facilitates cell migration and tissue remodelling. This has led to interest in its potential role in regenerative gynaecology, particularly in conditions associated with tissue atrophy, scarring, or post-traumatic structural deficiency.

However, evidence supporting true regenerative or disease-modifying effects of HA in pelvic tissues remains limited. Most proposed biological mechanisms, including fibroblast activation, collagen modulation, and angiogenic signalling, are extrapolated from dermatological, orthopaedic, or wound-healing literature rather than direct gynaecological studies. Consequently, while HA demonstrates clear structural and symptomatic benefits in selected indications, its regenerative potential in pelvic floor and vulvovaginal pathology remains largely theoretical and requires validation in controlled, disease-specific clinical trials.

Technical considerations and expected clinical outcomes related to both BoNT and HA procedures are detailed in Table 2.

Table 2: Technical Considerations, Expected Outcomes, and Safety Principles for Botulinum Toxin and Hyaluronic Acid Procedures in Gynaecology

Clinical Decision- Making Framework

A phenotype-driven approach is increasingly recognised as essential for optimising outcomes with botulinum toxin (BoNT) and hyaluronic acid (HA) interventions in functional gynaecology. Patients with pelvic floor dysfunction and chronic pelvic pain syndromes are best stratified according to dominant pathophysiological drivers, including myofascial hypertonicity, neuropathic sensitisation, hormonal atrophy, and mixed pain phenotypes.

BoNT is most appropriately considered in patients with demonstrable pelvic floor overactivity or spasm-dominant pathology, particularly when symptoms are refractory to conservative therapy.

In contrast, HA-based interventions are more suitable for structural and atrophic conditions characterised by loss of tissue elasticity, hydration, or volumetric support.

A sequential treatment model is therefore proposed, in which first-line conservative measures are optimised prior to consideration of injectable therapies, with escalation guided by symptom phenotype, response trajectory, and multidisciplinary assessment.

Clinical Applications

1. Established Indications (LEVEL I–II) Pelvic Floor Hypertonicity

Botulinum toxin (BoNT) reduces pelvic floor muscle spasm and improves EMG-measured relaxation (3,7). Meta-analyses demonstrate significant symptom improvement in selected cohorts (3). Clinical benefit is most consistently observed in patients with objectively documented pelvic floor hypertonicity, particularly when confirmed via clinical examination and/or electrophysiological assessment. Outcomes appear optimised when BoNT is integrated within structured multidisciplinary programmes, including pelvic floor physiotherapy, graded muscle retraining, and behavioural rehabilitation strategies. This combined approach is increasingly considered essential for sustained functional improvement rather than isolated pharmacological intervention. These clinical indications, dosing strategies, and injection approaches are detailed in Table 1.

Overactive Bladder

Randomised controlled trials demonstrate improved bladder capacity and reduced urgency symptoms following intradetrusor BoNT injection (4,5). These effects are primarily attributed to chemodenervation of detrusor smooth muscle, leading to reduced involuntary contractions and increased functional bladder storage capacity. Additional effects on afferent signalling pathways have been proposed, although their clinical relevance remains incompletely defined. Overall, BoNT is now an established third-line therapy for refractory overactive bladder in appropriately selected patients.

Refractory Vaginismus

BoNT combined with graded vaginal dilation therapy improves penetration success rates in clinical studies (6,19). The therapeutic effect is thought to arise from temporary reduction of involuntary pelvic floor hypertonicity, creating a neurophysiological “window of reduced guarding” that facilitates desensitisation-based rehabilitation. Best outcomes are consistently reported when BoNT is delivered as part of a multidisciplinary framework incorporating psychosexual counselling, behavioural therapy, and structured dilator programmes, highlighting the importance of addressing both neuromuscular and psychogenic components of the disorder.

Procedural considerations, expected outcomes, and treatment principles are outlined in Table 2.

2. Off-Label Indications (LEVEL II–III) Chronic Pelvic Pain

BoNT reduces pain scores in selected patients, particularly those with predominant pelvic floor hypertonicity, although heterogeneity across studies limits certainty (1-3). Clinical response appears more consistent in myofascial and peripheral pain phenotypes compared with centrally mediated or sensitisation-dominant pain syndromes. This suggests that careful phenotyping of chronic pelvic pain is critical in predicting therapeutic response and avoiding overgeneralisation of treatment effects.

Vulvodynia

Randomised controlled trial evidence suggests symptom reduction in provoked vestibulodynia (6,9). The magnitude of benefit appears greatest in patients with coexisting pelvic floor muscle overactivity, supporting a significant neuromuscular contribution to symptom generation in a subset of patients. However, variability in diagnostic criteria and outcome measures limits direct comparison between studies, and broader applicability remains uncertain.

Dyspareunia

Observational studies report improvement in sexual pain symptoms across mixed aetiologies (9). Reported benefits likely reflect the heterogeneous nature of dyspareunia, which may include hormonal, neuropathic, inflammatory, and musculoskeletal contributors. This variability significantly limits generalisability, and current evidence should be interpreted cautiously. Further stratified research is required to identify responders and define optimal treatment algorithms.

Comparative Positioning of BoNT and HA

BoNT and HA fillers occupy distinct but potentially complementary therapeutic roles within functional and reconstructive gynaecology. BoNT primarily targets neuromuscular dysfunction through reversible chemodenervation, making it most suitable for conditions characterised by pelvic floor hyperactivity and pain driven by muscular spasm.

By contrast, HA fillers provide mechanical and structural support through viscoelastic tissue augmentation, making them more relevant in conditions associated with tissue atrophy, volume loss, or compromised mucosal integrity.

While BoNT demonstrates stronger evidence across randomised controlled trials, HA interventions remain predominantly supported by observational data. Emerging clinical interest lies in the potential for combined or sequential use, particularly in complex phenotypes where both functional spasm and structural deficiency coexist.

Clinical selection, procedural strategy, and safety considerations are further synthesised