Whole-Body Cryotherapy as a Non-Pharmacological Treatment to Reduce Chronic Pelvic Pain and Improve Quality of Life in People With Endometriosis

Endometriosis is a chronic inflammatory and estrogen-dependent condition characterized by the presence of endometrial-like tissue outside the uterus, commonly associated with persistent pelvic pain, reduced quality of life, and significant long-term morbidity. Despite available hormonal and surgical treatments, a substantial proportion of individuals continue to experience chronic pain, highlighting an unmet need for novel therapeutic approaches. Current treatment strategies do not fully address the underlying inflammatory, neurovascular, and nociceptive mechanisms that contribute to pain persistence and central sensitization in endometriosis.

Whole-body cryotherapy (WBCT) is a non-pharmacological intervention involving brief exposure to extremely low temperatures, which has been associated with anti-inflammatory, analgesic, and neuromodulatory effects in other chronic conditions. Proposed mechanisms include modulation of systemic inflammatory pathways, reduction of oxidative stress, and effects on central pain processing. However, the potential role of WBC in the management of endometriosis-associated pain has not yet been established.

This study is a single-site, single-arm interventional pilot study designed to evaluate the feasibility, safety, acceptability, and preliminary efficacy of a structured WBCT intervention in individuals with symptomatic endometriosis. In addition to clinical outcomes, the study aims to explore biological mechanisms underlying potential treatment effects through the assessment of systemic inflammatory and other biomarkers.

Participants will undergo a standardized course of WBCT sessions over a two-week period, with repeated clinical and biological assessments conducted at predefined timepoints. Clinical outcomes will include patient-reported measures of pain, quality of life, fatigue, sleep, and other symptom domains, as well as analgesic use and global impression of change. Feasibility outcomes will include recruitment rates, retention, and participant acceptability of the intervention and study procedures.

Biological assessments will include the collection of blood (venous and capillary), saliva, urine, vaginal, and stool samples to evaluate markers of systemic inflammation, stress, and gut health. Samples will be collected at baseline, during the intervention period, and at follow-up, enabling exploration of temporal changes associated with WBC exposure.

Study visits will be conducted at baseline and post-intervention, with an additional remote follow-up evaluation. The intervention phase includes multiple WBC sessions delivered at a dedicated facility, with complementary data collection performed both in-clinic and through self-collected samples.

The findings from this exploratory study will provide preliminary evidence on the clinical and biological effects of WBCT in endometriosis, inform the feasibility of larger controlled trials, and contribute to understanding whether WBCT may represent a novel non-pharmacological approach targeting inflammatory and nociceptive pathways in endometriosis-associated pain.

• Change in average pain over the preceding week measured by an 11-point Numerical Rating Scale (NRS) [Срок оценки: From baseline to 15 weeks]
• Change in neuropathic pain assessed by the PainDETECT questionnaire (PD-Q) [Срок оценки: From baseline to 4 weeks and 15 weeks]
• Change in quality of life assessed by Endometriosis Health Profile (EHP-30) [Срок оценки: From baseline to 4 weeks and 15 weeks]
• Change in health-related quality of life assessed by EQ-5D-5L questionnaire [Срок оценки: From baseline to 4 weeks and 15 weeks]
• Change in severity of fibromyalgia symptoms assessed by Fibromyalgia Impact questionnaire [Срок оценки: From baseline to 4 weeks and 15 weeks]
• Change in fatigue assessed by the Fatigue Severity Scale (FSS) [Срок оценки: From baseline to 4 weeks and 15 weeks]
• Change in sleep quality assessed by the Sleep Timing Questionnaire (STQ) [Срок оценки: From baseline to 4 weeks and 15 weeks]
• Change in analgesic use during the study period [Срок оценки: From baseline to 4 weeks and 15 weeks]
• Feasibility assessed by recruitment and retention rates [Срок оценки: Frome baseline to study end. Up to 12 months]
• Patient satisfaction assessed by Patient Global Impression of Change (PGIC) questionnaire [Срок оценки: At 4 weeks and 15 weeks]
• Acceptability of the intervention assessed by a study-specific questionnaire [Срок оценки: At 4 weeks and 15 weeks]
• Change in cognitive symptoms (brain fog) assessed by the Brain Fog Scale (BFS) [Срок оценки: From baseline to 4 weeks and 15 weeks]