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.

Inclusion criteria

• Women or assigned female at birth
• Aged 16 or over
• Endometriosis identified at laparoscopy or imaging, performed within the last ten years
• Chronic pelvic pain for more than six months
• Willing to comply with the treatment
• Willing to use effective contraception throughout the trial (if needed)
• Willing and able to give informed consent

Exclusion criteria

• Pregnant, breastfeeding or actively trying to get pregnant
• Post-menopausal (no periods for >12 months and not taking hormonal treatments to prevent periods, or bilateral oophorectomy performed)
• Previous hysterectomy with bilateral oophorectomy
• Raynaud's Disease
• Current treatment for malignancy
• Diabetes
• Known hypothyroidism
• Pre-existing or current diagnosis of anaemia
• Cardiovascular disease: severe hypertension (180/100, unstable angina, arrhythmia, recent (<6months) myocardial infarction, peripheral artery disease, cardiac pacemaker, recent (<6months) stroke or transient ischaemic attack)
• Acute kidney and urinary tract diseases
• Cryoglobulinemia
• Previous venous thromboembolism or peripheral artery occlusive disease
• Cold urticaria
• Livedo reticularis
• Open wounds or ulcers, large-area bacterial and viral skin infections
• Uncontrolled seizure disorder
• Known coagulopathy (eg von Willibrand disease, haemophilia)
• Severe claustrophobia
• Acute infections and fever
• Intoxication (alcohol, drugs)
• Signs or symptoms of cold allergy
• Severe wasting diseases
• Known Hepatitis B/C and/or HIV (due to Royal Mail restrictions on biospecimen postage)