Male vs. Female Differences in Responding to Oxygen-Ozone Autohemotherapy (O<sub>2</sub>-O<sub>3</sub>-AHT) in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Evidence Atlas

Male vs. Female Differences in Responding to Oxygen-Ozone Autohemotherapy (O2-O3-AHT) in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Chirumbolo, Salvatore, Valdenassi, Luigi, Franzini, Marianno et al. · Journal of clinical medicine · 2021 · DOI

Quick Summary

This study looked at how well a treatment called oxygen-ozone autohemotherapy (O₂-O₃-AHT) worked for ME/CFS fatigue in men versus women. Two hundred patients received this treatment and filled out a fatigue questionnaire before and one month after. The results showed that women experienced more improvement in their fatigue than men did, especially among younger patients aged 14-29.

Why It Matters

Sex-based differences in ME/CFS symptom severity and treatment response are understudied, and identifying that women may respond better to ozone therapy could help personalize treatment approaches. This finding suggests that biological sex may be an important factor in treatment planning for ME/CFS patients, potentially improving clinical outcomes.

Observed Findings

Female patients showed significantly greater fatigue reduction than males after one month of O₂-O₃-AHT (p=0.0002).
In the youngest cohort (14-29 years), females improved by 5.3 points on the FSS-7 while males improved by 3.8 points (28.3% difference).
Mean patient age was 33±13 years with 200 total participants enrolled.

Inferred Conclusions

Females respond better than males to oxygen-ozone autohemotherapy for ME/CFS-related fatigue.
Sex-based differences in treatment response are particularly prominent in younger ME/CFS patients.

Remaining Questions

What biological mechanisms explain why females show better treatment response than males?
Does this sex-based difference persist beyond one month of follow-up?
How do these results compare to other ME/CFS treatments, and is ozone therapy more effective than standard care?
Are there hormonal, genetic, or immunological factors that account for the observed sex-based disparities?

What This Study Does Not Prove

This study does not prove that ozone therapy is an effective ME/CFS treatment overall—there was no untreated control group, so improvements could be due to placebo effect, natural disease fluctuation, or other concurrent interventions. The observational design cannot establish causation, only association. The study also cannot explain the biological mechanisms behind sex-based differences in treatment response.

Metadata

DOI: 10.3390/jcm11010173
PMID: 35011914
Review status: Editor reviewed
Evidence level: Single-study or moderate support from human research
Last updated: 12 April 2026

About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →