Endovaginal Ozone as an Adjuvant in Endometriosis: A 2026 Double-Blind Randomised Controlled Trial

Background: why endometriosis is being studied with ozone

Endometriosis is a chronic inflammatory gynaecological condition in which tissue similar to the lining of the uterus grows outside it. It is associated with pelvic pain, painful periods, pain during sex, fatigue and reduced fertility, and it has a well-documented effect on quality of life, sexual function and mental health. Conventional management relies on hormonal therapy, analgesia and surgery, and the authors' starting point is that these have limitations - side effects, recurrence and incomplete relief - which is why complementary strategies are being explored.

Ozone has been proposed as a candidate because of its reported anti-inflammatory, immunomodulatory and analgesic actions. Published human evidence in endometriosis has so far been thin - a 2020 Brazilian narrative review set out the rationale, and the authors describe this trial as, to their knowledge, among the first randomised clinical trials of endovaginal medical ozone in women with endometriosis.

Study design: 30 women, randomised and double-blind

The trial was run by Jynani Pichara Morais and colleagues at Universidade Brasil in São Paulo, with clinical applications delivered at a private clinic, and was published in March 2026 in Ozone: Science & Engineering, the journal of the International Ozone Association.

Thirty women with endometriosis were randomly allocated to two groups. The active group (OzA) received medical ozone applied endovaginally once a week for 10 weeks. The placebo group (OzP) went through the same procedure without ozone. The paper describes the trial as double-blind and placebo-controlled.

The abstract does not give the ozone dose. The trial's entry in the Brazilian clinical trials registry (ReBEC, RBR-5bzyrnq, same lead investigator and institution) specifies 1,000 mL of ozone-oxygen gas at a concentration of 30 µg/mL, delivered through a size 16 silicone probe, with the placebo consisting of probe placement with no gas applied. We report this from the registry rather than the paper itself, so it should be read as the planned protocol.

This was a supervised clinical protocol delivered by trained staff in a research setting, and ozone was used as an adjuvant - alongside, not instead of, each woman's existing care. It is a description of what was studied, not a set of instructions.

What was measured

Four validated questionnaires were completed at baseline and again after the 10-week course:

• Numeric Pain Rating Scale (NPRS) - pain intensity on a 0 to 10 scale.
• Endometriosis Health Profile-30 (EHP-30) - the standard endometriosis-specific quality of life instrument.
• Female Sexual Function Index (FSFI) - sexual function across desire, arousal, lubrication, orgasm, satisfaction and pain.
• Beck Anxiety Inventory (BAI) - anxiety symptoms.

Safety was tracked through adverse event reporting during the course.

Findings

Compared with the placebo group, the ozone group showed statistically significant reductions in pelvic pain and significant improvements in endometriosis-specific quality of life, sexual function and anxiety symptoms after 10 weeks.

No serious adverse events were recorded. The authors report a favourable short-term safety and tolerability profile.

We have not reproduced the effect sizes, score changes or p values here, as the full paper sits behind a paywall. Readers who want the figures should go to the paper itself, linked below.

What the authors concluded

The authors conclude that the intervention was safe and well tolerated in the short term and was associated with improvements in pelvic pain, quality of life, sexual function and anxiety symptoms. Within the limitations of the study, they suggest that endovaginal medical ozone "may represent a potential minimally invasive adjuvant strategy" in the clinical management of endometriosis.

They are equally clear about what comes next: further multicentre studies with larger samples, longer follow-up and biomarker evaluation are needed to confirm efficacy, how long the effects last, and the mechanisms behind them.

Limitations of this study

The limitations the authors themselves point to are the ones that matter most: this is a single trial with a small sample (30 women), the results are short term, and no biomarkers were evaluated. Their call for larger multicentre studies with longer follow-up reflects that.

To that we would add two points for readers. All four outcome measures are patient-reported questionnaires, so the trial speaks to symptoms rather than to the underlying lesions. And the trial tested ozone as an adjuvant against placebo, so it does not tell us how ozone compares with standard hormonal treatment.

The trial was funded by CAPES, the Brazilian federal research agency, which is not an industry source.

Endometriosis can only be diagnosed by a doctor, and pelvic pain can have many other causes. Anyone considering ozone therapy alongside treatment for endometriosis should discuss it with their own gynaecologist or GP.

Related reading

Ozone therapy: a potential therapeutic adjunct for improving female reproductive health - a review of the mostly preclinical evidence on ozone and the female reproductive system.

Morais JP, Tim CR, Martignago CCS, Volpi KPC, Assis L. Endovaginal Medical Ozone Treatment as an Adjuvant in Endometriosis: A Double-Blind Randomized Controlled Trial. Ozone: Science & Engineering. 2026;48(4):454-463. Published online 20 March 2026. doi:10.1080/01919512.2026.2644229