Ozone Therapy for Endometriosis: Evidence, Protocols, and Clinical Outcomes

If you're living with endometriosis or painful periods, please know this: your pain is real, and you're not alone.

For too many women, the journey to getting answers is exhausting and isolating. On average, it takes 4–12 years from the onset of symptoms just to receive a diagnosis [1]. Years of being told it's "normal," being dismissed, or feeling like something is wrong but not knowing what. That delay isn't your fault; it reflects a systemic dysfunction in healthcare.

When a diagnosis finally comes, the standard options like hormone suppression and surgery  can offer relief, but they come with real trade-offs. Hormonal treatments often bring their own side effects and typically suppress the disease rather than address its root causes [2]. Surgery can help, but with recurrence rates of 20–50% within five years [3]. For countless women, the struggle doesn't end in the operating room [2].

Several mechanisms drive the condition's pathophysiology:

• The peritoneal immune microenvironment is dysfunctional.
• Retrograde menstruation deposits endometrial fragments into the pelvic cavity, but immune dysfunction and estrogen responsiveness allow these fragments to implant, vascularize, and persist rather than be cleared.[4, 5]
• Oxidative stress plays a central role in this process, driving inflammation, tissue damage, and lesion progression. [6]

Standard treatments include hormonal suppression (GnRH agonists, progestins, combined oral contraceptives) and surgical excision. However, these approaches carry significant limitations and side effects, and do not cure the disease. Surgical removal carries recurrence and adhesion risks. [7,8,9,10,11,12,13,14,15]  Women who wish to conceive face an especially narrow set of options, since most medical therapies suppress ovulation. [16,17]

Ozone therapy helps by addressing inflammation, immune modulation, and oxidative balance without suppressing hormones or fertility. [1,18]

Bottom line: Endometriosis is a chronic inflammatory disease with limited treatment options, especially for women seeking fertility. Ozone therapy targets the oxidative and immune pathways central to endometriosis pathophysiology.

Why Ozone Therapy Is Relevant to Endometriosis Pathophysiology

The rationale for ozone therapy in endometriosis rests on several overlapping biological mechanisms.

Oxidative Stress and the Nrf2 Pathway

Endometriosis lesions generate excessive reactive oxygen species (ROS), which damage peritoneal tissues, promote adhesion formation, and sustain chronic inflammation. [6]

Ozone therapy activates Nrf2, a cellular master regulator of antioxidant defense which manages the production of antioxidant enzymes. In a study of healthy volunteers receiving three sessions of major autohemotherapy (MAH), ozone preconditioning stimulated Nrf2. [19] This controlled oxidative stimulus primes the body's own calibration against the chronic oxidative burden seen in endometriosis.

Peritoneal Immune Dysfunction

The peritoneal immune microenvironment in endometriosis is characterized by  [4,5]:

• Dysfunctional macrophages that fail to clear ectopic endometrial cells
• Elevated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in peritoneal fluid
• Impaired natural killer cell activity, allowing lesions to survive
• Increased angiogenesis supporting lesion growth

Ozone breaks this cycle of chronic inflammation. At the same time, ozone also helps increase anti-inflammatory proteins such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β) [20]. 

Aside from reducing inflammation, ozone treatment can modulate the immune response towards a healthier, more balanced state. It enhances NK cell activity towards targeting endometriosis cells and lesions [5,20]. Also, ozone treatments help correct Th1/Th2 ratios, shifting the balance away from the Th2 dominance typically found in endometriosis [5,20,21] .

In a rat model of pelvic inflammatory disease, ozone therapy reduced inflammation and endometrial injury, demonstrating direct anti-inflammatory effects on reproductive tissues. [22]  [PRELIMINARY]

Adhesion Prevention

Adhesion formation is a major source of pain and organ dysfunction in endometriosis [23]. Ozone therapy reduces postoperative adhesions in animal studies. It is possible that the anti-inflammatory and antioxidant effects help limit the fibrotic response to tissue injury [24].

When endometrial tissue grows outside the uterus, it bleeds (similar to a menstrual cycle) into the pelvic cavity [23]. This has several consequences: 

• Blood builds up in the abdominal cavity, so the body sends fibroblasts (repair cells) to wall off the area [23]. This creates the adhesions typical of endometriosis, and over time bands of scar tissue can fuse areas of the abdomen. 
• The trapped fluid is high in inflammatory cytokines, which encourages the survival and spread of new implants [17]. 
• Surgery to remove these implants can trigger more adhesions as the body heals [25]. 
• Scar tissue can block fallopian tubes or impact typical ovarian anatomy [23]. 

Ozone may help by blocking TGF-alpha, a scarring signal. It also supports antioxidant pathways, which reduce inflammation in the pelvis [24] 

In an animal model of uterine adhesions, a medical ozone/oxygen mix was injected into the abdominal cavity [24] . After three treatments, the ozone group had significantly fewer adhesions than the control group. 

Direct Clinical Evidence: Ozone Therapy for Endometriosis and Adenomyosis.

Endometriosis Implant Inhibition in Animal Models

The most direct preclinical evidence comes from a rat model of surgically induced endometriosis. Aktun et al. (2016) divided 15 rats into three groups (N=5 per group): control, low-dose ozone, and high-dose ozone. The ozone-oxygen mixture therapy inhibited endometrial implant growth compared to controls, providing the first experimental evidence that ozone directly suppresses ectopic endometrial tissue. [26]  [PRELIMINARY]

Ozone Sauna Therapy for Endometriosis Pain

The first human clinical data on ozone therapy specifically for endometriosis comes from Merhi et al. (2023). This study evaluated ozone sauna therapy (OST) combined with pulsed electromagnetic field therapy (PEMF) in women with endometriosis. The treatment improved endometriosis-related pain and lowered serum inflammatory markers. [1]  [PRELIMINARY]

This finding is significant because it demonstrates that systemic ozone exposure can reduce both subjective pain scores and objective inflammatory biomarkers in endometriosis patients.

Endovaginal Ozone for Endometriosis: Randomized Controlled Trial

Currently, the strongest clinical evidence comes from a double-blind randomized controlled trial by Pichara Morais et al. (2026). This study, enrolling 30 participants, evaluated endovaginal medical ozone as an adjuvant treatment for endometriosis. The ozone group (10 weekly endovaginal treatments) experienced significant reductions in pain and improved quality of life, sexual function, and anxiety symptoms compared with placebo. The double-blind, placebo-controlled design represents the highest level of clinical rigor applied to ozone therapy for this condition. [27] [MODERATE]

Ozone Therapy for Adenomyosis Pain

Adenomyosis (endometrial tissue invading the uterine muscle wall) is closely related to endometriosis and shares its inflammatory, pain-generating mechanisms. Uraeva et al. (2023) studied the influence of ozone therapy on emotional and pain stress in women with adenomyosis using both IV ozonated saline and vaginal ozone delivery routes. The treatment significantly reduced pain and emotional stress burden in these patients. [28] [PRELIMINARY]

Summary of preclinical and clinical evidence: Ozone therapy for Endometriosis and Closely Related Conditions

Bottom line: The evidence extends from animal models through to a double-blind RCT. Ozone therapy inhibits endometrial implant growth in animals and reduces pain and inflammation in human endometriosis and adenomyosis patients.

Ozone Therapy and Endometriosis-Related Infertility

Endometriosis-associated infertility affects a substantial proportion of patients. The causes range from anatomical distortion and tubal damage to subtler disruptions in ovarian function, peritoneal environment, and endometrial receptivity.  [16,17]

Personalized Reproductive Approaches

Vitiuk et al. (2025) proposed an adapted treatment strategy for women with endometriosis-associated infertility, emphasizing personalized reproductive approaches. Recent research stresses the need to minimize surgical trauma and explore adjunctive therapies that preserve or enhance fertility potential. [29]

Ozone's Role in Reproductive Health

Merhi et al. (2019) published a comprehensive review of ozone therapy as a potential therapeutic adjunct for improving female reproductive health. The review examined ozone's effects on tubal, ovarian, and endometrial factors relevant to fertility, concluding that ozone therapy is emerging as a new adjunct therapeutic agent for female infertility. [18]

A case series reported three cases where older women with endometriosis and previous failed IVF attempts were treated with 3–4 ozone autohemotherapy sessions (30–45 gamma with 150 mL of blood) with vitamins during the current IVF round. The IV treatments were stopped 7 days before embryo transfer. Subsequently, all three women (40, 39, and 47 years old) conceived with the IVF treatment and carried the pregnancy full-term [30]. While this is not conclusive proof that ozone therapy can help with IVF, it suggests that ozone therapy with medical supervision may be beneficial as a supportive treatment.

Pregravidar Endometrial Preparation

In a 2025 clinical study of 80 subjects, researchers looked at whether low-dose ozone could improve the uterine lining and blood clotting system in women preparing for assisted reproductive technology (ART) [31]. The 40 women in the intervention group received a 7-day course of ozone. Researchers looked at how ozone affected uterine blood flow, oxygenation, and uterine receptivity (readiness for embryo). They found that the ozone group significantly improved uterine receptivity and increased oxygen levels. They also saw benefits for endometrial remodelling and a significant increase in the frequency of successful pregnancies. 

This is particularly relevant for endometriosis patients, who frequently have impaired endometrial receptivity and require ART to conceive.

Delivery Routes Used in Endometriosis Research

Different ozone delivery methods have been studied in the context of endometriosis and related conditions. Each route targets different aspects of the disease.

Endovaginal Ozone Insufflation

Vaginal insufflation delivers ozone directly to the pelvic region, offering local anti-inflammatory and antimicrobial effects with some systemic absorption through the vaginal mucosa. The double-blind RCT by Pichara Morais et al. used this route as an adjuvant for endometriosis [27]. Uraeva et al. also used vaginal ozone delivery as part of a combined protocol for adenomyosis [28].

IV Ozonated Saline Rinse

Gur'eva et al. [31] used ozonated rinse in their gynecological protocols, targeting systemic inflammation and endometrial preparation.

Ozone Sauna (Transdermal)

Merhi et al. used ozone sauna therapy, which exposes the body to ozone transdermally in a steam cabinet. This systemic route reduced pain and inflammatory markers in endometriosis patients. [1]

Intraperitoneal/Injection Routes (Preclinical)

The animal studies by Aktun et al. [26], Wei et al. [22]  , and Uysal et al. [24] used direct injection or intraperitoneal administration. Currently, these routes are primarily research tools, but they demonstrate ozone's direct effects on endometrial tissue and peritoneal inflammation.

Limitations of Current Evidence

To be transparent, the scientific evidence ozone therapy for endometriosis faces several limitations, including:

• Small sample sizes: The direct endometriosis studies involve small cohorts (e.g., N=15 rats in Aktun et al.) or do not report exact participant numbers.
• Limited human RCTs: Only one double-blind RCT (Pichara Morais et al.) directly addresses endometriosis in humans. [27] 
• Heterogeneous protocols: Studies use different ozone delivery routes, concentrations, and treatment durations, making direct comparison difficult.
• Preclinical dominance: Much of the mechanistic evidence comes from animal models, which do not perfectly replicate human endometriosis.
• Short follow-up: Long-term outcomes (recurrence rates, sustained pain relief, live birth rates) remain unreported.
• Veterinary extrapolation: While biologically informative, equine and bovine endometritis differs from human endometriosis in important ways.

Therefore, personalized, multimodal approaches that combine ozone therapy with conventional management are likely the most rational path forward. [29 ,15]

⚠️ This content is for educational purposes and does not constitute medical advice or treatment recommendations. Endometriosis management should be individualized with a qualified healthcare provider.

Frequently Asked Questions

Can ozone therapy help with endometriosis pain?

Yes, all published studies and case reports to date confirm that ozone therapy can reduce endometriosis pain. [1,28, 27]

What ozone delivery method is used for endometriosis?

Researchers have used multiple routes:

• Endovaginal insufflation (the only route tested in a human RCT for endometriosis) [27]
• Ozonated saline rinse [28,31]
• Ozone sauna therapy (used for endometriosis pain) [1]

While there is currently no evidence, it’s possible that systemic treatments like autohemotherapy and rectal insufflation may also be beneficial for endometriosis.

Can ozone therapy improve fertility in women with endometriosis?

Ozone therapy is emerging as a potential adjunct for female reproductive health. [18]. Gur'eva et al. (2025) found that low-dose ozone therapy improved endometrial morpho-functional state during preparation for assisted reproductive technology. [31]. Scuderi et al reported three case studies of successful IVFs with live birth in endometriosis patients [32]. 

The evidence, although very positive, remains very limited.

Is ozone therapy safe for endometriosis patients?

Ozone therapy administered according to established protocols (such as those outlined by ISCO3 and WFOT) has a well-documented safety profile. Specific contraindications include G6PD deficiency, active hyperthyroidism, and severe anemia. Women with endometriosis should discuss ozone therapy with their healthcare provider, particularly if they are pregnant or planning pregnancy.

Conclusion

Endometriosis remains one of the most challenging conditions in gynecology, with current treatments offering incomplete relief and significant trade-offs. Ozone therapy targets the core pathological mechanisms of the disease: oxidative stress, peritoneal immune dysfunction, chronic inflammation, and adhesion formation. [6,4,24]. Currently, the limited evidence leans towards suggesting benefits when done correctly and with medical supervision.

This content is for educational purposes and does not constitute medical advice or treatment recommendations.

References: 

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