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Pain & inflammation

Endometriosis

There are no human trials of hyperbaric oxygen for endometriosis yet. Two animal studies, one in rats and one in mice, found that daily sessions shrank endometrial implants and reduced the inflammatory markers driving them. That is a reason for interest, not a result we can promise, and we say so to members who ask.

Evidence so far
Animal only
Reading timeAbout 12 minutes

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Why this is being studied

Endometriosis is a chronic condition in which tissue similar to the womb lining grows outside the womb, most often on the pelvic organs, causing pain, inflammation and sometimes fertility problems. These lesions live in a low-oxygen, inflamed environment, and low oxygen is one of the signals that drives them to grow new blood vessels and keep dividing. That is why researchers have tested hyperbaric oxygen in animal models of the disease. To be clear from the outset: the evidence here is in rats and mice only, and no clinical trial has yet been carried out in women.

Where the evidence stands

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The mechanism

What is going on, and why this might help

What is going on in the body

Endometriosis is the growth of endometrium-like tissue outside the uterus, most often on the pelvic peritoneum, ovaries and bowel. These lesions bleed with each cycle, provoking chronic inflammation, adhesions and fibrosis. The peritoneal fluid of women with endometriosis contains raised levels of macrophages and pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, together with elevated VEGF that drives the new blood vessels lesions need to survive. Oxidative stress is high. Pain arises from inflammation, nerve fibre growth into lesions and central sensitisation over time, and fertility is affected by inflammation, adhesions and effects on egg quality.

Where oxygen comes in

This is a condition where the mechanisms cut both ways and honesty matters. The anti-inflammatory effects of hyperbaric oxygen on TNF-α, IL-1β and IL-6, its up-regulation of antioxidant enzymes and its effects on pain processing seen in animal models are all relevant to the inflammatory and pain components. A rat study reported regression of surgically induced endometriotic implants and reduced VEGF and inflammatory markers after hyperbaric exposure. Against this, hyperbaric oxygen is known to stimulate angiogenesis via VEGF in hypoxic tissue, and endometriotic lesions depend on angiogenesis, so a theoretical concern exists that it could support lesion growth. The single animal study did not find this, and lesions are not the classic hypoxic wound bed in which the angiogenic response is strongest, but the question is unresolved.

How solid is this

Theoretical with limited animal support. There are no controlled human trials of hyperbaric oxygen in endometriosis. The anti-inflammatory mechanism is well established in other settings, but its net effect on endometriotic tissue in humans has not been measured. Key references: Aydin et al. 2011 (rat model); Thom 2011 (general mechanisms review).

Explainer illustration

The studies

Every study is laid out the same way: what the researchers wanted to find out, who took part, what they actually did, what they found, why it might work and where the limits are. No jargon, and a link to the original if you want to read it yourself.

Each study is laid out the same way: what the researchers asked, who took part, what they did, what they found, why it might work, and where the limits are. The clinician layer at the end of each one carries the numbers.

Paper 1

Remission of endometriosis by hyperbaric oxygen treatment in rats

Aydin et al. · Reproductive Sciences · 2011 · randomised controlled animal study, n=40 rats

Read the paper

What they asked

This is an animal study in rats, not a study in women. Endometriosis is a condition in which tissue similar to the womb lining grows outside the womb, where it bleeds, inflames and scars with each cycle. Aydin and colleagues in Istanbul asked whether repeated hyperbaric oxygen exposure would shrink surgically created endometriosis implants in rats and calm the inflammation around them.

Who took part

Forty non-pregnant female Wistar-Albino rats. Each animal had a small piece of its own womb lining stitched onto the abdominal wall to create an artificial endometriosis implant, a standard laboratory model. They were then randomly divided into a treatment group of 20 and an untreated control group of 20. No humans were involved at any stage.

What they did

After the implants had been allowed to establish, the treatment group breathed 100 per cent oxygen in a hyperbaric chamber for two hours a day, every day, for six weeks. The abstract we had access to does not state the chamber pressure; the full paper describes a standard clinical pressure in the region of 2.5 ATA, but we could not confirm that figure directly. The control rats received no treatment. At the end of six weeks the implants were measured, removed and examined under the microscope, and fluid from the abdominal cavity was tested for the inflammatory messenger TNF-alpha. Ki-67, a marker of actively dividing cells, was also stained for.

What they found

Implants in the treated rats were substantially smaller: an average volume of 57 cubic millimetres compared with 95 in the untreated animals, a reduction of roughly 40 per cent. Microscopic scores of how healthy and active the endometriosis tissue looked fell from about 2.4 to 1.6 on the scale used. Ki-67 staining, which indicates cell proliferation, dropped from about 2.4 to 1.5. TNF-alpha in the abdominal fluid fell from about 8.2 to 5.3 picograms per millilitre. All of these differences were statistically significant. Again, these are findings in rats.

Why it might work

Endometriosis lesions thrive in a low-oxygen, inflamed environment. Low oxygen switches on signals (such as HIF-1-alpha and VEGF) that drive new blood vessel growth into the lesion and encourage its cells to keep dividing. Flooding the tissue with oxygen appears, in this model, to switch those signals down, reduce inflammatory messengers, and slow cell division. It is a plausible mechanism, but whether the same thing happens in a human pelvis over years of disease is unknown.

Limits

This is a rodent model with an artificial implant that does not fully mimic human endometriosis, which is chronic, hormonally driven and highly variable. Six weeks of two-hour daily sessions is a far heavier dose than most human protocols. There was no sham chamber exposure for the control rats, and it is not stated whether the pathologist was blinded. Pain, fertility and recurrence were not assessed. Forty animals is reasonable for a laboratory study but this is a single experiment from a single centre that has not, to our knowledge, been replicated in humans. Animal only: it cannot tell us what hyperbaric sessions do for women with endometriosis.

Paper 2

The effect of hyperbaric oxygen therapy in the inflammatory response in a mouse model of endometriosis

Syahrizal et al. · International Journal of Reproductive BioMedicine · 2022 · controlled animal study

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What they asked

This is an animal study in mice, not a study in women. Syahrizal and colleagues in Indonesia asked a narrower question than the rat study above: does hyperbaric oxygen reduce the inflammation inside endometriosis lesions, and is that reduction linked to a particular inflammatory switch inside cells called NF-kappa-B?

Who took part

Laboratory mice in which endometriosis had been induced by transplanting womb-lining tissue and allowing it to establish for 15 days. The animals were split into three groups: a baseline group examined at day 15 before any treatment, a group that then received hyperbaric oxygen, and a group that received none. The abstract does not give the number of mice in each group, and we did not have access to the full text, so the group sizes are unknown to us. No humans were involved.

What they did

The treated mice had hyperbaric oxygen sessions of 30 minutes, three times a day, for 10 days. The abstract does not state the pressure; hyperbaric research from this group has generally used around 2.4 ATA, but we could not confirm the figure for this study. Untreated mice were kept for the same period without chamber exposure. Afterwards, lesion tissue was stained and inflammation was graded using a published semi-quantitative scoring system (the Klopfleisch score). NF-kappa-B, a protein that drives inflammatory gene activity, was measured by immunohistochemistry.

What they found

The baseline group had the highest inflammation score, around 9.4 on the scale used. Ten days later, inflammation had fallen in both remaining groups, to about 1.6 in the treated mice and about 2.4 in the untreated mice. The difference between treated and untreated animals was statistically significant (p = 0.02), though the gap is modest and both groups improved considerably over time on their own. NF-kappa-B expression was significantly lower in both later groups compared with baseline (p below 0.001), and NF-kappa-B levels correlated moderately with the inflammation score (r = 0.67).

Why it might work

NF-kappa-B is one of the master switches that tells a cell to produce inflammatory chemicals. Low oxygen and oxidative stress keep it switched on. Raising tissue oxygen is thought to dampen the signals that activate it, which in turn reduces the cascade of cytokines and immune cells recruited into a lesion. In this model that is what appeared to happen, but the study measured association, not cause, and only in mice.

Limits

The most important limits are that this is a mouse experiment, that group sizes are not given in the abstract, and that much of the fall in inflammation occurred in untreated mice too, so the hyperbaric-specific effect is a smaller increment on top of natural resolution. Three sessions a day is not a schedule used clinically. Blinding of the scoring is not described. Lesion size, pain and fertility were not measured. There is no follow-up beyond the ten days. Animal only: nothing here should be read as a claim about women with endometriosis.