Over the last couple of months, I’ve been seeing more and more women with endometriosis in my clinic. And one thing that has become abundantly clear to me in that time is that endometriosis shows up differently in different women.
For example, I have one client with some of the heaviest periods imaginable, including large clots. She has to get up multiple times at night while on her period to change pads. This is her biggest concern - any pain she has is minor and secondary to having to manage her bleeding. But then I have another client with an absent period due to the Mirena, who experiences crippling pain each month. Yet another client experiences breakthrough bleeding, despite being on birth control, and crippling pain, though she has very little clotting.
We still don’t know anywhere near enough about endometriosis - especially why it occurs and why it manifests so differently in different women. But research is finally starting to catch up and we’re learning more all the time, which means that we can tailor treatments more effectively for each woman. And researchers have just made a major new finding about pain in endometriosis.
The study
Earlier this year (2026), researchers published a study showing that local immune activity, not lesion burden or location, track with pain severity. This explains the surgery paradox (imaging shows disease, pain doesn't improve) and reframes what "severe" endometriosis actually means in the body.
The researchers analysed 27 tissue samples from 19 women with endometriosis, comparing gene activity between those experiencing pelvic pain and those without symptoms. They identified 890 genes that behaved differently between the two groups, including genes involved in inflammation, immune function, cell adhesion and nerve signalling. Further analysis identified several groups of genes whose activity was associated with pain, especially interleukin-16 (IL-16), an inflammatory signalling gene whose activity was also linked to the severity of symptoms.
Rather than just being about the lesions themselves, it’s about an inflammatory process more generally, which can manifest in many different ways, as my examples above highlight. What this means is that diagnosis and treatment, by necessity, ought to be different for each woman depending on her symptoms. And, because IL16 seems to impact pain specifically, this opens up the possibility of developing more targeted approaches to endometriosis pain, rather than assuming that removing lesions will necessarily resolve the underlying inflammatory processes.
Understanding the IL-16 pathway
Before we talk about what we can do to work on IL-16 directly, it’s worth understanding what IL-16 is responding to. This sets the scene for the long-term work I do in clinic with endometriosis clients - pain management is an incredibly useful short-term intervention to give them improved day-to-day functioning while we address the bigger picture.
One of the important drivers of inflammation in endometriosis is the accumulation of iron within endometriotic lesions. These lesions can undergo repeated bleeding in response to hormonal changes, but unlike menstrual blood shed from the uterus, blood released into surrounding pelvic tissues cannot easily escape. As red blood cells break down, they release haemoglobin and iron, which can accumulate in surrounding tissues and immune cells. Endometriotic lesions also develop new blood vessels that may be fragile and prone to leakage, contributing to further bleeding and iron deposition.
Under normal circumstances, immune cells called macrophages help clear damaged red blood cells and recycle their iron. However, repeated bleeding and inflammation can overwhelm this process. Research also suggests that endometriosis can disrupt the proteins responsible for regulating iron movement, including hepcidin and ferroportin, encouraging cells to retain more iron. This creates an environment in which excess iron promotes oxidative stress, inflammation and further blood vessel development, potentially perpetuating the cycle of bleeding and tissue damage.
More recently, researchers have identified a connection between this iron-rich inflammatory environment and IL-16 (surprise, surprise!). Experimental research suggests that excess local iron can contribute to activation of an enzyme called caspase-3 and a protein called gasdermin E, triggering inflammatory cell death and the release of active IL-16 from immune cells. IL-16 can then recruit and activate additional immune cells, amplifying inflammatory signalling within endometriotic lesions. Importantly, this pathway involves the activation and release of IL-16, rather than necessarily increased expression of the IL16 gene itself.
These findings suggest that repeated bleeding and local iron accumulation may sustain inflammation and contribute to pain in endometriosis.
Why doesn't surgery always fix the pain?
I’ve known clients who’ve had an ablation for endometriosis and found it incredibly useful, yet others haven’t noticed any improvements at all. Surgery can be enormously beneficial for some women with endometriosis, particularly when lesions and adhesions are contributing to pain or interfering with normal pelvic function. But as many women have discovered, removing the visible disease doesn't always mean the pain disappears.
One reason is that pain isn't simply a measure of how much endometriotic tissue is present. Ongoing inflammation can sensitise the nerves within the pelvis, making them more responsive to signals that wouldn't ordinarily be painful. Over time, the nervous system itself can become increasingly sensitive, meaning pain may persist even after the original source of irritation has been removed.
There can also be other factors contributing to pain. Pelvic floor muscles may become chronically tense in response to months or years of discomfort (known as guarding), while conditions such as adenomyosis can produce similar symptoms without necessarily being addressed during endometriosis surgery.
This doesn't mean surgery has failed, or that the pain is psychological. It means that surgery addresses some of the physical drivers of endometriosis, but not necessarily every process involved in producing pain.
And this is where I think the newer research becomes particularly valuable. If inflammatory pathways such as IL-16 contribute to pain severity, we may eventually be able to identify which women are more likely to benefit from treatments targeting those pathways, alongside surgery or other interventions.
Treating the whole picture, not just the lesions
This brings me back to the three women I mentioned at the beginning of this article. Although all three have endometriosis, their symptoms are remarkably different, and it makes little sense to assume that the same treatment approach will be equally effective for each of them.
For the woman experiencing extremely heavy periods, one of my priorities is understanding what's driving the bleeding and addressing the consequences, particularly iron deficiency. Heavy menstrual bleeding can substantially deplete iron stores, contributing to fatigue, reduced exercise tolerance and other symptoms that affect day-to-day functioning. It's also important to investigate whether other conditions, such as adenomyosis or fibroids, are contributing to the bleeding.
For someone whose predominant symptom is debilitating pain, the priorities may be quite different. Here, I'm particularly interested in inflammatory signalling, nervous system sensitivity and pelvic floor function. Pelvic floor physiotherapy can be enormously useful, particularly when chronic pain has led to persistent muscle tension and impaired relaxation.
There's also some encouraging research on exercise. A 2025 systematic review and meta-analysis, involving six randomised controlled trials and 251 women, found that physical activity and exercise were associated with improvements in pain, quality of life and pelvic floor dysfunction, although the researchers acknowledged limitations in the quality of the evidence.
Even more interestingly, a 2025 randomised controlled trial investigated the effects of supervised exercise and pelvic floor muscle training in 81 women with surgically confirmed endometriosis. After four months, women receiving the exercise intervention experienced an average improvement of 1.1 points in current pelvic pain compared with the control group, with benefits still evident at 12 months. Although the intervention didn't significantly improve their worst pain, these findings suggest that physical rehabilitation can make a meaningful contribution to symptom management.
For the woman experiencing both breakthrough bleeding and severe pain despite hormonal contraception, we need to consider both problems, including whether the current hormonal treatment is adequately controlling her symptoms.
This is why I think it's so important to look beyond the diagnosis itself. Endometriosis is not one uniform experience, and the factors contributing to a woman's symptoms may change over time. Effective treatment involves identifying what's actually happening in her body, addressing the most significant contributors and adapting the approach as her symptoms change.
Importantly, this doesn't mean choosing between surgery, hormonal treatment, physiotherapy or nutritional interventions. These approaches can complement one another, and the most useful combination will depend on the individual.
Can We Target Inflammation More Specifically?
One of the supplements I've been having particularly good results with in clinic is Boswellia, also known as frankincense. I've used it with women ranging from teenagers through to women in their fifties, and I've been impressed by how much it can help with menstrual pain and cramping.
Boswellia contains compounds called boswellic acids, which influence several inflammatory pathways, including the production of leukotrienes. Leukotrienes are inflammatory signalling molecules involved in immune activity and pain, and they sit alongside prostaglandins as part of the broader inflammatory response. Boswellia has also demonstrated effects on other inflammatory signalling pathways in laboratory studies, making it an interesting option when inflammation is contributing to symptoms.
And while the research is still developing, there are some encouraging findings.
A 2023 randomised, double-blind, placebo-controlled trial involving 60 women investigated a supplement combining Boswellia, turmeric and sesame oil for menstrual cramping. The researchers found significantly greater pain relief over six hours in women receiving the supplement compared with placebo. Because the intervention contained several ingredients, we can't attribute the results to Boswellia alone, but the findings are promising.
More recently, a 2025 study followed 33 women with dysmenorrhoea who hadn't obtained sufficient relief from anti-inflammatory medications. After three menstrual cycles using a combination of Boswellia and Acmella oleracea alongside their usual treatment, average pain scores decreased from 8.2 to 6.8 out of 10, and use of anti-inflammatory medication fell by 40%. This was a small retrospective study without a control group, so it isn't definitive evidence, but it adds to the emerging research.
One of the things I particularly like about Boswellia is that, in my clinical experience, women don't necessarily need to take it continuously to benefit. For clients whose pain follows a predictable monthly pattern, I generally have them begin taking it a few days before their usual cramping starts, then adjust the dose and duration according to their response. This allows us to target the period when symptoms are most troublesome rather than automatically committing to daily supplementation throughout the month.
It's worth distinguishing this approach from the published research, which has generally investigated specific formulations taken during menstruation or across several cycles. My approach to timing is based on what I've observed in clinic, rather than a dosing schedule that's been formally validated in trials.
And returning to the IL-16 research we discussed earlier, I think Boswellia is particularly interesting because of its broader effects on inflammatory signalling. We don't yet have clinical evidence demonstrating that it directly reduces IL-16 activity in women with endometriosis, but understanding these overlapping inflammatory pathways gives us more opportunities to investigate targeted approaches to pain management.
Of course, Boswellia isn't going to be the answer for every woman. It doesn't replace investigating the underlying causes of heavy bleeding, pelvic floor dysfunction or persistent pain, and suitability needs to be considered alongside medications and other health factors. But for some of my clients, it's proving to be a useful tool for making their periods considerably more manageable while we address the bigger picture.
Where Does This Leave Us?
One of the things I find most encouraging about the emerging endometriosis research is that we're beginning to understand why women with the same diagnosis can have such vastly different experiences. And, importantly, why removing endometriotic lesions doesn't always mean the end of their pain.
For too long, treatment has largely focused on the lesions themselves, or on suppressing the hormonal activity that supports them. Both approaches can be enormously valuable, but neither necessarily addresses every factor contributing to a woman's symptoms. Inflammation, immune activity, nervous system sensitivity, pelvic floor dysfunction and other underlying conditions can all influence how endometriosis manifests.
The newer research into IL-16 is particularly exciting because it gives us another piece of this puzzle. We're not yet at the point where we can routinely test for IL-16 activity or prescribe treatments specifically targeting it, but understanding these pathways opens up new possibilities for more precise and individualised care.
And that's ultimately what I want women with endometriosis to take away from this article. If you've had surgery and you're still experiencing pain, it doesn't mean you've run out of options. There may be other contributing factors that haven't yet been identified or adequately addressed.
The goal shouldn't simply be to treat endometriosis as a diagnosis. It should be to understand what's driving your symptoms, and to build a treatment approach around that.
If anything in this resonates with your own experience of being told your pain was normal when it clearly wasn't, it's worth taking seriously rather than managing around it indefinitely.
Want some help working out what's actually driving your period pain or hormonal symptoms, rather than just managing them? You can book a free discovery call to see if working together might be a good fit.