Three facts about endometriosis that prove it’s more than just a painful period disease

endometriosis systemic disease, endometriosis increase stroke risk, endometriosis cells vs. endometrial cells, endometriosis autoimmune, endometriosis cause anxiety, endometriosis risk for depression, endometriosis not just reproductive disorder
Pelvic pain stomachache concept. Hands of young woman on stomach as suffer on menstruation cramp, indigestion,gastrointestinal,diarrhea problem
Medically reviewed by J. Stuart Wolf, Jr., MD, FACS

When you think of endometriosis, what comes to mind? You may already know that endometriosis can cause painful periods, pelvic pain, or that it’s highly associated with infertility, but did you know that some people don’t experience endometriosis as a painful period disease at all? 

Furthermore, according to a brand new study published in the July 2022 edition of the American Stroke Association’s medical journal, while women have an overall lower risk of stroke than men, the risk is fully 34% higher in women with endometriosis than in women who don’t have the condition [1]. Now, you may be wondering, how could a disease that most people only associate with reproductive organs increase one’s stroke risk? 

Here we’ll cover three things you probably didn’t know about endometriosis, including why endometriosis isn’t just a gynecological disease, and why it may, in fact, be a systemic disease (i.e., a disease that affects the whole body).  

1. Endometriosis is connected to mood disorders 

Endometriosis is a debilitating, chronic condition that affects one in ten women, and recent research has found that women with endometriosis are more likely to have depression and anxiety [2]. In fact, one study estimates that 15.1% of women with endometriosis have clinical depression [3]. For comparison, according to this 2015 study, the prevalence of depression amongst women in general is about 5% [4]. Now, is the higher prevalence of mood disorders just because women with endometriosis experience inordinately long diagnostic times, or because they’re in pain for so long, or because they’re dismissed so often—or is there something more?

Research says that it may, in fact, be something more. MRI scans reveal that women with endometriosis have neurological changes in the part of the brain responsible for emotional and sensory nerve processing, specifically demonstrating hypersensitivity to pain [3]. Further research is needed to determine whether this apparent brain remodeling is because of the chronic pain experienced by women with endometriosis, or due to the endometriosis itself.

2. Presence of inflammatory factors in endometriosis patients suggests that it may be a chronic inflammatory condition

While the progression of endometriosis is influenced by the hormone estrogen, some researchers suggest that endometriosis is, in fact, more than just a “hormonal” or “gynecological” condition. In a recent article for The Lancet, researchers Taylor et al. argue that “Overall, increasing evidence suggests that endometriosis is more than a localised pelvic disease” [2]. They have proposed an entirely new way of thinking about endometriosis, proposing that it should be characterized primarily as an inflammatory condition [2]. This corroborates previous Natural Womanhood content on a possible connection between endometriosis and autoimmune disease. 

The retrograde menstruation theory doesn’t tell the whole story about endo

In their Lancet article, Taylor et al. define endometriosis as a chronic inflammatory condition where cells similar to those lining the uterus are found outside the uterus [2]. They note that, in the past, these endometriosis cells were considered to be simply endometrial cells that were displaced due to retrograde menstruation, which occurs when some menstrual cycle blood flows “backward” (retrograde) into the Fallopian tube(s) and out into the pelvis rather than flowing “forward” through the cervix and out of the vagina onto your pad, tampon, or other period product. Blood that flows in the “wrong direction” could theoretically bring endometrial cells with it. (In fact, the theory that normal endometrial cells being in the wrong anatomical place cause endometriosis symptoms is the reason why “endometriosis” and “endometrial” sound so similar, and why the condition has long been considered a gynecological condition.)

While Taylor et al. acknowledge that retrograde menstruation is still a possible explanation for the disease, they posit that it is not the only explanation, pointing to the secretion of inflammatory factors by endometriosis cells—primarily, cytokines and prostaglandins [2, 5]. These inflammatory factors can lead to pain and other symptoms wherever the endometriosis cells are found in the body, not just in the pelvis.

Endometriosis impacts healthy endometrial cells

Interestingly, the secretion of these inflammatory substances from endometriosis tissue also impacts the functioning of healthy endometrial cells [5]. Additionally, the peritoneal fluid (fluid in the abdominal and pelvic cavities), endometrium (uterine lining), and serum (the clear watery/yellow-appearing fluid component of blood) of women with endometriosis all contain abnormal amounts of cytokines, growth factors, and cancer-like substances [5].

Taylor et al. posits that, combined, these effects lead to an inflammatory environment in the body, contributing to the many symptoms of endometriosis [2]. However, they acknowledge there is still a question about “whether inflammation is part of the process that instigates the disease, or the factor that perpetuates the disease” [2]. In future, understanding these distinctions may prove vital for understanding the disease, its symptoms, its associated conditions, and its various treatment options. 

3. Endometriosis throws off hormone balance in a few different ways

Endometriosis leads to progesterone resistance

Taylor et al. also discuss the evidence for endometriosis cells’ resistance to the hormone progesterone [2]. Progesterone typically acts as an anti-inflammatory hormone, naturally balancing the inflammatory effects of estrogen, particularly in the uterine lining. However, as Taylor et al. argue, endometriosis lesions do not respond appropriately to progesterone, leaving estrogen and its actions uninhibited [2].

Endometrial lesions create their own supply of estrogen

Another important difference between endometrial cells and endometriosis cells is that endometriosis lesions produce estrogen [2]. Normally, estrogen is only created in the ovaries, fat cells, and adrenal glands. This is very important because it confirms that endometriosis cells are indeed abnormal, meaning they are not simply displaced endometrial cells in the “wrong” part of the body. 

The local supply of estrogen adds to the inflammatory environment and sustains the disease progression. Estrogen (specifically estradiol) stimulates prostaglandins, which stimulates more estrogen production [2]. And because the cells are progesterone resistant, estrogen becomes even more concentrated and uninhibited [2]. This process promotes the survival of endometriosis cells, and sustains the inflammatory state.  

Can hormonal birth control correct the hormonal imbalances associated with endo?

It also explains why some treatments, like hormonal birth control (HBC), may be ineffective at preventing the progression of the disease [6]. While some patients find some symptom relief from HBC, about one-third of patients do not respond to it [2]. This symptom relief may be because HBC reduces estrogen by suppressing the menstrual cycle, thereby preventing estrogen production from the ovaries. However, this does not affect the local estrogen production by endometriosis lesions. 

In short, hormonal birth control does not solve the underlying problem, plus it comes with its own host of potential side effects. Importantly, the same researchers proposing that we look at endometriosis as a primarily inflammatory disease also advocate for “novel, non-hormonal treatments. Such therapies can include immunomodulating agents, miRNA modulators, and stem-cell-based therapies” [2].  

Endometriosis is not just a painful period disorder

If you thought endometriosis was just a painful period disease, I assure you, you are not alone! Given its documented effects on multiple body systems, endometriosis may actually be best understood as a whole body (systemic) inflammatory disease. Chronic inflammation wreaks havoc in the body, and many studies have indeed demonstrated alterations in heart, brain, metabolic, and immune system function in women with endometriosis [2]. Hopefully, the more that is understood about endometriosis’ whole body impacts, the closer women will come to early diagnosis and effective treatments.

This article was updated on November 8th, 2022 to add an explanation of retrograde menstruation.

References

[1] Farland, Leslie V et al. “Laparoscopically confirmed endometriosis and risk of incident stroke: a prospective cohort study.” Stroke, (2022). https://doi.org/10.1161/STROKEAHA.122.039250 PMID: 35861076

[2]Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. The Lancet, yol. 397, no. 10276, (2021). Pp: 839-52. doi:10.1016/s0140-6736(21)00389-5

[3] Warzecha D, Szymusik I, Wielgos M, Pietrzak B. The Impact of Endometriosis on the Quality of Life and the Incidence of Depression—A Cohort Study. International Journal of Environmental Research and Public Health, vol. 17, no. 10 (2020). doi:10.3390/ijerph1710364

[4] Albert PR. Why is depression more prevalent in women? J Psychiatry Neurosci. vol. 40, no. 4 (2015): pp. 219-21. doi: 10.1503/jpn.150205. PMID: 26107348; PMCID: PMC4478054.

[5] Luckow Invitti A, Schor E, Martins Parreira R, et al. Inflammatory cytokine profile of co‑cultivated primary cells from the endometrium of women with and without endometriosis. Molecular Medicine Reports. Published online June 6, 2018; vol. 18, no. 2. doi:10.3892/mmr.2018.9137

[6] Ferrero S, Evangelisti G, Barra F. Current and emerging treatment options for endometriosis. Expert Opinion on Pharmacotherapy, vol. 19, no. 10 (2018): pp. 1109-25. doi:10.1080/14656566.2018.1494154

Additional Reading:

FAM Basics: Everything you need to know about your endometrium

“What causes endometriosis?” and other questions: a Natural Womanhood FAQ

Can endometriosis come back after surgery? 

3 reproductive-health issues NaProTechnology solves better than the alternatives

Adenomyosis vs. endometriosis: how they’re similar, and how they differ

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