What’s the link between endometriosis and stress?
- The vicious cycle of stress and endometriosis
- How does it work?
- Where’s the evidence that stress is linked to endometriosis?
- So what can you do to control stress?
- Are there any foods or supplements that can help with stress?
- The link between stress and adenomyosis in my own story
The vicious cycle of stress and endometriosis
If you’ve tried everything—conventional or natural—to relieve your endometriosis and/or adenomyosis, and you still aren’t feeling better, maybe its time to think about stress. Now, I know some women are resistant to the idea that stress could have anything to do with their symptoms. But that’s probably because they’ve been told their litany of complaints are all in their head, or callously handed a prescription for anxiety medication or an anti-depressant. Believe me, I’ve been there. So I get how frustrating this can sound. However, if you’ve had any interaction with me in our Facebook group, you might have already heard me say that tackling my stress was instrumental in my healing. There truly is a link between endometriosis and stress. But that doesn’t mean it’s all in your head!
Deep down inside, we all know stress can affect us. You’ve seen the cliché heart attack on TV by someone who’d just been given shocking news, or the power executive who develops ulcers from too much pressure on the job. But it isn’t fiction. Stress has been well established as a contributor to many a chronic disorder, from cardiovascular disease1 and cancer2 to thyroid disorders3 and infertility4 plus so much more.5 Yet, few of us seem to think its effects us. I didn’t. I didn’t even think I had any stress. (I was wrong).
You don’t need me to tell you that living with endometriosis, itself, can cause stress. The constant pain, the frequent doctors visits with often dismissive doctors and therapies that don’t help, surgeries (if you’ve had them). The decreased social interactions because you’d rather be on the couch with a heating pad, the absences from work, pain and discomfort during sex, or the inability to have sex at all because of all the bleeding. Infertility, low self-esteem, hopelessness. So it’s no surprise, that many studies have shown that endometriosis is associated with a low quality of life and high levels of chronic stress.6 7 8
Of course there are other kinds of stress beyond that related to living with endometriosis, that also “regardless of type (e.g. psychological, emotional, cognitive, physical), can directly impact pain processes.” 9 That’s because stress hormones release pro-inflammatory agents, only adding to the already-inflamed state of endometriosis, and you “are caught in a vicious cycle of high stress, inflammation and disease progression.”10
How does it work?
(The body’s stress response is multi-faceted and highly nuanced, so please note this is a simplified explanation.)
When you are exposed to stress, a series of hormonal and neural transactions are triggered, much like a relay runner passing a baton. The Hypothalamus produces corticotropin-releasing hormone (CRH). This triggers the Pituitary gland to secrete adrenocorticotropic hormone (ACTH), next. ACTH then activates cortisol in the Adrenal cortex. Together, the two parts of the brain involved in this communication, along with the adrenal glands (which sit upon the kidneys) is known as the HPA-axis, HPA standing for Hypothalamic-Pituitary-Adrenal.
Cortisol, probably the most widely studied biomarker of stress, spurs the immune system into action, which in the short term can be a good thing—to fight off infections. In fact, stress, if we recover from it, can be healthy—exercise, public speaking, accepting a new and better job. And when the stress is over, cortisol also tells the body to down-regulate the stress response.
But when stress is chronic, the immune system never shuts off, which then leads to a cascade of an assortment of cytokines—immune-regulating proteins—in an abnormal feedback loop known as HPA-axis dysregulation (sometimes incorrectly called adrenal fatigue). And this is considered a significant contribution to the establishment and progression of endometriotic lesions.11 12 In simple terms, the inflammation caused by the stress response makes the progression of the disease worse.
Sometimes the body produces too much cortisol in women with endo13 14 and sometimes it produces so much it exhausts its ability to produce enough, resulting in too little cortisol.15 16 17 In addition, cortisol competes with progesterone18 so being in a high-stress state likely contributes to estrogen dominance, a known factor of endometriosis. This is why I recommend getting your cortisol checked. It can be a key to understanding your current HPA-axis status.
Where’s the evidence that stress is linked to endometriosis?
In case you need evidence, there are plenty of animal and human studies that show the link between stress and endometriosis. In one study, mice were surgically induced with endometriosis, then threatened by the presence of a (starved) male cat circling their cage. This stress caused epigenetic changes in their brains and resulted in accelerated growth of their endometriotic lesions.19
Similarly, the prevalence of “spontaneous endometriosis” (not surgically induced) in baboons increased significantly with time spent in captivity—a stressful situation, from capture to prolonged isolation away from their social circle.20
Also, CRH is one of the hormones monitored in studies on stress, and CRH has been found to be “highly expressed in deep infiltrating endometriotic lesions,”21 compared to healthy women. A “significant increase” in CRH has also been observed in the endometriotic lesions of rats, compared to their uteruses.22 Interestingly, CRH has been shown to play a role in intestinal permeability,23 too, which is why stress is also related to gut disorders,24 and perhaps why so many of us with endo or adeno also complain of food sensitivities.25
But which came first? Stress or endometriosis?
It turns out, it isn’t just stress during endometriosis that can make symptoms worse. Experiencing stress even before endometriosis shows up can also cause severe symptoms later on. This was demonstrated in mice who were forcibly immobilized and deprived of food and water. This chronic stress was shown to accelerate the development of endometriosis even when that stress occurred before the mice were induced with endometriosis. Stress after induction also obviously caused an acceleration of the disease, and stress experienced by mice both before and after had the greatest negative effect on their lesions.26
Likewise, rats who were placed in a maze of water without ability to exit, forcing them to swim, presumably in a panic, were later surgically induced with endometriosis, along with another set of rats who had not been subjected to the swim-stress. At the end of the study, the swim-stress rats had “lesions of greater severity and number,”27 than those rats with endo who were not subjected to stress ahead of induction. They also had higher levels of tissue myeloperoxidase (MPO), an enzyme that reflects “the state of inflammation in the mucosa of the intestine.” The results were so significant, the authors surmised that the effects of stress on endometriosis are currently underestimated.
(On the other hand, the researchers show in another study that swimming as an exercise, without the stress aspect, was beneficial. It resulted in smaller lesions compared to those rats with endometriosis who were stuck in their cages without exercise at all). 28
There is also much evidence that chronic stress experienced in childhood is associated significantly more often with women who have endometriosis and symptoms such as chronic pelvic pain and sexual dysfunction later in life. Specifically, trauma from sexual abuse, emotional abuse or neglect.29 30 31 32 33
This is consistent with the longitudinal study by Danese et al.34 that “links exposure to childhood maltreatment in the first decade of life to specific, clinically significant biomarkers of inflammation in adulthood.” This increased inflammation found in a number of diseases, including cardiovascular disease, diabetes and chronic lung disease, is most likely due to “a reduced ability to control the stress response”35 (aka HPA-axis dysregulation), as well as “autonomic nervous system hyperreactivity”36 due to chronic stress experienced at an early stage in life.
Stress could even stem from the womb, and some studies have shown that women with endometriosis more often reported “complications during their gestation, such as prematurity, lower birth weight, and preeclampsia.”37 This could possibly cause epigenetic changes that predispose them to the onset of endometriosis in the future.
Regardless of whether your stress came before or after your endometriosis, you can see how important it is to get that stress under control.
So what can you do to control stress?
Even before the stress response activates the HPA-axis, it activates the Sympathetic Nervous System, which most people know as the “fight-or-flight” response. As the name suggests, it’s what gives you the ability to fight or flee from your threat. But in order to do this, blood flow is restricted to certain parts of your body (like your uterus and your stomach) and shunted to the parts of your body that need it (lungs, heart, large muscles). Because, obviously if you are under attack, you’re not thinking about sitting down to a good meal, or creating a baby with your partner.
Under normal conditions, when your threat has passed, the Parasympathetic Nervous System, often called the “rest and digest” mode, takes over. Now you can get back to wining and dining (and maybe some romance, too). Unless your stress response never turns off, then you’re stuck in high alert mode and the vicious cycle of inflammation we’ve already discussed.
Whether or not endometriosis is an autoimmune disease, it is a disease of inflammation, a product of the immune system gone haywire. So reducing stress, which calms the immune system and thus reduces inflammation, should be your primary goal. Researchers agree that non-pharmacological, non-surgical stress relief should be able to “produce a significant reduction in disease progression” and painful responses38 in the treatment of endometriosis.39
Remember the rats who were subjected to the swim stress? Well in another study, rats were placed in the same maze of water, but some were given a platform they could climb upon, which allowed them to control their stress. The researchers showed that those who were better able to control their stress had smaller lesions, while those who could not control their stress had an increase in the number of lesions as well as their severity.40
In another study, women suffering with endometriosis were given a ten-week protocol of weekly, two-and-a-half-hour sessions “in a comfortable room with relaxing ambient music.”41 The first hour included body awareness training, breathing and stretching exercises, as well as active free exercise, massage, transcutaneous electrical nerve stimulation (TENS) and relaxation techniques. The remainder of the session consisted of behavioral cognitive therapy. And the authors found that this combined physical and psychological therapy reduced perceived stress and normalized cortisol levels. The authors hypothesize that “any treatment that reduces stress could benefit women with endometriosis.”
Deep down you probably already know what things you need to do to reduce your own stress. Some are specific to your unique situation, but others are universal:
- eat healthy—see “The Best Diet for Endometriosis and Adenomyosis”
- get enough sleep
- get plenty of exercise—see the rat-exercise study, above—but don’t overdo it
- get out into the sunshine and fresh air more
- take long walks, preferably in nature
- carve out some you-time—a hobby is preferable, but even a pedicure is a start
- take a break from social media, the news
- hug your loved ones more
- terminate relationships that are unhealthy
- practice gratitude
- practice positive thinking (Not that positive thinking alone will get you out of the cycle, but a change in mood can calm your nervous system).
I also highly recommend meditation. While studies have shown that it positively changes the brain,42 regulates cortisol levels,43 44 and calms your nervous system,45 it can also bring up negative emotions you may have been avoiding. If you’re like I was before my diagnosis, and don’t think you have any stress, you might be surprised what arises when you’re at your calmest. Those negative emotions are not meant to be turned away and ignored. Rather they’re there for you to examine so you can determine what to do about them. Can you change the things that are causing you distress? If not, you have to learn how to mitigate them. And meditation can help with that as well.
Yoga is a physical form of meditation, which I also highly recommend. We are said to store our emotions in our bodies, particularly in the hips and pelvic area, and yoga helps move these emotions out of the body. I can vouch for this. After I was newly diagnosed with adenomyosis and began a new yoga routine, I found myself releasing tears after certain sessions, even though I couldn’t identify anything in particular I was sad about. Pain happened to also be released at the same time.
But don’t take it from me. Pain intensity was also shown to decrease significantly after eight weeks of yoga, five times a week for women with chronic pelvic pain46 or even just twice a week for women with endometriosis.47 In addition, yogic breathing techniques increased the ability to be introspective in women with endometriosis, which ultimately “reduced the use of pain and psychiatric medications.” The patients also “created ties among themselves, suggesting that the yoga group allowed psychosocial support.”48
(And by the way, if you’re intimidated by girls in cute Lululemon crop-tops, there are plenty of places—hospitals, community centers, etc.—where people of all shapes and sizes come together for yoga. Or you can get started with an app).
The importance of social contact was also demonstrated by the same researchers who subjected rats to the swim stress. This time, rats were placed in an “enriched environment”49 for eight weeks, were induced with endometriosis, then remained there for another 60 days. The rats who got to experience the larger environment that “allowed for more movement and exploration,” as well as increased social contact, ended up with less lesions than the those who were not afforded the enriched environment. Their lesions were also smaller and less severe. Some implants did not even develop into lesions at all.
The enriched environment also provided “novelty” by the “weekly change of toys, chewing, and nesting materials,” showing the importance of comfort and play, as well. The authors of the study also note that “environmental enrichment has been shown to have beneficial effects on symptoms in multiple diseases including, but not limited to, anxiety, addictive phenotype, depression-like behaviors, and neurodegenerative diseases such as” Alzheimer’s and Huntington’s.
Beyond the above at-home measures you can take to decreases stress, meta-analyses by both Lund and Lundberg50 and Xu et al.51 suggest that acupuncture reduces pain intensity, as well as serum CA-125 levels. Also, as Buggio et al.52 point out, electroacupuncture was shown to stimulate the anti-inflammatory system in a mouse model, while TENS (transcutaneous electrical nerve stimulation) has shown “statistically significant improvement” in pelvic pain and deep pain during intercourse. Chinese medicine has also been shown to “suppress endometriotic implants.”
You might also consider psychotherapy, especially if your stress originated in childhood. Sometimes just talk therapy is enough. Thomas et al.53 found that chronic pelvic pain patients with and without endometriosis have a tendency to suppress difficult emotions, especially from past trauma, and this is “thought to be maladaptive in the long-term.” They suggest that getting help in expressing “negative thoughts and emotions, particularly those related to past abuse may reduce pain experiences.”
Nemeroff et al.54 found patients with childhood trauma exhibited a superior response to cognitive behavior psychotherapy compared to pharmacological intervention. Some therapies specific to trauma you can try include: EMDR (Eye Movement Desensitization and Reprocessing, sensorimotor or somatic psychotherapy, Trauma Release Exercises (TRE) or check out any of these institutes at Bessel van der Kolk’s Trauma Research Foundation. (Also, if you haven’t read his book, The Body Keeps the Score, its excellent). Also look for trauma-informed meditation and mindfulness, to assist in your therapy. Please note, that most of these trauma-based therapies should be done with a professional or you might risk re-traumatizing yourself. (That happened to me!)
Also, please note that whatever method you choose to alleviate your stress, it will take time. One yoga session, one acupuncture or psychotherapy session, one meditation is not going to do it. You likely have been in chronic stress mode for a while so it may take practice for your body to remind the parasympathetic nervous system how to function normally. This may be especially true if you have historic trauma you need to sort through. But even that can be overcome with time and dedication.
Are there any foods or supplements that can help with stress?
Turmeric is a well-known anti-inflammatory, and is often prescribed for endometriosis. However, use of it over the long-term can reduce its efficacy, or for people with autoimmunity can cause food-allergy-like reactions. (That can be true of any food that someone with autoimmunity eats habitually). I have used turmeric on occasion when I have a flare-up, such as after being accidentally glutened, but its better to target the sources of stress rather than try to continually reduce inflammation after the fact.
However, Lopez et al.55 have shown that “stress exacerbates development of cysts in endometriosis through mechanisms that include macrophage recruitment, cytokine changes, and a potentially perturbed” Vitamin D to Vitamin D Receptor axis, suggesting that supplementing with Vitamin D can help. Eighty-five percent of women with endo are deficient in Vitamin D,56 along with 50% of the general population,57 and its benefits go far beyond helping endometriosis. Expose your skin to sunshine (without sunscreen) at least twenty minutes a day, or as long as possible without getting burned. (If you decide to supplement with Vitamin D, watch out for constipation. But taking beta carotene and Vitamin K at the same time will help.)
Magnesium is another supplement that many of us endo and adeno women are deficient in. Magnesium is a pain reliever,58 reduces anxiety and helps in HPA dysregulation.59 As an added benefit, it moves food through the system so that excess estrogen doesn’t build up in the body. Try increasing your intake of these magnesium-rich foods, or find the supplement that’s right for you (more about this in another post).
Resevertrol, a substance found in red wine as well as some nuts and berries, has also been shown to be anti-inflammatory, and it “significantly diminished the number and size of endometriotic lesions” in mice.60 Red wine is also relaxing, so as long as you don’t drink too much or choose cheap wine with a high-sugar profile, I can’t see how it can’t hurt now and again.
Cannabis may also be beneficial to endometriosis, as women with endometriosis have reduced endocannabinoid system function,61 suggesting a link to the development and progression of endometriosis62 and severe pain.63 Indeed, Leconte et al.64 found that cannabis inhibited the growth and development of deep infiltrating endometriotic cells (in vitro), consistent with its effect on cancer cells. Sinclair et al.65 also found (in a retrospective study) that cannabis appeared effective for pelvic pain.
In addition to pain relief, cannabis may also be able to help deal better with the emotional issues that come to surface during the process of healing from trauma.
The link between stress and adenomyosis in my own story
Thanks for making it this far. As you can see, I’m passionate about this subject, and as I’ve already mentioned, I believe working on my stress was the most important aspect in healing my adenomyosis. (And I believe adenomyosis and endometriosis are essentially the same disease). Once I learned I had low cortisol, I got to work on figuring out all the things in my life that could be causing me stress—and what to do about them. Because that’s the subject of my recently completed memoir I won’t go into too many details. But aside from the daily stress of being the mother of young children, a recent cross-country move, and some threats to my home security, in this process, I eventually uncovered the historic stress I carried from a childhood filled with emotional abuse.
I already had been eating an anti-inflammatory diet, and I believe that helped me heal faster. I also took a few essential supplements (including Vitamin D and magnesium, as well as dandelion root tea) to help my body rebalance my hormones.
But I also started a daily meditation practice, including the use of loving-kindness meditation, so I would remember to always talk to myself in a kindly manner, rather than internally criticizing. I also did yoga several times a week, which was a change from the overly exhausting Crossfit exercise I had been doing before. Within months of doing this, my adenomyosis symptoms dramatically improved.
I also went into talk therapy and spoke to someone about my childhood for the first time ever. And I tried EMDR, sensorimotor psychotherapy and Trauma Release Exercises, each with varying positive effects. Although, as I hinted earlier, the latter caused me to re-traumatize myself, so please use caution if you want to try it on your own. Or preferably do so under supervision.
Eventually, I also had to cut off relations with my abuser, because every interaction with him triggered my HPA-axis and fight-or-flight response that kept exacerbating my condition. I tried in earnest to smooth relations between us, but his nature was to be an abuser, and there was no changing that. The break-off did cause me to spiral into PTSD and deep depression, which caused my adenomyosis symptoms to return. But I continued with meditation. I also took medical marijuana to help me through the worst months.
Of all the therapies, I believe meditation over the long term helped me the most. Today, it (and yoga) are the only “therapies” I’ve continued, besides diet and supplements. I am 100% free of adenomyosis symptoms, and I hope you will soon be able to say the same.
1. Popovic D, Bjelobrk M, Tesic M, Seman S, Jayasinghe S, Hills AP, Babu AS, Jakovljevic DG, Stoner L, Ozemek C, Bond S, Faghy MA, Pronk NP, Lavie CJ, Arena R; HL – PIVOT Network. Defining the importance of stress reduction in managing cardiovascular disease – the role of exercise. Prog Cardiovasc Dis. 2022 Feb 4:S0033-0620(22)00015-9. doi: 10.1016/j.pcad.2022.01.008. Epub ahead of print. PMID: 35131232 ⮐
2. Chida Y, Hamer M, Wardle J, Steptoe A. Do stress-related psychosocial factors contribute to cancer incidence and survival? Nat Clin Pract Oncol. 2008 Aug;5(8):466-75. doi: 10.1038/ncponc1134. Epub 2008 May 20. PMID: 18493231 ⮐
3. Falgarone G, Heshmati HM, Cohen R, Reach G. Mechanisms in endocrinology. Role of emotional stress in the pathophysiology of Graves’ disease. Eur J Endocrinol. 2012;168:R13–8 ⮐
4. Palomba S, Daolio J, Romeo S, Battaglia FA, Marci R, La Sala GB. Lifestyle and fertility: the influence of stress and quality of life on female fertility. Reprod Biol Endocrinol. 2018 Dec 2;16(1):113. doi: 10.1186/s12958-018-0434-y. PMID: 30501641; PMCID: PMC6275085 ⮐
5. Tsigos C, Kyrou I, Kassi E, et al. Stress: Endocrine Physiology and Pathophysiology. [Updated 2020 Oct 17]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278995/ ⮐
6. Petrelluzzi KF, Garcia MC, Petta CA, Grassi-Kassisse DM, Spadari-Bratfisch RC. Salivary cortisol concentrations, stress and quality of life in women with endometriosis and chronic pelvic pain. Stress. 2008;11(5):390-397. doi:10.1080/10253890701840610 ⮐
7. Brasil DL, Montagna E, Trevisan CM, et al. Psychological stress levels in women with endometriosis: systematic review and meta-analysis of observational studies. Minerva Med. 2020;111(1):90-102. doi:10.23736/S0026-4806.19.06350-X ⮐
8. Reis FM, Coutinho LM, Vannuccini S, Luisi S, Petraglia F. Is Stress a Cause or a Consequence of Endometriosis?. Reprod Sci. 2020;27(1):39-45. doi:10.1007/s43032-019-00053-0 ⮐
9. Appleyard CB, Flores I, Torres-Reverón A. The Link Between Stress and Endometriosis: from Animal Models to the Clinical Scenario. Reprod Sci. 2020;27(9):1675-1686. doi:10.1007/s43032-020-00205-7 ⮐
10. Friggi Sebe Petrelluzzi K, Garcia MC, Petta CA, et al. Physical therapy and psychological intervention normalize cortisol levels and improve vitality in women with endometriosis. J Psychosom Obstet Gynaecol. 2012;33(4):191-198. doi:10.3109/0167482X.2012.729625 ⮐
11. Grandi G, Mueller M, Bersinger N, Papadia A, Nirgianakis K, Cagnacci A, McKinnon B. Progestin suppressed inflammation and cell viability of tumor necrosis factor-α-stimulated endometriotic stromal cells. Am J Reprod Immunol. 2016 Oct;76(4):292-8. doi: 10.1111/aji.12552. Epub 2016 Aug 12. PMID: 27515307. ⮐
12. Lima AP, Moura MD, Rosa e Silva AA. Prolactin and cortisol levels in women with endometriosis. Braz J Med Biol Res. 2006;39(8):1121-1127. doi:10.1590/s0100-879×2006000800015 ⮐
13. Ibid. ⮐
14. van Aken M, Oosterman J, van Rijn T, et al. Hair cortisol and the relationship with chronic pain and quality of life in endometriosis patients. Psychoneuroendocrinology. 2018;89:216-222. doi:10.1016/j.psyneuen.2018.01.001 ⮐
15. Petrelluzzi et al., 2008. ⮐
16. Smith MP, Keay SD, Margo FC, et al. Total cortisol levels are reduced in the periovulatory follicle of infertile women with minimal-mild endometriosis. Am J Reprod Immunol. 2002;47(1):52-56. doi:10.1034/j.1600-0897.2002.1o122.x ⮐
17. Quiñones M, Urrutia R, Torres-Reverón A, Vincent K, Flores I. Anxiety, coping skills and hypothalamus-pituitary-adrenal (HPA) axis in patients with endometriosis. J Reprod Biol Health. 2015;3:2. doi:10.7243/2054-0841-3-2 ⮐
18. Karalis K, Goodwin G, Majzoub JA. Cortisol blockade of progesterone: a possible molecular mechanism involved in the initiation of human labor. Nat Med. 1996 May;2(5):556-60. doi: 10.1038/nm0596-556. PMID: 8616715 ⮐
19. Guo SW, Zhang Q, Liu X. Social psychogenic stress promotes the development of endometriosis in mouse. Reprod Biomed Online. 2017;34(3):225-239. doi:10.1016/j.rbmo.2016.11.012 ⮐
20. D’Hooghe TM, Bambra CS, De Jonge I, Lauweryns JM, Koninckx PR. The prevalence of spontaneous endometriosis in the baboon (Papio anubis, Papio cynocephalus) increases with the duration of captivity. Acta Obstet Gynecol Scand. 1996 Feb;75(2):98-101. doi: 10.3109/00016349609033298. PMID: 8604618 ⮐
21. Carrarelli P, Luddi A, Funghi L, Arcuri F, Batteux F, Dela Cruz C, Tosti C, Reis FM, Chapron C, Petraglia F. Urocortin and corticotrophin-releasing hormone receptor type 2 mRNA are highly expressed in deep infiltrating endometriotic lesions. Reprod Biomed Online. 2016 Oct;33(4):476-483. doi: 10.1016/j.rbmo.2016.07.009. Epub 2016 Jul 29. PMID: 27567427 ⮐
22. Torres-Reverón A, Rivera LL, Flores I, Appleyard CB. Environmental Manipulations as an Effective Alternative Treatment to Reduce Endometriosis Progression. Reprod Sci. 2018 Sep;25(9):1336-1348. doi: 10.1177/1933719117741374. Epub 2017 Nov 14. PMID: 29137551; PMCID: PMC6346300 ⮐
23. Overman EL, Rivier JE, Moeser AJ. CRF induces intestinal epithelial barrier injury via the release of mast cell proteases and TNF-α. PLoS One. 2012;7(6):e39935. doi: 10.1371/journal.pone.0039935. Epub 2012 Jun 29. PMID: 22768175; PMCID: PMC3386952 ⮐
24. Konturek PC, Brzozowski T, Konturek SJ. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. J Physiol Pharmacol. 2011 Dec;62(6):591-9. PMID: 22314561 ⮐
25. Bungum HF, Vestergaard C, Knudsen UB. Endometriosis and type 1 allergies/immediate type hypersensitivity: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2014 Aug;179:209-15. doi: 10.1016/j.ejogrb.2014.04.025. Epub 2014 Apr 26. PMID: 24857310 ⮐
26. Long Q, Liu X, Qi Q, Guo SW. Chronic stress accelerates the development of endometriosis in mouse through adrenergic receptor β2. Hum Reprod. 2016;31(11):2506-2519. doi:10.1093/humrep/dew237 ⮐
27. Cuevas M, Flores I, Thompson KJ, Ramos-Ortolaza DL, Torres-Reveron A, Appleyard CB. Stress exacerbates endometriosis manifestations and inflammatory parameters in an animal model. Reprod Sci. 2012 Aug;19(8):851-62. doi: 10.1177/1933719112438443. Epub 2012 Apr 23. PMID: 22527982; PMCID: PMC4046310 ⮐
28. Hernandez S, Cruz ML, Torres-Reveron A, Appleyard CB. Impact of physical activity on pain perception in an animal model of endometriosis. J Endometr Pelvic Pain Disord. 2015 Jul-Sep;7(3):89-114. doi: 10.5301/je.5000231. Epub 2015 Dec 24. PMID: 28217664; PMCID: PMC5310711 ⮐
29. Liebermann C, Kohl Schwartz AS, Charpidou T, et al. Maltreatment during childhood: a risk factor for the development of endometriosis?. Hum Reprod. 2018;33(8):1449-1458. doi:10.1093/humrep/dey111 ⮐
30. Lampe A, Sölder E, Ennemoser A, Schubert C, Rumpold G, Söllner W. Chronic pelvic pain and previous sexual abuse. Obstet Gynecol. 2000;96(6):929-933. doi:10.1016/s0029-7844(00)01072-3 ⮐
31. Harrop-Griffiths J, Katon W, Walker E, Holm L, Russo J, Hickok L. The association between chronic pelvic pain, psychiatric diagnoses, and childhood sexual abuse. Obstet Gynecol. 1988;71(4):589-594 ⮐
32. Walling MK, Reiter RC, O’Hara MW, Milburn AK, Lilly G, Vincent SD. Abuse history and chronic pain in women: I. Prevalences of sexual abuse and physical abuse. Obstet Gynecol. 1994;84(2):193-199 ⮐
33. Fiala L, Lenz J, Bob P. Effect of psychosocial trauma and stress on sexual dysfunction in women with endometriosis. Medicine (Baltimore). 2021;100(31):e26836. doi:10.1097/MD.0000000000026836 ⮐
34. Danese A, Pariante CM, Caspi A, Taylor A, Poulton R. Childhood maltreatment predicts adult inflammation in a life-course study. Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1319-24. doi: 10.1073/pnas.0610362104. Epub 2007 Jan 17. PMID: 17229839; PMCID: PMC1783123 ⮐
35. Hänsel A, Hong S, Cámara RJ, von Känel R. Inflammation as a psychophysiological biomarker in chronic psychosocial stress. Neurosci Biobehav Rev. 2010 Sep;35(1):115-21. doi: 10.1016/j.neubiorev.2009.12.012. Epub 2009 Dec 22. PMID: 20026349 ⮐
36. Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall R, Miller AH, Nemeroff CB. Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA. 2000 Aug 2;284(5):592-7. doi: 10.1001/jama.284.5.592. PMID: 10918705⮐
37. Reis et al., 2020 ⮐
38. Appleyard et al., 2020 ⮐
39. van Aken et al., 2018 ⮐
40. Appleyard CB, Cruz ML, Hernández S, Thompson KJ, Bayona M, Flores I. Stress management affects outcomes in the pathophysiology of an endometriosis model. Reprod Sci. 2015;22(4):431-441. doi:10.1177/1933719114542022 ⮐
41. Petrelluzzi et al., 2012 ⮐
42. Fox KC, Nijeboer S, Dixon ML, Floman JL, Ellamil M, Rumak SP, Sedlmeier P, Christoff K. Is meditation associated with altered brain structure? A systematic review and meta-analysis of morphometric neuroimaging in meditation practitioners. Neurosci Biobehav Rev. 2014 Jun;43:48-73. doi: 10.1016/j.neubiorev.2014.03.016. Epub 2014 Apr 3. PMID: 24705269 ⮐
43. Brand S, Holsboer-Trachsler E, Naranjo JR, Schmidt S. Influence of mindfulness practice on cortisol and sleep in long-term and short-term meditators. Neuropsychobiology. 2012;65(3):109-18. doi: 10.1159/000330362. Epub 2012 Feb 24. PMID: 22377965 ⮐
44. Klimes-Dougan B, Chong LS, Samikoglu A, Thai M, Amatya P, Cullen KR, Lim KO. Transcendental meditation and hypothalamic-pituitary-adrenal axis functioning: a pilot, randomized controlled trial with young adults. Stress. 2020 Jan;23(1):105-115. doi: 10.1080/10253890.2019.1656714. Epub 2019 Sep 11. PMID: 31418329 ⮐
45. Telles S, Raghavendra BR, Naveen KV, Manjunath NK, Kumar S, Subramanya P. Changes in autonomic variables following two meditative states described in yoga texts. J Altern Complement Med. 2013;19(1):35-42. doi:10.1089/acm.2011.0282 ⮐
46. Saxena R, Gupta M, Shankar N, Jain S, Saxena A. Effects of yogic intervention on pain scores and quality of life in females with chronic pelvic pain. Int J Yoga. 2017 Jan-Apr;10(1):9-15. doi: 10.4103/0973-6131.186155. PMID: 28149062; PMCID: PMC5225749 ⮐
47. Gonçalves AV, Barros NF, Bahamondes L. The Practice of Hatha Yoga for the Treatment of Pain Associated with Endometriosis. J Altern Complement Med. 2017 Jan;23(1):45-52. doi: 10.1089/acm.2015.0343. Epub 2016 Nov 21. PMID: 27869485 ⮐
48. Gonçalves AV, Makuch MY, Setubal MS, Barros NF, Bahamondes L. A Qualitative Study on the Practice of Yoga for Women with Pain-Associated Endometriosis. J Altern Complement Med. 2016;22(12):977-982. doi:10.1089/acm.2016.0021 ⮐
49. Torres-Reverón A, Rivera LL, Flores I, Appleyard CB. Environmental Manipulations as an Effective Alternative Treatment to Reduce Endometriosis Progression. Reprod Sci. 2018;25(9):1336-1348. doi:10.1177/1933719117741374 ⮐
50. Lund I, Lundeberg T. Is acupuncture effective in the treatment of pain in endometriosis? J Pain Res. 2016 Mar 24;9:157-65. doi: 10.2147/JPR.S55580. PMID: 27069371; PMCID: PMC4818044 ⮐
51. Xu Y, Zhao W, Li T, Zhao Y, Bu H, Song S. Effects of acupuncture for the treatment of endometriosis-related pain: A systematic review and meta-analysis. PLoS One. 2017 Oct 27;12(10):e0186616. doi: 10.1371/journal.pone.0186616. PMID: 29077705; PMCID: PMC5659600 ⮐
52. Buggio L, Barbara G, Facchin F, Frattaruolo MP, Aimi G, Berlanda N. Self-management and psychological-sexological interventions in patients with endometriosis: strategies, outcomes, and integration into clinical care. Int J Womens Health. 2017;9:281-293. Published 2017 May 2. doi:10.2147/IJWH.S119724 ⮐
53. Thomas E, Moss-Morris R, Faquhar C. Coping with emotions and abuse history in women with chronic pelvic pain. J Psychosom Res. 2006;60(1):109-112. doi:10.1016/j.jpsychores.2005.04.011 ⮐
54. Nemeroff CB, Heim CM, Thase ME, Klein DN, Rush AJ, Schatzberg AF, Ninan PT, McCullough JP Jr, Weiss PM, Dunner DL, Rothbaum BO, Kornstein S, Keitner G, Keller MB. Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14293-6. doi: 10.1073/pnas.2336126100. Epub 2003 Nov 13. Erratum in: Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16530. PMID: 14615578; PMCID: PMC283585. ⮐
55. Lopez A, Cruz ML, Chompre G, et al. Influence of Stress on the Vitamin D-Vitamin D Receptor System, Macrophages, and the Local Inflammatory Milieu in Endometriosis. Reprod Sci. 2020;27(12):2175-2186. doi:10.1007/s43032-020-00235-1 ⮐
56. Ciavattini A, Serri M, Delli Carpini G, Morini S, Clemente N. Ovarian endometriosis and vitamin D serum levels. Gynecol Endocrinol. 2017 Feb;33(2):164-167. doi: 10.1080/09513590.2016.1239254. Epub 2016 Nov 4. PMID: 27809683 ⮐
57. Sizar O, Khare S, Goyal A, et al. Vitamin D Deficiency. [Updated 2021 Jul 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532266/ ⮐
58. Na HS, Ryu JH, Do SH. The role of magnesium in pain. In: Vink R, Nechifor M, editors. Magnesium in the Central Nervous System [Internet]. Adelaide (AU): University of Adelaide Press; 2011. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507245/ ⮐
59. Sartori SB, et al. (2012). Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment. DOI: 10.1016/j.neuropharm.2011.07.027 ⮐
60. Buggio et al., 2017 ⮐
61. Dmitrieva N, Nagabukuro H, Resuehr D, et al. Endocannabinoid involvement in endometriosis. Pain. 2010;151(3):703-710. doi:10.1016/j.pain.2010.08.037 ⮐
62. Luschnig P, Schicho R. Cannabinoids in Gynecological Diseases. Med Cannabis Cannabinoids. 2019;2(1):14-21. Published 2019 May 24. doi:10.1159/000499164 ⮐
63. Bouaziz J, Bar On A, Seidman DS, Soriano D. The Clinical Significance of Endocannabinoids in Endometriosis Pain Management. Cannabis Cannabinoid Res. 2017;2(1):72-80. Published 2017 Apr 1. doi:10.1089/can.2016.0035. ⮐
64. Leconte M, Nicco C, Ngô C, Arkwright S, Chéreau C, Guibourdenche J, Weill B, Chapron C, Dousset B, Batteux F. Antiproliferative effects of cannabinoid agonists on deep infiltrating endometriosis. Am J Pathol. 2010 Dec;177(6):2963-70. doi: 10.2353/ajpath.2010.100375. Epub 2010 Nov 5. PMID: 21057002; PMCID: PMC2993285.⮐
65. Sinclair J, Collett L, Abbott J, Pate DW, Sarris J, Armour M. Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms. PLoS One. 2021 Oct 26;16(10):e0258940. doi: 10.1371/journal.pone.0258940. PMID: 34699540; PMCID: PMC8547625. ⮐