insights

Read Times: 7 Minutes

Pelvic endometriosis, often manifested by chronic pelvic pain and infertility, is a complex syndrome characterized by an estrogen-dependent inflammatory process that affects pelvic tissues, including the ovaries.¹ Although endometriosis resembles other chronic inflammatory disorders associated with pain, its dependence on estrogen as the key biologic driver of inflammation makes endometriosis distinct and complex.¹

The development of endometriosis involves interacting endocrine, immunologic, proinflammatory, and proangiogenic processes; however, it is not known if any of these factors is causal or if they represent a feature of the pathophysiological process.² At present, endometriosis is thought to arise due to a wide variety of factors, including:

• Retrograde menstruation (which refers to the reflux of menstrual debris containing viable endometrial cells through the fallopian tubes into the peritoneal cavity).
• Cellular metaplasia (the transformation of peritoneal mesothelium into the glandular endometrium) and lymphatic and vascular metastasis (the transport of endometrial cells through lymphatic and blood vessels).
• Endometrial stem-cell and progenitor-cell populations, which are present in eutopic endometrium, being shed in retrograde menstruation. This may play a role in the development of endometriotic lesions.
• Other factors, including altered or impaired immunity, localized complex hormonal influences, genetics, and environmental contaminants.^2,3

Although the pathogenesis of endometriosis remains unclear, researchers agree that it is a chronic inflammatory disorder.⁴ The levels and concentrations of active macrophages; interleukin (IL)-1?, IL-6, IL-8; nerve growth factor (NGF); other immune cells; and inflammatory factors are increased in peritoneal fluid, and endometriotic lesions themselves form an inflammatory microenvironment.⁴ This environment interacts with endometriotic cells (including stromal cells and epithelial cells), which play an important role in the development and persistence of endometriosis.⁴

Endometriosis affects roughly 10% (190 million) of reproductive age women and girls globally² but is not easily diagnosed due to the broad spectrum and variability of its presenting symptoms, including pelvic pain and pain during intercourse, psychological distress, bladder and bowel problems, and more.^5,6 At present, there is no known cure for endometriosis, and treatment is usually aimed at controlling symptoms⁷ or surgical removal of the pelvic lesions, which often recur.¹ In the early stages of the disease, however, there may be a window of opportunity to improve quality of life with healthy lifestyle interventions and pain management strategies.

Lifestyle Intervention Studies

Few studies are published on the topic of lifestyle factors in the development or maintenance of pain in the pelvis or endometriosis, and as such, a systematic review has not been feasible. However, in 2021, Gutke et al compiled a “best-evidence review” to explore the field and present an agenda for future research.⁵ The authors outline the evidence on interventions for chronic pelvic pain in women:⁵

• Physical Activity: Two systematic reviews reported on endometriosis and physical activity/exercise.⁵ Hansen et al studied the recent evidence on the impact of exercise on pain perception in women with endometriosis.⁵ No general positive effect of exercise on pain could be concluded; however, the included studies generally had a high risk of bias. Ricci et al studied the role of physical activity on the risk for endometriosis in a meta-analysis. Included in the study were women with endometriosis performing recent physical activity and women performing physical activity in the past. The pooled estimate of adjusted odds ratios for current exercise indicated a significantly protective effect of exercise, but the overall estimates did not reach levels of significance, report Gutke et al. Furthermore, the authors report that the review did not specify the influence of physical activity on pain symptoms. These results are in line with the results of the earlier published narrative review of Bonocher et al that assessed the relationship between physical exercise and the prevalence and/or improvement of symptoms associated with endometriosis. Gutke et al conclude that the data available are inconclusive regarding the benefits of physical exercise on the risk of endometriosis, and no firm data exist on the added value of physical activity on pain in women with endometriosis.⁵ More research in this area is needed.⁵

• Diet & Nutritional Supplementation: In 2021, Nirgianakis et al performed a systematic review on the effectiveness of dietary interventions in the treatment of endometriosis, quantifying changes in endometriosis-associated symptoms measured with pain scales or patient-reported quality of life outcomes.⁵ Different dietary interventions were assessed, including supplementation of vitamin D; supplementation of vitamins A, C, and E; supplementation of omega-3/6, quercetin, vitamin B3, 5-methyltetrahydrofolate, turmeric, and parthenium; Mediterranean diet; low-FODMAP diet; low nickel diet; gluten-free diet, and individual dietary changes. Most studies identified a positive effect of the dietary intervention on endometriosis symptoms. However, all studies were of moderate and/or high-risk of bias, limiting the validity of the results, writes Gutke et al. It was concluded that more, and especially higher quality original research is needed to draw conclusions on the effectiveness of dietary intervention on pain in women with endometriosis.⁵ A 2022 systematic review of six studies found that diet had a positive impact on pain perception among women with endometriosis.⁸ However, the authors report that the majority of available evidence on dietary interventions in relation to endometriosis-associated pain was derived from non-randomized controlled trials, which may have multiple sources of bias.⁸

• Sleep: In women with endometriosis, poor sleep quality is reported to be associated with pelvic pain.⁵ In 2020, Arion et al performed a quantitative analysis of sleep quality in women with surgically confirmed endometriosis to assess which variables were associated with poorer sleep.⁵ Based on regression analyses, the following factors were independently associated with poorer sleep: functional quality of life, more depressive symptoms, and painful bladder syndrome. In an earlier cross-sectional study on the sleep quality of women with endometriosis and the relation between sleep quality and pressure pain thresholds, sleep quality was significantly poorer in women with endometriosis compared to women without endometriosis. Furthermore, the pressure pain threshold in the greater trochanter and abdomen was significantly lower in women with endometriosis when compared to women without endometriosis, which is indicative of an increased central sensitivity; however, there was no difference in pain intensity between women with and without endometriosis.⁵

Functional Medicine Clinical Applications

While very few studies on endometriosis and lifestyle interventions are available, some researchers suggest approaching women with endometriosis from a modern pain management point of view, which includes lifestyle factors.⁵ Physical activity may be a way to achieve exercise-induced analgesia and to promote self-efficacy (because of the experience of self-control). From a chronic pain science perspective, physical activity may also have sleep improving, stress-reducing, and general anti-inflammatory effects, which are all relevant for optimal pain management.⁵

Patient education also plays a role in lifestyle interventions. Gutke et all write that teaching women the science behind pain and the mechanisms related to pain in the pelvis (such as lifestyle factors) could be a strong protective factor for motivating them to maintain a healthy lifestyle.⁵ Pain neuroscience education, in the treatment of women with pelvic pain, might provide women with the necessary information to reach a sustained change toward a more active and healthier lifestyle.

The IFM Toolkit includes a patient handout that details lifestyle recommendations for chronic pain syndromes, including tips for sleep, relaxation, exercise and movement, nutrition, stress, relationships, and more. To access this educational resource, log in to the IFM website and select “My Toolkit,” then search for “Lifestyle Recommendations for Chronic Fatigue and Pain Syndromes.” Another toolkit item, called “Estrogen Metabolism,” presents a summary of factors that can promote or disrupt estrogen metabolism. For example, factors that may promote healthy estrogen metabolism include fiber, cruciferous vegetables, antioxidants, omega-3 fats, exercise, etc. And factors that may disrupt healthy estrogen metabolism include xenoestrogens, alcohol, etc.

Learn more about endometriosis and hormone imbalance in IFM’s Hormone Advanced Practice Module, where our expert faculty team will supply you with the foundational background, insight, and in-depth clinical thinking to confidently assess and treat patients who present with hormonal dysfunction. This program will provide a unique, experiential, case-based, clinically practical experience from which you will acquire the tools you need to apply a comprehensive functional medicine approach to hormone dysfunction in your patients.

Related Articles

Nutrition and Impacts on Hormone Signaling

Sex Hormones & the Female Brain: A Focus on Mood Disorders

A Functional Medicine Approach to Uterine Fibroids

References

1. Bulun SE, Yilmaz BD, Sison C, et al. Endometriosis. Endocr Rev. 2019;40(4):1048-1079. doi:1210/er.2018-00242
2. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020;382(13):1244-1256. doi:1056/nejmra1810764
3. Wen X, Xiong Y, Qu X, et al. The risk of endometriosis after exposure to endocrine-disrupting chemicals: a meta-analysis of 30 epidemiology studies. Gynecol Endocrinol. 2019;35(8):645-650. doi:1080/09513590.2019.1590546
4. Wei Y, Liang Y, Lin H, Dai Y, Yao S. Autonomic nervous system and inflammation interaction in endometriosis-associated pain. J Neuroinflammation. 2020;17(1):80. doi:1186/s12974-020-01752-1
5. Gutke A, Sundfeldt K, De Baets L. Lifestyle and chronic pain in the pelvis: state of the art and future directions. J Clin Med. 2021;10(22):5397. doi:3390/jcm10225397
6. Agarwal SK, Chapron C, Giudice LC, et al. Clinical diagnosis of endometriosis: a call to action. Am J Obstet Gynecol. 2019;220(4):354.e1-354.e12. doi:1016/j.ajog.2018.12.039
7. Johnson NP, Hummelshoj L; World Endometriosis Society Montpellier Consortium. Consensus on current management of endometriosis. Hum Reprod. 2013;28(6):1552-1568. doi:1093/humrep/det050
8. Sverrisdóttir UÁ, Hansen S, Rudnicki M. Impact of diet on pain perception in women with endometriosis: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2022;271:245-249. doi:1016/j.ejogrb.2022.02.028