Holistic approaches to living well with endometriosis

Nutrition

Numerous SRs support the role of nutrition in managing chronic pain conditions.^8,9 Optimising diet quality with a high intake of anti-inflammatory nutrients reduces pain severity by modulating the body’s inflammatory response.¹⁰ Gut microbiome dysbiosis in inflammatory pain conditions such as endometriosis is hypothesised to cause incorrect immune responses resulting in pain from central sensitisation pathways. Probiotics and FODMAP diets (omitting fermentable oligo-, di-, monosaccharides and polyols), are beneficial in treating visceral pain.¹¹ More research into dietary effects on endometriosis is recommended,¹² as many studies to date have small population sizes with heterogeneity between intervention groups.

A SR (one RCT and five observational studies) of low FODMAP, gluten-free and low-nickel diets as well as high intake of omega-3 polyunsaturated fatty acids (average treatment dose palmitoylethanolamide 400 mg & polydatin 40 mg twice daily for 3 months)^13–15 reported that all diets, with the exception of low FODMAP reduced pain.¹⁶ Those with concurrent irritable bowel syndrome (IBS) may benefit the most from low-FODMAPs; observational data (n=160) demonstrated symptom improvement compared to patients with IBS alone (72% vs. 40%, respectively, p = 0.001).¹⁷

Compared to controls, endometriosis patients may have a higher rate of nickel allergic contact mucositis (odds ratio: 2.474; 95% confidence interval: 1.023~5.988; p = 0.044),¹⁸ causing IBS-like symptoms. Reducing nickel-rich foods e.g. tomatoes, whole wheat, and soy, resulted in significant improvement of CPP (p < 0.05) in a prospective 3-month observational study of 31 women with endometriosis and gastrointestinal symptoms.¹⁹

Krabbenborg et al.²⁰ observed 157 women with endometriosis assessing which dietary modifications patients had already implemented improved their QOL using the EHP-30 score. The most used diets were the endometriosis diet (self-selecting nutrients to omit thought by the individual to worsen their symptoms), gluten free, low-FODMAP, low-lactose and weight loss diets. Although EHP-30 scores did not significantly alter with dietary modification, pain reduction was noted in 71.3% of patients, with gluten-free showing the greatest impact. Dietary modifications have a greater impact with longer adherence.

In a placebo-controlled triple-blind RCT (n = 120), garlic extract (400 mg daily over 12 weeks) showed a significant reduction in ERPP (p < 0.05). Purported mechanisms are reduction in oxidative stresses, prostaglandin production, endometriosis cell proliferation and increased oestrogen elimination.²¹

Endometriosis severity may be associated with both low and high BMI.²² The association between BMI and endometriosis severity might be more complicated than a simple correlation. A confounding factor for both endometriosis and obesity may be systemic inflammation.²³

It is tempting to speculate whether maintenance of a normal BMI is beneficial for symptom control, but studies designed to assess change in weight for ERPP are lacking.

Body & mind therapies

Poor mental health may result secondary to the multifactorial impact endometriosis has on physical, sexual, and psychological well-being.²⁴ Strategies such as cognitive behavioural therapy (CBT), yoga and relaxation techniques can be valuable. Increasing evidence suggests psychosocial factors, such as preoperative pain catastrophising independently impact pain experience, severity of symptoms and recurrence of endometriosis.^25,26 Patient awareness and self-uptake of psychological approaches for ERPP are increasingly popular, with 93.8% of women sampled in a cross-sectional survey distributed via The Endometriosis Network Canada (n = 434) utilising at least one psychological management strategy.²⁷

CBT

CBT is recognised as an effective treatment for chronic pain and associated mental health conditions, including CPP.²⁸ Current research interest is evidenced by the publication of three RCT protocols assessing efficacy of CBT^29,30 and yoga with CBT³¹ on QOL of patients with endometriosis. Boersen’s RCT³⁰ aims to recruit 100 patients undergoing endometriosis surgery, assessing benefits of CBT in postoperative care.

Wu et al.³² assessed the benefits of CBT plus usual care compared to usual care alone in post-surgical endometriosis patients with a case-control study (Intervention group n = 48, Control group n = 48), utilising one CBT session before and six sessions post-surgery. During a 6-month follow-up, participants provided a score on the depression, anxiety, and stress (DASS-21). Anxiety scores improved significantly (p = 0.0091).

Authors suggest patient education played a large role in self-management of ERPP following CBT.

Mindfulness

Mindfulness is a psychological technique that draws on awareness and non-judgemental acceptance of present personal experience. The mindfulness-based stress reduction (MBSR) programme, was first developed by Kabat-Zinn³³ as an adjunct to treatment for chronic pain, through relating physical and psychological conditions.

Moreira et al.³⁴ performed an RCT to assess the impact of mindfulness on CPP. They adapted the MBSR programme, forming a brief mindfulness-based intervention (bMBI, n = 31, usual care controls n = 32) which had a reduced intensity and reduced duration (4-weeks instead of 8-weeks). Formal meditation was practised around the theme of ‘reconceptualising pain.’ The intervention group showed reduced pain scores & unpleasantness and dyschezia.

Hansen et al.³⁵ found that psychological intervention, with a mindfulness focus, did not reduce perception of pain, but did improve QOL in a three-armed RCT. Participants were randomised to three groups: mindfulness and acceptance-based intervention (n = 20), non-specific psychological intervention that did not include mindfulness (relaxation and guided physical therapy) (n = 19), or a waitlist control that included usual treatment (n = 19). All participants received usual treatment which included analgesia. The ten-week programme developed (MY-ENDO), combined Kabat-Zinn’s MBSR programme and acceptance with commitment therapy. There was no statistically significant reduction in ERPP between the MY-ENDO group and non-specific intervention group (p = 0.144, d = 0.59). Psychological intervention significantly improved QOL-subscales ‘control and powerlessness’ (p = 0.019, d = 0.78), ‘emotional well-being’ (p = 0.003, d = 1.01), and ‘social support’ (p = 0.042, d = 0.66).

QOL was improved through the positive effects on bowel symptoms, specifically diarrhoea (P = 0.035, d = 0.25), within the two intervention groups, thought to be due to physical activity undertaken.

Further studies are needed to determine whether psychological interventions in general improves QOL or whether there is a need for a mindfulness aspect to the intervention.

Yoga

Yoga has a long tradition in managing chronic pain. In an AB-design pilot study of 42 women by Ravins et al.,³⁶ participants underwent eight-weeks of conventional therapy followed by eight-weeks of 90-minute endometriosis yoga sessions, bi-weekly. EHP-30 scores and numerical pain rating scale were lower following the completion of the yoga sessions (p = 0.001).

Gonçalves’ RCT³⁷ randomly allocated 40 women; an intervention group who practised 90-minutes of yoga bi-weekly for 8 weeks (n = 28) and a control group who did not practise yoga (n = 12). Daily pain was significantly lower among the intervention group (p = 0.0007). EHP-30 domains were assessed at the time of presentation and again at 8-week follow up; pain (p = 0.0046), well-being (p = 0.0009), and image (p = 0.0087) from the central questionnaire, and work (p = 0.0027) and treatment (p = 0.0245) from the modular questionnaire were significantly different. One limitation of this study was the high loss to follow up, with only 57% of participants in the intervention group completing the full yoga-programme, highlighting the challenges faced of adhering to regular yoga practice.

Similar findings were echoed by Saxena et al.³⁸ in a randomised case-control study of 60 women with CPP. The intervention group (n = 30) who received yoga therapy with conventional therapy (non-steroidal anti-inflammatory drugs, NSAIDs) were compared with the control group (n = 30) who received NSAIDs alone. Pain scores through VAS score and QOL by the World Health Organization quality of life-BREF (WHOQOL-BREF) questionnaire were assessed at the start of the study and again at an 8-week follow up. The yoga-practising group showed a significant decrease in pain intensity (p < 0.001) and improvement in the QOL with a significant increase (p < 0.001) in physical, psychological, social, and environmental domain scores of WHOQOL-BREF.

Enriched environments (consisting of enlarged space, increased physical activity and social interactions) suppresses the development of endometriosis in mice through attenuated adrenergic signalling, enhanced autophagy, and reduced leptin levels.³⁹ Extrapolating this to humans, offering group outdoor physical activities such yoga to optimise environmental enrichment showed significantly less ERPP and perceived stress, improved mood and emotional wellbeing QOL compared with control participants in a recent RCT by Flores.⁴⁰

Progressive muscle relaxation (PMR)

PMR improved anxiety and depression (p < 0.05), and health-related QOL (p < 0.05) for patients with endometriosis in a study of 100 women receiving Gonadotrophin-releasing hormone (GnRH) agonist treatment. Participants were randomly assigned either to a control group or PMR group, who received 12 weeks of PMR training.⁴¹

Psychological and physical interventions positively impact on QOL in patients with ERPP. However, there remains a lack of high-powered trials in mind and body therapies. Consideration must be taken for the barriers to accessing psychological interventions. Patients should not feel their pain is less validated if a physiological approach is offered. Smart-phone applications are nowadays suggested to simplify access to Mindfulness. However, those approaches require co-development with stakeholders to be acceptable and used regularly.⁴²

Physiotherapy

Pelvic floor muscle physiotherapy

Pelvic floor muscle dysfunction (specifically levator ani hypertonia and incomplete relaxation) contributes to ERPP with deep infiltrative endometriosis (DIE).^43–45

Pelvic floor physiotherapy (PFP), with 3D/4D trans-perineal ultrasound, increased levator hiatus area (LHA) which in turn improved dyspareunia and pelvic floor muscle relaxation (PFMR) reduced ERPP. Following a successful pilot study,⁴⁶ Forno et al. used trans-perineal ultrasound to assess LHA before and after PFP in an RCT of 34 women.⁴⁷ Participants were assigned to a no intervention group (n = 17), or the treatment group which involved five PFP sessions (n = 17). Physiotherapy sessions involved the Thiele massage, using digital pressure to elongate and relax muscles, restoring normal tone. PFMR improved on maximum Valsalva manoeuvre in the intervention group compared to the control (20.0 ± 24.8% vs –0.5 ± 3.3%, respectively; p = 0.02), and superficial dyspareunia pain scores reduced (p < 0.01).

Acupuncture

Previous studies have shown acupuncture to be a suitable tool in reducing ERPP, and is considered a safe therapy with minimal side effects.^48,49 Several recent case studies have shown symptomatic improvement with acupuncture.^50,51 Yan et al. published a protocol for SR and meta-analysis of RCTs on acupuncture benefits for endometriosis symptoms. ESHRE guidelines⁵² acknowledge that acupuncture may be a beneficial tool, however the studies that were available at that time were limited and not free from bias.

Wang et al.⁵³ recently published a systematic review of 15 RCTs (sample sizes between 10 and 54), which assessed the effectiveness of acupuncture and/or moxibustion for the treatment of endometriosis. Compared with sham acupuncture, actual acupuncture was more effective at reducing dysmenorrhoea VAS pain score (mean difference [MD] − 2.40, 95% CI [− 2.80, − 2.00]; moderate certainty evidence), pelvic pain VAS score (MD − 2.65, 95% CI [− 3.40, − 1.90]; high certainty evidence) and dyspareunia VAS scores (MD − 2.88, [− 3.83, − 1.93]), lessened the size of ovarian cyst (MD − 3.88, 95% CI [− 7.06, − 0.70]), and improved QOL. These promising results suggest that acupuncture is an effective adjunct to treating ERPP.

In a multicentre, randomised, single-blind, placebo-controlled trial⁵⁴ assessing the effects of acupuncture on endometriosis related symptoms (n = 106), acupuncture was delivered to the intervention group (n = 51) as 30-minute sessions once daily, three times a week, starting one week before expected onset of menstruation, for a total duration of 12-weeks. The control group (n = 53) received sham acupuncture. Lower VAS scores were seen in the intervention group at 12 weeks for dysmenorrhoea (-2.82 (-3.47, -2.18) and QOL, (EHPscore) -18.88 (-31.88, -5.87)), but not for pelvic pain and dyspareunia. At 24 weeks no statistical benefits were seen, suggesting acupuncture is a suitable immediate therapy for endometriosis related dysmenorrhoea, however the effects of acupuncture may not be sustainable over a long period of time and repeated therapy would be necessary.

Adjunct devices

Phallus length reducing devices

The Ohnut© device is a phallus length reducer worn over the penis or penetrating object with the intention to reduce endometriosis-associated deep dyspareunia. The effectiveness of this device is currently being assessed in a pilot RCT of 40 participants by Zhang⁵⁵ who will be randomised into an intervention group or a waitlist control group.

Transcutaneous electrical nerve stimulation (TENS)

A TENS unit passes a current through electrodes placed on the skin for targeted pain relief via the gate control theory.⁵⁶ Its use has been shown to reduce pain in primary dysmenorrhoea⁵⁷ and CPP.^58,59

Mira et al.⁶⁰ conducted a multicentre RCT of 101 participants with DIE. The study aimed to identify whether the addition of a TENS unit to hormonal therapy (intervention group; n = 53) would provide a greater therapeutic benefit than hormonal treatment alone (control group; n = 48). The TENS device was used twice a day, 20 minutes per day, for 8 weeks. CPP improved in the intervention group (VAS decreased from 7.11 ± 2.40–4.55 ± 3.08, p < 0.001, 36% decrease), whereas it did not in the control group (VAS from 7.33 ± 2.09–7.06 ± 2.33, p = 0.554, 3.68% decrease). A greater improvement in deep dyspareunia was found in the intervention group, 32.67% reduction vs. 13.84% reduction in the control group. There was a decrease in the number of days participants experienced pain from the first week to the eighth week (from 3.27 to 2.22, p = 0.028, 32.11% decrease), which was not identified in the control group (from 4.55 to 4.07, p = 0.203, 10.54% decrease). This study was conducted over a relatively short time interval, therefore due to the chronic nature of endometriosis, further research is needed to assess whether benefits from TENS units are sustained longer-term.

Cannabinoid (CBT)

A cross sectional survey⁶¹ of 113 women with pelvic, perineal pain, dyspareunia or endometriosis was conducted to gather information regarding patient cannabis use. 26/113 (23%) participants reported cannabis use, of which only 5/26 obtained cannabis through a medical programme, 25 had complete data and were analysed. 15/25 (60%) used a combination of cannabidiol (CBD) and tetrahydrocannabinol (THC). There was no significant difference between the demographics of cannabis users and nonusers. Overall, 24/25 (96%) of participants reported improvement in symptoms such as pain, depression and sleep disturbance with the use of cannabis. It is important to note that participants from both groups also utilised alternative medications and therapies, and therefore reported symptom improvement cannot be confidently solely attributed to cannabis use.

Traditional Chinese medicine (TCM)

Zhao et al.⁶² performed a non-blinded RCT of 320 patients undergoing endometriosis surgery to investigate the effects of TCM (activating blood circulation and removing blood stasis treatment based on syndrome differentiation; n = 131) and Western medicine (GnRH agonist or progesterones; n = 141) on QOL postoperatively.

Pre-treatment WHOQOL-BREF scores, a QOL assessment tool with four domains including physical health, psychological, social relationships and environment, showed no significant difference between the two groups (p > 0.05), however post-treatment scores in the TCM group were significantly improved (p < 0.05) and the scores of 4 items (mobility, activities of daily living, sexual activity, QOL score) were also statistically significantly better (p < 0.05).

Flower et al.⁶³ published a Cochrane review assessing the effects of Chinese herbal medicine (CHM) for endometriosis, however only 2 RCTs were included (n = 158), neither of which assessed CHM vs. placebo. The first showed no significant different in ERPP between CHM and gestrinone administration post laparoscopic treatment (95.65% vs. 93.87%; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.93 to 1.12, one RCT). Combined oral CHM and herbal enema provided better improvement in dysmenorrhoea than with danazol (RR 5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54, respectively). There was no significant difference in lumbosacral pain, rectal discomfort, or vaginal nodule tenderness between CHM and danazol. Flower reports a paucity of robust studies assessing the effects of CHM and that the current studies available have been too small to apply statistical analysis.