Diet quality and perceived effects of dietary changes in Dutch endometriosis patients: an observational study.

RESEARCH QUESTION: What is the current diet of women with endometriosis, in terms of adherence to dietary guidelines and use of diets, and what are the perceived effects of dietary modifications? DESIGN: In this online explorative observational study, the Dutch Healthy Diet 2015 index (DHD-15) and quality of life (QoL) with the Endometriosis Health Profile-30 questionnaire (EHP-30) were used to assess diet quality. RESULTS: The questionnaires were completed by 157 participants. Many participants made one or more dietary adaptations for their endometriosis, in the form of a specific diet (46.5%), with the use of dietary supplements (56.1%), with other dietary adjustments (64.3%), or all. Endometriosis patients had a significantly lower DHD-15 score, indicating a lower diet quality than a healthy reference group (P = 0.004). In the endometriosis group, diet users had a significantly higher total DHD-15 score than non-diet users (P < 0.0001). Diet quality was not correlated with QoL (Pearson's r = -0.010, P = 0.904). Many specific dietary adjustments (71.3%), however, were reported to reduce endometriosis pain-related symptoms. The removal of gluten, dairy or soy, as well as the addition of vegetables, showed the greatest perceived reductions of symptoms in participants. CONCLUSIONS: Although no specific dietary adjustment was found to increase QoL, endometriosis patients do feel that dietary adjustments have a beneficial effect on their symptoms. Therefore, more research is needed to gain evidence about the specific effects of nutrients on endometriosis symptoms.

The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis.

BACKGROUND: To our knowledge, data on the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis are limited. This study was conducted to determine the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis. METHODS: The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 18-40 years old) with endometriosis. Participants were randomly allocated into two groups (30 participants each group) to receive either 50,000 IU vitamin D or placebo each 2 weeks for 12 weeks. RESULTS: Vitamin D supplementation significantly decreased pelvic pain (ß - 1.12; 95% CI, -2.1, -0.09; p=.03) and total-/HDL-cholesterol ratio (ß - 0.29; 95% CI, -0.57, -0.008; p=.04) compared with the placebo. Moreover, vitamin D intake led to a significant reduction in high-sensitivity C-reactive protein (hs-CRP) (ß - 0.64 mg/L; 95% CI, -0.97, -0.30; p<.001) and a significant increase in total antioxidant capacity (TAC) (ß 47.54 mmol/L; 95% CI, 19.98, 75.11; p=.001) compared with the placebo. CONCLUSIONS: Overall, our study demonstrated that vitamin D intake in patients with endometriosis resulted in a significant improvement of pelvic pain, total-/HDL-cholesterol ratio, hs-CRP and TAC levels, but did not affect other clinical symptoms and metabolic profiles.

Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain.

Endometriosis is a chronic painful disease highly prevalent in women that is defined by growth of endometrial tissue outside the uterine cavity and lacks adequate treatment. Medical use of cannabis derivatives is a current hot topic and it is unknown whether phytocannabinoids may modify endometriosis symptoms and development. Here we evaluate the effects of repeated exposure to Δ9-tetrahydrocannabinol (THC) in a mouse model of surgically-induced endometriosis. In this model, female mice develop mechanical hypersensitivity in the caudal abdomen, mild anxiety-like behavior and substantial memory deficits associated with the presence of extrauterine endometrial cysts. Interestingly, daily treatments with THC (2 mg/kg) alleviate mechanical hypersensitivity and pain unpleasantness, modify uterine innervation and restore cognitive function without altering the anxiogenic phenotype. Strikingly, THC also inhibits the development of endometrial cysts. These data highlight the interest of scheduled clinical trials designed to investigate possible benefits of THC for women with endometriosis.

A two-arm parallel double-blind randomised controlled pilot trial of the efficacy of Omega-3 polyunsaturated fatty acids for the treatment of women with endometriosis-associated pain (PurFECT1).

BACKGROUND: Endometriosis is defined by the presence of endometrial-like tissue (lesions) outside the uterus, commonly on the pelvic peritoneum. It affects 6-10% of women and is associated with debilitating pelvic pain. Current management options are often unsatisfactory. Omega-3 polyunsaturated fatty acids (O-PUFA) have the potential to reduce the painful symptoms associated with endometriosis, reduce lesion size, preserve the patient's ability to conceive, and have minimal side effects. We performed a two-arm, parallel double-blinded randomised controlled trial to inform the planning of a future multicentre randomised controlled trial to evaluate the efficacy of O-PUFA for endometriosis-associated pain. OBJECTIVES: The primary objectives of the trial were to assess recruitment and retention rates. The secondary objectives were to determine the acceptability to women of the proposed methods of recruitment, randomisation, treatments and questionnaires, to estimate the variability in the proposed primary endpoints to inform the sample size calculation and to refine the research methodology for the future definitive trial. METHODS: We recruited women with endometriosis from June 2016 to June 2017 and randomised them to eight weeks of treatment with O-PUFA or olive oil. Pain scores and quality of life questionnaires were collected at baseline and eight weeks. We calculated the proportion of eligible women randomised, and of randomised participants who were followed up to eight weeks. Acceptability questionnaires were used to evaluate women's experiences of the trial. RESULTS: The proportion of eligible participants who were randomised was 45.2% (33/73) and 81.8% (27/33) completed the study. The majority of participants described their overall trial experience favourably and there were no adverse events in either group. CONCLUSION: Our pilot trial supports the feasibility of a future larger trial to definitively evaluate the efficacy of O-PUFA for endometriosis-associated pain. TRIAL REGISTRATION: The trial was registered on the ISRCTN registry (registration number ISRCTN44202346).

Strategies for Activating Blood Circulation-Regulating Gan (Liver)-Tonifying Shen (Kidney) Sequential Therapy of Endometriosis-Associated Infertility.

Endometriosis (EM) is a major cause of infertility and has a complex pathogenesis, which brings severe challenges in both clinical treatment and scientific research. Current clinical research focuses on the difficult problem of improving the pregnancy rate of EM patients. Our studies found that Chinese medicine has significant advantages in terms of improving the pregnancy rate of EM patients.

[Research progress on roles of vitamin D in endometriosis].

In addition to regulating calcium and phosphorus metabolism to maintain strong bones, vitamin D also has immune regulating and anti-inflammatory effects. Moreover, it is related to chronic inflammatory diseases, autoimmune diseases and cancer. Many studies indicate the roles of vitamin D in the development and progression of endometriosis including the effects on modulation of immune responses, inflammation reactions, cell proliferation and apoptosis, angiogenesis, adhesion and invasion. Vitamin D supplementation can relieve pain and improve endometrial receptivity associated with endometriosis and play a preventive and therapeutic role. This paper summarizes the roles of vitamin D in endometriosis.

Functional outcomes after disc excision in deep endometriosis of the rectum using transanal staplers: a series of 111 consecutive patients.

OBJECTIVE: To assess the postoperative outcomes of patients with rectal endometriosis managed by disc excision using transanal staplers. DESIGN: Prospective study using data recorded in the CIRENDO database (NCT02294825). SETTING: University tertiary referral center. PATIENT(S): A total of 111 consecutive patients managed between June 2009 and June 2016. INTERVENTION(S): We performed rectal disc excision using two different transanal staplers: [1] the Contour Transtar stapler (the Rouen technique); and [2] the end to end anastomosis circular transanal stapler. MAIN OUTCOMES MEASURE(S): Pre- and postoperative digestive function was assessed using standardized gastrointestinal questionnaires: the Gastrointestinal Quality of Life Index and the Knowles-Eccersley-Scott Symptom Questionnaire. RESULT(S): The two staplers were used in 42 (37.8%) and 69 patients (62.2%), respectively. The largest diameter of specimens achieved was significantly higher using the Rouen technique (mean ± SD, 59 ± 11 mm vs. 36 ± 7 mm), which was used to remove nodules located lower in the rectum (5.5 ± 1.3 cm vs. 9.7 ± 2.5 cm) infiltrating more frequently the adjacent posterior vaginal wall (83.3% vs. 49.3%). Associated nodules involving sigmoid colon were managed by distinct procedures, either disc excision (2.7%) or segmental resection of sigmoid colon (9.9%). Postoperative values for the Gastrointestinal Quality of Life Index increased 1 and 3 years after the surgery, but improvement in constipation was not significant. The probability of pregnancy at 1 year after the arrest of medical treatment was 73.3% (95% confidence interval 54.9%-88.9%), with a majority of spontaneous conceptions. CONCLUSION(S): Disc excision using transanal staplers is a valuable alternative to colorectal resection in selected patients presenting with rectal endometriosis, allowing for good preservation of rectal function.

Relating Chronic Pelvic Pain and Endometriosis to Signs of Sensitization and Myofascial Pain and Dysfunction.

Chronic pelvic pain is a frustrating symptom for patients with endometriosis and is frequently refractory to hormonal and surgical management. While these therapies target ectopic endometrial lesions, they do not directly address pain due to central sensitization of the nervous system and myofascial dysfunction, which can continue to generate pain from myofascial trigger points even after traditional treatments are optimized. This article provides a background for understanding how endometriosis facilitates remodeling of neural networks, contributing to sensitization and generation of myofascial trigger points. A framework for evaluating such sensitization and myofascial trigger points in a clinical setting is presented. Treatments that specifically address myofascial pain secondary to spontaneously painful myofascial trigger points and their putative mechanisms of action are also reviewed, including physical therapy, dry needling, anesthetic injections, and botulinum toxin injections.

A Qualitative Study on the Practice of Yoga for Women with Pain-Associated Endometriosis.

OBJECTIVES: To understand the meaning women with pain-associated endometriosis attribute to yoga practice regarding their physical and emotional state at the beginning of the practice; pain management by integrating body and mind; secondary benefits of the practice of yoga, such as self-knowledge, self-care, and autonomy; and the role of the yoga group as psychosocial support. DESIGN: Qualitative study conducted simultaneously with a randomized clinical trial. SETTING: Public university hospital in southeastern Brazil between August 2013 and December 2014. PARTICIPANTS: Fifteen women with pain-associated endometriosis who practiced yoga for 8 weeks. INTERVENTION: After completing the twice-a-week program, all women participated in a single, semi-structured interview. Interviews were recorded and transcribed verbatim, and thematic analyses were performed. OUTCOME MEASURES: The main themes of analysis were women's expectations regarding the practice of yoga, physical and emotional state of women at the beginning of yoga practice, control and pain management through the integration of body and mind, secondary benefits, acquisition of self-knowledge and autonomy, and the role of yoga group as psychosocial support. RESULTS: All participants reported that yoga was beneficial to control pelvic pain. They related that they were aware of the integration of body and psyche during yoga practice and that this helped in the management of pain. Women said they had identified a relationship between pain management and breathing techniques (pranayama) learned in yoga and that breathing increased their ability to be introspective, which relieved pain. The participants have developed greater self-knowledge, autonomy, and self-care and have reduced the use of pain and psychiatric medications. They created ties among themselves, suggesting that the yoga group allowed psychosocial support. CONCLUSIONS: Bodily and psychosocial mechanisms to control pain were identified in women with endometriosis. To reach such control, it is crucial that mind and body integrative techniques are learned.

Effect of warming Yang and removing blood stasis method on matrix metalloproteinases / tissue inhibitor metalloproteinases levels secreted by cultured endometrial cells from patients with endometriosis.

OBJECTIVE: To investigate the effect of Chinese medicines using the warming Yang and removing blood stasis method on levels of matrix metalloproteinases (MMPs)/tissue inhibitor metalloproteinases (TIMPs) secreted by cultured endometrial cells from patients with endometriosis. METHODS: Ectopic and eutopic endometrial cells obtaind from 15 endometriosis patients were cultured in vitro, and divided randomly into five groups: high dose; moderate dose; low dose; nemestran; blank control. The three dose groups were treated with a decoction prepared according to the principle of warming Yang and removing blood stasis; nemestran and 0.9% NaCl were administered to the nemestran group and balnk control group, respectively. Eutopic endometrial cells obtaind from 10 hysteromyoma patients were cultured in vitro, as the normal control group, 0.9% NaCl were administered to the normal control group. Cell culture supernatants were collected and levels of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tissue inhibitor metalloproteinase-1 (TIMP-1) and tissue inhibitor metalloproteinase-2 (TIMP-2) detected by enzyme-linked immuno sorbent assay (ELISA). RESULTS: Compared with the normal control group, levels of MMP-1, MMP-2, and MMP-9 in eutopic and ectopic endometrium cell supernatants in the blank control group were increased, whereas levels of TIMP-1 and TIMP-2 were decreased (P < 0.05). Compared with the blank control group, levels of MMP-1 and MMP-2 in ectopic and eutopic endometrium cell supernatants cultured in low-dose, middle-dose, and high-dose groups were decreased, whereas levels of TIMP-1 and TIMP-2 were increased significantly (P < 0.05). CONCLUSION: The warming Yang and removing blood stasis method affects expression of MMPs and TIMPs.

[Effectiveness of medical rehabilitation of women of reproductive age with fatigue syndrome].

Efficacy Erbisol in combination with Lymphomyosot and Echinacea compositum C in medical rehabilitation of women of reproductive age with fatigue syndrome and chronic gynecological pathology was studied. It was found that this complex of medications promotes faster and more effective reduction of the level of circulating immune complexes in the serum, achievement of persistent clinical remission of disease and liquidation of fatigue syndrome manifestations, what improves the quality of life of patients.

Effect of vitamin C on the growth of experimentally induced endometriotic cysts.

AIM: The aim of this study was to investigate the effect of vitamin C on the growth of experimental endometriotic cysts. MATERIAL AND METHODS: The endometrium of the uterine horn wall (diameter, 4 mm) was implanted onto the inner surface of the anterior abdominal wall of 40 Wistar albino adult female rats, by laparotomy. The day after the implantation, the rats were randomly assigned into four groups (control group and experimental groups [V1, V2, and V3]) comprising 10 rats each. For 6 weeks, the control group (Group C) received 1 mL distilled water, whereas the experimental groups (Groups V1, V2, and V3) received 0.5 mg, 1.25 mg, and 2.5 mg of vitamin C in 1 mL of distilled water, respectively. The doses were given via oral gavage once per day. At the end of the administration, a second laparotomy was performed and endometriotic cyst volumes and weights of rats among the groups were compared. In addition, the stromal and glandular tissue and the natural killer cell contents of the cysts were compared among the groups. RESULTS: The cyst volume in Group V3 and the cyst weights in Groups V2 and V3 were significantly lower than those in Group C. The natural killer cell content in Groups V1, V2, and V3 was significantly lower than that in Group C. Stromal and glandular tissue contents of the groups were not significantly different. CONCLUSIONS: The dose-dependent vitamin C supplementation significantly reduced the volumes and weights of the endometriotic cysts.

[The use of restorative medicine technologies for the rehabilitation of the patients presenting with endometriosis of external genitalia].

This paper reports the results of analysis of the psycho-emotional status and pain syndrome in the women presenting with endometriosis of external genitalia treated with a combination of hormonal preparations and balneotherapy. A total of 216 infertile patients were involved in the study. The duration of the infertility period varied from 1.5 to 19 years. All the patients underwent surgical intervention. The influence of rehabilitative therapy on the quantitative vital indices (psycho-emotional adaptation to the social environment and pain intensity) was estimated before and after the treatment. The patients were divided into 3 groups. Those of group 1 received an oral contraceptive (30 mcg of ethinylestradiol plus 2 mg dienogest) as a continuous three-cycle course (63 tablets) followed by its discontinuation for the 7 day menstrual period and the final three-cycle course (total duration of therapy 6 months). The patients of group 2 were treated with injections of agonists of gonadotropin releasing hormone (GnRH) at a dose of 3.75 mg once every 4 weeks (total duration 6 months). In group 3, the injections of GnRH agonists (3.75 mg once every 4 weeks, total duration 6 months) were combined with a course of balneotherapy using radon. All the three rehabilitative modalities produced a well-apparent positive effect. Chronic pelvic pain before treatment was reported by 90,3% of the patients. After the treatment, the number of such women in groups 1, 2, and 3 decreased to 20,8%, 12,5%, and 30,6% respectively Dyspareunia in the pre-treatment period was diagnosed in 66,7% of the patients. After treatment, this pathology persisted only in 23,6%, 18,1%, and 31,9% of the patients in groups 1, 2, and 3 respectively. Psycho-emotional disorders before treatment were documented in 90,3% of the patients compared with 27,8%, 25%, and 30,6% after therapy. It is concluded that all the three therapeutic modalities markedly improved health conditions of the patients presenting with endometriosis of external genitalia, but the combination of GnRH agonists with radon therapy produced the most pronounced clinical effect.

Xanthohumol inhibits growth and vascularization of developing endometriotic lesions.

BACKGROUND: Xanthohumol is a prenylated flavonoid isolated from hops, which is known to act as a pleiotropic cancer chemopreventive agent owing to its anti-proliferative, anti-inflammatory and anti-angiogenic properties. In the present study, we analyzed, for the first time, whether this dietary compound may also be used for the treatment of endometriosis. METHODS: Peritoneal and mesenteric endometriotic lesions were surgically induced in BALB/c mice by uterine tissue transplantation into the abdominal cavity. The animals were treated daily with 100 µM xanthohumol (n= 8) or vehicle (control, n= 8) via the drinking water, starting 3 days before tissue transplantations. Lesion growth, cyst formation and vascularization were subsequently analyzed by means of high-resolution ultrasound imaging (at Day 0 and then once per week for 28 days), caliper measurements, western blotting, histology and immunohistochemistry over 4 weeks. RESULTS: In the treatment and control groups, uterine grafts developed typical endometriotic lesions with cyst-like dilated glands surrounded by a vascularized endometrial stroma. However, xanthohumol efficiently decreased the size of these lesions at Day 28, independent of their localization within the peritoneal cavity, compared with control (peritoneal: P =0.041; mesenteric: P =0.038). This was associated with a reduced level of phosphoinositide 3-kinase protein. Moreover, vascularization of xanthohumol-treated lesions was suppressed, as indicated by a significantly lower microvessel density at Day 28 when compared with vehicle-treated controls (peritoneal: P =0.026; mesenteric: P =0.004). Additional analyses revealed that treatment with xanthohumol did not affect the histomorphology, proliferation and vascularization of the uterine horns and ovaries. CONCLUSIONS: Taken together, these experimental findings suggest that xanthohumol inhibits the development of endometriotic lesions in mice without inducing serious side effects in the reproductive organs. Thus, xanthohumol represents a promising dietary phytochemical that, after further testing, may be considered for the use in the selective treatment of endometriotic lesions.

The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis.

Gonadotropin-releasing hormone agonists (GnRHa) are an effective treatment of endometriosis-associated pelvic pain. The use of hormonal add-back therapy can alleviate the hypoestrogenic symptoms associated with GnRHa therapy, while preserving therapeutic efficacy. Norethindrone acetate (NETA) is a unique progestin that has both estrogenic and androgenic properties and is effective as an add-back regimen without estrogen supplementation. Through its estrogenic activity, NETA exerts beneficial effects on bone mineral density and vasomotor symptoms in women treated with GnRHa. In addition, NETA exhibits strong endometrial antiproliferative effects, which may result in further benefits for the endometriosis patient population. However, NETA add-back may be associated with progestogenic side effects and may lower high-density lipoprotein due to androgenic activity. These effects must be balanced with the overall benefits of NETA add-back therapy.

Valproic acid alleviates generalized hyperalgesia in mice with induced adenomyosis.

Emerging evidence suggests that adenomyosis, like endometriosis, may also be an epigenetic disease. In this study, we evaluated the effect of valproic acid (VPA) in ICR mice with adenomyosis, induced by neonatal dosing with tamoxifen. For all mice, we evaluated the bodyweight and the response to thermal stimuli by hotplate and tail-flick tests 4, 8, and 12 weeks after dosing, respectively, and then treated mice with low- and high-dose of VPA, progesterone (P4), P4 + VPA, or vehicle only. Three weeks after treatment, both bodyweight and thermal response tests were evaluated again before sacrifice, and the depth of myometrial infiltration was evaluated. We found that: (i) the induction of adenomyosis resulted in progressive generalized hyperalgesia as measured by hotplate and tail-flick tests, along with decreased bodyweight; (ii) treatment with VPA, P4, or a combination was efficacious in improving generalized hyperalgesia; and (iii) drug treatment appeared to reduce the myometrial infiltration, but the difference did not reach statistical significance. Thus, VPA seems to be a promising therapeutics for treating adenomyosis, as reported recently in some case series in humans.

A "conditionally essential" nutrient, L-carnitine, as a primary suspect in endometriosis.

L-carnitine, when administered to young female mice, has been shown to induce a pathologic condition resembling human endometriosis accompanied by a marked degree of infertility. Thus, the use of this nutrient by young women may be a potential risk factor responsible for the onset of endometriosis at a later stage of their lives.

[Effect of abdominal acupuncture on pain of pelvic cavity in patients with endometriosis].

OBJECTIVE: To compare the effect of abdominal acupuncture and Chinese medicine on pain relieving in pelvic cavity in patients with endometriosis. METHODS: Fifty-eight cases were randomly divided into 2 groups. Thirty cases were in abdominal acupuncture group and 28 cases in Chinese medicine group. Abdominal acupuncture points such as Zhongwan (CV 12), Xiawan (CV 10) and Qihai (CV 6), etc. were adopted for the abdominal acupuncture group, and Tianqi Tongjing Capsule (radix notoginseng capsule for dysmenorrhea) was taken by the Chinese medicine group. After a 3-month treatment, the scores of McGill pain questionaire, level of serum CA125, average value of the radial line of endometrial cyst of ovary and the sum of 3 radial lines of the uterus of patients with adenomyosis as the complication of both groups were observed before and after treatment. RESULTS: The McGill estimation of 6 items for both groups improved obviously after treatment (all P < 0.01, except numbers of selected deseriptors in Chinese medicine group). The differences of the result of McGill estimation of 6 items after treatment had statistical significance, the scores in the abdominal acupuncture group were obviously better than those in the Chinese medicine group (all P < 0.01). The differences of CA125 levels within one group or between 2 groups had statistical significance (P < 0.01, P < 0.05). The difference of the radial lines of patients with endometrial cyst of ovary within one group or between 2 groups after treatment had not statistical significance (all P > 0.05). For the value of 3 radial lines of the uterus of patients with adenomyosis within one group before and after treatment, only the difference in the abdominal acupuncture group had statistical significance (P < 0.01). The differences before and after treatment in the Chinese medicine group and the difference between 2 groups after treatment had no statistical significance (all P > 0.05). CONCLUSION: Effect of abdominal acupuncture on relieving pain of pelvic cavity caused by endometriosis, reducing the level of serum CA125 is obverious than Tianqi Tongjing Capsule (radix notoginseng capsule for dysmenorrhea). However, the effects on reducing the size of the ovarian endometrial cyst and the size of uterus with adenomyosis are not significant. Therefore, it is concluded that abdominal acupuncture is a better choice for endometriosis with pain as the chief complaints.

Current progress of Chinese medicinal treatment of endometriosis.

Endometriosis (EM) is one of the common and frequently encountered gynecological diseases that seriously influences women's health. Its morbidity reaches 10%-15% in women at reproductive ages, and shows an evident rising tendency. In recent years, the Chinese medicine treatment of EM has won favorable therapeutic effects with few adverse reactions. A brief review on this topic has been made through analyzing and summarizing recent pertinent literatures in terms of treatment depending on syndrome differentiation, cycle treatment, external treatment, integrative medicinal treatment, so as to try to know the status quo of Chinese medicine treatment on EM, and to provide some instructive views for clinical treatment and research.