Relationship between Symptoms in Women with Endometriosis and Lifestyles: a Qualitative Interview Study

Endometriosis is a common condition that affects reproductive-aged women and is characterized by the presence of endo - metrial tissue outside the uterine cavity with nodules and lesions. The study aimed to analyze lifestyles of women affected by endometriosis in relation with their symptoms. In this observational study, 735 Italian women have been interviewed online through a questionnaire structured in two parts. The first part was mainly anamnestic, focused on gathering information about the age, the stage of disease, comorbidities, involved organs, symptomatology, chirurgical treatment, induced menopause. The second part focused on the individual characteristics and lifestyle of the patients such as the body mass index, physical acti - vity, quality of sleep, and the diet. The results showed how a healthy diet and a regular physical activity reduce drastically the symptoms of the patients.

endometriosis, diet, physical activity, body mass index, quality of sleep

Endometriosis is a worldwide common gynecological condition that affects women in re- productive age. The pathology is characterized by the endometrium growth at the outside of its physiological localization, such as the myometrium, ovary, and peritoneum with consequent inflammation, fibrosis, and formation of adhesions (1). The disease can be as- ymptomatic or it can manifest with pelvic pain during menstrual bleeding and/or sexual intercourse, by influencing the quality of life (2). In addition, it represents the major cause of infertility (3). The exact pathogenetic mechanism has not been established but the most accepted hypotheses go from the retrograde menstruation and genetic or immunological- ly linked susceptibility (4) to Müllerian rests (5) or exposition to chemical sources that alter the endocrine system (6). The retrograde menstruation is characterized by an out - flow of the endometrial lining through the fallopian tubes. This retrograde flow, together with the potential hematogenous or lymphatic circulation, can result in the seeding of endometrial tissue into ectopic sites (7,8). Although most women have retrograde men - struation, not all of them have endometriosis. The immune dysfunction in the patients interferes with the elimination of the lesions themselves (9). Endometriosis is also associ- ated with an increased risk of autoimmune diseases and endometrioid ovarian cancer as well as other cancers, including lymphoma and non-Hodgkin’s melanoma (9). As above reported, endometriotic lesions can also result from Müllerian remains that have not un- dergone differentiated or failed to migrate properly during fetal development (10,11). Of note, Müllerian anomalies may be the cause of the obstruction of menstrual outflow (12). Furthermore, also somatic mutations resulting in growth dysregulation can be considered 1Department of Pharmaceutical Science, University of Perugia, Perugia, Italy *Corresponding author: Albi, E. *E-Mail: [email protected] DOI: 10.2478/ebtj-2020-0022 © 2020 Authors. This work was licensed under the Creative Commons Attribution- NonCommercial-NoDerivs 4.0 License. Relationship between Symptoms in Women with Endometriosis and Lifestyles: a Qualitative Interview Study Scavone M.1*, Gizzi C. 1, Albi E.1 179 The EuroBiotech Journal Medicine and Biotechnology etiological factors (9,10). Additional etiological factors may be prolonged exposure to endogenous estrogen such as due to early menarche, late menopause or obesity (12). The treatment can be pharmacological or surgical but the correct lifestyle is also relevant (13). Of considerable importance are the quality of sleep, sports activity and diet. In fact, the low physical ac - tivity and the poor sleep quality are associated with the endo - metriosis symptoms (14). Particular attention was payed to the diet, by indicating that endometriosis is associated with a low intake of vegetable, fruit (15), and vitamin D (16), and with a high trans-fatty acid (17), beef and other kinds of red meat and alcohol (18) consumption. This is relevant thanking in account that exists a relationship between lipids and vitamin D (19). On the other hand, the use of omega-3 fatty acids, antioxidants and a combination of vitamins and minerals positively influ - ences the endometriosis-associated symptoms (20), consid - ering that lipids are involved in immunity and inflammatory processes (21,22). There are currently no studies that establish a simultaneous correlation of the sleep quality, sports activi - ty and diet with the symptoms of endometriosis. The present work is a qualitative interview study aimed to highlight in the same patients different aspects of endometriosis in the Italian population.

Patients 735 women affected by endometriosis we included in the study realized between February 4th to March 4th 2020. The exclu - sion criteria were obesity and cancer. The patients were recruit- ed online on the Facebook page of National Association Endo- metriosis Project (APE-ODV) and participated to the study on a voluntary basis by giving their informed consent. Interview A specific questionnaire was prepared and administered on - line. The questionnaire was structured in two parts. The first part was mainly anamnestic, focused on gathering information about the age, the stage of disease, comorbidities, involved or - gans, symptomatology, chirurgical treatment, induced meno - pause. The second part focused on the individual characteris - tics and lifestyle of the patients such as the body mass index, physical activity, quality of sleep, and the diet.

Population characteristics The analysis of the interview indicated that the average age of the 735 women who agreed to participate in the study was 36.5+17.5 years. In particular, 5% aged 18-25, 37% aged 26-35, 48% aged 36-45, and 10% over the age of 46. From the results was evident that 85% aged 26-45. Interestingly, the mean age at the time of diagnosis was 28+4 years. It is important to high - light that 84% of patients had received the diagnosis more than 1 year after the onset of symptoms and only 2% within 1 year, by indicating that often the endometriosis diagnosis is tardive. The remaining 14% refers to women that have been diagnosed in few months. This result justifies the stage of the disease at the time of diagnosis, reported by the patients. In fact, 47% of women examined were already at IV stage of the disease, 12% at III stage, 6% at II stage, 6% at I stage, and 29% of patients didn’t remember the stage they belonged to. Only 18% of patients did not present comorbidities. Figure 1 shows the percentage of different pathologies of 72% of women with comorbidity. A data that caught particularly the attention is the high percent - age of women with autoimmune pathologies which covers 6% of the examined women of whom 62% were affected by celiac disease (Fig.1). The presence of comorbidities is another factor that sometimes makes early diagnosis difficult. Clinical picture From the interview it was clearly evident that several organs were involved in the endometriosis, many of these were simul- taneously present in the same patient. In figure 2, the percent- age of involved organs. As a consequence, the symptomatology linked to endome - triosis is wide and complex. The main reported symptom at the moment of the diagnosis was the dysmenorrhea (Fig.3). 180 | VOLUME 4 ISSUE 4 | OCTOBER 2020 Unfortunately, the symptom that leads to the diagnosis of endometriosis is not strictly related to this symptom. In fact, almost half of women had a chronic pelvic pain (47%), dys - paurenia (44%) and heavy menstrual flow (40%). These are symptoms until today underestimated, that caracterises the majoruty of women affected by endometriosis. A discrete percentage of women affected by this disease showed reptile discomfort (36%), interpreted as false sensation of needing to defecate, rectal pain, discomfort to stay normally seated, sense of posterior heaviness. In addition, chronic tiredness is often neglected, even though it is a frequent symptom; 36% of wom- en examined showed this symptom. Moreover, 26% of patients presented constipation, 21% diarrhea, 21% meteorism and flat- ulence phenomenon. Only 6% of patients were asymptomatic. Very relevant were the symptomatology in relation with menstrual cycle and in the fertility. 56% of women indicat - ed symptoms away from the menstrual cycle, 31% symptoms during the menstrual cycle and right before it and, 13% symp- toms only during the menstrual cycle. Often women find out to be affected by endometriosis only after a few failed attempts to conceive, followed by further investigations and studies that confirmed the incapability to conceive. According to this, from the 735 women, only 30% managed to conceive of whom 62% had a disease at the III o IV stage. As consequence, 44% of women were in menopause. Of these, 84% were on a pharma - cological menopause, 10% are on a surgical menopause and, 6% are on a spontaneous menopause. Considering that 78% of patients had undergone surgery, either laparoscopic or with laparotomy, it is evident that when patients arrived for surgery, many were already in pharmacological or spontaneous meno - pause. Among all women that had a surgical treatment, 36% faced a bowel resection or rectal shaving. Among the women examined, 62% followed a pharmacological therapy and of these 78% suffered from collateral effects. Many effects were simultaneously present in multiple patients. Therefore, 43% presented abnormal vaginal discharge, 30% increase in appe - tite, 28% vaginal candidiasis or other fungal infections, 55% headache, 44% hot flashes, 76% decreased libido, 13% hyper - trichosis, 72% body weight changes, 25% nausea, 8% diarrhea, 33% hair loss, 63% nervousness, 60% depression. Lifestyles BMI BMI is an important factor for the health of subject and its value is calculated considering height and weight. Generally, in adult, BMI between 18.50 and 24.99 is considered as nor - mal-weight, BMI between 16.00-18.49 as under-weight, BMI between 25.00 and 29.99 as over-weight and, BMI above 30 as obesity. As above reported, the patients with obesity were not included in the study. Of the 735 women, 68% were normal weight, 22% under-weight, and 10% over-weight. On a closer look the youngest women had more adequate BMI than older women. More specifically 69% of women over 36 were over - weight. These data are relevant considering that the high BMI is strictly related with inflammation of the adipose tissue and an inflammatory picture is not a positive factor for endometriosis. Physical activity From this study it has been observed how the physical activity is beneficial on those who work out on a regular basis. How - ever, only 17% of women examined worked out and reported positive results on their health conditions. In details, 33% of women did not work out and another important percentage (30%) worked out only when had time (Fig. 4). It has been observed how women over 46 years showed more interest in working out. It resulted evident that women with the age between 18 and 25 years and women over 45 did not like physical activity. In fact only 7% of women over 45 and 2% of women with the age between 18 and 25 years practiced physical activity. The majority of women confirmed that used walk for long distances. Among the sport most performed it has been mentioned: yoga, pilates, jogging, swimming e water gym. It is obvious the importance of a healthy and correct life- style in order to prevent some pathologies. Quality of sleep 21% had a bad quality of sleep, 46% of women reported a dis - creet quality of sleep, 28% had a good quality of sleep, and only 5% had an excellent quality of sleep. Interestingly, by compar- 181 The EuroBiotech Journal ing the chronic tiredness, as one of the symptoms in women affected by endometriosis, with the quality of sleep it appeared evident that among 36% of women that suffered from chronic fatigue syndrome, 76% suffered from poor- quality of sleep; in particular 27% of patients suffered from a very bad quality of sleep, while 49% suffered from discreet quality of sleep; only 23% had a good quality of sleep and a smaller percentage had an excellent quality of sleep. Diet 75% of the examined women thought that nutrition plays a key role on the reduction of the pain linked to the inflammation induced by endometriosis. 46% followed a healthy diet and in particular women aged from 36 to 45 years old. There are several nutritional regimes that can be associated to different ethical, environmental, religious choices and often influenced by current trends. (Fig. 5). According to this aspect, it has been observed that 77% of examined women followed an omnivo - rous diet, 9% follows a vegetarian diet, 2% follows a vegan diet, about 12% followed alternative diets (ketogenic, macrobiotic, dukan ect.). In the study we showed how milk and milk derivatives exacer- bated the most painful condition (on 59% of patients) followed by sugar, refined flour and baked goods form it derived (on 50% of patients), by indicating that these nutrients might facilitate inflammation process (Fig. 6). Notably, 35% of patients ingest- ed these nutrients 2-4 times a week. In the figure 6 it has been reported the consumption of each type of food during the week It is known that additional foods that contribute to pain con- ditions in endometriosis patients are soy and red meat. From the analysis of the responses it was highlighted that women had been alerted about this. In fact, most women did not consume soy and consumed red meat once a week (Fig. 7). Additionally, cured and processed meats (40% of cases), al- cohol (35% of cases), coffee, tea and drinks with caffeine (29% of cases), pre-cooked and readymade goods (28% of cases), chocolate (26% of cases), legumes (17% of cases) increased the pain. Only in some cases fruits (7%) and vegetables (10%) in - creased the pain condition. It is important to know how cooked vegetables, on 58% of cases, provoked more discomfort com - pared to raw vegetables. It is really difficult to establish exactly which food is responsible for a pain because several foods of - ten cause pain in the same patient. Patients were well educat - ed about the importance of water consumption. Despite this, 40% of women consumed 1 liter or less of water per day. The most relevant symptoms consequent to the consumption of the above nutrients included abdominal bloating (88%), pelvic pain (40%) and chronic tiredness (34%) (Fig. 8). 182 | VOLUME 4 ISSUE 4 | OCTOBER 2020 Some symptoms are less frequent, but still relevant such as diarrhea, constipation, migraine, dysuria, nausea, meteorism and dyspepsia.

Considering how nowadays lifestyle influences the health of the single person, this study aims to prove the association between lifestyle of a specific group of women who share a common disease. The results obtained in the present study support the difficulty in making an early diagnosis due to the variability of the tissues and organs presented and the comor - bidities. The symptoms of the disease are so constant, even if variable, that they become part of the patient’s life. It is diffi - cult to determine whether lifestyle is one of the causes of pain or whether pain determines lifestyle. It is likely that this is a vicious cycle. Therefore, it is essential to know all the factors that can block this cycle and a correct and continuous informa- tion on physical activity and nutrition is necessary. Besides the usual approaches, from a couple of years it has been suggested to follow a personalized nutrition regime in order to support the individual medical treatment. These nutritional regimes are mainly focused on the importance of supporting the caloric needs of the patient and potential preferences towards certain food, avoiding the consumption of the so-called pro-inflam - matory goods. A correct nutrition status is essential in order to reduce the symptomatology related to endometriosis. There are many foods identified by patients as the cause of increased pain. Therefore, it will be important to carry out a specific food plan in the individual subject and also in relation to the men - strual cycle. Red meat and soy are less ingested probably be - cause different scientific studies reported how these two partic- ular foods might cause the endometriosis disease. It has been demonstrated that a specific natural integrator based on lipoic acid, palmitoiletanolamide and myrrh reduces the pelvic pain in endometriosis (23). Moreover, very useful are omega-3 and omega-6 fatty acids (24) that play a role as antioxidant mole - cules (25). Moreover, the study has highlighted that the average age to conceive tends to rise. This can be related on one hand to socio-economical problems that affect couples nowadays, on the other hand to the pathology that often requires the inter - vention of assisted reproduction techniques. Therefore, an ear- ly diagnosis may be beneficial in terms of quality of life and in terms of fertility preservation.

In conclusion this study indicates how even for more complex pathologies like endometriosis, a regular physical activity and a correct nutritional strategy associated to the pharmacotherapy and surgical-therapy, visibly can improve the pain conditions of the patients and her lifestyle. Conflicts of Interest The authors declare no conflict of interest.

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