Quality of life and clinical factors in women with endometriosis, the role of Dienogest vs EE/ Dienogest over time: a single-center study.

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Antonio Maiorana, Pietro Alfano, Antonella Mercurio, Salvatore Marcantonio, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2148443/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Feb, 2023 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted 4 You are reading this latest preprint version Abstract Purpose: The aims of this observational study were: to assess the relationship between psychological variables, pain, Duration Untreated Endometriosis (DUE) in a sample of women with Endometriosis; and to assess the effect of Dienogest 2 mg/daily (DNG) and Dienogest/ethinylestradiol 0.03 mg/daily (EE/DNG) on Symptoms, QoL, HRQoL, pain and sexual satisfaction, over time. Methods: 64 women constituted the study group; (56%) took DNG and (44%) took EE/DNG. VAS, SF-36, EHP-30 and ISS were used to assess endometriosis-associated pelvic pain, QoL, HRQoL and sexual satisfaction, respectively. The study included one follow-up at 18 months. Results: At T0, a longer period of DUE was related both to worst HRQoL and Physical QoL. At T1, a correlation was found between longer DUE and worst HRQoL. At T0, a negative correlation was found between VAS and PCS and between VAS and EHP-30. At T1, the same above correlation was found between VAS and PCS/MCS and VAS and EHP-30 scale. There was a correlation between ISS and VAS. ANOVA showed a reduction in dysmenorrhea, in general pain level and an improvement in emotional wellbeing, relationship with medical profession, and PCS over time, regardless to type of treatment. Moreover, a significant time × treatment group interaction for dysmenorrhea was found. Conclusion: DUE and pain are important variables related to psychological aspects of women with endometriosis. Treatment with both DNG and EE/DNG may have positive effects on the QoL, HRQoL and symptoms. Moreover, DNG seems to have a greater effect than EE/DNG on dyspareunia reduction over time. dyspareunia Health Related Quality of life Sexual Satisfaction Pain Figures Figure 1 Figure 2 Take-home Message The results of this study highlight that diagnostic delay and pain are related to worsening of different component of both QoL and HRQoL of women with endometriosis. Moreover, DNG seems to have a greater effect than EE/DNG on dyspareunia reduction over time. Improvement in pain symptoms, and in QoL are central goals in treatment of endometriosis toward a global management of the disease. Introduction Endometriosis is a chronic nonmalignant estrogen-dependent condition characterized by the presence of endometrial-like tissue outside the uterus affecting 10% of women of reproductive age [ 1 ] including very young girls, from all ethnic and social groups [ 2 ]. The causes of endometriosis have not yet been determined [ 3 ]. Endometriosis is associated with symptoms of dysmenorrhea, chronic pelvic pain, dyspareunia, dyschezia [ 4 ], up to 50% of women with endometriosis experience infertility [ 5 ] with an impairment of QoL [ 6 ]. Recent studies consider endometriosis as a disabling condition that may affect the social relationships, mental health, and sexual activity of women [ 7 , 8 ]. Despite its considerable impact, endometriosis is often under-diagnosed; an Italian study suggests that only 6 out of 10 cases in the general population are diagnosed [ 9 ]. There are several factors that can complicate the diagnosis: asymptomatic cases, the late appearance of symptoms and the increased presence of comorbidities with similar symptoms to endometriosis. Symptoms begin during adolescence, thus, treatment is often started several years after use of NSAIDs [ 10 ], medical and psychosocial factors contribute to a delayed diagnosis [ 11 ]. In this study we consider the period between the onset of endometriosis symptoms and diagnosis as “Duration Untreated Endometriosis (DUE)”. Among current management approaches, surgery and hormonal drugs are considered as primary treatment to reduce recurrences and to improve the QoL in women suffering from endometriosis [ 12 ]. However medical treatment may be not a permanent solution for symptoms and infertility, so chronic pelvic pain and related symptoms can affect women throughout their fertile life. Pain and infertility may have negative effect on QoL for patients with endometriosis (13). Škegro et al. shown that higher pain level was related to poorer quality of life [ 14 ], emphasizing both physical and psychological aspect of the disease also for treatment project. A key factor correlated with disease and QoL is the available treatment method, this is one of the most crucial aspects for both physicians and patients, so major consideration should be given not only to efficacy but also to the long-term safety and tolerability of the treatment options that are available [ 1 ]. DNG is a synthetic progestin that is currently used for clinical treatment of endometriosis with a dose of 2 mg daily [ 15 ], it is an effective and well-tolerated treatment for endometriosis-related pain [ 16 ]. It is know that patients are willing to accept the spotting that DNG can cause given the pain relief experienced [ 17 ] and may also have positive effects on their QoL and sexual life [ 18 ]. Moreover, a reduction of pain was observed in patients using a combination of ethynylestradiol and dienogest in continuous regimen [ 19 ] as well as with dienogest alone [ 17 ]. Aims of the present study: To assess the relationship between psychological variables, pain, Duration Untreated Endometriosis (DUE) in a sample of women with endometriosis. To assess the 18-month effect of Dienogest 2 mg/daily (DNG) and Dienogest/ethinylestradiol 0.03 mg/daily (EE/DNG) on symptoms, QoL, HRQoL, pain and sexual satisfaction in women with endometriosis over time. Materials And Methods This observational, single-center study was conducted on a sample of women with endometriosis referred to a center for diagnosis and treatment of endometriosis with dedicated physicians, psychologists, and nurses, of the Department of Obstetrics and Gynecology at the ARNAS Civico Hospital in Palermo, in Southern Italy, between October 2019 and June 2021. Participants 85 women with endometriosis were consecutively recruited. All patients received personalized clinical indications regarding the use of medical therapy with DNG and EE/DNG administered orally. Side effects were collected during routine clinical practice, two participants reported vaginal bleeding and loss of libido were excluded from the final data analysis because they spontaneously suspended their therapy. Nineteen participants were excluded because of missing data. Finally, 64 women completed all study procedures, 36 (56%) took DNG and 28 (44%) took EE/DNG. These women reported that treatment was well tolerated and that the therapy wellness was superior to the side effects. According to routine practice, women came back for clinical assessment and psychological evaluation after 18 months (T1), and completed all measures at both Time 0 (T0) and Time 1 (T1), (Fig. 1). Some women (50%) performed the T1 procedures a few weeks after the visit scheduled at 18 months because of patients’ specific clinical needs; this variability was taken into account in the analysis as a covariate. All subjects gave written informed consent. The individual privacy of clinical data was guaranteed under Italian law. Eligible for the study were women aged 18 years or more not seeking pregnancy, with a surgical diagnosis or a clinical/instrumental diagnosis of endometriosis, who had been taking DNG or EE/DNG at the time of recruitment. Procedures Quality of life: questionnaire (QoL) Short Form Survey “SF-36” The questionnaire consisted of 36 items, and transformed to give eight summary scales measuring health concepts, summarized in two component factors: physical health (PCS) and mental health (MCS). The raw scores were converted into standard scores (M=50 ±10), range 0-100, in accordance with the questionnaire guidelines [20]. Health-Related Quality of Life (HRQoL) Endometriosis Health Profile 30 “EHP-30” This is a disease-specific tool to evaluate the HRQoL in women suffering from endometriosis. The EHP-30 is composed of two parts: a core questionnaire containing five scales applicable to all women with endometriosis (30 items): pain, control and powerlessness, emotional wellbeing, social support, self-image and a modular part containing six scales which do not necessarily apply to all women with endometriosis (23 items): work life, relationship with children, sexual intercourse, medical profession, treatment and infertility. The score ranging from 0 (best possible health status) to 100 (worst possible health status) [21]. Index of sexual satisfaction “ISS” This scale aims to assess problems relating to the sexual aspects of a relationship, measuring subject’s feelings about behaviors, attitudes, events, affective states and preferences associated with sexual intercourse between partners. It contains 25 questions, the obtained scores ranged from 0 to 150. A cutoff score ≥75, indicates a higher degree of sexual satisfaction [22]. Visual Analogical Scale “VAS” The Visual Analogic Scale was used to define endometriosis-associated pain, chronic pelvic pain, dysmenorrhea, dyspareunia and dyschezia. The instrument measures the pain level across a continuum of values, from the patient's perspective their pain does not make discrete jumps, as a categorization of none, mild, moderate and severe would suggest. VAS is a horizontal line, 100 mm in length, anchored by word descriptors at each end. The patient marks on the line the point that they feel represents their perception of their current state. VAS has been repeatedly used in the literature as a way to measure patients’ perceived pain [23-24]. Study variables Dysmenorrhea, dyspareunia and dyschezia; Presence of spotting, headache, weight gain, low libido Age Age at menarche Age diagnosis Age first symptoms Duration Untreated Endometriosis (DUE) refers to the period (years) between the onset of endometriosis symptoms and the diagnosis Presence of children in the household and their age Volume of endometrioma sagittal and antero-posterior compartment Statistical analysis All statistical analyses were performed using the SPSS statistical software version 20, with screening for missing data. A tool was performed [25] in order to determine the minimum total sample size required for this study, and the results showed that at least 54 participants were needed to register an alpha level of 0.05 and to have 80% power. Descriptive statistics were used to summarize the study participants’ clinical and psychological variables presented as mean (SD), median values (range) and frequency (%) as appropriate according to data distribution. The differences in patient characteristics between treatment groups (DNG and EE/DNG) were assessed with the Sample T Test and χ 2 . The psychological and clinical differences between treatment groups (DNG and EE/DNG) were performed using the Sample T Test and Mann Whitney’s U. The correlation between chronological, clinical and psychological variables both at T0 and at T1 were performed with R Pearson. The effect of treatment over time on the clinical and psychological variables were evaluated by a 2 (treatment) × 2 (time) mixed-design analysis of variance (ANOVA). The independent variable was given by the 2 approaches to treatment: DNG and EE/DNG. The dependent variables were EHP-30, SF-36, ISS, VAS, dysmenorrhea, dyspareunia and dyschezia with checks for clinical variables that differed by group (age diagnosis, DUE and time variability). The level of significance was set at alpha = 0.05. Results The 64 women with endometriosis who completed both time surveys were aged between 19 and 49 years old ( M = 32.61 SD = 7.3); 36 of them (56%) took DNG and 28 (44%) took EE/DNG. The descriptive statistics summarizing the participants’ demographic and clinical characteristics in the two treatment groups and the p values for test statistics assessing group differences at baseline are listed in Table 1. Table 1 Patient Characteristics at baseline χ 2 , Independent Sample T-Test, for DNG (n = 36) and EE/DNG (n = 28) Groups. DNG No (%) EE/DNG No (%) P value a Education Primary education 1(2%) 1(2%) NS Lower secondary education 14(22%) 8(12%) NS Upper secondary education 16(25%) 15(23%) NS Degree 5(8%) 4(6%) NS Marital status Single 8(12%) 4(6%) NS Unmarried couple 13(20%) 14(23%) NS Married 15(23%) 10(16%) NS Occupation Unemployed 15(23%) 13(20%) NS Student 3(5%) 5(8%) NS Housewife 4(6%) 3(5%) NS Employee 14(22%) 4(6%) NS Self-employed 0(0%) 3(5%) NS Chronological Variables Mean (SD) Mean (SD) P value b Age 34(8.3) 31(5.5) NS Age diagnosis 31(8.14) 27(5) .016 Age first symptoms 27(9.4) 23(6.1) .037 Age at menarche 12(1.39) 12.14 (1.27) NS Duration Untreated Endometriosis 3.55 (6.18) 3.64(5.05) NS Children Yes children 14(22%) 12(19%) NS Mean (SD) Mean (SD) P value b Age of children in household 14.85(8.53) 11.58 (6.65) NS No (%) No (%) P value a Symptoms Spotting 6(9%) 7(11%) NS Headache 2(3%) 1(2%) NS Weight gain 2(3%) 1(2%) NS Low libido 4(6%) 2(3%) NS a = χ 2. b= Sample T Test No significant group differences were found except for age of diagnosis ( t (62)= 2.48, p <.05), and age of onset of first symptoms ( t (62)= 2.13, p = <.05). Side effects prevalence was not significant different in both group. Neither at T1 we found significant differences concerning side effects for two groups. The descriptive statistics for psychological and clinical variables between treatment groups at T0 and T1 are listed in Table 2. No significant differences were found for SF-36, EHP-30, ISS, VAS, dysmenorrhea, dyschezia and dyspareunia between the groups. Table 2 Descriptive, Independent Sample T-Test, U Mann Whitney of psychological and clinical variables for DNG (n = 36) and EE/DNG (n = 28) Groups at T0 and T1. T0 T1 DNG EE/DNG p DNG EE/DNG p Mean (SD) Mean (SD) T Test Mean (SD) Mean (SD) T Test SF-36 PCS 41.14(10.7) 40.04(9.6) NS 49.64(13.05) 49.44(6.82) NS MCS 36.17(11.4) 40.39(11.1) NS 40.86(14.59) 41.14(9.78) NS VAS 8.6(1.7) 7.9(2.5) NS 3.22(3.05) 2.7(2.9) NS ISS 17.7(18.9) 11.8(11.1) NS 16(19.6) 11.1(12.2) NS EHP-30 Pain 52.6(22.5) 41.6(21.9) .041 16.4(20.9) 14.6(11) NS Control and powerlessness 44.1(31.7) 43.4(27.7) NS 13.3(23.1) 18.2(23.1) NS Emotional wellbeing 45.6(23.6) 43.5(23.8) NS 30.19(28.5) 26.8(20.9) NS Social support 47.8(31.8) 57.9(31) NS 32.6(33.9) 39.9(35) NS Self image 34.2(31.8) 24.7(31.9) NS 26.9(30.9) 15.41(25.2) NS Work 21.7(33.7) 13.4(24.4) NS 6.9(16.3) 4.6(15.6) NS Relationship with children 6.9(20.4) 7.1(21.4) NS 1.1(6.3) 1.4(7.3) NS Sexual intercourse 47.4(35.5) 45.5(31.01) NS 26.2(31.7) 27.6(32.1) NS Relationship with medical profession 21.4(31.5) 23(32.8) NS 4.3(14.5) 2.1(9.7) NS Treatment 0(0) 1.79(9.5) NS 6.7(22.5) 13(18.4) NS Infertility 28.6(34) 21(26.7) NS 31.4(34) 20.8(28.7) NS Dysmenorrhea 8.29(2.53) 6.24(4.23) NS 0(0) 0(0) NS Dyschezia 3.87(4.02) 2.96(4.09) NS 1.74(3.32) 1.40(2.9) NS Dyspareunia 5.71(3.87) 6(3.89) NS 3.35(3.79) 3.04(3.60) NS Median (range) Median (range) U Mann Whitney Median (range) Median (range) U Mann Whitney Volume sagittal compartment 39(14–77) 25.5(0–41) NS 26(0–63) 18(8–29) < .05 Volume antero-posterior compartment 27(12–61) 17.5(0–35) NS 18(0–44) 13(5–23) NS At T0 one sample T Test found significant differences between the PCS mean values of our sample ( M =40.66 SD =10.20) and the Italian female standardization sample values ( t (63)= -6.46, p =. 000) but not at T1 ( M =49.64 SD =10.70). The MCS mean values were also significantly lower than the mean for the Italian general female population both at T0 (M =38.02, SD =11.40) ( t (63)= -4.90, p =.000) and at T1 (M =40.98, SD =12.62) ( t (63)= -2.54, p<.05 ). Table 3 Correlation for psychological variables in all the sample at T0 and T1 T0 T1 VAS DUE VAS DUE SF-36 PCS r =-234, p < .001 r =-.263, p < .05 r =-400, p = .001 MCS r =-.272 p < .05 ISS r = .428, p = .001 EHP-30 Pain r = .548, p < .001 r = .289, p < .05 r = .612, p < .001 r = .277, p < .05 Control and Powerlessness r = .411, p = .001 r = .467, p < .001 r = .338, p < .01 Emotional wellbeing r = .377, p < .01 r = .283, p < .05 Social support r = .383, p < .01 r = .274, p < .05 Self-image Work r = .340, p < .01 r = .350, p < .01 Relationship with children Sexual intercourse r = .313, p = < .05 r = .431, p = .001 Relationship with medical profession r = .336, p < .01 Treatment r = .258, p < .05 r = .338, p < .01 r = .258, p < .05 r = .338, p < .01 Infertility In the entire sample no score was found for significant clinical symptoms for the 11 investigated scales of EHP-30. No clinical scores concerning sexual problems (ISS) in relationships were evaluated both at T0 than at T1 . Table 3 shows the correlation between psychological variables, VAS and DUE, in all the sample. Anova Direct effect Age of diagnosis and DUE were included as covariates in the ANOVA analyses to check the important influence of diagnosis time in the medical history of the patients. Also, the difference in time from T0 and T1 was inserted as a covariate to account for this variability. The mixed model revealed a significant main effect for dysmenorrhea over time ( F (1, 59)= 16.27, p < .001): at the follow-up, the dysmenorrhea score was significantly lower than the dysmenorrhea score at T0 regardless of the type of treatment. The same significant main effect over time was also found for VAS: general pain level decreases over time ( F (1,58)= 30 p< .001) for both groups treatment. EHP-30 areas also improved significantly over time, regardless of the type of treatment: emotional wellbeing F (1, 59)= 4.45, p< .05), and the relationship with the medical profession F (1, 59)= 6, p < .05). As concerns SF-36, an improvement in the physical component was found over time ( F (1, 59)= 7.21, p< .01). No significant results were found for the mental component. Interaction effect A mixed-design analysis of variance revealed a significant time × treatment group interaction for dysmenorrhea ( F (1, 59)= 5.13, p < .05). More specifically, the dysmenorrhea level of women taking DNG decreased more than that of the EE/DNG group over time; the differences between groups were not constant for the two times (Figure 2). Discussion This study aimed primarily to assess the relationship between psychological variables, pain and Duration Untreated Endometriosis (DUE) in a sample of women with endometriosis. Secondly, to evaluate the effect of DNG and EE/DNG on symptoms, QoL, HRQoL, pain and sexual satisfaction in endometriosis patients over time, at 18 months (follow-up). The impact of endometriosis on a woman’s perception of her quality of life is substantial and wide ranging. The sample studied presented low QoL levels for both the mental and physical components compared to Italian standard population, so it represents an important indicator of a disease-related disabling state. The quality of life of women with endometriosis is influenced by many factors. At T0 women described limitations in their physical health, social and personal activities due to emotional and health problems, physical pain, loss of strength and considered their health as poor. Both at T0 and at T1 most patients reported psychological distress, social and personal limitations due to emotional and health problems. We called the time between the onset of endometriosis symptoms and diagnosis Duration Untreated Endometriosis (DUE) analyzing the relationship with psychological variables. Diagnosis delays have been well documented: Nnoaham [26] reported an average diagnosis delay of 6.7 years, Soliman in 2017 [27] of 4.4 years and in our group the DUE mean was reduced to 3.59. We consider that our results show both that diagnosis in an endometriosis reference center may be faster and also that, over the last years, there has been an increase of information in the medical-scientific field and hence a reduction in diagnosis time [28]. Our results are in line with the literature, which negatively considers a delay in appropriate treatment both for the QoL of a woman and for progression of endometriosis [29]. We point out that a longer DUE is related to worse HRQoL in different components, showing higher pain perception, work problems, lack of confidence in the medical profession and in treatment. Also PCS was more compromised in women with a longer DUE period: they described higher limitations with regard to physical, social and personal activities because of the disease. At T1 women with longer DUE referred greater impairment regarding pain perception, social support and symptom control and less trust in treatment than women with shorter DUE. In line with several studies [8, 14] we confirmed the role of pain as an important factor influencing physical, psychosocial or emotional limitations. In our sample higher pain perception is related to worse QoL as regards the physical component at T0 and both physical and mental components at T1, with more limitations in self-care, physical, social and personal activities, fatigue, distress, emotional problems and poor perception of health. So, according to Pessoa [30], it is important to consider clinical manifestation as central goals in treatment of endometriosis, not only infertility. As concerns HRQoL we did not find significant clinical alerts of impairment in our group. However, different areas were related to pain both at T0 and at T1, meaning that women that experienced a higher pain level expressed more difficulty in management of pain and symptom controls in their daily activities, mood swings, concern about pains during sexual intercourse, and lack of confidence in treatment. Work difficulties are only related to pain at T0 and misunderstanding by others at T1. Nor, as concerns couples’ sexual problems, did we find clinical levels for all the group, only a few people reporting significant problems in the sexual area. Couples’ sexual problems were greater when women experienced high pain levels, but only at T1. Poor satisfaction in sexual life worsens the overall quality of life and can lead to anxiety and mood symptoms [31]. As concerns the effect of DNG and EE/DNG over time we found significant results: dysmenorrhea, VAS, emotional wellbeing, the relationship with the medical profession, and the PCS improved for both the DNG and EE/DNG groups over time. Hence general and psychological wellbeing can increase in a setting of trust where doctor and patient cooperate to manage the symptoms successfully, regardless of the type of treatment. Moreover, we noted an interaction effect between time and treatment only for dysmenorrhea. Even if dysmenorrhea decreased in both group, patients that took DNG showed a more rapid reduction compared with women that took EE/DNG, DNG treatment works faster than EE/DNG over time in symptom reduction, so, according to the literature, DNG was the best choice in the treatment of dysmenorrhea over time. Techatraisak [32] showed that DNG already improved scores for all EHP-30 scales at month 6 of treatment, until month 24. Caruso [19] considered that DNG was well tolerated with a favorable safety profile until a period of 65 weeks. Women typically ask how the treatment will improve their symptoms but they also want to know the possible side effects and it is well know that these can lead to a dropout of the therapy. So, in clinical practice, these are important information to share with patients. Counselling patients regarding the expected side effects, weighing up the efficacy and safety of each treatment approach [17]. We agree with the principles of evidence-based medicine that claim that effective and safe medical management of disease is a major clinical aim for the patients with endometriosis. The therapy must be personalized for each patient and also depends on the woman’s goal [12] considering pain as an important problem affecting the QoL of women [33]. As suggested by the NICE guidelines [34], a multidisciplinary approach, including psychologist and a patient association representative, is necessary due to the complexity of the disease and its impact on psychological wellbeing too. Study limitations and strengths As any observational study, this clinical experience has a huge risk of bias. A limitation of the present study was the small sample size. Variables like endometrioma volume need a larger group. Only a small number had endometrioma, so we could not insert the size of endometrioma as a dependent variable. In further research it will be interesting to study if DNG improves QoL, HRQoL and symptoms over time regardless to the reduction of endometrioma size. Moreover a better understanding of all the bio-psycho-social aspects involved in women’s wellbeing and pain experience regarding endometriosis needs further research in longer periods. The side effect profile was collected in the routine clinical practice and not systematically studied. Failure to evaluation for this variable may have introduced a confounding bias. In further randomized research it will be important to study the relation between effect sides and QoL patients other then the risk of dropout of the therapy. A strength of our study was strict inclusion criteria, accuracy in choice of different measure to assess psychological wellness. Another advantage is the cooperation among different qualified researchers with high experience. Conclusion The results of this study highlight that endometriosis causes a general worsening in many areas of the QoL of patients suffering from it. In particular, women with endometriosis show both poor physical and mental components of QoL. Pain perception is associated with worsening of different components of generic QoL, specific HRQoL and sexual problems. DUE is related to worsening of different component of both QoL and HRQoL. As concerns the effect of treatment over time, the current findings demonstrate an improvement in the physical component of QoL, in general pain perception, in different areas of HRQoL (emotional wellbeing, relationship with the medical profession) and in symptoms (dysmenorrhea) using both DNG and EE/DNG. Moreover, DNG seems to have a greater effect than EE/DNG on dyspareunia reduction over time. Consequently, as well as improvement in pain symptoms, an improvement in QoL is a crucial aspect in endometriosis toward a global management of the disease. The results of this study, highlight the need for multidisciplinary approach and clinician education to decrease the effect of endometriosis on women’s QoL and to reduce the duration of untreated endometriosis. Abbreviations (DUE) Duration Untreated Endometriosis - (DNG) Dienogest 2 mg/daily - (EE/DNG) Dienogest/ethinylestradiol 0.03 mg/daily - QoL Quality of Life - HRQoL Health Related Quality of Life - (T0) Time 0 - (T1) Time 1 - Visual Analogic Scale (VAS) - Short Form-36 (SF-36) - Endometriosis Health Profile-30 (EHP-30) - Index of Sexual Satisfaction (ISS). Declarations Acknowledgments The authors would like to thank all the women who participated in this study. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Conflict of interest statement: The authors declare that the research was conducted in the absence of any potential conflict of interest. Consent to participate Informed consent was obtained from all individual all subjects involved in the study Ethical approval: N° 18/14feb 2018. Author Contribution: Antonio Maiorana: Project development, Manuscript writing Pietro Alfano: Manuscript writing and editing Antonella Mercurio: Data collection and management Salvatore Marcantonio: Data analysis Gabriella Minneci: Data collection and management Domenico Incandela Data collection and management Palma Audino: Manuscript writing, Data analysis References Della Corte L, Di Filippo C, Gabrielli O, Reppuccia S, La Rosa VL, Ragusa R, Fichera M, Commodari E, Bifulco G, Giampaolino P (2020) The burden of endometriosis on women’s lifespan: a narrative overview on quality of life and psychosocial wellbeing. International Journal of Environmental Research and Public Health 17(13), 4683. http//doi.org/10.3390/ijerph17134683 Bougie O, Yap MI, Sikora L, Flaxman T, Singh S (2019) Influence of race/ethnicity on prevalence and presentation of endometriosis: a systematic review and meta-analysis. 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Journal of Obstetrics and Gynaecology 40(1):83-89. http//doi.org/10.1080/01443615.2019.1603217 D’Alterio, MN, Saponara S, Agus, M, Laganà AS, Noventa M, Stochino Loi E, Feki A, Angioni S (2021) Medical and surgical interventions to improve the quality of life for endometriosis patients: a systematic review. Gynecological Surgery 18(1):1-14. https://doi.org/10.1186/s10397-021-01096-5 Mikuš M, Matak L, Vujić G, Škegro B, Škegro I, Augustin G, Lagana AS, Ćorić M (2022) The short form endometriosis health profile questionnaire (EHP-5): psychometric validity assessment of a Croatian version. Archives of Gynecology and Obstetrics 11. https://doi.org/10.21203/rs.3.rs-1627557/v1 Škegro B, Bjedov S, Mikuš M, Mustač F, Lešin J, Matijević V, Ćorić M, Elveđi Gašparović V, Medić F, Sokol Karadjole V (2021) Endometriosis, Pain and Mental Health. Psychiatria Danubina 33(4):632-636. PMID: 34718292 Harada M, Osuga Y, Izumi G, Takamura M, Takemura Y, Hirata T, Yoshino O, Koga K, Yano T, Taketani Y (2011) Dienogest, a new conservative strategy for extragenital endometriosis: a pilot study. Gynecological Endocrinology 27(9):717-720. http//doi.org/10.3109/09513590.2010.533800 Maiorana A, Incandela D, Parazzini F, Alio W, Mercurio A, Giambanco L, Alio L (2017) Efficacy of dienogest in improving pain in women with endometriosis: a 12-month single-center experience. Archives of Gynecology and Obstetrics 296(3):429-433. http//doi.org/10.1007/s00404-017-4442-5 Murji A, Biberoğlu K, Leng J, Mueller MD, Römer T, Vignali M, Yarmolinskaya M (2020) Use of dienogest in endometriosis: a narrative literature review and expert commentary. Current Medical Research and Opinion 36(5):895-907. http//doi.org/10.1080/03007995.2020.1744120 Caruso S, Iraci M, Cianci S, Vitale SG, Fava V, Cianci A (2019) Effects of long-term treatment with Dienogest on the quality of life and sexual function of women affected by endometriosis-associated pelvic pain. Journal of Pain Research 29(12):2371-2378. http//doi.org/10.2147/JPR.S207599 Caruso S, Iraci M, Cianci S, Fava V, Casella E, Cianci A (2016) Comparative, open-label prospective study on the quality of life and sexual function of women affected by endometriosis-associated pelvic pain on 2 mg dienogest/30 microg ethinyl estradiol continuous or 21/7 regimen oral contraceptive. Journal of Endocrinological Investigation 39(8):923–931. http//doi.org/10.1007/s40618-016-0460-6 Ware JE Jr, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Medical care(6):473-483. Jones G, Kennedy S, Barnard A, Wong J, Jenkinson C (2001) Development of an endometriosis quality-of-life instrument: The Endometriosis Health Profile-30. Obstetrics & Gynecology 98(2):258-264. http//doi.org/10.1016/s0029-7844(01)01433-8 Hudson WW (1992) The WALMYR Assessment Scale Scoring Manual. WALMYR Publishing Co., Temple, AZ. Hjermstad MJ, Fayers PM, Haugen DF, Caraceni A, Hanks GW, Loge JH, Fainsinger R, Aass N, Kaasa S, European Palliative Care Research Collaborative EPCRC (2011) Studies comparing numerical rating scales, verbal rating scales, and visual analogue scales for assessment of pain intensity in adults: a systematic literature review. Journal of Pain and Symptom Management 41(6):1073-1093. http//doi.org/ 10.1016/j.jpainsymman.2010.08.016 Aitken RC (1969) Measurement of feelings using visual analogue scales. Proceedings of the royal society of medicine 62(10):989-983. Rosner B (2011) Fundamentals of Biostatistics (The 7th edition). Brooks/Cole Boston Nnoaham KE, Hummelshoj L, Webster P, d’Hooghe T, de Cicco Nardone F, de Cicco Nardone C, Jenkinson C, Kennedy SH, Zondervan KT, Study WERFG (2011) Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertility and Sterility 96(2):366-373. http//doi.org/10.1016/j.fertnstert.2011.05.090 Soliman AM, Fuldeore M, Snabes MC (2017) Factors associated with time to endometriosis diagnosis in the United States. Journal of Women's Health 26(7):788-797. http//doi.org/10.1089/jwh.2016.6003 Maiorana A, Scafidi Fonti GM, Audino P, Rosini R, Alio L, Oliveri AM, Milito AM (2012) The role of EHP-30 as specific instrument to assess the quality of life of Italian women with endometriosis. Minerva Ginecologica 64(3):231-238 Márki G, Bokor A, Rigó J, Rigó A (2017) Physical pain and emotion regulation as the main predictive factors of health-related quality of life in women living with endometriosis. Human Reproduction 32(7):1432-1438. http//doi.org/10.1093/humrep/dex091 Pessoa de Farias Rodrigues M, Lima Vilarino F, de Souza Barbeiro Munhoz A, da Silva Paiva L, de Alcantara Sousa LV, Zaia V, Parente Barbosa C (2020) Clinical aspects and the quality of life among women with endometriosis and infertility: A cross-sectional study. BMC Women's Health 20(1):124. https://doi.org/10.1186/s12905-020-00987-7 Ruszała M, Dłuski DF, Winkler I, Kotarski J, Rechberger T, Gogacz M (2022) The State of Health and the Quality of Life in Women Suffering from Endometriosis. Journal of Clinical Medicine 11(7):2059. https://doi.org/10.3390/jcm11072059 Techatraisak K, Hestiantoro A, Soon R, Banal-Silao MJ, Kim MR, Seong SJ, Hidayat ST, Cai L, Shin S, Lee BS (2022) Impact of Long-Term Dienogest Therapy on Quality of Life in Asian Women with Endometriosis: the Prospective Non-Interventional Study ENVISIOeN. Reproductive Sciences, 29(4):1157-1169. http//doi.org/10.1007/s43032-021-00787-w Facchin F, Barbara G, Saita E, Mosconi P, Roberto A, Fedele L, Vercellini P (2015) Impact of endometriosis on quality of life and mental health: pelvic pain makes the difference. Journal of Psychosomatic Obstetrics & Gynecology 36(4):135-141. http//doi.org/10.3109/0167482X.2015.1074173 NICE National Institute for Health and Care Excellence (2017) Endometriosis: Diagnosis and management (NG73), London, UK Cite Share Download PDF Status: Published Journal Publication published 04 Feb, 2023 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted Editorial decision: Accept as is 17 Jan, 2023 Editor assigned by journal 16 Jan, 2023 Editor invited by journal 02 Jan, 2023 First submitted to journal 02 Jan, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2148443","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":168968675,"identity":"6d4f6f71-30de-41f4-905b-58181d1f5d60","order_by":0,"name":"Antonio Maiorana","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Antonio","middleName":"","lastName":"Maiorana","suffix":""},{"id":168968676,"identity":"928da5ff-ff0e-4acb-a170-0dd003a9d270","order_by":1,"name":"Pietro Alfano","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9ElEQVRIie3PsWrDMBCA4TOC86LU64kMeQV7iV1oyas09B2KhmBkAupS6NpA6WN4LhjaRQ8RCHiul849Uwc8xErGDPoHyTZ83BkgFLrGxHDfiE8+NSXDO/lIZPob8YFPR+plIB4zJpGFI5kek8fi+6A1LBBFu+8+ClqBaA8ainKK3G5xXTkHmUXMs11NJIEfnGextJFZVVleaWGW81lNpQSJynhJ0vVkZTH+nc/e+ylniYx6srYoeYq5gPC/ZDvj6JHJk3r7YtLgUpmUmJ0uT5p9Z/Td/SvGNf1sSoqft60yukwmBKT/13gLMfruIaFQKBTy9AeF8z8wOML2pQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-6725-7415","institution":"Istituto di Farmacologia Traslazionale Consiglio Nazionale delle Ricerche","correspondingAuthor":true,"prefix":"","firstName":"Pietro","middleName":"","lastName":"Alfano","suffix":""},{"id":168968677,"identity":"78616c97-3bbc-4302-a8ef-f8161d98d080","order_by":2,"name":"Antonella 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17:54:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2148443/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2148443/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00404-023-06942-9","type":"published","date":"2023-02-04T18:41:11+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":31838776,"identity":"c616aa79-1599-47cf-b0b5-972de23d02f3","added_by":"auto","created_at":"2023-01-20 04:52:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":47335,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the study\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-2148443/v1/be1e28fa4370372957ea8ee0.png"},{"id":31838777,"identity":"b3047397-c63e-4dab-bdae-999e19c0ce0a","added_by":"auto","created_at":"2023-01-20 04:52:51","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":58952,"visible":true,"origin":"","legend":"\u003cp\u003eInteraction effect for time and treatment on dysmenorrhea\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-2148443/v1/0a72547a883172c11a5b1e00.png"},{"id":44718799,"identity":"27e25968-8674-441d-a5ea-80d4f32a7aea","added_by":"auto","created_at":"2023-10-16 18:50:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":435172,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2148443/v1/644995a5-c45a-4740-8571-54d4804f4f6d.pdf"}],"financialInterests":"","formattedTitle":"Quality of life and clinical factors in women with endometriosis, the role of Dienogest vs EE/ Dienogest over time: a single-center study.","fulltext":[{"header":"Take-home Message","content":"\u003cp\u003eThe results of this study highlight that diagnostic delay and pain are related to worsening of different component of both QoL and HRQoL of women with endometriosis. Moreover, DNG seems to have a greater effect than EE/DNG on dyspareunia reduction over time. Improvement in pain symptoms, and in QoL are central goals in treatment of endometriosis toward a global management of the disease.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eEndometriosis is a chronic nonmalignant estrogen-dependent condition characterized by the presence of endometrial-like tissue outside the uterus affecting 10% of women of reproductive age [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] including very young girls, from all ethnic and social groups [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The causes of endometriosis have not yet been determined [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Endometriosis is associated with symptoms of dysmenorrhea, chronic pelvic pain, dyspareunia, dyschezia [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], up to 50% of women with endometriosis experience infertility [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] with an impairment of QoL [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Recent studies consider endometriosis as a disabling condition that may affect the social relationships, mental health, and sexual activity of women [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Despite its considerable impact, endometriosis is often under-diagnosed; an Italian study suggests that only 6 out of 10 cases in the general population are diagnosed [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. There are several factors that can complicate the diagnosis: asymptomatic cases, the late appearance of symptoms and the increased presence of comorbidities with similar symptoms to endometriosis. Symptoms begin during adolescence, thus, treatment is often started several years after use of NSAIDs [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], medical and psychosocial factors contribute to a delayed diagnosis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In this study we consider the period between the onset of endometriosis symptoms and diagnosis as “Duration Untreated Endometriosis (DUE)”. Among current management approaches, surgery and hormonal drugs are considered as primary treatment to reduce recurrences and to improve the QoL in women suffering from endometriosis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However medical treatment may be not a permanent solution for symptoms and infertility, so chronic pelvic pain and related symptoms can affect women throughout their fertile life. Pain and infertility may have negative effect on QoL for patients with endometriosis (13). Škegro et al. shown that higher pain level was related to poorer quality of life [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], emphasizing both physical and psychological aspect of the disease also for treatment project.\u003c/p\u003e\u003cp\u003eA key factor correlated with disease and QoL is the available treatment method, this is one of the most crucial aspects for both physicians and patients, so major consideration should be given not only to efficacy but also to the long-term safety and tolerability of the treatment options that are available [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. DNG is a synthetic progestin that is currently used for clinical treatment of endometriosis with a dose of 2 mg daily [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], it is an effective and well-tolerated treatment for endometriosis-related pain [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. It is know that patients are willing to accept the spotting that DNG can cause given the pain relief experienced [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and may also have positive effects on their QoL and sexual life [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMoreover, a reduction of pain was observed in patients using a combination of ethynylestradiol and dienogest in continuous regimen [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] as well as with dienogest alone [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAims of the present study:\u003c/p\u003e\u003cul\u003e \u003cli\u003e \u003cp\u003eTo assess the relationship between psychological variables, pain, Duration Untreated Endometriosis (DUE) in a sample of women with endometriosis.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eTo assess the 18-month effect of Dienogest 2 mg/daily (DNG) and Dienogest/ethinylestradiol 0.03 mg/daily (EE/DNG) on symptoms, QoL, HRQoL, pain and sexual satisfaction in women with endometriosis over time.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003eThis observational, single-center study was conducted on a sample of women with endometriosis referred to a center for diagnosis and treatment of endometriosis with dedicated physicians, psychologists, and nurses, of the Department of Obstetrics and Gynecology at the ARNAS Civico Hospital in Palermo, in Southern Italy, between October 2019 and June 2021.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eParticipants\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e85 women with endometriosis were consecutively recruited. All patients received personalized clinical indications regarding the use of medical therapy with DNG and EE/DNG administered orally. Side effects were collected during routine clinical practice, two participants reported vaginal bleeding and loss of libido were excluded from the final data analysis because they spontaneously suspended their therapy. Nineteen participants were excluded because of missing data.\u003c/p\u003e\n\u003cp\u003eFinally, 64 women completed all study procedures, 36 (56%) took DNG and 28 (44%) took EE/DNG. These women reported that treatment was well tolerated and that the therapy wellness was superior to the side effects.\u003c/p\u003e\n\u003cp\u003eAccording to routine practice, women came back for clinical assessment and psychological evaluation after 18 months (T1), and completed all measures at both Time 0 (T0) and Time 1 (T1), (Fig.\u0026nbsp;1). Some women (50%) performed the T1 procedures a few weeks after the visit scheduled at 18 months because of patients\u0026rsquo; specific clinical needs; this variability was taken into account in the analysis as a covariate.\u003c/p\u003e\n\u003cp\u003eAll subjects gave written informed consent. The individual privacy of clinical data was guaranteed under Italian law. Eligible for the study were women aged 18 years or more not seeking pregnancy, with a surgical diagnosis or a clinical/instrumental diagnosis of endometriosis, who had been taking DNG or EE/DNG at the time of recruitment.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eProcedures\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eQuality of life: questionnaire (QoL) Short Form Survey \u0026ldquo;SF-36\u0026rdquo;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe questionnaire consisted of 36 items, and transformed to give eight summary scales measuring health concepts, summarized in\u0026nbsp;two component factors: physical health (PCS) and mental health (MCS). The raw scores were converted into standard scores (M=50 \u0026plusmn;10), range 0-100, in accordance with the questionnaire guidelines\u0026nbsp;[20].\u003c/p\u003e\n\u003cp\u003eHealth-Related Quality of Life (HRQoL) Endometriosis Health Profile 30 \u0026ldquo;EHP-30\u0026rdquo;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis is a disease-specific tool to evaluate the HRQoL in women suffering from endometriosis. The EHP-30 is composed of two parts: a core questionnaire containing five scales applicable to all women with endometriosis (30 items): pain, control and powerlessness, emotional wellbeing, social support, self-image and a modular part containing six scales which do not necessarily apply to all women with endometriosis (23 items): work life, relationship with children, sexual intercourse, medical profession, treatment and infertility. The score ranging from 0 (best possible health status) to 100 (worst possible health status)\u0026nbsp;[21].\u003c/p\u003e\n\u003cp\u003eIndex of sexual satisfaction \u0026ldquo;ISS\u0026rdquo;\u003c/p\u003e\n\u003cp\u003eThis scale aims to assess problems relating to the sexual aspects of a relationship, measuring subject\u0026rsquo;s feelings about behaviors, attitudes, events, affective states and preferences associated with sexual intercourse between partners. It contains 25 questions, the obtained scores ranged from 0 to 150. A cutoff score \u0026ge;75, indicates a higher degree of sexual satisfaction\u0026nbsp;[22].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eVisual Analogical Scale \u0026ldquo;VAS\u0026rdquo;\u003c/p\u003e\n\u003cp\u003eThe Visual Analogic Scale was used to define endometriosis-associated pain, chronic pelvic pain, dysmenorrhea, dyspareunia and dyschezia.\u003c/p\u003e\n\u003cp\u003eThe instrument measures the pain level across a continuum of values, from the patient\u0026apos;s perspective their pain does not make discrete jumps, as a categorization of none, mild, moderate and severe would suggest. VAS is a horizontal line, 100 mm in length, anchored by word descriptors at each end. The patient marks on the line the point that they feel represents their perception of their current state. VAS has been repeatedly used in the literature as a way to measure patients\u0026rsquo; perceived pain\u0026nbsp;[23-24].\u003c/p\u003e\n\u003cp\u003eStudy variables\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eDysmenorrhea, dyspareunia and dyschezia;\u003c/li\u003e\n \u003cli\u003ePresence of spotting, headache, weight gain, low libido\u003c/li\u003e\n \u003cli\u003eAge\u003c/li\u003e\n \u003cli\u003eAge at menarche\u003c/li\u003e\n \u003cli\u003eAge diagnosis\u003c/li\u003e\n \u003cli\u003eAge first symptoms\u003c/li\u003e\n \u003cli\u003eDuration Untreated Endometriosis (DUE) refers to the period (years) between the onset of endometriosis symptoms and the diagnosis\u003c/li\u003e\n \u003cli\u003ePresence of children in the household and their age\u003c/li\u003e\n \u003cli\u003eVolume of endometrioma sagittal and antero-posterior compartment\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eStatistical analysis\u003c/h3\u003e\n\u003cp\u003e\u0026nbsp;All statistical analyses were performed using the SPSS statistical software version 20, with screening for missing data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA tool was performed\u0026nbsp;[25]\u0026nbsp;in order to determine the minimum total sample size required for this study, and the results showed that at least 54 participants were needed to register an alpha level of 0.05 and to have 80% power.\u003c/p\u003e\n\u003cp\u003eDescriptive statistics were used to summarize the study participants\u0026rsquo; clinical and psychological variables presented as mean (SD), median values (range) and frequency (%) as appropriate according to data distribution. The differences in patient characteristics between treatment groups (DNG and EE/DNG) were assessed with the Sample T Test and \u0026chi;\u003csup\u003e2\u003c/sup\u003e. \u0026nbsp;The psychological and clinical differences between treatment groups (DNG and EE/DNG) were performed using the Sample T Test and Mann Whitney\u0026rsquo;s U. The correlation between chronological, clinical and psychological variables both at T0 and at T1 were performed with R Pearson. The effect of treatment over time on the clinical and psychological variables were evaluated by a 2 (treatment) \u0026times; 2 (time) mixed-design analysis of variance (ANOVA). The independent variable was given by the 2 approaches to treatment: DNG and EE/DNG. The dependent variables were EHP-30, SF-36, ISS, VAS, dysmenorrhea, dyspareunia and dyschezia with checks for clinical variables that differed by group (age diagnosis, DUE and time variability). The level of significance was set at alpha = 0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cspan style=\"text-align: inherit;\"\u003eThe 64 women with endometriosis who completed both time surveys were aged between 19 and 49 years old (\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003eM\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e= 32.61\u0026nbsp;\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003eSD\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e= 7.3); 36 of them (56%) took DNG and 28 (44%) took EE/DNG.\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003e\u0026nbsp;\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003eThe descriptive statistics summarizing the participants\u0026rsquo; demographic and clinical characteristics in the two treatment groups and the\u0026nbsp;\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003ep\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e\u0026nbsp;values for test statistics assessing group differences at baseline are listed in Table 1.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cdiv class=\"SimplePara\"\u003ePatient Characteristics at baseline \u0026chi;\u003csup\u003e2\u003c/sup\u003e, Independent Sample T-Test, for DNG (n\u0026thinsp;=\u0026thinsp;36) and EE/DNG (n\u0026thinsp;=\u0026thinsp;28) Groups.\u003c/div\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDNG\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo (%)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eEE/DNG\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo (%)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eP value \u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eEducation\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003ePrimary education\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1(2%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1(2%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLower secondary education\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e14(22%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e8(12%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUpper secondary education\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e16(25%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15(23%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDegree\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e5(8%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4(6%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eMarital status\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eSingle\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e8(12%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4(6%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUnmarried couple\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e13(20%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e14(23%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eMarried\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15(23%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10(16%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eOccupation\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUnemployed\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15(23%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e13(20%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eStudent\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3(5%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e5(8%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHousewife\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4(6%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3(5%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eEmployee\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e14(22%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4(6%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eSelf-employed\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0(0%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3(5%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eChronological Variables\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eMean (SD)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eMean (SD)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eP value\u003c/span\u003e \u003csup\u003eb\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAge\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e34(8.3)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e31(5.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAge diagnosis\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e31(8.14)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e27(5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003e.016\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAge first symptoms\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e27(9.4)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e23(6.1)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003e.037\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAge at menarche\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e12(1.39)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e12.14 (1.27)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDuration Untreated Endometriosis\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3.55 (6.18)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3.64(5.05)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eChildren\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eYes children\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e14(22%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e12(19%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eMean (SD)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eMean (SD)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eP value\u003c/span\u003e \u003csup\u003eb\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAge of children in household\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e14.85(8.53)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e11.58 (6.65)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eNo (%)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eNo (%)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eP value\u003c/span\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eSymptoms\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eSpotting\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e6(9%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e7(11%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHeadache\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2(3%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1(2%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWeight gain\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2(3%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1(2%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLow libido\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4(6%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2(3%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003e= \u0026chi; \u003csup\u003e2. b=\u003c/sup\u003e Sample T Test\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eNo significant group differences were found except for age of diagnosis (\u003cem\u003et\u003c/em\u003e(62)= 2.48, \u003cem\u003ep\u003c/em\u003e\u0026lt;.05), and age of onset of first symptoms (\u003cem\u003et\u003c/em\u003e(62)= 2.13, \u003cem\u003ep\u003c/em\u003e= \u0026lt;.05). Side effects prevalence was not significant different in both group. Neither at T1 we found significant differences concerning side effects for two groups. The descriptive statistics for psychological and clinical variables between treatment groups at T0 and T1 are listed in Table 2. No significant differences were found for SF-36, EHP-30, ISS, VAS, dysmenorrhea, dyschezia and dyspareunia between the groups.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDescriptive, Independent Sample T-Test, U Mann Whitney of psychological and clinical variables for DNG (n\u0026thinsp;=\u0026thinsp;36) and EE/DNG (n\u0026thinsp;=\u0026thinsp;28) Groups at T0 and T1.\u003c/div\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"9\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"5\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eT0\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eT1\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDNG\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eEE/DNG\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDNG\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eEE/DNG\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eMean (SD)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eMean (SD)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eT Test\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eMean (SD)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eMean (SD)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eT Test\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eSF-36\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"8\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003ePCS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e41.14(10.7)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e40.04(9.6)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e49.64(13.05)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e49.44(6.82)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eMCS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e36.17(11.4)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e40.39(11.1)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e40.86(14.59)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e41.14(9.78)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eVAS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e8.6(1.7)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e7.9(2.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3.22(3.05)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2.7(2.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eISS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e17.7(18.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e11.8(11.1)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e16(19.6)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e11.1(12.2)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eEHP-30\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"8\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003ePain\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e52.6(22.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e41.6(21.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e.041\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e16.4(20.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e14.6(11)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eControl and powerlessness\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e44.1(31.7)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e43.4(27.7)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e13.3(23.1)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e18.2(23.1)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eEmotional wellbeing\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e45.6(23.6)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e43.5(23.8)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e30.19(28.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e26.8(20.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eSocial support\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e47.8(31.8)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e57.9(31)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e32.6(33.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e39.9(35)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eSelf image\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e34.2(31.8)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e24.7(31.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e26.9(30.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15.41(25.2)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eWork\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e21.7(33.7)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e13.4(24.4)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e6.9(16.3)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.6(15.6)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eRelationship with children\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e6.9(20.4)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e7.1(21.4)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.1(6.3)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.4(7.3)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eSexual intercourse\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e47.4(35.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e45.5(31.01)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e26.2(31.7)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e27.6(32.1)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eRelationship with medical profession\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e21.4(31.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e23(32.8)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4.3(14.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2.1(9.7)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eTreatment\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0(0)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.79(9.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e6.7(22.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e13(18.4)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eInfertility\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e28.6(34)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e21(26.7)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e31.4(34)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e20.8(28.7)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eDysmenorrhea\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e8.29(2.53)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e6.24(4.23)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0(0)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0(0)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eDyschezia\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3.87(4.02)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2.96(4.09)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.74(3.32)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.40(2.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eDyspareunia\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e5.71(3.87)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e6(3.89)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3.35(3.79)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3.04(3.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eMedian (range)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eMedian\u003c/span\u003e\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003e(range)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eU Mann Whitney\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eMedian\u003c/span\u003e\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003e(range)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eMedian\u003c/span\u003e\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003e(range)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eU Mann Whitney\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eVolume sagittal compartment\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e39(14\u0026ndash;77)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e25.5(0\u0026ndash;41)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e26(0\u0026ndash;63)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e18(8\u0026ndash;29)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003e\u0026lt;\u0026thinsp;.05\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eVolume antero-posterior compartment\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e27(12\u0026ndash;61)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e17.5(0\u0026ndash;35)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e18(0\u0026ndash;44)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e13(5\u0026ndash;23)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003eNS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cspan style=\"text-align: inherit;\"\u003eAt T0 one sample T Test found significant differences between the PCS mean values of our sample (\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003eM\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e=40.66\u0026nbsp;\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003eSD\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e=10.20) and the Italian female standardization sample values (\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003et\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e(63)= -6.46,\u0026nbsp;\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003ep\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e=.\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003e000)\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e\u0026nbsp;but not at T1 (\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003eM\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e=49.64\u0026nbsp;\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003eSD\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e=10.70). The MCS mean values were also significantly lower than the mean for the Italian general female population both at T0\u0026nbsp;\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003e(M\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e=38.02,\u0026nbsp;\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003eSD\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e=11.40) (\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003et\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e(63)= -4.90,\u0026nbsp;\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003ep\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e=.000) and at T1\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003e(M\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e=40.98,\u0026nbsp;\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003eSD\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e=12.62) (\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003et\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e(63)= -2.54,\u0026nbsp;\u003c/span\u003e\u003cem style=\"text-align: inherit;\"\u003ep\u0026lt;.05\u003c/em\u003e\u003cspan style=\"text-align: inherit;\"\u003e).\u003c/span\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eCorrelation for psychological variables in all the sample at T0 and T1\u003c/div\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eT0\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eT1\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eVAS\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDUE\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eVAS\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDUE\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eSF-36\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003ePCS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e=-234, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e=-.263, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.05\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e=-400, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eMCS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e=-.272 \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.05\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eISS\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.428, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eEHP-30\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003ePain\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.548, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.289, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.05\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.612, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.277, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.05\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eControl and Powerlessness\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.411, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.467, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.338, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.01\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eEmotional wellbeing\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.377, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.01\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.283, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.05\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eSocial support\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.383, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.01\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.274, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.05\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eSelf-image\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eWork\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.340, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.01\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.350, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.01\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eRelationship with children\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eSexual intercourse\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.313, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;.05\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.431, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.001\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eRelationship with medical profession\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.336, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.01\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eTreatment\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.258, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.05\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.338, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.01\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.258, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.05\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003er\u003c/span\u003e\u0026thinsp;=\u0026thinsp;.338, \u003cspan class=\"Italic\" name=\"Emphasis\" type=\"Italic\"\u003ep\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.01\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan class=\"Bold\" name=\"Emphasis\" type=\"Bold\"\u003eInfertility\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cspan style=\"text-align: inherit;\"\u003eIn the entire sample no score was found for significant clinical symptoms for the 11 investigated scales of EHP-30.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eNo clinical scores concerning sexual problems (ISS) in relationships were evaluated both at T0 than at T1\u003cem\u003e.\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 shows the correlation between psychological variables, VAS and DUE, in all the sample.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAnova Direct effect\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAge of diagnosis and DUE were included as covariates in the ANOVA analyses to check the important influence of diagnosis time in the medical history of the patients. Also, the difference in time from T0 and T1 was inserted as a covariate to account for this variability. The mixed model revealed a significant main effect for dysmenorrhea over time (\u003cem\u003eF\u003c/em\u003e(1, 59)= 16.27, \u003cem\u003ep \u0026lt;\u0026nbsp;\u003c/em\u003e.001): at the follow-up, the dysmenorrhea score was significantly lower than the dysmenorrhea score at T0 regardless of the type of treatment. The same significant main effect over time was also found for VAS: general pain level decreases over time (\u003cem\u003eF\u003c/em\u003e(1,58)= 30 \u003cem\u003ep\u0026lt;\u0026nbsp;\u003c/em\u003e.001) for both groups treatment. EHP-30 areas also improved significantly over time, regardless of the type of treatment: emotional wellbeing \u003cem\u003eF\u003c/em\u003e(1, 59)= 4.45, \u003cem\u003ep\u0026lt;\u0026nbsp;\u003c/em\u003e.05), and the relationship with the medical profession \u003cem\u003eF\u003c/em\u003e(1, 59)= 6, \u003cem\u003ep \u0026lt;\u003c/em\u003e.05). As concerns SF-36, an improvement in the physical component was found over time (\u003cem\u003eF\u0026nbsp;\u003c/em\u003e(1, 59)= 7.21, \u003cem\u003ep\u0026lt;\u0026nbsp;\u003c/em\u003e.01). No significant results were found for the mental component.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eInteraction effect\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA mixed-design analysis of variance revealed a significant time \u0026times; treatment group interaction for dysmenorrhea (\u003cem\u003eF\u003c/em\u003e(1, 59)= 5.13, \u003cem\u003ep\u003c/em\u003e\u0026lt; .05). More specifically, the dysmenorrhea level of women taking DNG decreased more than that of the EE/DNG group over time; the differences between groups were not constant for the two times (Figure 2).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study aimed primarily to assess the relationship between psychological variables, pain and Duration Untreated Endometriosis (DUE) in a sample of women with endometriosis. Secondly, to evaluate the effect of DNG and EE/DNG on symptoms, QoL, HRQoL, pain and sexual satisfaction in endometriosis patients over time, at 18 months (follow-up). \u0026nbsp;The impact of endometriosis on a woman\u0026rsquo;s perception of her quality of life is substantial and wide ranging. The sample studied presented low QoL levels for both the mental and physical components compared to Italian standard population, so it represents an important indicator of a disease-related disabling state. The quality of life of women with endometriosis is influenced by many factors. At T0 women described limitations in their physical health, social and personal activities due to emotional and health problems, physical pain, loss of strength and considered their health as poor. Both at T0 and at T1\u003cem\u003e\u0026nbsp;\u003c/em\u003emost patients reported psychological distress,\u0026nbsp;social and personal limitations due to emotional and health problems.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe called the time between the onset of endometriosis symptoms and diagnosis Duration Untreated Endometriosis (DUE) analyzing the relationship with psychological variables. Diagnosis delays have been well documented: Nnoaham [26] reported an average diagnosis delay of 6.7 years, Soliman in 2017 [27] of 4.4 years and in our group the DUE mean was reduced to 3.59. \u0026nbsp;We consider that our results show both that diagnosis in an endometriosis reference center may be faster and also that, over the last years, there has been an increase of information in the medical-scientific field and hence a reduction in diagnosis time [28].\u0026nbsp;Our results are in line with the literature, which negatively considers a delay in appropriate treatment both for the QoL of a woman and for progression of endometriosis\u0026nbsp;[29]. We point out that a longer DUE is related to worse HRQoL in different components, showing higher pain perception, work problems, lack of confidence in the medical profession and in treatment. Also PCS was more compromised in women with a longer DUE period: they described higher limitations with regard to physical, social and personal activities because of the disease. At T1 women with longer DUE referred greater impairment regarding pain perception, social support and symptom control and less trust in treatment than women with shorter DUE.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn line with several studies [8, 14] we confirmed the role of pain as an important factor influencing physical, psychosocial or emotional limitations. In our sample higher pain perception is related to worse QoL as regards the physical component at T0 and both physical and mental components at T1, with more limitations in self-care, physical, social and personal activities, fatigue, distress, emotional problems and poor perception of health. So, according to Pessoa [30], it is important to consider clinical manifestation as central goals in treatment of endometriosis, not only infertility. As concerns HRQoL we did not find significant clinical alerts of impairment in our group. However, different areas were related to pain both at T0 and at T1, meaning that women that experienced a higher pain level expressed more difficulty in management of pain and symptom controls in their daily activities, mood swings, concern about pains during sexual intercourse, and lack of confidence in treatment. Work difficulties are only related to pain at T0 and misunderstanding by others at T1. \u0026nbsp;Nor, as concerns couples\u0026rsquo; sexual problems, did we find clinical levels for all the group, only a few people reporting significant problems in the sexual area. Couples\u0026rsquo; sexual problems were greater when women experienced high pain levels, but only at T1. Poor satisfaction in sexual life worsens the overall quality of life and can lead to anxiety and mood symptoms [31].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs concerns the effect of DNG and EE/DNG over time we found significant results: dysmenorrhea, VAS, emotional wellbeing, the relationship with the medical profession, and the PCS improved for both the DNG and EE/DNG groups over time. Hence general and psychological wellbeing can increase in a setting of trust where doctor and patient cooperate to manage the symptoms successfully, regardless of the type of treatment. Moreover, we noted an interaction effect between time and treatment only for dysmenorrhea. Even if dysmenorrhea decreased in both group, patients that took DNG showed a more rapid reduction compared with women that took EE/DNG, DNG treatment works faster than EE/DNG over time in symptom reduction,\u0026nbsp;so,\u0026nbsp;according to the literature, DNG was the best choice in the treatment of dysmenorrhea over time.\u0026nbsp;Techatraisak\u0026nbsp;[32]\u0026nbsp;showed that DNG already improved scores for all EHP-30 scales at month 6 of treatment, until month 24.\u0026nbsp;Caruso [19] considered that DNG was well tolerated with a favorable safety profile until a period of 65 weeks.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWomen typically ask how the treatment will improve their symptoms but they also want to know the possible side effects and it is well know that these can lead to a dropout of the therapy. So, in clinical practice, these are important information to share with patients. Counselling patients regarding the expected side effects, weighing up the efficacy and safety of each treatment approach [17].\u003c/p\u003e\n\u003cp\u003eWe agree with the principles of evidence-based medicine that claim that effective and safe medical management of disease is a major clinical aim for the patients with endometriosis. The therapy must be personalized for each patient and also depends on the woman\u0026rsquo;s goal [12] considering pain as an important problem affecting the QoL of women [33]. As suggested by the NICE guidelines [34], a multidisciplinary approach, including psychologist and a patient association representative, is necessary due to the complexity of the disease and its impact on psychological wellbeing too.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy limitations and strengths\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs any observational study, this clinical experience has a huge risk of bias.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA limitation of the present study was the small sample size. Variables like endometrioma volume need a larger group. Only a small number had endometrioma, so we could not insert the size of endometrioma as a dependent variable. In further research it will be interesting to study if DNG improves QoL, HRQoL and symptoms over time regardless to the reduction of endometrioma size.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMoreover a better understanding of all the bio-psycho-social aspects involved in women\u0026rsquo;s wellbeing and pain experience regarding endometriosis needs further research in longer periods.\u003c/p\u003e\n\u003cp\u003eThe side effect profile was collected in the routine clinical practice and not systematically studied.\u0026nbsp;Failure to evaluation for this variable may have introduced a confounding bias.\u0026nbsp;In further\u0026nbsp;randomized\u0026nbsp;research it will be important to study the relation between effect sides and QoL patients other then the risk of dropout of the therapy.\u003c/p\u003e\n\u003cp\u003eA strength of our study was strict inclusion criteria, accuracy in choice of different measure to assess psychological wellness. Another advantage is the cooperation among different qualified researchers with high experience.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe results of this study highlight that endometriosis causes a general worsening in many areas of the QoL of patients suffering from it. In particular, women with endometriosis show both poor physical and mental components of QoL. Pain perception is associated with worsening of different components of generic QoL, specific HRQoL and sexual problems. DUE is related to worsening of different component of both QoL and HRQoL. As concerns the effect of treatment over time, the current findings demonstrate an improvement in the physical component of QoL, in general pain perception, in different areas of HRQoL (emotional wellbeing, relationship with the medical profession) and in symptoms (dysmenorrhea) using both DNG and EE/DNG. Moreover, DNG seems to have a greater effect than EE/DNG on dyspareunia reduction over time. Consequently, as well as improvement in pain symptoms, an improvement in QoL is a crucial aspect in endometriosis toward a global management of the disease.\u003c/p\u003e\n\u003cp\u003eThe results of this study, highlight the need for multidisciplinary approach and clinician education to decrease the effect of endometriosis on women\u0026rsquo;s QoL and to reduce the duration of untreated endometriosis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e(DUE) Duration Untreated Endometriosis - (DNG) Dienogest 2 mg/daily - (EE/DNG) Dienogest/ethinylestradiol 0.03 mg/daily - QoL Quality of Life - HRQoL Health Related Quality of Life - (T0) Time 0 - (T1) Time 1 - Visual Analogic Scale (VAS) - Short Form-36 (SF-36) - Endometriosis Health Profile-30 (EHP-30) - Index of Sexual Satisfaction (ISS).\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the women who participated in this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest statement:\u0026nbsp;\u003c/strong\u003eThe authors declare that the research was conducted in the absence of any potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual\u0026nbsp;all subjects involved in the study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u0026nbsp;\u003c/strong\u003eN\u0026deg; 18/14feb 2018.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAntonio Maiorana: Project development, Manuscript writing\u003c/p\u003e\n\u003cp\u003ePietro Alfano: Manuscript writing and editing\u003c/p\u003e\n\u003cp\u003eAntonella Mercurio:\u0026nbsp;Data collection and management\u003c/p\u003e\n\u003cp\u003eSalvatore Marcantonio: Data analysis\u003c/p\u003e\n\u003cp\u003eGabriella Minneci:\u0026nbsp;Data collection and management\u003c/p\u003e\n\u003cp\u003eDomenico Incandela\u0026nbsp;Data collection and management\u003c/p\u003e\n\u003cp\u003ePalma Audino: Manuscript writing, Data analysis\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eDella Corte L, Di Filippo C, Gabrielli O, Reppuccia S, La Rosa VL, Ragusa R, Fichera M, Commodari E, Bifulco G, Giampaolino P (2020) The burden of endometriosis on women\u0026rsquo;s lifespan: a narrative overview on quality of life and psychosocial wellbeing. 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Archives of Gynecology and Obstetrics 11.\u0026nbsp;https://doi.org/10.21203/rs.3.rs-1627557/v1\u003c/li\u003e\n \u003cli\u003e\u0026Scaron;kegro B, Bjedov S, Miku\u0026scaron; M, Mustač F, Le\u0026scaron;in J, Matijević V, Ćorić M, Elveđi Ga\u0026scaron;parović V, Medić F, Sokol Karadjole V (2021) Endometriosis, Pain and Mental Health. Psychiatria Danubina 33(4):632-636. PMID: 34718292\u003c/li\u003e\n \u003cli\u003eHarada M, Osuga Y, Izumi G, Takamura M, Takemura Y, Hirata T, Yoshino O, Koga K, Yano T, Taketani Y (2011) Dienogest, a new conservative strategy for extragenital endometriosis: a pilot study. Gynecological Endocrinology 27(9):717-720. http//doi.org/10.3109/09513590.2010.533800\u003c/li\u003e\n \u003cli\u003eMaiorana A, Incandela D, Parazzini F, Alio W, Mercurio A, Giambanco L, Alio L (2017) Efficacy of dienogest in improving pain in women with endometriosis: a 12-month single-center experience. 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BMC Women\u0026apos;s Health 20(1):124. https://doi.org/10.1186/s12905-020-00987-7\u003c/li\u003e\n \u003cli\u003eRuszała M, Dłuski DF, Winkler I, Kotarski J, Rechberger T, Gogacz M (2022) The State of Health and the Quality of Life in Women Suffering from Endometriosis. Journal of Clinical Medicine 11(7):2059. https://doi.org/10.3390/jcm11072059\u003c/li\u003e\n \u003cli\u003eTechatraisak K, Hestiantoro A, Soon R, Banal-Silao MJ, Kim MR, Seong SJ, Hidayat ST, Cai L, Shin S, Lee BS (2022) Impact of Long-Term Dienogest Therapy on Quality of Life in Asian Women with Endometriosis: the Prospective Non-Interventional Study ENVISIOeN. Reproductive Sciences, 29(4):1157-1169. http//doi.org/10.1007/s43032-021-00787-w\u003c/li\u003e\n \u003cli\u003eFacchin F, Barbara G, Saita E, Mosconi P, Roberto A, Fedele L, Vercellini P (2015) Impact of endometriosis on quality of life and mental health: pelvic pain makes the difference. Journal of Psychosomatic Obstetrics \u0026amp; Gynecology 36(4):135-141. http//doi.org/10.3109/0167482X.2015.1074173\u003c/li\u003e\n \u003cli\u003eNICE National Institute for Health and Care Excellence (2017) Endometriosis: Diagnosis and management (NG73), London, UK\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"dyspareunia, Health Related Quality of life, Sexual Satisfaction, Pain","lastPublishedDoi":"10.21203/rs.3.rs-2148443/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2148443/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e The aims of this observational study were: to assess the relationship between psychological variables, pain, Duration Untreated Endometriosis (DUE) in a sample of women with Endometriosis; and to assess the effect of Dienogest 2 mg/daily (DNG) and Dienogest/ethinylestradiol 0.03 mg/daily (EE/DNG) on Symptoms, QoL, HRQoL, pain and sexual satisfaction, over time.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e 64 women constituted the study group; (56%) took DNG and (44%) took EE/DNG. VAS, SF-36, EHP-30 and ISS were used to assess endometriosis-associated pelvic pain, QoL, HRQoL and sexual satisfaction, respectively. The study included one follow-up at 18 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e At T0, a longer period of DUE was related both to worst HRQoL and Physical QoL. At T1, a correlation was found between longer DUE and worst HRQoL. At T0, a negative correlation was found between VAS and PCS and between VAS and EHP-30.\u003c/p\u003e\n\u003cp\u003eAt T1, the same above correlation was found between VAS and PCS/MCS and VAS and EHP-30 scale. There was a correlation between ISS and VAS.\u003c/p\u003e\n\u003cp\u003eANOVA showed a reduction in dysmenorrhea, in general pain level and an improvement in emotional wellbeing, relationship with medical profession, and PCS over time, regardless to type of treatment. Moreover, a significant time × treatment group interaction for dysmenorrhea was found.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e DUE and pain are important variables related to psychological aspects of women with endometriosis. Treatment with both DNG and EE/DNG may have positive effects on the QoL, HRQoL and symptoms. Moreover, DNG seems to have a greater effect than EE/DNG on dyspareunia reduction over time.\u003c/p\u003e","manuscriptTitle":"Quality of life and clinical factors in women with endometriosis, the role of Dienogest vs EE/ Dienogest over time: a single-center study.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-01-20 04:52:46","doi":"10.21203/rs.3.rs-2148443/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accept as is","date":"2023-01-18T02:35:59+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-01-17T01:58:47+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Archives of Gynecology and Obstetrics","date":"2023-01-03T01:42:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Gynecology and Obstetrics","date":"2023-01-02T11:18:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8a12ff50-4aae-417b-90c2-9d908abf334b","owner":[],"postedDate":"January 20th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T18:46:52+00:00","versionOfRecord":{"articleIdentity":"rs-2148443","link":"https://doi.org/10.1007/s00404-023-06942-9","journal":{"identity":"archives-of-gynecology-and-obstetrics","isVorOnly":false,"title":"Archives of Gynecology and Obstetrics"},"publishedOn":"2023-02-04 18:41:11","publishedOnDateReadable":"February 4th, 2023"},"versionCreatedAt":"2023-01-20 04:52:46","video":"","vorDoi":"10.1007/s00404-023-06942-9","vorDoiUrl":"https://doi.org/10.1007/s00404-023-06942-9","workflowStages":[]},"version":"v1","identity":"rs-2148443","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2148443","identity":"rs-2148443","version":["v1"]},"buildId":"WvIrzKhiLBfengagbw6Ux","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}