Female Sexual Function in Women with Suspected Deep Infiltrating Endometriosis

► endometriosis ► sexuality ► deeply in filtrating endometriosis

Objective To evaluate the quality of the sexual function of women with suspected deep in filtrating endometriosis.

A cross-sectional, observational and prospective study was conducted between May 2015 and August 2016, in which 67 patients with deep in filtrating endometriosis, suspected or diagnosed, wer e assessed for epidemiological and clinical characteristics, such as pain level through a visual analog scale (VAS), features of deep infiltrating endometriosis lesions and score on the Female Sexual Function Index (FSFI) before the onset of treatment. The stati stical analysis was performed using the software STATA version 12.0 (StataCorp LLC, College Station, TX, USA) to compare the variables through multiple regression analysis.

The average age of the patients was 39.2 years old; most patients were symptomatic (92.5%); and the predominant location of the deep in filtrating lesions was on the rectosigmoid colon (50%), closely followed by the retrocervical region (48.3%). The median overall score on the FSFI was 23.4; in 67.2% of the cases the score was/C20 26.5 (cutoff point for sexual dysfunction). Deep dyspareunia (p ¼ 0.000, confidence interval [CI]: 0.64– 0.83) and rectosigmoid endometriosis lesions ( p ¼ 0.008, CI: 0.72 –0.95) showed signifi- cant correlation with lower FSFI scores, adjusted by bladder lesion, patients’ age and size of lesions. Deep dyspareunia (p ¼ 0.003, CI: 0.49–0.86) also exhibited significant correlation with FSFI pain domain, adjusted by cyclic bowel pain, vaginal lesion and use of gonadotro- pin-releasing hormone (GnRH) analog. These results re flect the in fluence of deep dyspareunia on the sexual dysfunction of the analyzed population.

Most patients exhibited sexual dysfunction, and deep dyspareunia was the pelvic painful symptom that showed correlation with sexual dysfunction. Resumo Objetivo Avaliar a qualidade da função sexual em pacientes com suspeita de endometriose profunda in filtrativa. Métodos Foi realizado um estudo observacional transversal prospectivo entre maio de 2015 e agosto de 2016, no qual foram analisados os dados clínicos e received September 16, 2017 accepted January 24, 2018 DOI https://doi.org/ 10.1055/s-0038-1639593. ISSN 0100-7203. Copyright © 2018 by Thieme Revinter Publicações Ltda, Rio de Janeiro, Brazil THIEME Original Article 115

Endometriosis is characterized by the presence of endome- trium-like functional tissue located outside the uterine cavity, most often on the pelvic peritoneum and ovaries. It might present as deep and in filtrating lesions in the organs adjacent to the uterus —the bladder in the anterior pelvic compartment, retrocervical region, rectovaginal septum, vaginal fornices, rectosigmoid colon and cecal appendix in the posterior compartment. 1,2 While the etiopathogenesis of the disease is not well known, some evidences suggest that a combination of retrograde menstrual flow with genetic, hormonal and immune factors and the cell response of the eutopic endometrium might contribute to the formation and development of endometriosis lesions. 3 According to the available studies, the prevalence of this disease is 10–20% among women of reproductive age, 4 but it might vary to be as high as 50% in populations of patients with speci fic clinical characteristics, such as infertility and chronic pelvic pain. 5 With the help of laparoscopy, endometriosis might be classified according to its anatomical localization and exten- sion. Among the available classi fication systems is the one formulated by the American Society of Reproductive Medi- cine, which is based on the appearance, size and depth of peritoneal and ovarian implants, presence, extension and type of adhesions, and degree of cul-de-sac obliteration. 6 More recently, the ENZIAN classi fication was developed for deeply infiltrating lesions, in which the stages of disease are defined according to their localization and size. 7,8 The bowel is frequently affected in the deep form of the disease, de fined as endometriosis in filtrating deeper than 5 mm under the peritoneum.7 Deep in filtrating lesions can be identi fied by physical examination,1 but transvaginal ultrasound 9 and magnetic resonance imaging 10 have been used for de finition of the extension of the lesions with adequate accuracy. There is no con firmed correlation between extension of the disease and severity of symptoms, reproductive progno- sis or recurrence of pain in the long run. 11 The clinical presentation of the disease is quite variable. Up to 25% of the patients might be asymptomatic, 12 30–50% might report infertility, 12,13 and up to 80% complain of chronic pelvic pain (severe dysmenorrhea, deep dyspareunia and painful ovulation). 14 In addition, perimenstrual urinary or rectal symptoms and chronic fatigue are common clinical complaints.12,15 The quality of life of patients with endometriosis is significantly impaired, while deep dyspareunia considerably affects their sexual life. 16 In addition, dyspareunia is associ- ated with anxiety, 17,18 reduced frequency of sexual inter- course, reduction of sexual desire and arousal, and less orgasmic experiences. 19,20 While these are subjective phe- nomena, assessment of the sexual function through validat- ed questionnaires affords a better understanding of the impact of endometriosis on the quality of female sexuality. One of the best-established questionnaires for this purpose is the Female Function Sexual Index (FSFI), which has been validated for the Brazilian Portuguese language. 21–23 Laparoscopic excision of endometriotic nodules, pharma- cological treatment and the combination of both proved to be efficacious to reduce deep dyspareunia. 24–28 Considering the intimate relationship between endome- triosis and sexual dysfunction, 17–20 we sought to assess the quality of the sexual function of women with suspected deep infiltrating endometriosis (DIE). epidemiológicos de 67 pacientes com endometriose profunda presuntiva ou diag- nosticada, níveis de dor através de escala visual analógica (EVA) e Índice de Função Sexual Feminina (questionário IFSF) antes do i nício do tratamento. A análise estatística foi realizada utilizando o programa estatístico STATA, na versão 12.0 (StataCorp LLC, College Station, TX, USA), para comparar as variáveis por meio de regressão múltipla. Resultados A idade média foi de 39,2 anos; houve predominância de mulheres sintomáticas (92,5%) e da localização de lesões de endometriose profunda em retossigmoide (50%) seguida pela topogra fia retrocervical (48,3%). A pontuação total no IFSF mostrou uma mediana de 23,4, e em 67,2% das mulheres a pontuação foi /C20 26,55 ( cut-off que indica disfunção sexual). Dispareunia ( p ¼ 0.000, intervalo de confiança [IC]: 0.64 –0.83) e lesão endometriótica em retossigmoide ( p ¼ 0.008, IC: 0.72–0.95) exibiram uma relação estatisticamente signi ficante com valores baixos de pontuação no IFSF, ajustados por lesão em bexiga, idade da paciente e tamanho da lesão. A dispareunia de profundidade também mostrou correlação signi ficante com o domínio dor do IFSF ajustado por dor cíclica intestinal, lesão vaginal e uso de análogo de hormônio liberador de gonadotro fina (GnRH). Os resultados re fletem a in fluência da dispareunia de profundidade na disfunção sexual da população do estudo. Conclusão A maioria das pacientes apresentav a disfunção sexual e o sintoma mais relacionado a esta disfunção foi dispareunia de profundidade. Palavras-chave ► endometriose ► sexualidade ► endometriose profunda in filtrativa Rev Bras Ginecol Obstet Vol. 40 No. 3/2018 Female Sexual Function with Suspected Endometriosis Lima et al.116

The present prospective, observational and cross-sectional study was approved by the Brazilian national ethics committee. On their first appointment at the endometriosis and chronic pelvic pain outpatient clinic of Hospital do Servidor Público Estadual Francisco Morato de Oliveira (HSPE-FMO), 67 consecutive patients with clinical suspicion of DIE were invited to participate in this study from May of 2015 to August of2016. We included sexually active women of reproductive age with suspected DIE at gynecological examination, ultraso- nography (US) or magnetic resonance (MR) images and who agreed to participate in the study by signing an informed consent form. The participants were assured as to the confidentiality of the data and were informed they could withdraw their consent at any time. All women were treated by means of continuous con- traceptive or gonadotropin-releasing hormone (GnRH) ana- log to induce amenorrhea, and the surgical procedure was determined by non-responsive pain symptoms 1 or intestinal and urinary risk of complications. The surgical procedures were performed laparoscopically with the aim of complete resection of DIE ’s lesions and histological exam was con- ducted in all specimen. The exclusion criteria consisted of incomplete filling out of the sexual function questionnaire and the withdraw of the informed consent. We first collected data on the patients ’ age, number of pregnancies, surgical history of endometriosis, previous treatment, fertility condition, urinary and intestinal com- plains and pain symptoms: dysmenorrhea, dyspareunia and non-cyclic pelvic pain, which were quanti fied by means of the visual analog scale (VAS). Also, the characteristics of the endometriotic lesions on imaging tests (size, location and degree of in filtration) were described and classi fied preoperatively according to the ENZIAN classi fication, as it affords a satisfactory morphological description per affected compartment and lesion size. 8 At first, before any surgical treatment, the participants filled out the FSFI questionnaire; some of them had already received clinical treatment previously but that information was taken into account as a possible confounding factor toward statistical analysis. The FSFI is a short, speci fica n d multidimensional scale, previously adapted to the Portu- guese language, with signi ficant reliability and validity, 21 which transforms subjective assessments into objective, quantifiable and analyzable data. 23 The FSFI includes 19 questions corresponding to 6 domains — desire, arousal, lubrication, orgasm, satisfaction and pain or discomfort; the questions are scored from 0 to 5. We calculated the overall score by adding the scores of the individual items in each domain, then we multiplied the sum by the domain factor— provided by the scale authors— and finally added the six domain scores. The overall score might vary from 2 to 36, being that the higher the score the better the sexual func - tion. 21,22 Scores equal to or lower than 26.55 indicate sexual dysfunction.29 The collected data were entered in a Microsoft Excel for Windows spreadsheet (Microsoft Corp., Redmond, WA, USA). The statistical software STATA version 12.0 (StataCorp LLC, College Station, TX, USA) was used to perform descriptive and comparative analysis by means of Poisson ’so rl o g i s t i cr e - gression to investigate the correlation of the epidemiological and clinical data with the scores on the FSFI. The categorical variables were expressed as percentages and the numerical ones as mean and standard deviation, when parametric distribution was observed, or as median and quartiles when their distribution was nonparametric. For the logistic and Poisson regression models, we employed the forward stepwise method to select the varia- bles potentially correlated with the outcomes. After univari- ate correlation analysis, the variables with p /C20 0.20 or others with clinical relevance were selected to perform the multiple regressions. To improve the model fit, the signi ficance level for the final correlations and adjusted multiple analysis was set at p /C20 0.05 with 95% con fidence interval (CI). We sub- jected the final models to reliability tests to establish their goodness-of-fit, to wit, the Hosmer-Lemeshow test was used for the logistic regression model and the Pearson goodness- of-fit test for the Poisson regression model.

From the 67 patients selected to participate in the study, none matched the exclusion criteria. Data corresponding to 67 women with age varying from 20 to 52 years old (mean: 39.19 /C6 6.67) were analyzed. Relative to the obstetrical history of the participants, 47.8% (32) had never been pregnant and 52.2% (35) had one to three children. The most prevalent delivery route was cesarean section, corre- sponding to 65.6% (21) of the cases, information that was found in patients ’ the medical records. About 19.4% (13) of the sample had history of miscarriage, and 52.2% (35) had history of infertility. Finally, 26.2% (17) of the participants had history of pelvic gynecological surgery. About 92.5% (62) of the participants were symptomatic, the median duration of symptoms being 84 months (24 – 120), that is, 7 years, varying from 1 to 420 months (35 years). The most prevalent symptoms included dysmenorrhea (94%), dyspareunia (71.2%) and non-cyclic pain (67.2%). The distribution of painful symptoms according to the VAS scores is described on ►Table 1 . Table 1 Distribution of painful symptoms on the VAS of w o m e nw i t hd e e pi nfiltrating endometriosis VAS Dysmenorrhea n (%) Dyspareunia n (%) Non-cyclic pain n (%) 0–4( m i l d ) 4( 6 ) 2 4( 3 6 . 9 ) 3 2( 4 7 . 8 ) 5–6 (moderate) 9 (13.5) 14 (21.5) 14 (20.9) 7–10 (severe) 54 (80.5) 29 (41.6) 21 (31.3) Abbreviations: n, number of subjects; p,p - v a l u e ;V A S ,v i s u a la n a l o g scale. Rev Bras Ginecol Obstet Vol. 40 No. 3/2018 Female Sexual Function with Suspected Endometriosis Lima et al. 117 Specific bowel and urinary symptoms were reported by the patients, and the most common clinical presentation of these specific symptoms is the non-cyclic variety: constipation (28.4%), non-cyclic dyschezia (20.9%), cyclic dyschezia (16.4%), non-cyclic abdominal bowel pain (16.4%), cyclic ab- dominal bowel pain (9%), non-cyclic hematochezia (7.5%), cyclic hematochezia (6%), non-cyclic urinary pain (3%), cyclic urinary pain (1.5%). About 28.4% of the sample reported constipation, with an average interval of 2.28 days between stools. Some patients (34.3%) were referred to the outpatient clinic already receiving treatment, which included combined oral contraceptives (COC) (17.9%), progestin alone (11.9%), and GnRH analog (4.5%). Sixty medical records had information on the localization of deep in filtrating endometriosis lesions by means of spe- cialized imaging tests, such as magnetic resonance imaging of the pelvis and transvaginal ultrasound with bowel prepa- ration. About 45% (27) of the sample exhibited lesions suspected of cystic ovarian endometriosis concomitant with bowel lesions, which were bilateral in 16.6% (9) of the cases. As to the distribution of lesions, 50% (30) were located on the rectosigmoid colon, 48.3% (29) in the retrocervical region, 11.7% (7) in the vaginal fornices, 8.3% (5) in the vaginal septum and 5.9% (3) on the bladder re flection. The mean size of the lesions was 2.3 cm (1.6 –3.0 cm), varying from 0.7 to 11.4 cm. Forty-nine cases could be classified according to the ENZIAN system ( ►Table 2 ). Lesions on the vaginal fornices, vagina or rectovaginal sep- tum were classi fied as ENZIAN stage A, retrocervical lesions as stage B and bowel lesions as stage C. About 80% (24) of the lesions reached the muscle layer of the affected bowel loop wall, while 20% extended into the submucosal layer. Most lesions (73.3%) affected up to 25% of the bowel loop circumference. The median overall score on the FSFI was 23.4 (18 –28.6); the proportion of cases with score /C20 26.55 was 67.2% (45). The domain scores were: desire 3 (2.4 –3.6), arousal 3.9 (2.7 – 4.5), lubrication 4.8 (3.3 –5.7), orgasm 4.4 (2.8 –5.6), satisfac - tion 4.8 (33.2 –5.2) and pain 3.6 (2 –5.2). We analyzed the correlation between predictor variables by means of multiple regression analysis to identify possible confounding factors and selected the ones with higher statistical signi ficance or better fit to the model, thus reduc - ing the odds of colinearity or confusion in the final model. Multiple logistic regression evidenced signi ficant correla- tion between dyspareunia and sexual dysfunction (FSFI score /C20 26.55) adjusted by lesion size and patients ’ age, as shown in ►Table 3 . The Poisson multiple regression detected signi ficant in- verse correlation of variables dyspareunia and rectosigmoid localization with higher overall score on the FSFI, adjusted by age, lesion size and presence of lesions in the bladder, as described in ►Table 4 . The Poisson multiple regression was also used to analyze the correlation between the study variables and sexual function domains — desire, arousal, lubrication, orgasm, satisfaction and pain or discomfort. No statistically signi fi- cant correlation was found between the selected predictor variables and desire, arousal, lubrication, orgasm or satisfac - tion. In turn, variable deep dyspareunia exhibited inverse correlation with higher score on the FSFI domain pain, adjusted by cyclic bowel pain, endometriosis lesion on the vaginal fornix and use of GnRH analog ( ►Table 5 ).

The average age of the patients in the present study corre- sponds to the age range in which endometriosis is usually diagnosed, that is, the fourth decade of life. 30,31 Relative to the obstetrical history, the prevalence of women with no previous pregnancy and primary or secondary infertility was Table 2 Distribution of deep in filtrating endometriosis lesions according to the ENZIAN classi fication Lesion size (cm) Grade Compartment AB C 33 1 4 5 Table 3 Multiple logistic regression of predictor variables and sexual dysfunction corresponding to patients with deep infiltrating endometriosis Variables Unadjusted analysis p (CI) Final adjusted model p (CI) Dyspareunia 0.002 (0.68 –3.01) 0.003 (2.75 –140.54) Lesion size 0.112 ( /C0 0.01–0.11) 0.052 (0.991.22) Age 0.225 ( /C0 0.02–0.12) 0.069 (0.99 –1.23) Abbreviations: CI, con fidence interval; p,p - v a l u e . Hosmer-Lemeshow ¼ 0.6255. Table 4 P o i s s o nm u l t i p l er e g r e s s i o na n a l y s i so fp r e d i c t o r variables and overall score on FSFI corresponding to patients with deep in filtrating endometriosis Variables Unadjusted analysis p (CI) Adjusted analysis p (CI) Dyspareunia 0.000 ( /C0 0.34–0.13) 0.000 (0.64 –0.83) Rectosigmoid lesion 0.041 ( /C0 0.21–0.00) 0.008 (0.72 –0.95) Bladder reflection lesion 0.052 ( /C0 0.35–0.00) 0.151 (0.43 –0.13) Lesion size 0.059 ( /C0 0.007–0.00) 0.470 (0.99 –1.00) Age 0.067 ( /C0 0.01–0.00) 0.174 (0.98 –1.00) Abbreviations: CI, con fidence interval; FSFI, female sexual function index; p,p - v a l u e . Pearson goodness-of- fit ¼ 0.2304. Rev Bras Ginecol Obstet Vol. 40 No. 3/2018 Female Sexual Function with Suspected Endometriosis Lima et al.118 high, which might be explained by the effect of immune cells and the hostile environment caused by the disease. 32 As the sample was composed of women cared for at an outpatient clinic for treatment of chronic pelvic pain, the high prevalence of symptomatic patients (92.5%) is easy to understand. In the present study, the prevalence of dysmenorrhea and dyspareunia was 94% and 71.2%, respectively. These rates are much higher than the ones reported by Bellelis et al (2010);29 however, these authors only considered severe painful symptoms. Despite the low prevalence, speci fic bowel and urinary symptoms were also reported by the patients. As the present study also shows, bowel complaints are common manifestations among patients with DIE and might interfere with the bowel function; 2 and overall quality of life and sexual function·. We were not able to establish a direct relationship between lesion size or location and FSFI scores indicative of sexual dysfunction, which agrees with reports by other authors. 11 As concerns the negative impact of symptoms on the female sexual function, the prevalence of sexual dysfunction among the patients with suspected or confirmed diagnosis of DIE was 67.2%. In the studies by Di Donato et al (2014) 16 and Jia et al (2013), 33 this rate was 58% and 73%, respectively. We found a direct correlation between dyspareunia and sexual dysfunction, de fined as an FSFI score below 26.55. 29 In addition, we detected an inverse correlation between dyspareunia and bowel lesion with a higher FSFI score. The correlation is inverse in this case because higher FSFI scores indicate better sexual function, therefore, lesion size and dyspareunia correlated with lower scores, which is indicative of sexual dysfunction. Relative to the individual FSFI domains, our models detected a correlation between dyspar- eunia and the pain domain. It is a fact well established in the literature that the experience of pain is reinforced in subsequent intercourse experiences, which creates a cognitive pattern characterized by negative expectations, which in turn affects the sexual function and causes suffering, anguish or interpersonal difficulties, making the women unable to participate in intercourse as they would wish. 18,20,34,35 Rectosigmoid lesions are the most prevalent form of presentation of DIE and usually cause painful symptoms, and its prevalence might account for the inverse correlation found between FSFI scores and lesions in that location. We did not find a statistically signi ficant correlation between the analyzed predictor variables and the FSFI domains desire, arousal, lubrication, orgasm or satisfaction. Only the variable deep dyspareunia exhibited an inverse correlation with higher scores on the pain domain. Other authors observe that patients with endometriosis develop strategies to cope with pain due, for instance, to a desire to become pregnant, which may have increased the individual scores on the other FSFI domains. 36 The lack of information on the partners ’ or relationship status is a limitation of the FSFI. Further limitations of the present study derive from the lack of assessment of other factors, such as comorbidities, family and religious aspects, and the women ’s personal values, which determine their sexual choices and behaviors. In addition, the lack of randomization, the study design and the small sample size might limit the interpretation and external validity of the results of the present study. However, we have already developed a research line to continue the longitudinal investigation so as to compare the sexual func - tion outcomes before and after treatment for DIE, as the

might afford a better understanding of the effects of therapeutic interventions on the quality of the female sexual experience.

The results of the present study show that dyspareunia exerts a negative in fluence on the overall FSFI score and also on the pain domain. These findings reinforce the fact that female sexual dysfunction is a public health problem in women with suspected DIE, thus demanding special atten- tion from gynecologists. Conflicts to interest The authors declare that there are no con flicts of interest.

1 Abrão MS, Petraglia F, Falcone T, Keckstein J, Osuga Y, Chapron C. Deep endometriosis infiltrating the recto-sigmoid: critical factors to consider before management. Hum Reprod Update 2015;21 (03):329–339. Doi: 10.1093/humupd/dmv003 2 Wolthuis AM, Meuleman C, Tomassetti C, D’Hooghe T, de Buck van Overstraeten A, D ’Hoore A. Bowel endometriosis: colorectal surgeon’s perspective in a multidisciplinary surgical team. World J Gastroenterol 2014;20(42):15616 –15623. Doi: 10.3748/wjg. v20.i42.15616 3 Kennedy S, Bergqvist A, Chapron C, et al; ESHRE Special Interest Group for Endometriosis and Endometrium Guideline Develop- ment Group. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 2005;20(10):2698 –2704. Doi: 10.1093/humrep/dei135 4 Bricou A, Batt RE, Chapron C. Peritoneal fluid flow in fluences anatomical distribution of endometriotic lesions: why Sampson seems to be right. Eur J Obstet Gynecol Reprod Biol 2008;138(02): 127–134. Doi: 10.1016/j.ejogrb.2008.01.014 Table 5 Poisson multiple regression of predictor variables and domain pain in patients with deep in filtrating endometriosis Variables Unadjusted analysis p (CI) Adjusted analysis p (CI) Dyspareunia 0.000 (0.45 –0.75) 0.003 (0.49 –0.86) Cyclic bowel pain 0.065 (0.97 –2.12) 0.256 (0.84 –1.87) Lesion on vaginal fornix 0.152 (0.43 –1.13) 0.236 (0.46 –1.21) Use of GnRH analogue 0.159 (0.24 –1.25) 0.291 (0.06 –2.29) Abbreviations: CI, con fidence interval; GnRH, gonadotropin-releasing hormone; p,p - v a l u e . Pearson goodness-of- fit ¼ 0.99. Rev Bras Ginecol Obstet Vol. 40 No. 3/2018 Female Sexual Function with Suspected Endometriosis Lima et al. 119 5 Alkatout I, Egberts JH, Mettler L, et al. [Interdisciplinary Diagnosis and Treatment of Deep In filtrating Endometriosis]. Zentralbl Chir 2016;141(06):630–638. Doi: 10.1055/s-0034-1383272 6 Nácul AP, Spritzer PM. [Current aspects on diagnosis and treat- ment of endometriosis]. Rev Bras Ginecol Obstet 2010;32(06): 298–307. Doi: 10.1590/S0100-72032010000600008 7 Haas D, Chvatal R, Habelsberger A, Wurm P, Schimetta W, Oppelt P. Comparison of revised American Fertility Society and ENZIAN staging: a critical evaluation of classifications of endometriosis on the basis of our patient population. Fertil Steril 2011;95(05): 1574–1578. Doi: 10.1016/j.fertnstert.2011.01.135 8 Haas D, Wurm P, Shamiyeh A, Shebl O, Chvatal R, Oppelt P. Efficacy of the revised Enzian classi fication: a retrospective analysis. Does the revised Enzian classi fication solve the problem of duplicate classification in rASRM and Enzian? Arch Gynecol Obstet 2013; 287(05):941–945. Doi: 10.1007/s00404-012-2647-1 9 Guerriero S, Ajossa S, Orozco R, et al. Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in the rectosig- moid: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2016;47(03):281 –289. Doi: 10.1002/uog.15662 10 Medeiros LR, Rosa MI, Silva BR, et al. Accuracy of magnetic resonance in deeply in filtrating endometriosis: a systematic review and meta-analysis. Arch Gynecol Obstet 2015;291(03): 611–621. Doi: 10.1007/s00404-014-3470-7 11 Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Cro- signani PG. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod 2007;22 (01):266–271. Doi: 10.1093/humrep/del339 12 Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet 2010;27(08):441 –447. Doi: 10.1007/s10815-010-9436-1 13 Jacobson TZ, Barlow DH, Koninckx PR, Olive D, Farquhar C. Laparoscopic surgery for subfertility associated with endome- triosis. Cochrane Database Syst Rev 2002;(04):CD001398. Doi: 10.1002/14651858.CD001398 14 Vercellini P , Somigliana E, Buggio L, Barbara G, Frattaruolo MP , Fedele L. “I can’t get no satisfaction”: deep dyspareunia and sexual functioning in women with rectovaginal endometriosis. Fertil Steril 2012;98(06):1503–11.e1. Doi: 10.1016/j.fertnstert.2012.07.1129 15 Morsch DM, Carneiro MM, Lecke SB, et al. c -fos gene and protein expression in pelvic endometriosis: a local marker of estrogen action. J Mol Histol 2009;40(01):53–58. Doi: 10.1007/s10735-009-9212-7 16 Di Donato N, Montanari G, Benfenati A, et al. Do women with endometriosis have to worry about sex? Eur J Obstet Gynecol Reprod Biol 2014;179:69–74. Doi: 10.1016/j.ejogrb.2014.05.022 17 Jones G, Jenkinson C, Kennedy S. The impact of endometriosis upon quality of life: a qualitative analysis. J Psychosom Obstet Gynaecol 2004;25(02):123–133. Doi: 10.1080/01674820400002279 18 Pluchino N, Wenger JM, Petignat P, et al. Sexual function in endometriosis patients and their partners: effect of the disease and consequences of treatment. Hum Reprod Update 2016;22 (06):762–774. Doi: 10.1093/humupd/dmw031 19 Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999;281(06): 537–544. Doi: 10.1001/jama.281.6.537 20 Elmerstig E, Wijma B, Berterö C. Why do young women continue to have sexual intercourse despite pain? J Adolesc Health 2008;43 (04):357–363. Doi: 10.1016/j.jadohealth.2008.02.011 21 Leite APL, Moura EA, Salles AAS, Mattar R, Souza E, Camano L. Validation of the Female Sexual Function Index in Brazilian pregnant women. Rev Bras Ginecol Obstet 2007;29:396 –401. Doi: 10.1590/ S0100-72032007000800003 22 Hentschel H, Alberton DL, Capp E, Goldim JR, Passos EP. Validação do Female Sexual Function Index (FSFI) para uso em português. Rev HCPA 2007;27:10 –14 23 Rosen R, Brown C, Heiman J, et al. The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther 2000;26 (02):191–208. Doi: 10.1080/009262300278597 24 Thomassin I, Bazot M, Detchev R, Barranger E, Cortez A, Darai E. Symptoms before and after surgical removal of colorectal endo- metriosis that are assessed by magnetic resonance imaging and rectal endoscopic sonography. Am J Obstet Gynecol 2004;190 (05):1264–1271. Doi: 10.1016/j.ajog.2003.12.004 25 Van den Broeck U, Meuleman C, Tomassetti C, et al. Effect of laparoscopic surgery for moderate and severe endometriosis on depression, relationship satisfaction and sexual functioning: comparison of patients with and without bowel resection. Hum Reprod 2013;28(09):2389 –2397. Doi: 10.1093/humrep/det260 26 Crosignani PG, Luciano A, Ray A, Bergqvist A. Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain. Hum Reprod 2006; 21(01):248–256. Doi: 10.1093/humrep/dei290 27 Vercellini P, Pietropaolo G, De Giorgi O, Pasin R, Chiodini A, Crosignani PG. Treatment of symptomatic rectovaginal endome- triosis with an estrogen-progestogen combination versus low- dose norethindrone acetate. Fertil Steril 2005;84(05):1375 –1387. Doi: 10.1016/j.fertnstert.2005.03.083 28 Schlaff WD, Carson SA, Luciano A, Ross D, Bergqvist A. Subcuta- neous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-asso- ciated pain. Fertil Steril 2006;85(02):314 –325. Doi: 10.1016/j. fertnstert.2005.07.1315 29 Wiegel M, Meston C, Rosen R. The female sexual function index (FSFI): cross-validation and development of clinical cutoff scores. J Sex Marital Ther 2005;31(01):1–20. Doi: 10.1080/00926230590475206 30 Bellelis P, Dias JA Jr, Podgaec S, Gonzales M, Baracat EC, Abrão MS. Epidemiological and clinical aspects of pelvic endometriosis –a case series. Rev Assoc Med Bras 2010;56:467 –471. Doi: 10.1590/ S0104-42302010000400022 31 Arruda MS, Petta CA, Abrão MS, Benetti-Pinto CL. Time elapsed from onset of symptoms to diagnosis of endometriosis in a cohort study of Brazilian women. Hum Reprod 2003;18(04):756 –759. Doi: 10.1093/humrep/deg136 32 Giudice LC, Kao LC. Endometriosis. Lancet 2004;364(9447):1789- –1799. Doi: 10.1016/S0140-6736(04)17403-5 33 Jia SZ, Leng JH, Sun PR, Lang JH. Prevalence and associated factors of female sexual dysfunction in women with endo- metriosis. Obstet Gynecol 2013;121(03):601 –606. Doi: 10.1097/ AOG.0b013e3182835777 34 Lara LA, Rosa e Silva AC, Romão AP, Junqueira FR. [The assess- ment and management of female sexual dysfunction]. Rev Bras Ginecol Obstet 2008;30(06):312 –321. Doi: 10.1590/S0100- 72032008000600008 35 Mendonça CR, Silva TM, Arrudai JT, García-Zapata MTA, Amaral WN. Função sexual feminina: aspectos normais e patológicos, prevalência no Brasil, diagnóstico e tratamento. Femina 2012; 40:195–202 36 Evangelista A, Dantas T, Zendron C, Soares T, Vaz G, Oliveira MA. Sexual function in patients with deep in filtrating endometriosis. J Sex Med 2014;11(01):140 –145. Doi: 10.1111/jsm.12349 Rev Bras Ginecol Obstet Vol. 40 No. 3/2018 Female Sexual Function with Suspected Endometriosis Lima et al.120