{"paper_id":"962cd762-dead-457d-be69-76c099ddca86","body_text":"Nouri et al. Reproductive Biology and Endocrinology 2010, 8:85\nhttp://www.rbej.com/content/8/1/85\nOpen AccessRESEARCH\n© 2010 Nouri et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Com mons\nAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in\nany medium, provided the original work is properly cited.\nResearchFamily incidence of endometriosis in first-, second-, \nand third-degree relatives: case-control study\nKazem Nouri*1, Johannes Ott1, Birgitt Krupitz2, Johannes C Huber1 and Rene Wenzl3\nAbstract\nBackground: Initial publications examining the hereditary aspects of endometriosis appeared in the early seventies \nand demonstrated an up to seven-fold risk for endometriosis in first-degree relatives of endometriosis patients. The aim \nwas to evaluate the influence of hereditary aspects on the endometriosis risk in our patient collective.\nMethods: In a retrospective cohort study we evaluated the incidence of endometriosis among first-, second-, and \nthird-degree relatives of endometriosis patients and compare it with its incidence among first-, second-, and third-\ndegree relatives of patients without endometriosis.\nResult(s): Eighty patients in whom endometriosis had been confirmed laparoscopically and histologically by biopsy \nand 60 patients in whom no endometriosis had been found during laparoscopy were given a questionnaire about the \npresence of symptoms associated with endometriosis and its family incidence. Patients of both the endometriosis and \nthe control group were 37.7 ± 6.2 and 45.9 ± 12.0 years of age at the time of the interview, respectively (p < 0.05). \nInformation about the presence of endometriosis was more readily available for relatives of those in the endometriosis \ngroup than for those in the control group (325/749 [43.4%] vs. 239/425 [56.2%], p < 0.05). In 5/136 (3.7%) and 8/134 \n(6.0%) first-degree relatives of endometriosis patients and the control group, respectively, information about the \npresence of endometriosis was not available (p = 0.554). Endometriosis was found in 8/136 (5.9%) first-degree relatives \nof patients and in 4/134 (3.0%) first-degree relatives of controls in the real-case analysis (p = 0.248). When comparing \nendometriosis characteristics between endometriosis patients with and without a history of familial endometriosis, no \nsignificant differences were found.\nConclusion(s): There is a trend toward an increased familial incidence of endometriosis. In contrast to the literature, we \nfound a less dramatic increase in familial risk for the development of endometriosis.\nBackground\nEndometriosis is one of the most common gynecological\ndiseases, and occurs in 2-10% of women of reproductive\nage [1]. Symptoms include severe pelvic pain, dysmenor-\nrhoea, bladder and bowel discomfort, and infertility. To\ndate, very little is known about its etiology and pathogen-\nesis. Because a number of studies have demonstrated an\nincreased risk for developing the disease in mothers and/\nor sisters of patients, endometriosis likely has a genetic\nbasis [2-6].\nInitial publications examining the hereditary aspects of\nendometriosis appeared in the early seventies [3]. In\n1981, Simpson et al. were able to demonstrate that the\nrisk for endometriosis in first-degree relatives of endo-\nmetriosis patients is seven-fold compared to the normal\npopulation [4]. Five years later, only a four-fold increased\nrisk for developing the disease was estimated for mothers\nand sisters of an endometriosis patient. [5]. A study con-\nducted in twins demonstrated that the incidence of endo-\nmetriosis in monozygotic twins was twice that in\ndizygotic twins [6]. In addition, it has been shown that\nthe severity of endometriosis is higher among patients\nwith a positive family history [7]. Accordingly, one could\nconclude that if a woman has endometriosis, the risk that\nher first-degree relatives will also have endometriosis\ncould be anywhere from 4-7 times higher than that of the\ngeneral population [4,5].\nFor practical reasons, only a few studies have dealt with\nthe endometriosis incidence in second- and third-degree\nrelatives of endometriosis patients [8]. The purpose of\n* Correspondence: kazem.nouri@meduniwien.ac.at\n1 Department of Gynecologic Endocrinology and Reproductive Medicine, \nMedical University of Vienna, Vienna, Austria\nFull list of author information is available at the end of the article\n\nNouri et al. Reproductive Biology and Endocrinology 2010, 8:85\nhttp://www.rbej.com/content/8/1/85\nPage 2 of 7\nthis study was to evaluate the risk of familial endometrio-\nsis among first-, second-, and third-degree relatives of\nwomen with and without laparoscopically diagnosed\nendometriosis.\nMethods\nThe primary objective was to evaluate genetic predisposi-\ntion for endometriosis in a group of patients in whom\nendometriosis had been confirmed by laparoscopy and\nbiopsy (the study group), and to compare these results to\npatients in whom endometriosis had been ruled out by\nlaparoscopy (the control group). All procedures were car-\nried out according to the \"Good Scientific Practice\"\nguidelines set forth by the Medical University Vienna\nbased on the Helsinky declaration. Informed consent was\nobtained from all participants.\nPatient collective\nIn a retrospective control-group study, all infertile\nwomen who underwent gynecologic laparoscopy at the\nDepartment of Obstetrics and Gynecology of the Medical\nUniversity of Vienna, Vienna, Austria, between January\n2003 and December 2004 were included. Of a total of 318\npatients, 178 patients (56.0%) had to be excluded for the\nfollowing reasons: 163 patients were not willing to partic-\nipate in the study, or their contact addresses and phone\nnumbers were missing. In 15 patients, the endometriosis\nwas diagnosed only by laparoscopy without biopsy and\nhistological confirmation, and thus, these patients could\nnot be reliably assigned to one of the two groups.\nThe remaining 140 patients (44.0%) were assigned to\none of the two study groups: patients in whom endo-\nmetriosis had been confirmed laparoscopically and histo-\nlogically by biopsy (n = 80, endometriosis group); and\npatients in whom no endometriosis had been found dur-\ning laparoscopy (n = 60, control group). Patients in the\ncontrol group had been operated for various indications\nthat are listed in Table 1.\nStudy design\nClinical endpoints and parameters\nIn the course of a retrospective chart review, we focused\non the presence and severity of symptoms associated with\nendometriosis, including dyspareunia, chronic pelvic\npain, infertility, dysmenorrhea and pain at defecation.\nEndometriosis was classified according to the revised\nseverity score of the American Fertility Society (rAFS)\nclassification.\nPatients were contacted by telephone and, using the\nself-developed questionnaire, asked about gynecologic\ndiseases in all first-degree relatives (i.e., mother, sisters,\nand daughters), as well as in all second- and third-degree\nrelatives (aunts, cousins). Information about daughters\nwas included as of their 17\nth year of age onward since\nendometriosis is known to be hormonally influenced.\nThe maternal and the paternal lines of relatives were eval-\nuated separately. Information about grandmothers was\nexcluded from the study, since reliable information about\ntheir medical history could only be provided by a minor-\nity of patients. We focused on the following points when\nrequesting relatives' medical history: gynaecologic opera-\ntions and possible detection of endometriosis; and symp-\ntoms such as chronic pelvic pain, infertility, and\ndysmenorrhea. If the interviewees were not aware of this\ninformation, the answer on the questionnaire's was rated\nas \"unknown.\"\nPatients' relatives were considered to have endometrio-\nsis when the disease had been diagnosed by laparoscopy\nor laparotomy. A genetic predisposition to endometriosis\nwas assumed if, in addition to the endometriosis patient,\none other female family member was found to suffer from\nendometriosis.\nStatistical analysis\nVariables are described by frequencies and mean ± stan-\ndard deviation (SD). Statistical analysis was performed in\nSPSS 15.0.1 for Windows (SPSS Inc, 1989-2006). Contin-\ngency tables and chi-square analysis were used in order to\ncompare incidences between groups. The endometriosis\nincidences are presented as absolute risks (percentages);\nin order to compare the risks between groups, odds ratios\nwere calculated. All values are given with a 95% confi-\ndence interval (95% CI).\nSince exact information on the endometriosis-related\nmedical history was not available for all relatives\n(\"unknown\" answers in the completed questionnaire), the\nfamilial incidence of endometriosis in first-degree rela-\ntives was calculated using two different approaches: (a)\n\"real case analysis\": all family members with insufficient\ninformation about presence of endometriosis were rated\nas non-endometriotic subjects; (b) \"worst case analysis\":\nall relatives of endometriosis patients with insufficient\ninformation were rated as affected by endometriosis.\nSince, the number of relatives with incomplete informa-\ntion about endometriosis-related health issues increased\nwith the degree of relationship, a worst-case analysis was\nnot performed for second- and higher-degree relatives;\nTable 1: Indications for gynecologic laparoscopy in the \ncontrol group (n = 60)\nuterine leiomyoma 25 (41.7%)\novarian cysts or polycystic \novarian syndrome\n24 (40.0%)\nhydrosalpinx 8 (13.3%)\nuterine malformations 2 (3.3%)\novarian mass 1 (1.7%)\n\nNouri et al. Reproductive Biology and Endocrinology 2010, 8:85\nhttp://www.rbej.com/content/8/1/85\nPage 3 of 7\nthe incidence of relatives with endometriosis would have\nbeen inordinately high in the endometriosis group.\nResults\nPatients in the endometriosis (n = 80) and the control\ngroup (n = 60) were 37.7 ± 6.2 and 45.9 ± 12.0 years of age\nat the time of the interview, respectively (p < 0.05). The\ntotal number of first-, second-, and third-degree relatives\nwas 425 in the endometriosis group and 749 in the con-\ntrol group. The information about the presence of endo-\nmetriosis was more readily available for relatives of those\nin the endometriosis group than for relatives of those the\ncontrol group (325/749 [43.4%] vs. 239/425 [56.2%], p <\n0.05).\nIn order to rule out a bias based on family size and the\nnumber of affected family members, the study collective\nwas divided in two subgroups: families with four or less\nfemale family members who were affected; and families\nwith more than four affected female family members. The\nincidence of endometriosis was 13.0% and 17.6%, respec-\ntively. This difference was statistically not significant (p <\n0.05). Thus, it was assumed that family size had no major\ninfluence on the incidence of endometriosis.\nGeneral characteristics and information about the pres-\nence of symptoms associated with endometriosis are\nlisted in Table 2.\nTable 3 gives an overview of the incidence of endo-\nmetriosis in first-degree relatives of endometriosis\npatients and controls. In 5/136 (3.7%) and 8/134 (6.0%)\nfirst-degree relatives of endometriosis patients and the\ncontrol group, respectively, information about the pres-\nence of endometriosis was not available (p = 0.554).\nBy pooling all first-degree relatives, there was no signif-\nicant difference between relatives of patients and con-\ntrols: endometriosis was found in 8/136 (5.9%) first-\ndegree relatives of patients and in 4/134 (3.0%) first-\ndegree relatives of controls in the real-case analysis (p =\n0.248). The worst-case analysis revealed a higher inci-\ndence of endometriosis in first-degree relatives of\npatients (9.6%; 13/136) than in first-degree relatives of\ncontrols (3.0%; 4/134) (p = 0.042).\nDetails of real-case analysis in second- and third-degree\nrelatives are listed in Table 4. In the course of the inter-\nview, information about the presence of endometriosis\nwas evaluated separately for maternal and paternal sec-\nond- and third-degree relatives.\nBoth cases of endometriosis in aunts and cousins of the\ncontrol group were paternal relatives (2/2, 100%),\nwhereas 3/4 affected second- and third-degree relatives\n(2 aunts and 1 cousin) of endometriosis patients were\nmaternal relatives (3/4, 75.0%).\nA total of 12/80 endometriosis patients (15.0%) with\none relative suffering from endometriosis were found.\nThe family trees of these cases with familial clustering are\nshown in Figure 1.\nWhen comparing endometriosis characteristics\nbetween endometriosis patients with and without an\nincidence of familial endometriosis, no significant differ-\nences were found. Details are given in Table 5.\nDiscussion\nIn our data, a tendency toward increased risk of endo-\nmetriosis in first-degree relatives of endometriosis\npatients (5.9% vs. 3.0% in real-case analysis, odds ratio\n2.03) was found. However, this tendency did not reach\nstatistical significance (p < 0.05). This is in contrast to\nother studies that clearly demonstrate a stronger herita-\nbility [4,5,7-10]. Table 6 provides an overview of these\nresearch articles.\nThe first publication about this topic reported a seven-\nfold increased risk for the development of endometriosis\nin first-degree relatives of endometriosis patients in con-\ntrast to a control group [4]. The absolute risk of endo-\nmetriosis in patients' mothers and sisters was 8.1% and\n5.8%, respectively. Similarly, a Norwegian study, con-\nd u c t e d  b y  M o e n  a n d  M a n gu s  [ 7 ] ,  a l s o  s h o w e d  a  s ev e n -\nfold greater risk for endometriosis in first-degree relatives\nof endometriosis patients. One study examining only rel-\natives of patients with endometriosis reported even\nhigher rates: The authors found that even 22% of patients'\nsisters of reproductive age and 16% of the mothers had a\nsurgical diagnosis of endometriosis [11].\nConsidering the above-mentioned up to seven-fold\nincreased risk for the development of endometriosis in\nTable 2: Characteristics of endometriosis patients (n = 80)\nage at onset of \nendometriosis symptoms < \n25 years\n27 (33.8%)\nsevere endometriosis (rAFS\na \nIV)\n21 (26.3%)\ndysmenorrhea 66 (82.5%)\nsevere dysmenorrhea \n(V.A.S.** ≥ 7)\n20 (25.0%)\nchronic pelvic pain 16 (20.0%)\nsevere chronic pelvic pain \n(V.A.S.** ≥ 7)\n14 (17.5%)\ninfertility 43 (53.8%)\npain on defecation 29 (36.3%)\nsevere pain on defecation \n(V.A.S.** ≥ 7)\n21 (26.3%)\ndyspareunia 13 (16.3%)\nsevere dyspareunia (V.A.S.** \n≥ 7)\n24 (30.0%)\na rAFS = Revised American Fertility Society classification of \nendometriosis\n** V.A.S. = Visual analog score\n\nNouri et al. Reproductive Biology and Endocrinology 2010, 8:85\nhttp://www.rbej.com/content/8/1/85\nPage 4 of 7\nfirst-degree relatives of endometriosis patients, as well as\nthe life-time risk for endometriosis of about 10% in the\ngeneral female population, one would expect a clearly\nincreased rate of affected first-degree relatives of endo-\nmetriosis patients. However, this was not the case in our\nstudy collective. Notably, patients of the control group\nwere significantly older than the endometriosis patients\n(45.9 ± 12.0 vs. 37.7 ± 6. years) in our study collective. It\ncould be that the age-factor influenced the results of our\nstudy and contributed to the only slightly increased risk\nfor endometriosis in first-degree relatives of endometrio-\nsis patients. However, several probands of the non-endo-\nmetriosis group belonged to an older generation. A\ndetailed diagnostic work-up of endometriosis, which\nincluded diagnostic laparoscopy, was not routine then.\nThus, several cases of endometriosis may have remained\nundiagnosed. On the other hand, the greater age of the\ncontrols increased the possibility of having first-degree\nrelatives, especially daughters, thus potentially increasing\nthe number of first-degree relatives with endometriosis.\nTable 3: Incidence of endometriosis-affected first-degree relatives of endometriosis patients and controls\nReal-case analysis\nRelatives Endometriosis group \n(n = 80)\nControl group (n = \n60)\nOdds ratio\n[95% CI]*\nP-value\nMothers 5/80 (6.3%) 2/60 (3.3%) 1.93 [0.32; 14.98] n.s.+\nDaughters 0/9 (0%) 1/15 (6.2%) - n.s.+\nSisters 3/47 (6.4%) 1/59 (1.7%) 3.95 [0.35;100.59] n.s.+\nTotal 8/136 (5.9%) 4/134 (3.0%) 2.03 [0.54; 8.25] n.s.+\nWorst-case analysis\nRelatives Endometriosis group \n(n = 80)\nControl group (n = \n60)\nOdds ratio\n[95% CI]*\nP-value\nMothers 9/80 (11.3%) 2/60 (3.3%) 3.67 [0.70; 25.68] n.s.+\nDaughters 0/9 (0%) 1/15 (6.2%) - n.s.+\nSisters 4/47 (8.5%) 1/59 (1.7%) 5.40 [0.55; 129.08] n.s.+\nTotal 13/136 (9.6%) 4/134 (3.0%) 3.46 [1.01; 13.00] 0.042\n* 95% CI = 95% confidence interval;+ n.s. = not significant\nTable 4: Incidence of endometriosis-affected second- and third-degree relatives of endometriosis patients and controls\nRelatives Endometriosis group \n(n = 80)\nControl group (n = \n60)\nOdds ratio\n[95% CI]*\nP-value\nAunts 2/159 (1.3%) 1/127 (0.8%) 1.61 [0.11; 44.62] n.s.+\nCousins 2/139 (1.4%) 1/134 (0.8%) 1.94 [0.14; 54.00] n.s.+\nTotal 4/298 (1.3%) 2/261 (0.8%) 1.76 [0.28; 13.95] n.s.+\n* 95% CI = 95% confidence interval;+ n.s. = not significant\n\nNouri et al. Reproductive Biology and Endocrinology 2010, 8:85\nhttp://www.rbej.com/content/8/1/85\nPage 5 of 7\nHowever, as mentioned in the Results section, we ruled\nout the influence of family size on the incidence of endo-\nmetriosis. The difference in patients' and probands' age\nwas less than a whole generation. Thus, we consider it\nunlikely that age had any influence on the incidence of\nendometriosis in relatives.\nAnother factor that may have contributed to the mod-\nerate difference in endometriosis incidence between rela-\ntives of the patient and the control groups might be the\npatient selection method in our study. For the patient\ngroup, we chose endometriosis patients who presented at\nour department with infertility rather than chronic pelvic\npain. The control group, however, consisted of patients\nwho had undergone laparoscopy for reasons other than\ninfertility. Nonetheless, we compared endometriosis\npatients to patients without endometriosis and our study\ncollective might represent the general population more\naccurately than a study collective including patients with\nchronic pelvic pain.\nIn the worst-case analysis, we rated all first-degree fam-\nily members of endometriosis patients for whom the\nmedical history was unknown as \"affected by endometri-\nosis.\" Thus, we found a significantly higher endometriosis\nincidence in patients' relatives. However, the calculated\nFigure 1 Family tree of patients with a familial incidence of endo-\nmetriosis.\nFamily 1 Family 2 Family 3 \nFamily 11 \n \nFamily 4 \n \nFamily 5 \n \nFamily 6 \n \nFamily 10 \n \nFamily 7 \n \nFamily 8 \n \nFamily 9 \n \nFamily 12 \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n    = female;    = male;       =patient’s father;      = relative suffering from endometriosis \nthe arrows mark patients in whom endometriosis was confirmed by laparoscopy \nTable 5: Comparison of characteristics between endometriosis patients with and without familial clustering\npatients with a familial \nincidence (n = 12)\npatients without a familia \nincidence (n = 68)\nP-value\nage at onset of endometriosis \n< 25 years\n5/12 (41.7%) 22/68 (32.4%) n.s.*\nsevere endometriosis (rAFS** \nIV)\n5/12 (41.7%) 16/68 (23.5%) n.s.*\ndysmenorrhea 10/12 (83.3%) 56/68 (82.4%) n.s.*\nsevere dysmenorrhea \n(V.A.S.*** ≥ 7)\n4/12 (33.3%) 16/68 (23.5%) n.s.*\nchronic pelvic pain 3/12 (25.0%) 13/68 (19.1%) n.s.*\nsevere chronic pelvic pain \n(V.A.S.*** ≥ 7)\n4/12 (33.3%) 10/68 (14.7%) n.s.*\ninfertility 4/12 (33.3%) 39/68 (57.4%) n.s.*\npain on defecation 3/12 (25.0%) 26/68 (38.2%) n.s.*\nsevere pain on defecation \n(V.A.S.*** ≥ 7)\n8/12 (66.6%) 13/68 (19.1%) n.s.*\ndyspareunia 3/12 (25.0%) 10/68 (14.7%) n.s.*\nsevere dyspareunia\n(V.A.S.*** ≥ 7)\n4/12 (33.3%) 20/68 (29.4%) n.s.*\n* n.s. = not significant\n** rAFS = Revised American Fertility Society classification of endometriosis\n*** V.A.S. = Visual analog score\n\nNouri et al. Reproductive Biology and Endocrinology 2010, 8:85\nhttp://www.rbej.com/content/8/1/85\nPage 6 of 7\nodds ratio of 3.5 was still lower than that reported in the\nliterature.\nTaking all these considerations together, we consider\nour results sound. Thus, the familial incidence of endo-\nmetriosis demonstrated in our study supports the theory\nthat a genetic predisposition is only a contributing factor\nfor the development of endometriosis. As known from\ntwin-studies, endometriosis seems to have a genetic\nbasis: increased concordance rates for endometriosis of\n75% and 88% in monozygous twins have been demon-\nstrated [12]. However, since we found a moderately\nincreased risk for first-degree relatives, with an odds ratio\nof about 2, genetics may play a less important role than\npreviously thought. Thus, the cause of the development\nof endometriosis is likely mo re multifactorial. Life-style,\nthe use of hormonal contraceptives, nutrition, age at first\nand/or last pregnancy, and other factors, may contribute\nto the disease. Furthermore, it might be argued that in\nfamilies with affected members there is a greater aware-\nness about endometriosis, which might lead to a more\ninvasive diagnostic work-up, including diagnostic lap-\naroscopy, which has been suggested [13]. This might also\ncontribute to the higher rates of affected relatives of\nendometriosis patients in other studies.\nMost of the reported studies have not evaluated the\nincidence of endometriosis in second- and third-degree\nrelatives, since the patients' information on the medical\nhistory of these relatives was considered unreliable. Nota-\nbly, Lamb et al. reported an endometriosis incidence\n(absolute risk) in second-degree relatives of endometrio-\nsis patients, specifically, the patients' aunts and grand-\nmothers, of 1.9% [5]. Despite the fact that we did not\nevaluate the rate of endometriosis in patients' grand-\nmothers in our study collective, we found a similar endo-\nmetriosis incidence in second-degree relatives of 1.3%. In\n1999, a Brazilian study evaluated the risk for endometrio-\nsis in third-degree relatives, for the first time, and\nreported an incidence of 2.4% [8]. With regard to second-\nand third-degree relatives, there were no differences in\nthe endometriosis incidences between the patient and the\ncontrol groups. Interestingly, 3/4 cases of endometriosis\nin second- and third-degree relatives of the endometrio-\nsis group were maternal relatives in contrast to 0/2 in the\ncontrol group. This finding is clearly consistent with a\ngenetic basis for the incidence of familial endometriosis.\nSeveral studies have shown higher severity scores of\nendometriosis-associated symptoms in patients with a\nfamily history of endometriosis [14]. In our study, endo-\nmetriosis patients with a greater familial incidence of\nendometriosis than other endometriosis patients suffered\nfrom severe endometriosis (41.7% vs. 23.5%), severe\nchronic pelvic pain (33.3% vs 14.7%), and severe pain on\ndefecation (66.6% vs. 19.1%). However, this may be due to\nthe low sample size, and thus, these differences were not\nstatistically significant. In addition, more patients with a\ngreater familial incidence of endometriosis showed an\nearly age at onset of < 25 years (41.7% vs. 32.4%). These\nfindings all support the theory of a polygenous hereditary\nsystem.\nThe fact that all patients from the control group were\nproven laparoscopically not to be affected by endometri-\nosis is a major strength of our study. This is in contrast to\nother studies that did not include patients for whom\nendometriosis had been ruled out by laparoscopy as con-\ntrol groups [4,8,9,15]. The sub- analysis of patients with a\ngreater incidence of endometriosis versus patients with-\nout a familial incidence of endometriosis seems under-\npowered. A surgical diagnosis of the disease was not per-\nformed in the relatives and, then, several cases of endo-\nmetriosis may have remained undiagnosed. We consider\nthis a limitation of the study.\nSeveral genetic studies aiming to discover the genes\ninvolved the susceptibility to endometriosis are ongoing.\nFuture genomic studies may lead to new non-invasive\nd i a g n o s t i c  s t r a t e g i e s  a s  w e l l  a s  p o s s i b l e  n e w  t h e r a p i e s .\nThese data will hopefully improve our understanding of\nthe etiology of endometriosis [16].\nTable 6: Overview of research on the familial incidence of endometriosis in first-degree relatives\nStudy Endometriosis group \n(absolute risk)\nControl group \n(absolute risk)\nOdds ratio\n[95% CI]*\nP-value\nSimpson et al. [4] 6.9% 0.9% 7.7 [1.7; 48.6] < 0.005\nMoen & Magnus [7] 3.9% - 4.8% 0.6% - 0.7% 7.2 [2.1; 24.3] < 0.01\nCoxhead & Thomas [9] 5.8% 0.8% 7.9 [1.5; 55.7] < 0.01\nLamb et al. [5] 4.9% ~ 1.0% ~ 5.0 unknown\ndos Reis et al. [8] 8.6% 0% - < 0.01\nNouri et al. 6.3% 3.3% 1.9 [0.3; 15.0] n.s. *\n* n.s. = not significant\n\nNouri et al. Reproductive Biology and Endocrinology 2010, 8:85\nhttp://www.rbej.com/content/8/1/85\nPage 7 of 7\nConclusion\nIn summary, our case-control study demonstrates a trend\ntoward greater familial incidences of endometriosis. In\ncontrast to the literature, we found a less dramatic\nincrease in familial risk for the development of endo-\nmetriosis.\nCompeting interests\nThe authors declare that they have no competing interests.\nAuthors' contributions\nKNO performed analysis and reporting of the study. BKZ performed acquisition\nof the data presented in Tables 1, 2, 3, 4, 5 and Figure 1. JOH performed acquisi-\ntion of the data presented in Tables 6 and analysis. JCH organized the program.\nRWL performed revision of the manuscript. All authors read and approved the\nfinal manuscript.\nAuthor Details\n1Department of Gynecologic Endocrinology and Reproductive Medicine, \nMedical University of Vienna, Vienna, Austria, 2LKH Gmunden, Upper Austria, \nAustria and 3Department of Gynecology and Gynecologic Oncology, Medical \nUniversity of Vienna, Vienna, Austria\nReferences\n1. Eskenazi B, Warner ML: Epidemiology of endometriosis.  Obstet Gynecol \nClin North Am 1997, 24:235-238.\n2. Bischoff F, Simpson JL: Heritability and molecular genetic studies of \nendometriosis.  Hum Reprod Update 2000, 6:37-44.\n3. Ranney B: Endometriosis. IV. Hereditary tendency.  Obstet Gynecol 1971, \n37:734-737.\n4. Simpson JL, Elias S, Malinak LR, Buttram VC: Heritable aspects of \nendometriosis. 1. Genetic studies; 2. Clinical Characteristics of familial \nendometriosis.  Am J Obstet Gynecol 1980, 154:596-601.\n5. Lamb RNK, Hoffmann R, Nichols TR: Family trait analysis: A case-control \nstudy of 43 women with endometriosis and their best friends.  Am J \nObstet Gynecol 1986, 154:596-601.\n6. Treloar SA, O'Connor DT, O'Connor VM, Martin NG: Genetic influences on \nendometriosis in an Australian twin sample.  Fertil Steril 1999, \n71:701-710.\n7. Moen MH, Magnus P: The familial risk of endometriosis.  Acta Obstet \nGynecol Scand 1993, 72:560-564.\n8. dos Reis RM, de Sá MF, de Moura MD, Nogueira AA, Ribeiro JU, Ramos ES, \nFerriani RA: Familial risk among patients with endometriosis.  J Assist \nReprod Genet 1999, 16:500-503.\n9. Coxhead D, Thomas EJ: Familial inheritance of endometriosis in a British \npopulation. A case control study.  J Obstet Gynaecol 1993, 13:42-44.\n10. Bischoff F, Simpson JL: Genetic Basis of Endometriosis.  Ann NY Acad Sci \n2004, 1034:284-299.\n11. Hull DB, Gibson C, Hart A, Dowsett S, Meade M, Ward K: The heritability of \nendometriosis in large Utah families.  Fertil Steril 2002, 77(suppl 2):S21.\n12. Hadfield RM, Mardon HJ, Barlow DH, Kennedy SH: Endometriosis in \nmonozygotic twins.  Fertil Steril 1997, 68:941-942.\n13. Guo SW: Epigenetics of endometriosis.  Mol Hum Reprod 2009, \n15:587-607.\n14. Malinak LR, Buttram VC, Elias S, Simpson JL: Heritable aspects of \nendometriosis II Clinical characteristics of familial endometriosis.  Am J \nObstet Gynecol 1980, 137:332-337.\n15. Kashima K, Ishimaru T, Okamura H, Suginami H, Ikuma K, Murakami T, \nIwashita M, Tanaka K: Familial risk among Japanese patients with \nEndometriosis.  Int J Gynaecol Obstet 2004, 84:61-64.\n16. Hansen KA, Eyster KM: Genetics and genomics of endometriosis.  Clin \nObstet Gynecol 2010, 53:403-412.\ndoi: 10.1186/1477-7827-8-85\nCite this article as: Nouri et al., Family incidence of endometriosis in first-, \nsecond-, and third-degree relatives: case-control study Reproductive Biology \nand Endocrinology 2010, 8:85\nReceived: 12 May 2010 Accepted: 11 July 2010 \nPublished: 11 July 2010\nThis article is available from: http://www.rbej.com/content/8/1/85© 2010 Nouri et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Reproductive Biology and Endocrinology  2010, 8:85","source_license":"CC0","license_restricted":false}