{"paper_id":"1bc87468-53db-4a64-8dd7-f60a1c5be9cb","body_text":"Sonomorphologic Changes in Colorectal Deep Endometriosis: The\nLong-Term Impact of Age and Hormonal Treatment\nSonomorphologische Veränderungen bei tief-infiltrierender\nkolorektaler Endometriose: Der Langzeiteffekt von Alter und\nhormoneller Therapie\nAuthors\nSimon Keckstein 1 , Juergen Dippon 2, Gernot Hudelist 3, Philippe Koninckx 4, George Condous 5, Lennard Schroeder 1,\nJoerg Keckstein 6, 7, 8\nAffiliations\n1 Department of Obstetrics and Gynecology, LMU University\nH o s p i t a l ,M u n i c h ,G e r m a n y\n2 Institute for Stochastics and Applications, University of\nStuttgart, Stuttgart, Germany\n3 Gynaecology, Hospital St. John of God, Vienna, Austria\n4 Department for Gynecology , Latifa Hospital, Dubai,\nUnited Arab Emirates\n5 Acute Gynecology, Early Pregnancy & Advanced\nEndoscopic Surgery Unit, University of Sydney - Sydney\nMedical School Nepean, Sydney, Australia\n6 (SEF), Stiftung Endometrioseforschung, Westerstede,\nGermany\n7 Gynecological Clinic, Gynecological Clinic Drs Keckstein,\nVillach, Austria\n8 Department of Obstetrics and Gynecology, Ulm University\nHospital, Ulm, Germany\nKey words\ndeep infiltrating endometriosis, transvaginal sonography,\nhormonal therapy, bowel endometriosis, long-term observa-\ntion\nreceived 8.8.2023\naccepted after revision 6.11.2023\npublished online 15.12.2023\nBibliography\nUltraschall in Med 2024; 45: 285 –292\nDOI 10.1055/a-2209-5653\nISSN 0172-4614\n© 2023. Thieme. All rights reserved.\nGeorg Thieme Verlag KG, Rüdigerstraße 14,\n70469 Stuttgart, Germany\nCorrespondence\nDr. Simon Keckstein\nDepartment of Obstetrics and Gynecology, LMU University\nHospital, Marchioninistraße 15, 81377 Munich, Germany\nsimon.keckstein@med.uni-muenchen.de\nAdditional material is available at https://doi.org/\n10.1055/a-2209-5653.\nABSTRACT\nPurpose The progression of deep endometriosis (DE) in wom-\nen of reproductive age is highly variable. This study aimed to\nanalyze the sonomorphological changes of rectal endome-\ntriosis over long periods of time and the influence of hormo-\nnal treatment.\nMethods This retrospective study included premenopausal\nwomen with rectal DE treated conservatively between 2002\nand 2021. The lesion length and thickness of the nodule\nwere evaluated at regular intervals over time. We created sta-\ntistical models with mixed effects to identify potential factors\ninfluencing lesion progression and regression.\nResults 38 patients were monitored over a mean period of 7.2\n(± 4.2) years with a mean of 3.1 (± 2.1) check-ups within the\nobservation period. We detected a significant increase in le-\nsion length until the end of the fourth decade of life. In addi-\ntion, we found a substantial decrease in the length and thick-\nness of the nodule depending on the length of hormonal\ntreatment.\nConclusion In conservatively managed patients with rectal\nendometriosis, without hormonal therapy, lesion size can ex-\nhibit a moderate increase up to the end of the fourth decade\nof life, after which it appears to stabilize. This increase does\nnot follow a linear pattern. Hormonal therapy is crucial in im-\npeding further progression, resulting in either a cessation or a\nregression of lesion growth.\nZUSAMMENFASSUNG\nZiel Das Wachstumsverhalten tie f-infiltrierender Endome-\ntriose bei Frauen im reproduktionsfähigen Alter variiert stark.\nZiel dieser Studie war es, die sonomorphologischen Verände-\nrungen einer rektalen Endometriose im zeitlichen Verlauf zu\nanalysieren und den Einfluss einer Hormontherapie zu unter-\nsuchen.\nMaterial und Methoden In dieser retrospektiven Studie wur-\nden prämenopausale Frauen mit rektosigmoidaler Endome-\ntriose eingeschlossen, die zwischen 2002 und 2021 primär\nkonservativ behandelt wurden. Hierzu wurden Länge und\nDicke der Herde in regelmäßig en Abständen sonographisch\ngemessen. Um Faktoren zu identifizieren, welche das Wach-\nOriginal Article\n285Keckstein S et al. Sonomorphologic Changes in … Ultraschall in Med 2024; 45: 285 –292 | © 2023. Thieme. All rights reserved.\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\nArticle published online: 2023-12-15\n\nstumsverhalten beeinflussen könnten, wurden „Mixed-ef-\nfect“-Modelle zur statistischen Analyse angewandt.\nErgebnisse Achtunddreißig Patientinnen wurden über einen\nZeitraum von 7,2 (± 4,2) Jahren mit einer durchschnittlichen\nAnzahl von 3,1 (± 2,1) Untersuchungen überwacht. Wir konn-\nten eine signifikante Zunahme der Herdlängen bis zum Ende\ndes vierten Lebensjahrzehnts feststellen. Abhängig von der\nDauer der Hormonbehandlung zeigte sich eine signifikante\nAbnahme der Länge und Dicke der Herde.\nSchlussfolgerung Bei konservativ behandelten Patientinnen\nmit rektosigmoidaler Endometriose, ohne hormonelle Thera-\npie, kann die Größe der Läsionen bis zum Ende des vierten Le-\nbensjahrzehnts moderat zunehmen. Danach scheint diese\nsich zu stabilisieren. Die hormonelle Therapie kann eine wei-\ntere Progression des Wachstums verhindern und führt bei län-\ngerer Einnahme sogar zu einer Regression der Herde.\nIntroduction\nThe natural history of deep endometriosis in reproductive-aged\nwomen is unclear [1] since the pathophysiology of onset and\ngrowth are unclear [2, 3]. Deep endometriosis lesions are less fre-\nquent and smaller in adolescence. Therefore, the lesions must\nhave grown after initiation, at least for a certain period of time.\nHowever, growth itself has not been documented, and growth\nmight be self-limiting, as suggested by the volumes of deep endo-\nmetriosis lesions at different ages [4].\nAlthough imaging of DE by magnetic resonance imaging (MRI)\nor transvaginal ultrasound (TVS) has been established as a reliable\nand accurate diagnostic method to measure deep endometriosis\n[5, 6], sequential measurements over longer periods of time in\nwomen not undergoing surgery have not been performed, except\nto evaluate the effect of medical therapy.\nDeep endometriosis is treated by medical therapy or surgical\nexcision [7]. Medical therapy is often the first line of therapy to\navoid often difficult and complication-prone surgery. If pain\nsymptoms are sufficiently reduced, this therapy can be continued\nfor longer. It was estimated that some two-thirds of patients can\nbe managed by medical therapy [8]. It is equally well documented\nthat during medical therapy, lesions regress. Fedele et al. ob-\nserved no relevant progression of colorectal DE lesions in most\nasymptomatic and untreated women over six years using trans-\nrectal sonography [9]. Barra and colleagues observed a significant\nreduction in the volume of the nodule during the administration\nof dienogest [10]. Netter et al. demonstrated that the length of\namenorrhea, induced through hormonal intake or pregnancy, cor-\nrelated with regression of the size of rectal DE [1].\nHowever, endometriosis lesions are biochemically heteroge-\nneous with a variable degree of aromatase activity and progester-\none resistance. This might explain why some 10 % of women do\nnot respond and 20 % respond poorly to medical therapy [11]. It\nis unclear whether a decrease in the nodule volume and symptom\nrelief correlate. Abrao et al. found that pain symptoms correlate\nwith the sonographic dimensions of DE [6]. Since some o ccasional\nnodules were observed to progress during medical therapy, ex-\nplained by the variable response and the biochemical heterogene-\nity, follow-up with US was recommended [6].\nThere are no data on the growth or microscopic changes of DE\nmanaged without treatment [10, 12].\nSince data of longitudinal follow-up range from 6 months to 10\nyears, we decided to review our patients managed conservatively\nwithout surgery with a follow-up of up to 18 years.\nPatients and methods\nStudy design\nThe study was conducted as a monocentric case series of all wom-\nen with deep endometriosis of the rectum not undergoing sur-\ngery and managed conservatively. Informed consent about the\nanonymous use and publication of the data was obtained.\nThe ethical committee approved the study (approval number\nS2022–16) on the August 10, 2022.\nStudy population and data collection:\nThe inclusion criteria were women with deep infiltrating endome-\ntriosis of the rectum followed up clinically and by US by JK at the\ntertiary center between July 2002 and May 2021. Patients were\nseen at irregular intervals. Their symptoms, the type and duration\nof hormone intake, possible pregnancies and interventions, and\nDE dimensions were documented. For data analysis, every visit\nwas screened, but only those in which there were changes com-\npared to the previous visit were included in the study.\nTransvaginal examination followed a standardized protocol.\nThe typical transvaginal sonogr aphic pattern of rectal endome-\ntriosis is a hypoechogenic widening of the muscle layer, visualized\nin the sagittal plane ( ▶ Fig. 1) and documented photographically.\nThe rectosigmoid was also inspected caudally and cranially to the\nlesion to identify or exclude additional separate lesions. The meas-\nurement included the length of the nodule, measured between\nthe cranial and caudal poles of the nodule, where the musculature\npattern looks normal. The thickness measurement was perpendi-\ncular to the length measurement and was taken at the widest part\nof the lesion [13, 14, 15]. The individual measurements of nodule\nlength and thickness for each patient over time are depicted in\n▶ Fig. 2. TVS was performed using the ultrasound device Sonoace\nSA-X8LV-GER (Samsung Medison Co. Ltd.; Seoul, South Korea)\nwith a 5.0 –9.0 MHz transvaginal probe and the ultrasound device\nSamsung WS80A (Samsung Medison Co. Ltd.; Seoul, South Korea)\nwith a 5.0 –9.0 MHz transvaginal probe.\nThe results were also classified using the Enzian and #Enzian\nclassification, whereby only the C-compartment was calculated\nfor the study [16].\n286 Keckstein S et al. Sonomorphologic Changes in … Ultraschall in Med 2024; 45: 285 –292 | © 2023. Thieme. All rights reserved.\nOriginal Article\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\nStatistical analysis\nData collection and management for this paper were performed\nusing the OpenClinica open-source software (Version 3.1, Copy-\nright OpenClinica LLC and coll aborators, Waltham, MA, USA,\nwww.OpenClinica.com). The data set for this analysis can be\nfound in the online supplement.\nTo model the temporal development of the length and thick-\nness of the lesions, we fitted mixed-effects models using the cu-\nmulative duration of hormone treatment (CDHT) up to the con-\nsidered visit and associated age as explanatory variables. To be\nmore precise, lesion size is assumed to be the sum of a random\neffect for each individual, a quadratic function of CDHT, a cubic\nfunction of age, and a residual error for each observation. The ran-\ndom effect allows us to adjust for the serial correlation of the\nmeasurements within each patient and each patient ’ss t a r t i n g\nsize of the lesion. The choice of a quadratic function in CDHT re-\n▶ Fig. 2 These charts show each patient ’s development of nodule length and thickness with increasing age. Periods without hormone treatment\nare depicted with dashed lines.\n▶ Fig. 1 The sonographic image shows sample images of rectal endometriosis in three different patients. Measurement of length (D1) and thick-\nness (D2).\n287Keckstein S et al. Sonomorphologic Changes in … Ultraschall in Med 2024; 45: 285 –292 | © 2023. Thieme. All rights reserved.\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\nflects the expectation that the longer the treatment, the stronger\nits impact on lesion size, possibly non-linearly. The cubic function\ncan model the hypothesis that lesion size may initially increase\nwith age and then stagnate or even decrease. To interpret the fit-\nted model, it is preferable to represent the quadratic (cubic) func-\ntion as a weighted sum of two positive quadratic (three positive\ncubic) hat-shaped basis funct ions of CDHT (age), see panel A1\n(A2) in supplementary fig. 1 . Technically speaking, the quadratic\n(cubic) functions in our models are represented as B-splines of or-\nder 2 (3); see panel B1 (B2) in the supplementary fig. 1 and for\nmore details, see [17]. We have also made the data set available\nin supplementary table 1 .\nData processing and statistical analysis were performed using\nthe statistical programming environment R, version 4.1.2 [18]\nand R-libraries lme4 and lmerTest to fit and evaluate random ef-\nfects models.\nResults\nOur study included 38 premenopausal women with a mean age at\nfirst examination of 34.28 years. The average observation time\nwas 7.24 years. Data points of an average of 3.10 examinations\nper patient were considered during the observation period. Twen-\nty women had at least one previous gynecological operation be-\nfore the first presentation (rectal endometriosis operation exclud-\ned). Only four women had been successfully pregnant before the\nprimary presentation, and 18 were under hormonal treatment at\nthe first visit. During the observational period, 14 women under-\nwent surgery (rectal endometriosis operation excluded), 11 had\nbeen pregnant, and 15 were under hormonal treatment at their\nlast visit ( ▶ Table 1).\nAll women only had one rectal nodule detected sonographical-\nly. The average nodule length at the first visit was 23.26 mm, and\nthe average length at the last v isit regressed to 22.53 mm. The\naverage nodule thickness at the first visit was 10.55 mm. Also,\nthe thickness regressed slightly at the last visit to an average of\n8.81 mm. Accordingly, there wer e hardly any changes in the C-\ncompartment of the #Enzian classification ( ▶ Table 2).\nTo study the influence of age and duration of hormone treat-\nment (CDHT) on lesion size, we fitted mixed-effects models to\nour data. Since our data contain long-term observations, it is to\nbe expected that age and duration of hormone treatment will\nhave a non-linear effect on the temporal development of the le-\nsion size.\nAs some women were successfully pregnant between two vis-\nits and subsequently started hormone therapy again (and there\nwas no visit during the pregnancy), we decided not to include\nthe pregnancy factor in our calculations to avoid possible misin-\nterpretation. Our model based on rectal nodule length has a sig-\nnificant negative correlation with CDHT. Furthermore, there is a\nsignificant positive correlation with age, where an increase in the\nlength of the lesion until the 4th decade of life can be seen with a\nstabilization effect of length afterwards ( ▶ Table 3). Regarding\nthe thickness of rectal endometriosis, only CDHT shows a signifi-\ncant negative correlation. Age does not seem to influence nodule\nthickness ( ▶ Table 3) significantly.\nDiscussion\nRectal endometriosis is a deeply infiltrating form of the disease.\nT h eo r i g i na n dt h er e a s o nf o rt h es p e c i f i cl o c a t i o no ft h i sf o r m ,\nand especially the time at which the rectal lesion started, have\nnot been clarified yet [4]. The extensive fibroblastic reaction with\n▶ Table 1 Characteristics of the study population. For numerical\nvariables, the mean and standard deviations are given. For classifi-\ncation, frequencies and, in brackets, relative frequencies are shown.\nCharacteristics of the study population\nNumber of patients 38\nMean age at first visit in years 33.60 ± 6.21\nMean age at last visit in years 40.85 ± 5.96\nMean time of observation in years 7.24 ± 4.21\nMean number of included visits 3.10 ± 2.16\nWomen with a\nprevious gynecological operation\n20 (52.6 %)\nWomen with operations during the observa-\ntional period\n14 (36.8 %)\nWomen with previous pregnancies 4 (10.5 %)\nWomen who got pregnant during the ob-\nservational period\n11 (28.9 %)\nHormone intake at first visit 18 (47.3 %)\nHormone intake at last visit 15 (39.4 %)\n▶ Table 2 The characteristics of rectal endometriosis are shown.\nThe values of nodule length and thickness show the mean and the\nstandard deviation. The #Enzian classification classifies the rectal\nendometriosis into three grades depending on the length of the\nnodules (C1: < 1cm; C2: 1 –3cm; C3: > 3 cm).\nCharacteristics of rectal endometriosis\nNodule length at first visit 23.26 ± 8.44 mm\nNodule length at last visit 22.53 ± 8.42 mm\nNodule thickness at first visit 10.55 ± 4.17 mm\nNodule thickness at last visit 8.81 ± 4.11 mm\n#Enzian C compartment at first visit\nC1 0\nC2 29\nC3 9\n#Enzian C compartment at last visit\nC1 1\nC2 28\nC3 9\n288 Keckstein S et al. Sonomorphologic Changes in … Ultraschall in Med 2024; 45: 285 –292 | © 2023. Thieme. All rights reserved.\nOriginal Article\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\nentrapped endometrial foci leads to marked thickening of the rec-\ntal wall of varying length, thickness, and width. Some cases show\nclinically relevant lumen narrowing and stiffening of the entire\nintestinal tube [19]. The extent of findings plays an important\nrole in evaluating symptoms and planning and managing noninva-\nsive and invasive treatments [20, 21]. Transvaginal sonography\nand MRI of the pelvis have become the methods of choice for ima-\n▶ Table 3 The table shows the mixed effects models of the length and thickness of the rectal nodule. For each patient, her random effect is con-\nsidered as the realization of independent normally distributed random variables with zero mean and unknown standard deviation whose estimate is\ngiven in sub-tables a). These random effects may be considered as the patient ’s individual deviation from a common intercept. Similarly, the resi-\ndual errors are assumed to be normally distributed with zero mean and common standard deviation. CDHT and age enter the model as the sum of\ntwo weighted sums of two and three B-spline basis functions, respectively. The basis functions and the weighted sums are depicted in the upper\nand lower row of Figure 1 in the Supplement, respectively. The weights are given in the “Estimate” column in sub-tables b). For more details, see\nthe section Statistical Analysis. An analysis of the variance table in sub-tables c) examines the contribution of each B-spline to the fit of the model .\nSignificant results are marked with asterisks (p < 0.05: *); SE: standard error, DF: degrees of freedom.\nNodule length\na) Random effects\nGroups Purpose Variance Estimate of standard deviation\nPatients (n = 38) One random effect for each patient 71.441 8.452\nResidual error (n = 154) One random error for each observation 9.957 3.156\nb) Fixed effects\nBasis function Estimate SE DF T-value P-value\nIntercept 15.9672 3.449 131.649 4.630 < 0.0001*\nB-spline (CTHT, degree = 2) 1st 0.3499 2.296 147.000 0.152 0.8791\n2nd –7.3109 3.129 137.063 –2.336 0.0209*\nB-spline (age, degree = 3) 1st 10.9956 6.437 136.187 1.708 0.0899\n2nd 9.5019 4.083 147.636 2.327 0.0213\n3 rd 8.1569 5.480 134.320 1.486 0.1397\nc) Type III analysis of variance table with Satterthwaite ’s method\nSum of squares Mean squares DF numerator DF denomi-\nnator\nF-value P-value\nB-spline (CTHT, degree = 2) 67.805 33.902 2 118.27 3.405 0.0365 *\nB-spline (age, degree = 3) 80.846 26.949 3 117.33 2.706 0.0485 *\nNodule thickness\na) Random effects\nGroups Purpose Variance Estimate of standard deviation\nPatients (n = 38) One random effect for each patient 11.657 3.414\nResidual error (n = 154) One random error for each observation 3.445 1.856\nb) Fixed effects\nBasis function Estimate SE DF T-value P-value\nIntercept 9.539 1.761 128.262 5.415 < 0.0001*\nB-spline (CTHT, degree = 2) 1st –2.987 1.232 147.503 –2.426 0.0165*\n2nd –3.876 1.597 124.012 –2.426 0.0167*\nB-spline (age, degree = 3) 1st –0.464 3.587 145.233 –0.129 0.8972\n2nd 3.469 2.166 144.323 1.602 0.1114\n3 rd 0.590 2.780 117.067 0.212 0.8323\nc) Type III analysis of variance table with Satterthwaite ’s method\nSum of squares Mean squares DF numerator DF denomi-\nnator\nF-value P-value\nB-spline (CTHT, degree = 2) 32.343 16.172 2 109.27 4.695 0.0111*\nB-spline (age, degree = 3) 9.058 3.010 3 107.42 0.877 0.4557\n289Keckstein S et al. Sonomorphologic Changes in … Ultraschall in Med 2024; 45: 285 –292 | © 2023. Thieme. All rights reserved.\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\nging and measuring deep infiltrating endometriosis with high sen-\nsitivity and specificity.\nSince there is still little information about the onset of the dis-\nease and possible factors influencing its growth or regression,\nboth imaging techniques might help to understand the growth\ndynamics of rectal endometriosis over time and the influence of\nage and hormonal treatment. Fedele et al. could not detect any\nfurther growth trend during the observation period using trans-\nrectal ultrasound [9].\nIn contrast, Netter et al., who monitored the TIE of the rectum\nvia MRI, found partially progressive nodules [1]. They could de-\nmonstrate that hormonal treatments, which induce amenorrhea,\nmay prevent the growth of nodules and may even result in the re-\ngression of lesions. However, the regression or stability of nodule\nsize did not correlate with pain relief in many patients.\nBarra et al. observed the regression of rectosigmoid endome-\ntriosis under Dienogest therapy using a standardized ultrasound\nexamination in a 3 D model [10]. However, the observation period\nwas maximum overall 36 months, and no findings were recorded\nafter cessation of therapy. A mean volume reduction of the no-\ndules was observed by at least 10 %, but 5 –10 % of patients experi-\nenced an increase in volume without worsening clinical symp-\ntoms. Knez et al. conducted a retrospective investigation on a\ncohort of women with deep endometriosis who were not under-\ngoing hormonal therapy from various locations. The findings\ndemonstrated that the number of endometriotic nodules is a neg-\native predictor for disease progression [22].\nThe effect of hormonal therapy on rectal endometriosis has\nbeen demonstrated by various studies analyzing only the symp-\ntoms [12, 23]. The use of the oral contraceptive pill, norethister-\none acetate (NETA) [24], desogestrel, and triptorelin [25] decrea-\nses symptoms and improves quality of life. However, the\nrelationship between the size of the finding and the symptomatol-\nogy is controversial. The available data show partially divergent re-\nsults regarding the growth behavior of the nodule in terms of pro-\ngression and regression, depending on the different affecting\nfactors.\nOur study aims to investigate the influence of hormone ther-\napy and the age of the patient on the growth and regression of\nt h ed e e pl e s i o ni nt h er e c t a lw a l lin a multifactorial analysis. We\nobserved the lesions intraindividually over a period of time, with\nthe longest period being more than 16 years.\nTo describe the growth pattern of the length and the thickness\nof the rectal foci, we fitted multiple mixed-effects models, includ-\ning the factors of age and hormone intake (represented by the\nCDHT).\nOur study shows that continuous administration of a progesto-\ngen or an estrogen/progestogen medication in the long cycle re-\nduces nodule size and thickness. As our models show, there is no\nlinear correlation between the regression of nodule length and\nthickness and the duration of therapy. The histopathological com-\nposition of the nodule can explain this. Most of the findings con-\nsist of fibrosis in which stroma and epithelial cells are embedded.\nFibroblasts are much less responsive to hormone modulation than\nstromal and epithelial cells, which may explain the small reduction\nin size [26]. The fact that the relative length changes more than\nthe thickness ( ▶ Fig. 3) of the foci could be explained by mobility\n(fixation with surrounding structures) and partly by the different\ndimensions. Proliferation may occur more in a longitudinal direc-\ntion than in a radial direction.\nThe growth tendency of the rectal lesions, depending on the\npatient’s age, was significantly increased between 20 and 40 years\nof age. Similar trends were found by Koninckx in his retrospective\nstudy comparing the different focal sizes with age [27]. His data\nrefer only to surgical and histological findings. The accuracy of\nthe measurements can be compared with the sonography find-\nings to a limited extent.\nThe #Enzian classification within the C-compartment\n(< 1 cm = C1, 1 –3c m=C 2 , >3c m=C 3 ) c a n i d e n t i f y t h e c h a n g e s\nin rectal foci size. However, the threshold values for the individual\nC-compartments are probably too large to be able to calculate a\nsignificance of the change in the sizes.\nOur study has several limitations. Firstly, we have a study pop-\nulation in which a primarily conservative approach was chosen,\nand no operative treatment of rectal endometriosis was necessary\nuntil the end of the observation period. For instance, Roman et al.\nd e s c r i b e ds y m p t o m a t i ca n ds i z e -progressive rectal nodules that\nrequired rapid surgical treatment [28]. The exclusion of patients\nwith nodules exhibiting a more aggressive growth behavior hin-\nders the generalizability of the study results to all patients with\ndeep infiltrating rectal endometriosis. However, this limitation is\na common issue, as the few other studies investigating growth\npatterns over time have also focused on women without prior rec-\ntal surgery [1, 6]. Another limitation of our study is the rather\nsmall study population.\nWith correspondingly fewer data points from patients in their\nearly 20 s or late 40 s, this naturally leads to a larger confidence in-\nterval. Therefore, the curves should not be overinterpreted in\nthese specific ranges. Howeve r, it must also be acknowledged\nthat a single experienced gynecologist examined all patients.\nThus, high accuracy and precision of the measurements can be as-\nsumed. Additionally, our study was designed retrospectively, and\ndata was collected from patient records. Finally, there is a known\ninter- and intra-observer variability of measurements using TVS,\nas observed by Egekvist et al., which may influence the presented\nresults [29]. Therefore, further studies covering the entire repro-\nductive period are warranted to gain a more comprehensive un-\nderstanding of the growth behavior of rectal endometriosis.\nConclusion\nTransvaginal sonography is an ideal method to study and monitor\nmorphologic changes of rectal endometriosis over time for clini-\ncal management considerations.\nThe growth pattern of deep endometriosis (DE) is influenced\nby patient age and the duration of conservative therapy. In pa-\ntients without any treatment, rectal endometriosis shows a mod-\nerate increase in size until the end of the fourth decade of life,\nafter which it tends to stabilize. While hormonal therapy can re-\nduce the size or prevent the further progression of deep endome-\ntriosis, its growth does not follow a linear function.\n290 Keckstein S et al. Sonomorphologic Changes in … Ultraschall in Med 2024; 45: 285 –292 | © 2023. Thieme. All rights reserved.\nOriginal Article\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\n▶ Fig. 3 Images A and D show the relative change in nodule length and thickness depending on age, as predicted by our model as described in\n▶ Table 3 while assuming that there is no hormone intake. Images B and E show the predicted relative change in nodule length and thickness de-\npending on the cumulative time of hormone treatment (CDHT) so far, assuming the patient is 35 years old. The gray bands indicate point-wise 95 %\nconfidence intervals. Images C and F show the growth behavior of the length and thickness of rectal endometriosis depending on the duration of\nhormone intake. The age is shown in years. While the sample patient on the black curve has never taken hormones (same curve as in images A and\nD), the sample patient on the green curve has taken hormones continuously over a period of 15 years. The patients shown in the red and blue\ncurves started hormone therapy at the age of 25 and paused therapy after 5 and 10 years, respectively. 291Keckstein S et al. Sonomorphologic Changes in … Ultraschall in Med 2024; 45: 285 –292 | © 2023. Thieme. All rights reserved.\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.\n\n\nConflict of Interest\nGeorge Condous: Luminary for GE Healthcare and Samsung\nReferences\n[1] Netter A et al. Progression of deep infiltrating rectosigmoid endome-\ntriotic nodules. Human Reproduction 2019; 34 (11): 2144 –2152\n[2] Vercellini P et al. Endometriosis: pathogenesis and treatment. Nature\nReviews Endocrinology 2014; 10 (5): 261 –275\n[3] Gordts S, Koninckx P, Brosens I. Pathogenesis of deep endometriosis.\nFertility and sterility 2017; 108 (6): 872 –885\n[4] Koninckx PR et al. The epidemiology of endometriosis is poorly known as\nthe pathophysiology and diagnosis are unclear. 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Sonomorphologic Changes in … Ultraschall in Med 2024; 45: 285 –292 | © 2023. Thieme. All rights reserved.\nOriginal Article\nThis document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.","source_license":"public-domain-us","license_restricted":false}