今日の臨床サポート

子宮内膜増殖症

著者: 伊藤潔 東北大学 災害産婦人科学分野

監修: 青木大輔 慶應義塾大学医学部産婦人科学教室

著者校正/監修レビュー済:2021/02/24
参考ガイドライン:
  1. 日本産科婦人科学会]/日本産婦人科医会:産婦人科診療ガイドライン 婦人科外来編 2020. p56-57
  1. 日本婦人科腫瘍学会:子宮体がん治療ガイドライン 2018年版. p166-179
患者向け説明資料

概要・推奨   

  1. 異型のない子宮内膜増殖症で、不正出血や過多月経など症状を伴わない症例では、まず経過観察することが勧められる(推奨度2)
  1. 外来生検で子宮内膜異型増殖症と診断された患者では、診断は慎重に行うことが勧められる(推奨度2)
  1. 子宮内膜細胞診異常や子宮内膜肥厚ありと判断した場合には、子宮内膜組織検査によって確定診断を行う(推奨度2)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
伊藤潔 : 未申告[2021年]
監修:青木大輔 : 講演料(アストラゼネカ株式会社,武田薬品工業株式会社,中外製薬株式会社),研究費・助成金など(アストラゼネカ株式会社,中外製薬株式会社,インサイト・バイオサイエンシズ・ジャパン合同会社)[2021年]

改訂のポイント:
  1. 日本産科婦人科学会/日本産婦人科医会編:産婦人科診療ガイドライン―婦人科外来編2020に基づき、レボノルゲストレル放出子宮内システムに関する記載を追加した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 子宮内膜増殖症は、細胞異型を伴わない子宮内膜腺の過剰増殖と定義される。細胞異型を伴うものは子宮内膜異型増殖症として、別に定義される[1]<図表>
  1. 構築によって、子宮内膜増殖症は単純simple型と複雑complex型に分けられていた[1]<図表>。しかし、2014年公表の新しいWHO分類では、構築による分類がなくなり、細胞異型のみによって分けられることとなった[2]。日本でも2017年の取扱い規約改訂で、取り入れられることとなった[3]
 
子宮内膜増殖症の分類

子宮内膜増殖症は、構造異常の程度と細胞異型により分類される。

 
  1. 治療方針の決定で重要なことは、それが異型のない子宮内膜増殖症か、あるいは異型のあるもの(子宮内膜異型増殖症)かを鑑別することである。疑われる場合には内膜全面掻爬による診断を行う必要がある[4][5]
  1. 症状として不正出血や過多月経を伴う場合が多い。また、若年者の場合には不妊症の原因となる場合がある。発症年齢のピークは40歳代で子宮内膜癌よりも若い。
  1. 異型のない子宮内膜増殖症は、自然退縮する場合が多く、また子宮内膜癌への進展率も低い。
  1. 異型のある増殖症(子宮内膜異型増殖症)は、癌との鑑別がときに困難であり、慎重な取り扱いが必要である。
問診・診察のポイント  
問診:
  1. 不正出血、月経異常の有無を確認する。不妊症の有無も確認する。

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文献 

著者: Yukihisa Minagawa, Shinya Sato, Masayuki Ito, Yoshimasa Onohara, Shu Nakamoto, Junzo Kigawa
雑誌名: Gynecol Obstet Invest. 2005;59(3):149-54. doi: 10.1159/000083089. Epub 2005 Jan 3.
Abstract/Text OBJECTIVE: To determine whether the combined use of transvaginal ultrasonography and endometrial cytology is an effective diagnostic schema for endometrial cancer and hyperplasia of the uterus.
METHODS: Five hundred fifty-two women were enrolled in this study. For all subjects, endometrial thickness was evaluated by transvaginal ultrasonography. Endometrial cytology was carried out according to the following criteria: all women with atypical uterine bleeding, for asymptomatic postmenopausal women with endometrial thickness >or=5 mm, and for asymptomatic premenopausal women with endometrial thickness >or=20 mm. When the cytological findings were abnormal, we performed a hysteroscopy-guided biopsy within 2 weeks. Women who received transvaginal ultrasonography alone, or those who showed negative cytology, underwent repeated gynecological examination and transvaginal ultrasonography 3, 6, and 12 months after the first examination.
RESULTS: Endometrial cytology was done on 129 women (23.4% of all subjects), of whom 14 were diagnosed as 'positive' cytology, 20 as 'suspicious positive', and 95 as 'negative'. A total of 34 women with 'positive' or 'suspicious positive' cytological result underwent hysteroscopy-guided endometrial biopsy. The histological diagnosis of the endometrium included 13 endometrial cancers, 9 endometrial hyperplasias (one atypical hyperplasia and 3 hyperplastic polyps), and 10 normal endometria. As a diagnostic schema for endometrial cancer, this combined method resulted in 100% sensitivity, 99.1% specificity, 92.9% positive predictive value, and 100% negative predictive value. For endometrial hyperplasia, the method resulted in 100% sensitivity, 89.6% specificity, 40.0% positive predictive value, and 100% negative predictive value.
CONCLUSION: A combination of transvaginal ultrasonography and endometrial cytology may be an effective diagnostic schema for endometrial cancer and hyperplasia.

Copyright (c) 2005 S. Karger AG, Basel.
PMID 15637434  Gynecol Obstet Invest. 2005;59(3):149-54. doi: 10.1159/・・・
著者: American College of Obstetricians and Gynecologists
雑誌名: Obstet Gynecol. 2009 Feb;113(2 Pt 1):462-4. doi: 10.1097/AOG.0b013e31819930cc.
Abstract/Text The clinical approach to postmenopausal bleeding requires prompt and efficient evaluation to exclude or diagnose carcinoma. Women with postmenopausal bleeding may be assessed initially with either endometrial biopsy or transvaginal ultrasonography;this initial evaluation does not require performance of both tests.Transvaginal ultrasonography can be useful in the triage of patients in whom endometrial sampling was performed but tissue was insufficient for diagnosis. When transvaginal ultrasonography is performed for patients with postmenopausal bleeding and an endometrial thickness of less than or equal to 4 mm is found, endometrial sampling is not required. Meaningful assessment of the endometrium by ultrasonography is not possible in all patients. In such cases, alternative assessment should be completed. When bleeding persists despite negative initial evaluations, additional assessment usually is indicated.

PMID 19155921  Obstet Gynecol. 2009 Feb;113(2 Pt 1):462-4. doi: 10.109・・・
著者: B Karlsson, S Granberg, M Wikland, P Ylöstalo, K Torvid, K Marsal, L Valentin
雑誌名: Am J Obstet Gynecol. 1995 May;172(5):1488-94.
Abstract/Text OBJECTIVE: The purpose of this study was to use transvaginal ultrasonographic measurements to find the thickness of the endometrium below which the risk of endometrial abnormality in women with postmenopausal bleeding is low.
STUDY DESIGN: This multicenter study was carried out at eight clinics in four Nordic countries. The study included 1168 women with postmenopausal bleeding scheduled for curettage Before the curettage was performed, the thickness of the endometrium was measured with transvaginal ultrasonography. The measurement included both endometrial layers (double-layer technique). The transvaginal ultrasonographic measurement was compared with the histopathologic diagnosis of the curettage specimens.
RESULTS: In women with atrophic endometrium the mean endometrial thickness (+/- SD) was 3.9 +/- 2.5 mm. The corresponding figures for women with endometrial cancer were 21.1 +/- 11.8 mm. No malignant endometrium was thinner than 5 mm. In 30 women (2.8%) it was not possible to measure the thickness of the endometrium; one of these women had endometrial cancer. The 95% confidence limit for the probability of excluding endometrial abnormality was 5.5% when the endometrial thickness was < or = 4 mm as measured by transvaginal ultrasonography.
CONCLUSION: The risk of finding pathologic endometrium at curettage when the endometrium is < or = 4 mm as measured by transvaginal ultrasonography is 5.5%. Thus in women with postmenopausal bleeding and an endometrium < or = 4 mm it would seem justified to refrain from curettage.

PMID 7755059  Am J Obstet Gynecol. 1995 May;172(5):1488-94.
著者: H Tsuda, M Kawabata, K Kawabata, K Yamamoto, A Hidaka, N Umesaki, S Ogita
雑誌名: Am J Obstet Gynecol. 1995 May;172(5):1494-5.
Abstract/Text
PMID 7755060  Am J Obstet Gynecol. 1995 May;172(5):1494-5.
著者: R J Kurman, P F Kaminski, H J Norris
雑誌名: Cancer. 1985 Jul 15;56(2):403-12.
Abstract/Text Endometrial curettings from 170 patients with all grades of endometrial hyperplasia, who did not undergo a hysterectomy for at least 1 year were evaluated in order to correlate the histopathologic features with behavior. Follow-up ranged from 1 to 26.7 years (mean, 13.4 years). Cytologic and architectural alterations were analyzed separately in order to assess their respective roles in predicting the likelihood of progression to carcinoma. Classification of proliferative lesions based solely on the presence of cytologic atypia revealed that atypia was a discriminant factor. Proliferations lacking cytologic atypia were designated hyperplasia and those displaying atypia were designated atypical hyperplasia. Only 2 (1.6%) of 122 patients with hyperplasia progressed to carcinoma compared with 11 (23%) of women with atypical hyperplasia (P = 0.001). Subclassification of the two forms of hyperplasia (those with cytologic atypia and those without) was performed using the degree of architectural abnormalities. Hyperplasia and atypical hyperplasia displaying marked glandular complexity and crowding producing a back-to-back appearance were designated complex hyperplasia (CH) and complex atypical hyperplasia (CAH), respectively. Hyperplasia and atypical hyperplasia with lesser degrees of glandular complexity and crowding were designated simple hyperplasia (SH) and simple atypical hyperplasia (SAH), respectively. Progression to carcinoma occurred in 1 (1%) of 93 patients with SH, in 1 (3%) of 29 patients with CH, in 1 (8%) of the patients with SAH, and in 10 (29%) of the patients with CAH. The differences between the four subgroups suggest a trend but are not statistically significant. The findings in this study provide a rationale for classifying noninvasive endometrial proliferations primarily on the basis of cytologic atypia since this is the most useful criterion in predicting the likelihood of progression to carcinoma. In addition, the presence of concommitant architectural alterations appears to identify a particularly high-risk subgroup.

PMID 4005805  Cancer. 1985 Jul 15;56(2):403-12.
著者: R J Kurman, H J Norris
雑誌名: Cancer. 1982 Jun 15;49(12):2547-59.
Abstract/Text Endometrial curettings from 204 patients containing severe forms of atypical hyperplasia, carcinoma in situ, and well-differentiated carcinoma were compared with subsequent hysterectomy specimens to evaluate and identify the most useful histologic criteria for predicting the presence of invasive carcinoma. Endometrial stromal invasion, increased degrees of nuclear atypism, mitotic activity, cellular stratification, and epithelial necrosis in curettings were associated with a greater likelihood of carcinoma in the uterus. Of these, stromal invasion was the most significant feature. When stromal invasion was absent, carcinoma was present in the uterus in only 17%, and the carcinomas were well differentiated and confined to the endometrium or only superficially invasive. When stromal invasion was present in curettings, residual carcinoma was present in the uterus in half, and of these, one third were moderately or poorly undifferentiated and a quarter invaded deeply into the myometrium. The criteria for invasion are 1) an irregular infiltration of glands associated with an altered fibroblastic stroma or desmoplastic response; 2) a confluent glandular pattern in which individual glands are uninterrupted by stroma and merge to form a cribriform pattern of stromal replacement; 3) an extensive papillary pattern; and 4) replacement of stroma by masses of squamous epithelium. To qualify as invasion, 2, 3, and 4 must occupy at least one half (2.1 mm) of low power field 4.2 mm in diameter. Because of the important role of stromal invasion in predicting prognosis, future classifications of endometrial neoplasia should utilize this feature in distinguishing atypical hyperplasia from well differentiated adenocarcinoma.

PMID 7074572  Cancer. 1982 Jun 15;49(12):2547-59.
著者: Cornelia L Trimble, James Kauderer, Richard Zaino, Steven Silverberg, Peter C Lim, James J Burke, David Alberts, John Curtin
雑誌名: Cancer. 2006 Feb 15;106(4):812-9. doi: 10.1002/cncr.21650.
Abstract/Text BACKGROUND: Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for approximately 36,000 diagnoses of invasive carcinoma annually. The most common histologic type, endometrioid adenocarcinoma (EC), accounts for 75-80% of patients. The objective of this work was to estimate the prevalence of concurrent carcinoma in women with a biopsy diagnosis of the precursor lesion, atypical endometrial hyperplasia (AEH).
METHODS: This prospective cohort study included women who had a community diagnosis of AEH. Diagnostic biopsy specimens were reviewed independently by three gynecologic pathologists who used International Society of Gynecologic Pathologists/World Health Organization criteria. Study participants underwent hysterectomy within 12 weeks of entry onto protocol without interval treatment. The hysterectomy slides also were reviewed by the study pathologists, and their findings were used in the subsequent analyses.
RESULTS: Between November 1998 and June 2003, 306 women were enrolled on the study. Of these, 17 women were not included in the analysis: Two patients had unreadable slides because of poor processing or insufficient tissue, 2 patients had only slides that were not endometrial, the slides for 5 patients were not available for review, and 8 of the hysterectomy specimens were excluded because they showed evidence of interval intervention, either progestin effect or ablation. In total, 289 patients were included in the current analysis. The study panel review of the AEH biopsy specimens was interpreted as follows: 74 of 289 specimens (25.6%) were diagnosed as less than AEH, 115 of 289 specimens (39.8%) were diagnosed as AEH, and 84 of 289 specimens (29.1%) were diagnosed as endometrial carcinoma. In 5.5% (16 of 289 specimens), there was no consensus on the biopsy diagnosis. The rate of concurrent endometrial carcinoma for analyzed specimens was 42.6% (123 of 289 specimens). Of these, 30.9% (38 of 123 specimens) were myoinvasive, and 10.6% (13 of 123 specimens) involved the outer 50% of the myometrium. Among the women who had hysterectomy specimens with carcinoma, 14 of 74 women (18.9%) had a study panel biopsy consensus diagnosis of less than AEH, 45 of 115 women (39.1%) had a study panel biopsy consensus diagnosis of AEH, and 54 of 84 women (64.3%) had a study panel diagnosis of carcinoma. Among women who had no consensus in their biopsy diagnosis, 10 of 16 women (62.5%) had carcinoma in their hysterectomy specimens.
CONCLUSIONS: The prevalence of endometrial carcinoma in patients who had a community hospital biopsy diagnosis of AEH was high (42.6%). When considering management strategies for women who have a biopsy diagnosis of AEH, clinicians and patients should take into account the considerable rate of concurrent carcinoma.

Copyright 2006 American Cancer Society.
PMID 16400639  Cancer. 2006 Feb 15;106(4):812-9. doi: 10.1002/cncr.216・・・
著者: Richard J Zaino, James Kauderer, Cornelia Liu Trimble, Steven G Silverberg, John P Curtin, Peter C Lim, Donald G Gallup
雑誌名: Cancer. 2006 Feb 15;106(4):804-11. doi: 10.1002/cncr.21649.
Abstract/Text BACKGROUND: Most gynecologists determine therapy based on current International Society of Gynecologic Pathologists (ISGP)/World Health Organization classification of endometrial hyperplasia, the reproducibility of which has been questioned. The Gynecologic Oncology Group (GOG) initiated a protocol to assess the efficacy of hormonal therapy of atypical endometrial hyperplasia (AEH). Primary goals of the first phase (Part A) were to prospectively determine reproducibility of referring institution's pathologist's diagnosis of AEH by a panel of 3 gynecologic pathologists and to determine reproducibility of diagnoses by panel members.
METHODS: Three hundred six women were entered on this protocol with a referring institution's pathologist diagnosis of AEH based on biopsy or curettage. Available slides were assessed independently and interpreted by each of a panel of 3 gynecologic pathologists who used International Society of Gynecologic Pathologists (ISGP)/World Health Organization criteria. The majority diagnosis was based on diagnostic concordance by at least 2 of the 3 panelists.
RESULTS: The referring institution's pathologist's diagnosis of AEH was supported by the majority of the panel in only 38% of cases. Overall kappa value for the panel diagnosis of AEH was 0.28. The majority diagnosis was adenocarcinoma in 29%, cycling endometrium in 7%, and nonatypical hyperplasia in 18% of cases. Unanimous agreement for any diagnosis was reached among all 3 of the panel in 40% of cases. For the panel, paired kappa values for any diagnosis ranged 0.34-0.43, with an overall kappa value of 0.40.
CONCLUSION: Reproducibility of referring institution's pathologists' diagnosis of AEH by a panel of gynecologic pathologists is poor. Both underestimation and overestimation of the severity of the lesion are very common. The level of reproducibility among subspecialist panel members for diagnosis of AEH in these specimens also is poor. Better criteria and better sampling are needed to improve reproducibility of this diagnosis, particularly if it is to be used for clinical decisions.

Copyright 2006 American Cancer Society.
PMID 16400640  Cancer. 2006 Feb 15;106(4):804-11. doi: 10.1002/cncr.21・・・
著者: N Terakawa, J Kigawa, Y Taketani, H Yoshikawa, A Yajima, K Noda, H Okada, J Kato, M Yakushiji, O Tanizawa, S Fujimoto, S Nozawa, T Takahashi, K Hasumi, N Furuhashi, T Aono, A Sakamoto, M Furusato
雑誌名: J Obstet Gynaecol Res. 1997 Jun;23(3):223-30.
Abstract/Text OBJECTIVE: To clarify the behavior of endometrial hyperplasia in a prospective study.
METHOD: Fifty-one patients with endometrial hyperplasia were followed up for 6 months. Samples of endometrial tissues were taken by uterine endometrial biopsy every 4 weeks during the first 3 months and at the end of follow-up.
RESULTS: In 69% (35/51) of the patients histological picture of the endometrium became normal during the observation period. The lesions persisted in 17% (6/35) of the patients with simple hyperplasia, in 25% (1/4) of those with complex hyperplasia, in 14% (1/7) of those with simple atypical hyperplasia, and in 80% (4/5) of the patients with complex atypical hyperplasia. In the remaining 3 patients with simple hyperplasia, the lesions progressed to complex atypical hyperplasia by the end of follow-up, after showing a normal endometrium.
CONCLUSION: Most cases of endometrial hyperplasia, except for complex atypical hyperplasia, disappeared spontaneously within a short period of time.

PMID 9255033  J Obstet Gynaecol Res. 1997 Jun;23(3):223-30.
著者:
雑誌名: JAMA. 1996 Feb 7;275(5):370-5.
Abstract/Text OBJECTIVE: To report the histological findings of the endometrium of postmenopausal women who were randomized to receive placebo, estrogen only, or one of three estrogen plus progestin (E+P) regimens in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.
DESIGN: A 3-year multicenter, randomized, double-masked, placebo-controlled trial.
PARTICIPANTS: A total of 596 postmenopausal women aged 45 through 64 years without contraindication to hormone therapy.
INTERVENTION: Participants were randomized and stratified in equal numbers to one of the following treatments in 28-day cycles: placebo, 0.625 mg/d of conjugated equine estrogens (CEE), 0.625 mg/d of CEE plus 10 mg/d of medroxyprogesterone acetate (MPA) for the first 12 days, 0.625 mg/d of CEE plus 2.5 mg/d of MPA, or 0.625 mg/d of CEE plus 200 mg/d of micronized progesterone (MP) for the first 12 days.
OUTCOME MEASURE: Histology of endometrium collected at baseline, annual, or unscheduled visits by biopsy, curettage, or hysterectomy.
ANALYSIS: Intention to treat.
RESULTS: During follow-up women assigned to estrogen alone were more likely to develop simple (cystic), complex (adenomatous), or atypical hyperplasia than those given placebo (27.7% vs 0.8%, 22.7% vs 0.8%, and 11.8% vs 0%, respectively) for the same types of hyperplasia (P < .001). Participants administered one of the three E+P regimens had similar rates of hyperplasia as those given placebo (P = .16). The occurrence of hyperplasia was distributed evenly across the 3 years of the trial. Women taking estrogens alone also had more unscheduled biopsies (66.4% vs 8.4%; P < .001) and curettages (17.6% vs 0.8%; P < .001) than women receiving placebo. The number of surgical procedures was similar for women receiving placebo and women receiving the E+P regimens (P = .38). Of the 45 women with complex (adenomatous) or atypical hyperplasia, study medications were discontinued in all, and the biopsy results of 34 (94%) of 36 women with hyperplasia reverted to normal with progestin therapy. The remainder had dilatation and curettage (n = 2) or hysterectomy with (n = 2) or without (n = 6) prior medical therapy, or refused further biopsies (n = 1). One woman developed adenocarcinoma of the endometrium while receiving placebo.
CONCLUSIONS: At a dosage of 0.625 mg, the daily administration of CEE enhanced the development of endometrial hyperplasia. Combining CEE with cyclic or continuous MPA or cyclic MP protected the endometrium from hyperplastic changes associated with estrogen-only therapy.

PMID 8569016  JAMA. 1996 Feb 7;275(5):370-5.
著者: D E Marsden, N F Hacker
雑誌名: Best Pract Res Clin Obstet Gynaecol. 2001 Jun;15(3):393-405. doi: 10.1053/beog.2000.0184.
Abstract/Text The optimal management of endometrial hyperplasia is the subject of considerable debate. In this chapter the development of our current classification of endometrial hyperplasias is outlined in some detail in order to give an understanding of the complexity of the problem of determining the malignant potential of the hyperplasia which is the central issue in determining optimal treatment. While hysterectomy is still the definitive treatment for older women with hyperplasia, conservative therapy is perfectly acceptable in a defined group of younger women who are closely monitored.

Copyright 2001 Harcourt Publishers Ltd.
PMID 11476561  Best Pract Res Clin Obstet Gynaecol. 2001 Jun;15(3):393・・・
著者: Rajesh Varma, Hemi Soneja, Kalsang Bhatia, Raji Ganesan, Terence Rollason, T Justin Clark, Janesh K Gupta
雑誌名: Eur J Obstet Gynecol Reprod Biol. 2008 Aug;139(2):169-75. doi: 10.1016/j.ejogrb.2008.02.022. Epub 2008 Apr 28.
Abstract/Text OBJECTIVES: Medical treatment of non-atypical endometrial hyperplasia with oral progestogens has limited efficacy and poor compliance. A levonorgestrel-releasing intrauterine system (LNG-IUS) has been shown to successfully treat hyperplasia in small-sized studies. Our aim was to examine the effectiveness of LNG-IUS in a larger study with long-term follow up.
STUDY DESIGN: Prospective observational study of 105 women diagnosed with endometrial hyperplasia and treated with LNG-IUS between 1999 and 2004 at a University Teaching hospital. Baseline characteristics and outpatient endometrial Pipelle sampling were undertaken at 3 and 6 months post LNG-IUS insertion and 6-monthly intervals thereafter in all cases. Outcome included histological data derived from both Pipelle and uterine histologies at 1 and 2 years LNG-IUS therapy.
RESULTS: LNG-IUS achieved endometrial regression in 90% (94/105) of cases by 2 years, with a significant proportion (96%, 90/94) achieving this within 1 year. Regression occurred in 88/96 (92%) of non-atypical and 6/9 (67%) of atypical hyperplasias, and in all 22 cases of endometrial hyperplasia associated with HRT. Regression rates did not differ between histological types of hyperplasia. Twenty-three women (22%) underwent hysterectomy of which 13 were indicated and 10 were performed at patient request despite regressed endometrium. Two cases of cancer (one uterine and one ovarian) were identified.
CONCLUSION: LNG-IUS is highly effective in treating endometrial hyperplasia. Beneficial effects are observed by the majority within 1 year. Treatment can be reliably monitored through regular 6-montly outpatient endometrial Pipelle surveillance. LNG-IUS treatment of non-atypical hyperplasias is likely to reduce the number of hysterectomies performed in this subgroup.

PMID 18440693  Eur J Obstet Gynecol Reprod Biol. 2008 Aug;139(2):169-7・・・
著者: Kimio Ushijima, Hideaki Yahata, Hiroyuki Yoshikawa, Ikuo Konishi, Toshiharu Yasugi, Toshiaki Saito, Toru Nakanishi, Hiroshi Sasaki, Fumitaka Saji, Tsuyoshi Iwasaka, Masayuki Hatae, Shoji Kodama, Tsuyoshi Saito, Naoki Terakawa, Nobuo Yaegashi, Masamichi Hiura, Atsuhiko Sakamoto, Hitoshi Tsuda, Masaharu Fukunaga, Toshiharu Kamura
雑誌名: J Clin Oncol. 2007 Jul 1;25(19):2798-803. doi: 10.1200/JCO.2006.08.8344.
Abstract/Text PURPOSE: To assess the efficacy of fertility-sparing treatment using medroxyprogesterone acetate (MPA) for endometrial carcinoma (EC) and atypical endometrial hyperplasia (AH) in young women.
PATIENTS AND METHODS: This multicenter prospective study was carried out at 16 institutions in Japan. Twenty-eight patients having EC at presumed stage IA and 17 patients with AH at younger than 40 years of age were enrolled. All patients were given a daily oral dose of 600 mg of MPA with low-dose aspirin. This treatment continued for 26 weeks, as long as the patients responded. Histologic change of endometrial tissue was assessed at 8 and 16 weeks of treatment. Either estrogen-progestin therapy or fertility treatment was provided for the responders after MPA therapy. The primary end point was a pathologic complete response (CR) rate. Toxicity, pregnancy rate, and progression-free interval were secondary end points.
RESULTS: CR was found in 55% of EC cases and 82% of AH cases. The overall CR rate was 67%. Neither therapeutic death nor irreversible toxicities were observed; however, two patients had grade 3 body weight gain, and one patient had grade 3 liver dysfunction. During the 3-year follow-up period, 12 pregnancies and seven normal deliveries were achieved after MPA therapy. Fourteen recurrences were found in 30 patients (47%) between 7 and 36 months.
CONCLUSION: The efficacy of fertility-sparing treatment with a high-dose of MPA for EC and AH was proven by this prospective trial. Even in responders, however, close follow-up is required because of the substantial rate of recurrence.

PMID 17602085  J Clin Oncol. 2007 Jul 1;25(19):2798-803. doi: 10.1200/・・・
著者: J T Thigpen, M F Brady, R D Alvarez, M D Adelson, H D Homesley, A Manetta, J T Soper, F T Given
雑誌名: J Clin Oncol. 1999 Jun;17(6):1736-44.
Abstract/Text PURPOSE: Progestins have definite activity against advanced or recurrent endometrial carcinoma. Both parenteral and oral progestins yield similar serum levels and response rates, which range from 18% to 34%. The one major study that used oral medroxyprogesterone acetate (MPA) noted a response rate at the lower end of the range (18%) and much poorer progression-free and overall survival times (4 and 10.5 months, respectively) than previously reported. The present study sought to confirm this earlier study of oral MPA, to assess the importance of prognostic factors such as histologic grade and receptor levels, and to determine whether a higher dose of MPA would yield a higher response rate.
PATIENTS AND METHODS: Two hundred ninety-nine eligible women with advanced or recurrent endometrial carcinoma were randomized to receive oral MPA either 200 mg/d or 1, 000 mg/d until unacceptable toxicity intervened or their disease progressed.
RESULTS: Among 145 patients receiving the low-dose regimen, there were 25 complete (17%) and 11 partial (8%) responses for an overall response rate of 25%. The 154 patients receiving the high-dose regimen experienced 14 (9%) complete and 10 (6%) partial responses for an overall response rate of 15%. Median durations of progression-free survival were 3.2 months and 2.5 months for the low-dose and high-dose regimens, respectively. Median survival durations were 11.1 months and 7.0 months, respectively. The adjusted relative odds of responding to the high-dose regimen compared with the low-dose regimen was 0.61 (90% confidence interval, 0.36 to 1.04). Prognostic factors having a significant impact on the probability of response included initial performance status, age, histologic grade, and progesterone receptor concentration. Compliance with oral therapy was documented with serum levels 1 month after starting therapy, when possible. MPA levels were commensurate with the assigned dose and schedule.
CONCLUSION: Oral MPA is active against endometrial carcinoma. Response to progestin therapy is more frequent among patients with a well-differentiated histology and positive progesterone receptor status. This study provides no evidence to support the use of MPA 1,000 mg/d orally instead of MPA 200 mg/d orally. In fact, the trends suggest the opposite. The use of oral MPA 200 mg/d is a reasonable initial approach to the treatment of advanced or recurrent endometrial carcinoma, particularly those lesions that are well-differentiated and/or progesterone receptor-positive (> 50 fmol/mg cytosol protein). Patients with poorly differentiated and/or progesterone receptor levels less than 50 fmol/mg cytosol protein had only an 8% to 9% response rate.

PMID 10561210  J Clin Oncol. 1999 Jun;17(6):1736-44.

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