Uterine Cancer pp 143-160 | Cite as

Primary Hormonal Therapy of Endometrial Cancer

  • Linda R. DuskaEmail author
Part of the Current Clinical Oncology book series (CCO)


This chapter discusses the treatment of endometrioid adenocarcinoma of the endometrium with hormonal therapy for the purpose of preserving the corpus and future fertility. This treatment obviously pertains to premenopausal women. An occasional postmenopausal woman who is not a candidate for surgery may benefit from similar approaches.


Endometrial cancer Premenopausal Fertility preservation Hormonal treatment 


  1. 1.
    Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. Cancer Statistics, 2008. CA Cancer J Clin 2008;58(2):271–296.CrossRefGoogle Scholar
  2. 2.
    Creasman W, Odicino F, Maisonneuve P, Benedet J, Shephard J, Sideri M, et al. Carcinoma of the corpus uteri. J Epid Biostats 1998;3(35–61).Google Scholar
  3. 3.
    Peterson EP. Endometrial carcinoma in young women. A clinical profile. Obstet & Gynecol 1968;31(5):702–7.CrossRefGoogle Scholar
  4. 4.
    Kempson RL. Adenocarcinoma of the endometrium in women aged forty and younger. Cancer 1968;21(4):650–62.PubMedCrossRefGoogle Scholar
  5. 5.
    Crissman JD, Azoury RS, Barnes AE, Schellhas HF. Endometrial carcinoma in women 40 years of age or younger. Obstet & Gynecol 1981;57(6):699–704.Google Scholar
  6. 6.
    Gallup DG, Stock RJ. Adenocarcinoma of the endometrium in women 40 years of age or younger. Obstet & Gynecol 1984;64(3):417–20.Google Scholar
  7. 7.
    Farhi DC, Nosanchuk J, Silverberg SG. Endometrial adenocarcinoma in women under 25 years of age. Obstet & Gynecol 1986;68(6):741–5.Google Scholar
  8. 8.
    Jeffery JD, Taylor R, Robertson DI, Stuart GC. Endometrial carcinoma occurring in patients under the age of 45 years. Am J Obstet & Gynecol 1987;156(2):366–70.Google Scholar
  9. 9.
    Gitsch G, Hanzal E, Jensen D, Hacker NF. Endometrial cancer in premenopausal women 45 years and younger. Obstet & Gynecol 1995;85(4):504–8.CrossRefGoogle Scholar
  10. 10.
    Evans-Metcalf ER, Brooks SE, Reale FR, Baker SP. Profile of women 45 years of age and younger with endometrial cancer. Obst & Gynecol 1998;91(3):349–54.CrossRefGoogle Scholar
  11. 11.
    Soliman PT, Oh JC, Schmeler KM, Sun CC, Slomovitz BM, Gershenson DM, et al. Risk factors for young premenopausal women with endometrial cancer. Obstet Gynecol 2005;105(3):575–80.PubMedCrossRefGoogle Scholar
  12. 12.
    Duska LR, Garrett A, Rueda BR, Haas J, Chang Y, Fuller AF. Endometrial Cancer in Women 40 Years Old or Younger. Gynecol Oncol 2001;83(2):388–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Schmeler KM, Soliman PT, Sun CC, Slomovitz BM, Gershenson DM, Lu KH. Endometrial cancer in young, normal-weight women. Gynecol Oncol 2005;99(2):388–92.PubMedCrossRefGoogle Scholar
  14. 14.
    Lu KH, Dinh M, Kohlmann W, et al. Gynecologic cancer as a “sentinel cancer” for women with hereditary nonpolyposis colorectal cancer syndrome. Obstet Gynecol 2005;105(3):569–74.PubMedCrossRefGoogle Scholar
  15. 15.
    Kurman RJ, Norris HJ. Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. Cancer 1982;49(12):2547–59.PubMedCrossRefGoogle Scholar
  16. 16.
    Zaino RJ, Kauderer J, Trimble CL, et al. Reproducibility of the diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer 2006;106(4):804–11.PubMedCrossRefGoogle Scholar
  17. 17.
    Trimble CL, Kauderer J, Zaino R, Silverberg S, Lim PC, Burke JJ, 2nd, et al. Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer 2006;106(4):812–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer 1987;60(8 Suppl):2035–41.PubMedCrossRefGoogle Scholar
  19. 19.
    Cowles TA, Magrina JF, Masterson BJ, Capen CV. Comparison of clinical and surgicalstaging in patients with endometrial carcinoma. Obstet Gynecol 1985;66(3):413–6.PubMedGoogle Scholar
  20. 20.
    Daniel AG, Peters WA, 3rd. Accuracy of office and operating room curettage in the grading of endometrial carcinoma. Obstet Gynecol 1988;71(4):612–4.PubMedGoogle Scholar
  21. 21.
    Eltabbakh GH, Shamonki J, Mount SL. Surgical stage, final grade, and survival of women with endometrial carcinoma whose preoperative endometrial biopsy shows well-differentiated tumors. Gynecol Oncol 2005;99(2):309–12.PubMedCrossRefGoogle Scholar
  22. 22.
    Del Maschio A, Vanzulli A, Sironi S, Spagnolo D, Belloni C, Garancini P, et al. Estimating the depth of myometrial involvement by endometrial carcinoma: efficacy of transvaginal sonography vs MR imaging. Am J Roentgenol 1993;160(3):533–8.Google Scholar
  23. 23.
    Gordon AN, Fleischer AC, Dudley BS, Drolshagan LF, Kalemeris GC, Partain CL, et al. Preoperative assessment of myometrial invasion of endometrial adenocarcinoma by sonography (US) and magnetic resonance imaging (MRI). Gynecol Oncol 1989;34(2):175–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Kim SH. Detection of deep myometrial invasion in endometrial carcinoma: comparison of transvaginal ultrasound, CT, and MRI. J Cell Biol 1995;130(5):1127–36.CrossRefGoogle Scholar
  25. 25.
    Zerbe MJ, Bristow R, Grumbine FC, Montz FJ. Inability of preoperative computed tomography scans to accurately predict the extent of myometrial invasion and extracorporal spread in endometrial cancer. Gynecol Oncol 2000;78(1):67–70.PubMedCrossRefGoogle Scholar
  26. 26.
    Hardesty LA, Sumkin JH, Hakim C, Johns C, Nath M. The ability of helical CT to preoperatively stage endometrial carcinoma. Am J Roentgenol 2001;176(3):603–6.Google Scholar
  27. 27.
    Sanjuan A, Cobo T, Pahisa J, Escaramis G, Ordi J, Ayuso JR, et al. Preoperative and intraoperative assessment of myometrial invasion and histologic grade in endometrial cancer: role of magnetic resonance imaging and frozen section. Int J Gynecol Cancer 2006;16(1):385–90.PubMedCrossRefGoogle Scholar
  28. 28.
    Frei KA, Kinkel K, Bonel HM, Lu Y, Zaloudek C, Hricak H. Prediction of deep myometrial invasion in patients with endometrial cancer: clinical utility of contrast-enhanced MR imaging-a meta-analysis and Bayesian analysis. Radiology 2000;216(2):444–9.PubMedGoogle Scholar
  29. 29.
    Kinkel K, Kaji Y, Yu KK, et al. Radiologic staging in patients with endometrial cancer: a meta-analysis. Radiology 1999;212(3):711–8.PubMedGoogle Scholar
  30. 30.
    Saez F, Urresola A, Larena JA, et al. Endometrial carcinoma: assessment of myometrial invasion with plain and gadolinium-enhanced MR imaging. J Magn Reson Imaging 2000;12(3):460–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Ramirez PT, Frumovitz M, Bodurka DC, Sun CC, Levenback C. Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review. Gynecol Oncol 2004;95(1):133–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Gottlieb WH, Beiner ME, Shalmon B, et al. Outcome of fertility-sparing treatment with progestins in young patients with endometrial cancer. Obstet Gynecol 2003;102(4):718–25.CrossRefGoogle Scholar
  33. 33.
    Bokhman JV, Chepick OF, Volkova AT, Vishnevsky AS. Can primary endometrial carcinoma stage I be cured without surgery and radiation therapy? Gynecol Oncol 1985;20(2):139–55.PubMedCrossRefGoogle Scholar
  34. 34.
    Randall TC, Kurman RJ. Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol 1997;90(3):434–40.PubMedCrossRefGoogle Scholar
  35. 35.
    Wang CB, Wang CJ, Huang HJ, et al. Fertility-preserving treatment in young patients with endometrial adenocarcinoma. Cancer 2002;94(8):2192–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Niwa K, Tagami K, Lian Z, Onogi K, Mori H, Tamaya T. Outcome of fertility-preserving treatment in young women with endometrial carcinomas. BJOG 2005;112(3):317–20.PubMedCrossRefGoogle Scholar
  37. 37.
    Kim YB, Holschneider CH, Ghosh K, Nieberg RK, Montz FJ. Progestin alone as primary treatment of endometrial carcinoma in premenopausal women. Report of seven cases and review of the literature. Cancer 1997;79(2):320–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Rubatt JM, Slomovitz BM, Burke TW, Broaddus RR. Development of metastatic endometrial endometrioid adenocarcinoma while on progestin therapy for endometrial hyperplasia. Gynecol Oncol 2005;99(2):472–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Kaku T, Yoshikawa H, Tsuda H, et al. Conservative therapy for adenocarcinoma and atypical endometrial hyperplasia of the endometrium in young women: central pathologic review and treatment outcome. Cancer Lett 2001;167(1):39–48.PubMedCrossRefGoogle Scholar
  40. 40.
    Yang YC, Wu CC, Chen CP, Chang CL, Wang KL. Reevaluating the safety of fertility-sparing hormonal therapy for early endometrial cancer. Gynecol Oncol 2005;99(2):287–93.PubMedCrossRefGoogle Scholar
  41. 41.
    Ferrandina G, Zannoni GF, Gallotta V, Foti E, Mancuso S, Scambia G. Progression of conservatively treated endometrial carcinoma after full term pregnancy: a case report. Gynecol Oncol 2005;99(1):215–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Ogawa S, Koike T, Shibahara H, et al. Assisted reproductive technologies in conjunction with conservatively treated endometrial adenocarcinoma. A case report. Gynecol & Obstet Investigation 2001;51(3):214–6.CrossRefGoogle Scholar
  43. 43.
    Jobo T, Imai M, Kawaguchi M, Kenmochi M, Kuramoto H. Successful conservative treatment of endometrial carcinoma permitting subsequent pregnancy: report of two cases. Eur J Gynaecol Oncol 2000;21(2):119–22.PubMedGoogle Scholar
  44. 44.
    Sardi J. Primary hormonal treatment for early endometrial carcinoma. Hum Reprod 1997;12(8):1649–53.CrossRefGoogle Scholar
  45. 45.
    Shibahara H. Successful pregnancy in an infertile patient with conservatively treated endometrial adenocarcinoma after transfer of embryos obtained by intracytoplasmic sperm injection. Cancer Letters 2001;167(1):39–48.CrossRefGoogle Scholar
  46. 46.
    Kung FT, Chen WJ, Chou HH, Ko SF, Chang SY. Conservative management of early endometrial adenocarcinoma with repeat curettage and hormone therapy under assistance of hysteroscopy and laparoscopy. Hum Reproduct 1997;12(8):1649–53.CrossRefGoogle Scholar
  47. 47.
    Mazzon I, Corrado G, Morricone D, Scambia G. Reproductive preservation for treatment of stage IA endometrial cancer in a young woman: hysteroscopic resection. Int J Gynecol Cancer 2005;15(5):974–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Yarali H, Bozdag G, Aksu T, Ayhan A. A successful pregnancy after intracytoplasmic sperm injection and embryo transfer in a patient with endometrial cancer who was treated conservatively. Fertil Steril 2004;81(1):214–6.PubMedCrossRefGoogle Scholar
  49. 49.
    Nakao Y, Nomiyama M, Kojima K, Matsumoto Y, Yamasaki F, Iwasaka T. Successful pregnancies in 2 infertile patients with endometrial adenocarcinoma. Gynecol Obstet Invest 2004;58(2):68–71.PubMedCrossRefGoogle Scholar
  50. 50.
    Pinto AB. Successful in vitro fertilization pregnancy after conservative management of endometrial cancer. Obstet & Gynecol 1981;57(6):699–704.Google Scholar
  51. 51.
    Kimmig R, Strowitzki T, Muller-Hocker J, Kurzl R, Korell M, Hepp H. Conservative treatment of endometrial cancer permitting subsequent triplet pregnancy. Gynecol Oncol 1995;58(2):255–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Walsh C, Holschneider C, Hoang Y, Tieu K, Karlan B, Cass I. Coexisting ovarian malignancy in young women with endometrial cancer. Obstet Gynecol 2005;106(4):693–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Zaino R, Whitney C, Brady MF, DeGeest K, Burger RA, Buller RE. Simultaneously detected endometrial and ovarian carcinomas--a prospective clinicopathologic study of 74 cases: a gynecologic oncology group study. Gynecol Oncol 2001;83(2):355–62.PubMedCrossRefGoogle Scholar
  54. 54.
    Morice P, Fourchotte V, Sideris L, Gariel C, Duvillard P, Castaigne D. A need for laparoscopic evaluation of patients with endometrial carcinoma selected for conservative treatment. Gynecol Oncol 2005;96(1):245–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Mitsushita J, Toki T, Kato K, Fujii S, Konishi I. Endometrial carcinoma remaining after term pregnancy following conservative treatment with medroxyprogesterone acetate. Gynecol Oncol 2000;79(1):129–32.PubMedCrossRefGoogle Scholar
  56. 56.
    Montz FJ, Bristow RE, Bovicelli A, Tomacruz R, Kurman RJ. Intrauterine progesterone treatment of early endometrial cancer. Am J Obstet Gynecol 2002;186(4):651–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Dhar KK, NeedhiRajan T, Koslowski M, Woolas RP. Is levonorgestrel intrauterine system effective for treatment of early endometrial cancer? Report of four cases and review of the literature. Gynecol Oncol 2005;97(3):924–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Jones K, Georgiou M, Hyatt D, Spencer T, Thomas H. Endometrial adenocarcinoma following the insertion of a Mirena IUCD. Gynecol Oncol 2002;87(2):216–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Jeon YT, Park IA, Kim YB, et al. Steroid receptor expressions in endometrial cancer: clinical significance and epidemiological implication. Cancer Lett 2006;239(2):198–204.PubMedCrossRefGoogle Scholar
  60. 60.
    Ehrlich CE, Young PC, Cleary RE. Cytoplasmic progesterone and estradiol receptors in normal, hyperplastic, and carcinomatous endometria: therapeutic implications. Am J Obstet & Gynecol 1981;141(5):539–46.Google Scholar
  61. 61.
    Ehrlich CE, Young PC, Stehman FB, Sutton GP, Alford WM. Steroid receptors and clinical outcome in patients with adenocarcinoma of the endometrium. Am J Obstet & Gynecol 1988;158(4):796–807.Google Scholar
  62. 62.
    Creasman WT, Soper JT, McCarty KS, Hinshaw W, Clarke-Pearson DL. Influence of cytoplasmic steroid receptor content on prognosis of early stage endometrial carcinoma. Am J Obstet & Gynecol 1985;151(7):922–32.Google Scholar
  63. 63.
    Benraad TJ, Friberg LG, Koenders AJ, Kullander S. Do estrogen and progesterone receptors (E2R and PR) in metastasizing endometrial cancers predict the response to gestagen therapy? Acta Obstetricia et Gynecologica Scandinavica 1980;59(2):155–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Creasman WT, McCarty KS, Sr., Barton TK, McCarty KS, Jr. Clinical correlates of estrogenand progesterone-binding proteins in human endometrial adenocarcinoma. Obstet & Gynecol 1980;55(3):363–70.Google Scholar
  65. 65.
    Martin PM, Rolland PH, Gammerre M, Serment H, Toga M. Estradiol and progesterone receptors in normal and neoplastic endometrium: correlations between receptors, histopathological examinations and clinical responses under progestin therapy. Int J Cancer 1979;23(3):321–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Kauppila A, Kujansuu E, Vihko R. Cytosol estrogen and progestin receptors in endometrial carcinoma of patients treated with surgery, radiotherapy, and progestin. Clinical correlates. Cancer 1982;50(10):2157–62.PubMedCrossRefGoogle Scholar
  67. 67.
    Smid-Koopman E, Kuhne LC, Hanekamp EE, et al. Progesterone-induced inhibition of growth and differential regulation of gene expression in PRA- and/or PRB-expressing endometrial cancer cell lines. J Soc Gynecol Investig 2005;12(4):285–92.PubMedCrossRefGoogle Scholar
  68. 68.
    Hanekamp EE, Gielen SC, Smid-Koopman E, et al. Consequences of loss of progesterone receptor expression in development of invasive endometrial cancer. Clin Cancer Res 2003;9(11):4190–9.PubMedGoogle Scholar
  69. 69.
    Smid-Koopman E, Blok LJ, Kuhne LC, et al. Distinct functional differences of human progesterone receptors A and B on gene expression and growth regulation in two endometrial carcinoma cell lines. J Soc Gynecol Investig 2003;10(1):49–57.PubMedCrossRefGoogle Scholar
  70. 70.
    Miyamoto T, Watanabe J, Hata H, et al. Significance of progesterone receptor-A and –B expressions in endometrial adenocarcinoma. J Steroid Biochem Mol Biol 2004;92(3):111–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Conneely OM. Progesterone receptors in reproduction: functional impact of the A and B isoforms. Science 2000;289(5485):1751–4.PubMedCrossRefGoogle Scholar
  72. 72.
    Conneely OM, Mulac-Jericevic B, Lydon JP, De Mayo FJ. Reproductive functions of the progesterone receptor isoforms: lessons from knock-out mice. Mol Cell Endocrinol 2001;179(1-2):97–103.PubMedCrossRefGoogle Scholar
  73. 73.
    Conneely OM. Perspective: female steroid hormone action. Arthritis & Rheumatism 2001;44(4):782–93.CrossRefGoogle Scholar
  74. 74.
    Rowan BG, Bai W. Progesterone receptor coactivators Differential phosphorylation of chicken progesterone receptor in hormone-dependent and ligand-independent activation. Steroids 2000;65(10-11):545–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Spitz IM. Progesterone receptor modulators at the start of a new millennium. Steroids 2000;65(10-11):817–23.PubMedCrossRefGoogle Scholar
  76. 76.
    Bouchard P. Progesterone and the progesterone receptor. J Reprod Med 1999;44(2 Suppl):153–7.PubMedGoogle Scholar
  77. 77.
    Arnett-Mansfield RL, deFazio A, Wain GV, et al. Relative expression of progesterone receptors A and B in endometrioid cancers of the endometrium. Cancer Res 2001;61(11):4576–82.PubMedGoogle Scholar
  78. 78.
    Dai D, Kumar NS, Wolf DM, Leslie KK. Molecular tools to reestablish progestin control of endometrial cancer cell proliferation. Am J Obstet Gynecol 2001;184(5):790–7.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Division of Gynecologic OncologyDepartment of Obstetrics and Gynecology University of VirginiaCharlottesville

Personalised recommendations