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What Is the Place of Hormone Replacement Therapy in Ovarian, Endometrial, and Breast Cancer?

  • Inge T. A. Peters
  • Fiona C. Brownfoot
  • J. Baptist Trimbos
  • Martha Hickey
Chapter

Abstract

Menopause is the last menstrual period and represents the end of reproductive life. Menopause is commonly associated with symptoms that may negatively impact on quality of life and function such as hot flushes and night sweats, vaginal dryness, and sleep disturbance. Hormone replacement therapy (HRT) effectively alleviates these climacteric symptoms but may have adverse consequences for some women. The role of HRT for the management of menopausal symptoms following breast cancer and gynecological malignancy has been controversial. Relatively few studies have addressed the safety of HRT in these circumstances to provide clinical guidance. HRT has also been implicated in the development or growth of some cancers. Unopposed estrogens increase the risk of endometrial cancer, as does combined HRT without an adequate dose or duration of progestagen exposure. Combined HRT increases the risk of breast cancer, but estrogen only HRT does not appear to increase breast cancer risk and may even be protective in some women. Sequential combined HRT may also increase the risk of ovarian cancer. In those with a history of gynecological cancer, limited evidence supports the safety of HRT. Following breast cancer, available evidence suggests that HRT may increase the risk of new or recurrent breast cancer and so HRT is avoided. The care of women with menopausal symptoms following breast or gynecological cancer should take a multidisciplinary approach.

Keywords

Breast Cancer Ovarian Cancer Breast Cancer Risk Endometrial Cancer Hormone Replacement Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. for the STRAW 10 Collaborative Group. Executive summary of the stages of reproductive aging workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause. 2012;19(4):387–95.Google Scholar
  2. 2.
    Furness S, Roberts H, Marjoribanks J, Lethaby A, Hickey M, Farquhar C. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Libr. 2010;11:1–221.Google Scholar
  3. 3.
    American Cancer Society. Cancer facts & figures 2006. Atlanta: American Cancer Society; 2006.Google Scholar
  4. 4.
    Heintz APM, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, et al. Carcinoma of the ovary. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynecol Obstet. 2006;95:S161–92.CrossRefGoogle Scholar
  5. 5.
    Garrett A, Quinn MA. Hormonal therapies and gynecological cancers. Best Pract Res Clin Obstet Gynaecol. 2008;22(2):407–21.PubMedCrossRefGoogle Scholar
  6. 6.
    Riman T, Dickman PW, Nilsson S, Correia N, Nordlinder H, Magnusson CM, et al. Hormone replacement therapy and the risk of invasive epithelial ovarian cancer in Swedish women. J Natl Cancer Inst. 2002;94:497–504.PubMedCrossRefGoogle Scholar
  7. 7.
    Beral V, Bull D, Green J. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet. 2007;369:1703–10.PubMedCrossRefGoogle Scholar
  8. 8.
    Purdie DM, Bain CJ, Siskind V, Russell P, Hacker NF, Ward BG, et al. Hormone replacement therapy and risk of epithelial ovarian cancer. Br J Cancer. 1999;81(3):559–63.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Lacey JV, Brinton LA, Leitzmann MF, Mouw T, Hollenbeck A, Schatzkin A, et al. Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP diet and health study cohort. J Natl Cancer Inst. 2006;98:1397–405.PubMedCrossRefGoogle Scholar
  10. 10.
    Rodriquez C, Patel AV, Call EE, Jacob EJ, Thun MJ. Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women. JAMA. 2001;285(11):1460–5.CrossRefGoogle Scholar
  11. 11.
    Danforth KN, Tworoger SS, Hecht JL, Rossner BA, Colditz GA, Hankinson SE. A prospective study of postmenopausal use and ovarian cancer risk. Br J Cancer. 2007;96(1):151–6.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, et al. Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynecol Obstet. 2006;95:S105–43.CrossRefGoogle Scholar
  13. 13.
    Beral V, Bull D, Reeves G. Endometrial cancer and hormone replacement therapy in the Million Women Study. Lancet. 2005;365:1543–51.PubMedCrossRefGoogle Scholar
  14. 14.
    Jaakkola S, Lyytinen HK, Tadeusz D, Ylikorkala O, Pukkala E. Endometrial cancer associated with various forms of postmenopausal hormone therapy: a case–control study. Int J Cancer. 2011;128:1644–51.PubMedCrossRefGoogle Scholar
  15. 15.
    Wells M, Sturdee DW, Barlow DH, Ulrich LG, O’Brien K, Campbell MJ, et al. Effect on endometrium of long-term treatment with continuous combined oestrogen-progestogen replacement therapy: follow-up study. BMJ. 2002;325:239–43.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Razavi P, Pike MC, Horn-Ross PL. Long-term postmenopausal hormone therapy and endometrial cancer. Cancer Epidemiol Biomarkers Prev. 2010;19:475–83.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Key TJ, Pike MC. The dose-effect relationship between ‘unopposed’ estrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. Br J Cancer. 1988;57:205–12.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Benshushan A, Brzezinski A. Hormonal manipulations and breast cancer. Obstet Gynecol Surv. 2002;57(5):314–23.PubMedCrossRefGoogle Scholar
  19. 19.
    National Cancer Institute Annual Cancer Statistics Review. Including cancer trends: 1950–1985. Bethesda: National Institutes of Health; 1989.Google Scholar
  20. 20.
    Early Breast Cancer Trialists’ Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet. 2000;355:1757–70.CrossRefGoogle Scholar
  21. 21.
    Colditz G, Hankinson S, Hunter D, Willett W, Manson J, Stampfer M, et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med. 1995;332(24):1589–93.PubMedCrossRefGoogle Scholar
  22. 22.
    Lilienfeld AM. The relationship of cancer of the female breast to artificial menopause and marital status. Cancer. 1956;9:927–34.PubMedCrossRefGoogle Scholar
  23. 23.
    Feinleib M. Breast cancer and artificial menopause: a cohort study. J Natl Cancer Inst. 1968;41:315–29.PubMedGoogle Scholar
  24. 24.
    Rosner B, Colditz GA, Willett WC. Reproductive risk factors in a prospective study of breast cancer: the Nurse’s Health Study. Am J Epidemiol. 1994;139:819–35.PubMedGoogle Scholar
  25. 25.
    Paffenbarger RS, Kampert JB, Chang H. Characteristics that predict breast cancer before and after the menopause. Am J Epidemiol. 1980;112:258–62.PubMedGoogle Scholar
  26. 26.
    Cauley JA, Gutai JP, Kuller LH, LeDonne D, Powell JG. The epidemiology of serum sex hormones in postmenopausal women. Am J Epidemiol. 1989;129:1120–31.PubMedGoogle Scholar
  27. 27.
    Trerli S. Height and weight in relation to breast cancer morbidity and mortality: a prospective study of 570,000 women in Norway. Int J Cancer. 1989;44:23–30.CrossRefGoogle Scholar
  28. 28.
    Lew EA, Garfinkel L. Variations in mortality by weight among 750,000men and women. J Chronic Dis. 1979;32:563–76.PubMedCrossRefGoogle Scholar
  29. 29.
    Symmers WSC. Carcinoma of the breast in transsexual individuals after surgical and hormonal influence with the primary and secondary sexual characteristics. Br Med J. 1968;1:83–7.CrossRefGoogle Scholar
  30. 30.
    Podhajcer OL, Bravo A, Dain L, Guman N, Bover L, Mordoh J. In vitro analysis of the cellular proliferative response to 17b-estrahiol of human breast cancer. Cancer. 1988;61:1807–12.PubMedCrossRefGoogle Scholar
  31. 31.
    Trichopoulos D, MacMahon B, Cole P. Menopause and breast cancer risk. J Natl Cancer Inst. 1972;48:605–10.PubMedGoogle Scholar
  32. 32.
    Staffa JA, Newschaffer CJ, Jones JK. Progestins and breast cancer: an epidemiological review. Fertil Steril. 1992;57:473–91.PubMedGoogle Scholar
  33. 33.
    Henderson BE, Pike MC, Casagrande JT. Breast cancer and the estrogen window hypothesis. Lancet. 1981;2:363–4.PubMedCrossRefGoogle Scholar
  34. 34.
    Hardy EE, Pinotti JA, Algaba M. Reproductive variables and breast cancer risk: a case control study carried out in Campinas, Sao Paulo. Rev Bras Ginecol Obstet. 1989;11:212–6.Google Scholar
  35. 35.
    Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003;362:419–27.CrossRefGoogle Scholar
  36. 36.
    Anderson GL, Limacher M, Assaf R, Bassford T, Beresford SA, Black H, et al. The Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy – the women’s health initiative randomized controlled trial. JAMA. 2004;291:1701–12.Google Scholar
  37. 37.
    Collaborative group on hormonal factors in breast cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52.705 women with breast cancer and 108.411women without breast cancer. Lancet. 1997;350:1047–59.Google Scholar
  38. 38.
    Nanda K, Bastian LA, Schultz K. Hormone replacement therapy and the risk of death from breast cancer: a systematic review. Am J Obstet Gynecol. 2002;186:325–34.PubMedCrossRefGoogle Scholar
  39. 39.
    Fowler B, Hanlon A, Freedman G, Patchefsky A, Kessler H, Nicolaou N, et al. Postmenopausal hormone replacement therapy: effect on diagnosis and outcome in early- stage invasive breast cancer treated with conservative surgery and radiation. J Clin Oncol. 1999;17:1680–8.Google Scholar
  40. 40.
    Bonnier P, Sakr R, Bessenay F, Lejeune C, Charpin C, Martin PM, et al. Effects of hormone replacement therapy for menopause on prognostic factors of breast cancer. Gynecol Obstet Fertil. 2000;28:745–53.PubMedCrossRefGoogle Scholar
  41. 41.
    Delgado RC, Lubian Lopez DM. Prognosis of breast cancers detected in women receiving hormone replacement therapy. Maturitas. 2001;38:147–56.PubMedCrossRefGoogle Scholar
  42. 42.
    Manjer J, Malina J, Berglund G, Bondeson L, Garne JP, Janzon L. Increased incidence of small and well-differentiated breast tumors in post-menopausal women following hormone replacement therapy. Int J Cancer. 2001;92:919–22.PubMedCrossRefGoogle Scholar
  43. 43.
    Cheek J, Lacy J, Toth-Fejel S, Morris K, Calhoun K, Pommier RF. The impact of hormone replacement therapy on the detection and stage of breast cancer. Arch Surg. 2002;137:1015–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Lower EE, Blau R, Gazder P, Stahl DL. The effect of estrogen usage on the subsequent hormone receptor status of primary breast cancer. Breast Cancer Res Treat. 1999;58:205–11.PubMedCrossRefGoogle Scholar
  45. 45.
    Gajdos C, Tartter PI, Babinszki A. Breast cancer diagnosed during hormone replacement therapy. Obstet Gynecol. 2000;95:513–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Sacchini V, Zurrida S, Andreoni G, Luini A, Galimberti V, Veronesi P, et al. Pathologic and biological prognostic factors of breast cancers in short and long term hormone replacement therapy users. Ann Surg Oncol. 2002;9:266–71.PubMedCrossRefGoogle Scholar
  47. 47.
    Stolier AJ, Mera R, Schapira D. The impact of current use of hormone replacement therapy on prognostic factors and surgical treatment of new breast cancers. Oncol Rep. 1998;5:61–4.PubMedGoogle Scholar
  48. 48.
    Gapstur SM, Morrow M, Sellers TA. Hormone replacement therapy and risk of breast cancer with a favourable histology: results of the Iowa Women’s Health Study. JAMA. 1999;281:2091–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Antoine C, Liebens F, Carly B, Pastijn A, Rozenberg S. Influence of HRT on prognostic factors for breast cancer: a systematic review after the women’s health initiative trial. Hum Reprod. 2004;19(3):741–56.PubMedCrossRefGoogle Scholar
  50. 50.
    Holli K, Isola J, Cuzick J. Low biologic aggressiveness in breast cancer in women using hormone replacement therapy. J Clin Oncol. 1998;16:3115–20.PubMedGoogle Scholar
  51. 51.
    O’Connor IF, Shembekar MV, Shousha S. Breast carcinoma developing in patients on hormone replacement: a histological and immunohistological study. J Clin Pathol. 1998;51:935–8.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Kennedy DL, Baum C, Forbes MB. Noncontraceptive estrogens and progestins: use patterns over time. Obstet Gynecol. 1985;65:441–6.PubMedGoogle Scholar
  53. 53.
    Smith DC, Prentice R, Thompson DJ, Herrmann WL. Association of exogenous estrogen and endometrial carcinoma. N Engl J Med. 1975;293:1164–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Zeil HK, Finkle WD. Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med. 1975;293:1167–70.CrossRefGoogle Scholar
  55. 55.
    Hemminki E, Kennedy DL, Baum C, McKinlay SM. Prescribing of noncontraceptive estrogens and progestins in the United States 1974–86. Am J Public Health. 1988;78:1479–81.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Ross RK, Paganini-Hill A, Roy S, Chao A, Henderson BE. Past and present preferred prescribing practices of hormone replacement therapy among Los Angeles gynaecologists: possible implications for public health. Am J Public Health. 1988;78:516–9.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Bush T, Whiteman M, Flaws J. Hormone replacement therapy and breast cancer: a qualitative review. Obstet Gynecol. 2001;98(3):498–508.PubMedCrossRefGoogle Scholar
  58. 58.
    Chen WY, Manson JE, Hankinson SE, Rosner B, Holmes M, Willett W, et al. Unopposed estrogen therapy and the risk of invasive breast cancer. Arch Intern Med. 2006;166:1027–32.PubMedCrossRefGoogle Scholar
  59. 59.
    The Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy. The women’s health initiative randomised controlled trial. JAMA. 2004;291(14):1701–12.CrossRefGoogle Scholar
  60. 60.
    LaCroix A, Chlebowski R, Manson JE, Aragaki A, Johnson K, Marin L. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy. A randomised control trial. JAMA. 2011;305(13):1305–14.PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Ross RK, Paganini-Hill A, Wan PC, Pike MC. Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. J Natl Cancer Inst. 2000;92(4):328–32.PubMedCrossRefGoogle Scholar
  62. 62.
    Pike MC, Spicer DV, Dahmoush L, Press MF. Estrogens, progestogens, normal breast cell proliferation and breast cancer risk. Epidemiol Rev. 1993;15:17–35.PubMedGoogle Scholar
  63. 63.
    Oza AM, Boyd NR. Mammographic parenchymal patterns: a marker of breast cancer risk. Epidemiol Rev. 1993;15:196–208.PubMedGoogle Scholar
  64. 64.
    Greendale GA, Reboussin BA, Sie A, Singh HR, Olson LK, Gatewod O, et al. Effects of estrogen and estrogen-progestin on mammographic parenchymal density. Postmenopausal estrogen/progestin interventions (PEPI) investigators. Ann Intern Med. 1999;130:262–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Gadducci A, Biglia N, Cosio S, Sismondi P, Genazzani AR. Gynaecologic challenging issues in the management of BRCA mutation carriers: oral contraceptives, prophylactic salpingo-oophorectomy and hormone replacement therapy. Gynecol Endocrinol. 2010;26(8):568–77.PubMedCrossRefGoogle Scholar
  66. 66.
    Consensus NIH. Conference. Ovarian cancer – screening, treatment and follow-up. JAMA. 1995;273:491–7.CrossRefGoogle Scholar
  67. 67.
    Finch A, Narod SA. Quality of life and health status after prophylactic salpingo-oophorectomy in women who carry a BRCA mutation: a review. Maturitas. 2011;70:261–5.PubMedCrossRefGoogle Scholar
  68. 68.
    Finch A, Metcalfe KA, Chiang JK, Elit L, McLaughin J, Springate C, et al. The impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual function in women who carry a BRCA mutation. Gynecol Oncol. 2011;121:163–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Madalinska JB, Van Beurden M, Bleiker EMA, Valdimarsdottir HB, Hollenstein J, Massuger LF, et al. The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy. J Clin Oncol. 2006;24:3576–82.PubMedCrossRefGoogle Scholar
  70. 70.
    Kotsopoulos J, Lubinski J, Neuhausen SL, Lynch HT, Rosen B, Ainsworth P, et al. Hormone replacement therapy and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers. Gynecol Oncol. 2006;100:83–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Rebbeck TR, Friebel T, Wagner T, Lynch HT, Garber JE, Daly MB, et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE study group. J Clin Oncol. 2005;23:7804–10.PubMedCrossRefGoogle Scholar
  72. 72.
    Armstrong K, Sanford Schwartz J, Randall T, Rubin SC, Weber B. Hormone replacement therapy and life expectancy after prophylactic oophorectomy in women with BRCA1/2 mutations: a decision analysis. J Clin Oncol. 2004;22(6):1045–54.PubMedCrossRefGoogle Scholar
  73. 73.
    Ayhan A, Taskiran C, Simsek S, Sever A. Does immediate hormone replacement therapy affect the oncologic outcome in endometrial cancer survivors? Int J Gynecol Cancer. 2006;16:805–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Suriano KA, McHale M, McLaren CE, Li KT, Re A, Disaia PJ. Estrogen replacement therapy in endometrial cancer patients: a matched control study. Obstet Gynecol. 2001;97:555–60.PubMedCrossRefGoogle Scholar
  75. 75.
    Barakat RR, Bundy BN, Spirtos NM, Bell J, Mannel RS. Randomized double-blind trial of estrogen replacement therapy versus placebo in stage I or II endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2006;24:587–92.PubMedCrossRefGoogle Scholar
  76. 76.
    Mascarenhas C, Lambe M, Bellocco R, Bergfeldt K, Riman T, Persson I, et al. Use of hormone replacement therapy before and after ovarian cancer diagnosis and ovarian cancer survival. Int J Cancer. 2006;119:2907–15.PubMedCrossRefGoogle Scholar
  77. 77.
    Singh P, Oehler MK. Hormone replacement therapy after gynaecological cancer. Maturitas. 2010;65:190–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Rees M. Gynecologic oncology perspective on management of the menopause. Eur J Surg Oncol. 2006;32:892–7.PubMedCrossRefGoogle Scholar
  79. 79.
    Sturdee DW, Pines A. Updated IMS recommendations on postmenopausal hormone therapy and preventive strategies for midlife health. International Menopause Society. Climacteric. 2011;14:302–20.PubMedCrossRefGoogle Scholar
  80. 80.
    Hickey M, Elliot J, Davison SL. Hormone replacement therapy. BMJ. 2012;344:1–6.Google Scholar
  81. 81.
    Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326:469.PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Shifren JL, Braunstein GD, Simon JA. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med. 2000;343:682–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Hickey M, Saunders C, Patridge A, Santoro N, Joffe H, Steams V. Practical clinical guidelines for assessing and managing menopausal symptoms after breast cancer. Ann Oncol. 2008;19(10):1669–80.PubMedCrossRefGoogle Scholar
  84. 84.
    Chin S, Trinkaus M, Simmons C, Flynn C, Dranitsaris G, Bolivar R, et al. Prevalence and severity of urogenital symptoms in postmenopausal women receiving endocrine therapy for breast cancer. Clin Breast Cancer. 2009;9(2):108–17.PubMedCrossRefGoogle Scholar
  85. 85.
    Brennan ME, Houssami N. Overview of long term care of breast cancer survivors. Maturitas. 2011;69(2):106–12.PubMedCrossRefGoogle Scholar
  86. 86.
    Carpenter S, Andrykowski AM, Cordova M. Hot flashes in postmenopausal women treated for breast carcinoma: prevalence, severity, correlates, management and relation to quality of life. Cancer. 1998;82:1682–91.PubMedCrossRefGoogle Scholar
  87. 87.
    Couzi RJ, Helzlsouer KJ, Fetting JH. Prevalence of menopausal symptoms among women with a history of breast cancer and attitude toward estrogen replacement therapy. J Clin Oncol. 1995;13:2737–44.PubMedGoogle Scholar
  88. 88.
    Freeman EW. Associations of depression with the transition to menopause. Menopause. 2010;17:823–7.PubMedCrossRefGoogle Scholar
  89. 89.
    Losif CS, Bekassy Z. Prevalence of genito-urinary symptoms in the late menopause. Acta Obstet Gynecol Scand. 1984;63(3):257–60.Google Scholar
  90. 90.
    Bygdeman M, Swahn ML. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas. 1996;23(3):259–63.PubMedCrossRefGoogle Scholar
  91. 91.
    Loibl S, Lintermans A, Dieudonne AS, Neven P. Management of menopause symptoms in breast cancer patients. Maturitas. 2010;68:148–54.PubMedCrossRefGoogle Scholar
  92. 92.
    Holmberg G, Anderson H. HABITS (hormonal replacement therapy after breast cancer – is it safe?) a randomised comparison: trial stopped. Lancet. 2004;363:453–5.PubMedCrossRefGoogle Scholar
  93. 93.
    Holmberg L, Iverson OE, Rudenstam CM. Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. J Natl Cancer Inst. 2008;100:475–82.PubMedCrossRefGoogle Scholar
  94. 94.
    Schoultz EV, Rutqvist LE. Menopausal hormone therapy after breast cancer: the Stockholm randomised trial. J Natl Cancer Inst. 2005;97:533–5.CrossRefGoogle Scholar
  95. 95.
    Kenemans P, Bundred NJ, Fiodart JM. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non inferiority trial. Lancet Oncol. 2009;10:135–46.PubMedCrossRefGoogle Scholar
  96. 96.
    Suckling J, Lethaby AM, Kennedy H. Local estrogen for vaginal atrophy in postmenopausal women (review). In: Collaboration IC, editor. The Cochrane library. Wiley, Auckland, New Zealand; 2006.Google Scholar
  97. 97.
    Palacios S. Managing urogenital atrophy. Maturitas. 2009;63:315–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Kendall A, Dowsett M, Tolkerd L, Smith I. Caution: vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol. 2006;17(4):584–7.PubMedCrossRefGoogle Scholar
  99. 99.
    Melisko M, Rugo II, DeLuca A. A phase II study of vaginal testosterone cream vs estring for vaginal dryness or decreased libido in women with early stage breast cancer treated with aromatase inhibitors. Cancer Res. 2009; (Suppl 3) 69(24):5038.Google Scholar
  100. 100.
    Dew JL, Wren BG, Lden JA. A cohort study of topical vaginal estrogen therapy in women previously treated for breast cancer. Climacteric. 2003;6(1):45–52.PubMedGoogle Scholar
  101. 101.
    Barentsen H, Van de Weijer PH, Schram JH. Continuous low dose estradiol released from a vaginal ring versus estriol vaginal cream for urogenital atrophy. Eur J Obstet Gynecol Reprod Biol. 1997;71(1):73–80.PubMedCrossRefGoogle Scholar
  102. 102.
    Mattson LA, Cullberg G. A clinical evaluation of treatment with estriol vaginal cream versus suppository in postmenopausal women. Acta Obstet Gynecol Scand. 1983;63:397–401.CrossRefGoogle Scholar
  103. 103.
    Anderson GL, Chlebowski RT, Aragaki AK, Kuller LH, Manson JE, Gass M, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the women’s health initiative randomised placebo-controlled trial. Lancet Oncol. 2012;13(5):476–86.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  • Inge T. A. Peters
    • 1
  • Fiona C. Brownfoot
    • 2
  • J. Baptist Trimbos
    • 1
  • Martha Hickey
    • 3
  1. 1.Department of GynecologyLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Obstetrics and GynaecologyRoyal Women’s HospitalMelbourneAustralia
  3. 3.Obstetrics and GynaecologyRoyal Women’s Hospital and University of MelbourneMelbourneAustralia

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