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Vaginal estrogen therapy in postmenopausal breast cancer patients treated with aromatase inhibitors

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Introduction

Breast cancer is the most frequent cancer among women with about 1.38 million new cases worldwide every year. Most of these patients are postmenopausal and suffer from hormone receptor positive breast tumors. About 50% of postmenopausal women between 50 and 60 years and 72% of women over 70 years suffer from vulvovaginal athrophy (VVA). Adjuvant treatment with aromatase inhibitors (AIs) improves outcomes in postmenopausal women with hormone receptor positive early stage breast cancer compared with tamoxifen. A frequent side effect of AI use is VVA with symptoms like vaginal dryness, vaginitis, pruritus, dyspareunia and cystitis.

Materials and methods

We searched major databases (i.e. pubmed) with the following selection criteria: breast cancer, hormone therapy, vaginal estrogen, aromatase inhibitor, vaginal atrophy, serum estrogen levels.

Conclusions

Vaginal administration of estradiol is a well known and safe alternative to systemic estrogen therapy, but studies demonstrated significant increases in plasma concentrations of estradiol. Such observations have also been reported in postmenopausal breast cancer patients treated with AIs. Further studies are needed to explore risk of breast cancer recurrence after vaginal estrogen application for patients on adjuvant endocrine therapy with AIs.

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References

  1. International Agency for Research on Cancer (iarc). GLOBOCAN 2008: breast cancer incidence and mortality worldwide. http://globocan.iarc.fr/factsheets/cancers/breast.asp. Accessed 23 January 2011

  2. Robert Koch Institut Krebs in Deutschland 2005/2006 Häufigkeit und Trends, 7. Ausgabe. http://www.edoc.rki.de/documents/rki_fv/re2vZ21t28Ir8Y/…/22aJOdYnmXV0I.pdf. Accessed 23 January 2011

  3. Rossin-Amar B (2000) Vaginal dryness in the menopausal woman (physiological and psychological aspects). Gynecol Obstet Fertil 28:245–249

    PubMed  CAS  Google Scholar 

  4. Berman JR, Berman LA, Werbin TJ, Goldstein I (1999) Female sexual dysfunction: anatomy, physiology, evaluation and treatment options. Curr Opin Urol 9:563–568

    Article  PubMed  CAS  Google Scholar 

  5. Joslyn SA (2002) Hormon receptors in breast cancer: Racial differences in distribution and survival. Breast Cancer Res Treat 73:45–59

    Article  PubMed  CAS  Google Scholar 

  6. Forbes JF, Cuzick J, Buzdar A et al (2008) Arimidex, tamoxifen, alone or in combination (ATAC) trialists’ group. effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 9:45–53

    Article  PubMed  Google Scholar 

  7. Kendall A, Dowsett M, Folkerd E, Smith I (2006) Caution: vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol 17:584–587

    Article  PubMed  CAS  Google Scholar 

  8. Fallowfield L, Cella D, Cuzick J et al (2004) Quality of life of postmenopausal women in the arimidex, tamoxifen, alone or in combination (ATAC) adjuvant breast cancer trial. J Clin Oncol 22:4261–4271

    Article  PubMed  CAS  Google Scholar 

  9. Ganz PA, Rowland JH, Desmond K et al (1998) Life after breast cancer: understanding women’s health- related quality of life and sexual functioning. J Clin Oncol 16:501–514

    PubMed  CAS  Google Scholar 

  10. Höffler D, Lusek R, Berthold HK, Tiaden JD (2003) Arzneimittelkommission der Deutschen Ärzteschaft 2003. Hormontherapie im Klimakterium. Therapieempfehlungen. Arzneiverordnung in der Praxis 3:19–26

    Google Scholar 

  11. New Zealand Guideline Group (NZGG) ( 2001) Best practice evidence-based guideline. The appropriate prescribing of hormone replacement therapy. Published May ISBN: 0-473-44714185

  12. North American Menopause Society (NAMS Board) (2007) Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of the North American Meno-pause Society. Menopause 14:168–182

    Article  Google Scholar 

  13. North American Menopause Society (NAMS Board) (2008) Estrogen and progestogen use in post- menopausal women: July 2008 position statement of the North American Menopause Society. Menopause 15:584–603

    Article  Google Scholar 

  14. Collins JA, Blake JM, Crosignani PG (2005) Breast cancer risk with postmenopausal hormonal treatment. Hum Reprod Update 11:545–560

    Article  PubMed  CAS  Google Scholar 

  15. Eberhardt S, Kulp W, von der Schulenburg JM, et al (2007) Hormone zur Therapie von Beschwerden im Klimakterium und zur Primärprävention von Erkrankungen in der Postmenopause. http://gripsdb.dimdi.de/de/hta/hta_berichte/hta127_bericht_de.pdf. Accessed 23 January 2011

  16. Farquhar CM, Marjoribanks J, Lethaby A, Lamberts Q, Suckling JA, The Cochrane HT Study Group (2005) Long-term hormone therapy for perimenopausal and postmenopausal women (review). Cochrane Database Syst Rev 3:CD004143

    PubMed  Google Scholar 

  17. Farquhar CM, Marjoribanks J, Lethaby A, Lamberts Q, Suckling JA, and the Cochrane HT Study Group (2008) Long-term hormone therapy for perimenopausal and postmenopausal women (review). In: new search for studies completed, conclusions not changed. The Cochrane Library. 2:CD004143

  18. Greiser CM, Greiser EM, Dören M (2005) Menopausal hormone therapy and risk of breast cancer: a meta-analysis of epidemiological studies and randomized controlled trials. Human Reprod Update 11:561–573

    Article  CAS  Google Scholar 

  19. IARC Monographs on the evaluation of carcinogenic risks to humans: combined estrogen- progestogen contraceptives and combined estrogen-progestogen menopausal therapy. (2007) 91 http://www.monographs.iarc.fr/ENG/Meetings/vol100-listagents.pdf

  20. Lee SA, Ross RK, Pike MC (2005) An overview of menopausal oestrogen- progestin hormone therapy and breast cancer risk. Br J Cancer 92:2049–2058

    Article  PubMed  CAS  Google Scholar 

  21. Shah NR, Borenstein J, Dubois RW (2005) Postmenopausal hormone therapy and breast cancer: a systematic review and meta-analysis. Menopause 12:668–678

    Article  PubMed  Google Scholar 

  22. Beral V (2003) Million Women Study Collaborators: breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 362:419–427 (Erratum in: Lancet 2003; 362:1160)

    Article  PubMed  CAS  Google Scholar 

  23. Heiss G, Wallace R, Anderson GL, Aragaki A, Beresford SA, Brzyski R, Chlebowski RT, Gass M, LaCroix A, Manson JE, Prentice RL, Rossouw J, Stefanick ML (2008) Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA 9:1036–1045

    Article  Google Scholar 

  24. Ravdin PM, Cronin KA, Howlader N et al (2007) The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med 356:1670–1674

    Article  PubMed  CAS  Google Scholar 

  25. Noss D, Ortmann O (2009) Hormone therapy (HT) and Cancer. J Gynaecol Endokrinol 19:6–10

    Google Scholar 

  26. Holmberg L, Anderson H (2004) HABITS (hormonal replacement therapy after breast cancer—is it safe?), a randomized comparison: trial stopped. Lancet 363:453–455

    Article  PubMed  CAS  Google Scholar 

  27. Kenemans P, Bundred NJ, Foidart JM, Kubista E, von Schoultz B et al (2009) LIBERATE Study Group: safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double- blind, randomized, non inferiority trial. Lancet Oncol. 10:135–146

    Article  PubMed  CAS  Google Scholar 

  28. Von Schoultz E, Rutqvist LE (2005) Menopausal hormone therapy after breast cancer: the Stockholm randomized trial. J Natl Cancer Inst 97:533–535

    Article  Google Scholar 

  29. Vassilopoulou-Sellin R, Theriault R, Klein MJ (1997) Estrogen replacement therapy in women with prior diagnosis and treatment for breast cancer. Gynecol Oncol 65:89–93

    Article  PubMed  CAS  Google Scholar 

  30. Wile AG, Opfell RW, Margileth DA (1993) Hormone replacement therapy in previously treated breast cancer patients. Am J Surg 165:372–375

    Article  PubMed  CAS  Google Scholar 

  31. Stoll BA (1989) Hormone replacement therapy in women treated for breast cancer. Eur J Cancer Clin Oncol 25:1909–1913

    Article  PubMed  CAS  Google Scholar 

  32. Powles TJ, Hickish T, Casey S, O’Brien M (1993) Hormone replacement after breast cancer. Lancet 342:60–61

    Article  PubMed  CAS  Google Scholar 

  33. Eden JA, Bush T, Nand S, Wren BG (1995) A case-controlled study of combined continuous hormone replacement therapy amongst women with a personal history of breast cancer. Menopause 2:67–72

    Article  Google Scholar 

  34. Ursic-Vrscaj M, Bebar S (1999) A case-control study of hormone replacement therapy after primary surgical breast cancer treatment. Eur J Surg Oncol 25:146–151

    Article  PubMed  CAS  Google Scholar 

  35. Vassilopoulou-Sellin R, Asmar L, Hortobagyi GN et al (1999) Estrogen replacement therapy after localized breast cancer: clinical outcome of 319 women followed prospectively. J Clin Oncol 17:1482–1487

    PubMed  CAS  Google Scholar 

  36. DeSaia PJ, Brewster WR, Ziogas A, Anton-Culver H (2000) Breast cancer survival and hormone replacement therapy: a cohort analysis. Am J Clin Oncol 23:541–545

    Article  Google Scholar 

  37. Marsden J, Whitehead M, A’Hern R, Baum M, Sacks N (2000) Are randomized trials of hormone replacement therapy in symptomatic women with breast cancer feasible? Fertil Steril 37:292–299

    Article  Google Scholar 

  38. O’Meara ES, Rossing MA, Daling JR, Elmore JG, Barlow WE, Weiss NS (2001) Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality. J Natl Cancer Inst 93:754–762

    Article  PubMed  Google Scholar 

  39. Beckmann MW, Mohrmann T, Kuschel B et al (1998) Hormonersatztherapie (HRT) nach Mammakarzinomerkrankung Ergebnisse einer Beobachtungsstudie. Geburtshilfe Frauenheilkd 58:193–196

    Article  Google Scholar 

  40. Col N, Hirota L et al (2001) Hormone replacement therapy after breast cancer: a systemic review and quantitative assessment of risk. J Clin Oncol 19:2357–2363

    PubMed  CAS  Google Scholar 

  41. Decker D, Pettinga J et al (2003) Estrogen replacement therapy in breast cancer survivors: a matched-controlled series. Menopause 4:277–285

    Article  Google Scholar 

  42. Cardozo L, Bachmann G, McClish D, Fonda D, Bigerson L (1998) Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the hormones and urogenital therapy commmittee. Obstet Gyncol 92:722–727

    Article  CAS  Google Scholar 

  43. Suckling J, Lethaby A, Kennedy R (2003) Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev 4:CD001500

    PubMed  Google Scholar 

  44. North American Menopause Society (2007) Menopause practice: a clinican’s guide, 3rd edn edn. North American Menopause Society, Mayfield Heights

    Google Scholar 

  45. Nilsson K, Heimer G (1992) Low- dose oestradiol in the treatment of urogentital oestrogen deficiency- a pharmacokinetic and pharmacodynamic study. Maturitas 15:121–127

    Article  PubMed  CAS  Google Scholar 

  46. Sindberg P, Rasmussen H (1992) Low- dose 17β- estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study. Eur J Obstetet Gynecol 44:137–144

    Article  Google Scholar 

  47. Ascenzi P, Bodeci A, Marino M (2006) Structure- function relationship of estrogen receptor alpha and beta: impact on human health. Mol Aspects 27:299–402

    Article  CAS  Google Scholar 

  48. Ruggiero RJ, Likis FE (2002) Estrogen: physiology, pharmacology, and formulations for replacement therapy. J Midwifery Women’s Health 47:130–138

    Article  Google Scholar 

  49. Van der Vies J (1982) The pharmacology of oestriol. Maturitas. 4:291–299

    Article  PubMed  Google Scholar 

  50. Babuna C, Aksu MF, Erez R (1982) Management of lower genital tract atrophy with a vaginal cream containing oestriol. In: The menopause: clinical endocrinological and pathophysiological aspects. Academic Press, London, pp 557–562

    Google Scholar 

  51. Boselli F, Volpe A, Genazzani AR (1987) Topical therapy: estriol vaginal cream in postmenopausal women: gynecological endocrinology. Parthenon publishing, Carnforth, pp 687–694

    Google Scholar 

  52. Boselli F, Cicoli C, Volpe A, Genazzani AR (1987) Endometrial morphology after long-term topical oestriol therapy in postmenopausal women. In: Abstracts of the 5th International Congress on the Menopause Sorrento. Parthenon Publishing, Carnforth. p 75

  53. Genazzani AR, Inaudi P, La Rosa R, De Leo V, Ricci-Danero MG, Danero S (1980) Estriol and menopause—clinical and endocrinological results of vaginal administration. In: International symposium on the menopause: clinical, endocrinological and pathophysiological aspects

  54. Gerbaldo D, Ferraiolo A, Croce S, Truini M, Capitanio GL (1991) Endometrial morphology after 12 months of vaginal oestriol therapy in postmenopausal women. Maturitas 13:269–274

    Article  PubMed  CAS  Google Scholar 

  55. Kicovic PM, Cortes-Prieto J, Milojevic S, Haspels AA, Aljinovic A (1980) The treatment of postmenopausal vaginal atrophy with Ovestin® vaginal cream or suppositories: clinical, endocrinological and safety aspects. Maturitas 2:275–282

    Article  PubMed  CAS  Google Scholar 

  56. Lauritzen C (1979) Erfahrungen mit einer oestriol-vaginalcreme. Ther Gegenw 118:567–577

    Google Scholar 

  57. Luisi M, Franchi F, Kicovic PM (1980) A group-comparative study of effects of Ovestin® cream versus premarin cream in postmenopausal women with vaginal atrophy. Maturitas 2:311–319

    Article  PubMed  CAS  Google Scholar 

  58. Mattsson LA, Cullberg G (1983) A clinical evaluation of treatment with estriol vaginal cream versus suppository in postmenopausal women. Acta Obstet Gynecol Scand 62:397–401

    Article  PubMed  CAS  Google Scholar 

  59. Foidart JM, Vervliet J, Buytaert Ph (1991) Efficacy of sustained- release vaginal oestriol in alleviating urogenital and systemic climacteric complaints. Maturitas 13:99–107

    Article  PubMed  CAS  Google Scholar 

  60. Fink RS, Collins WP, Papadaki L, O’Reilly B, Ginsburg J (1985) Vaginal estriol: effective menopausal therapy not associated with endometrial hyperplasia. J Gynaecol Endocrinol 1:1–2

    Google Scholar 

  61. Pfeiler G, Glatz C, Königsberg R et al (2011) Vaginal estriol to overcome side-effects of aromatase inhibitors in breast cancer patients. Climacteric 14:339–344

    Article  PubMed  CAS  Google Scholar 

  62. Vooijs GP, Geurts TBP (1995) Review of the endometrial safety during intravaginal treatment with estriol. Eur J Obstet Gynecol Reprod Biol 62:101–106

    Article  PubMed  CAS  Google Scholar 

  63. Kendall A, Dowsett M, Folkerd E, Smith I (2006) Caution: vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol 17:584–587

    Article  PubMed  CAS  Google Scholar 

  64. Labrie F, Cusan L, Gomez JL et al (2009) Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women. Menopause 16:30–36

    Article  PubMed  Google Scholar 

  65. Derzko C, Elliott S, Lam W (2007) Management of sexual dysfunction in postmenopausal breast cancer patients taking adjuvant aromatase inhibitor therapy. Curr Oncol 14:20–40

    Article  Google Scholar 

  66. Bachmann GA, Nevadunsky NS (2000) Diagnosis and treatment of atrophic vaginitis. Am Fam Physician 61:3090–3096

    PubMed  CAS  Google Scholar 

  67. Murray A, Freedman MA (2008) Vaginal pH, estrogen and genital atrophy. Menopause Manag 17:9–11

    Google Scholar 

  68. American College of Obstetricians and Gynaecologists, Committee on Patient Education (2007) Disorders of the vulva. ACOG, Washington, DC http://www.acog.org/publications/patient_education/bp088.cfm. Accessed 23 January 2011

  69. Bygdeman M, Swahn ML (1996) Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in post- menopausal women. Maturitas 23:259–263

    Article  PubMed  CAS  Google Scholar 

  70. Society of Obstetricians, Gynaecologists of Canada (2005) Clinical practice guidelines: the detection and management of vaginal atrophy. Int J Gynaecol Obstet 88:222–228

    Article  Google Scholar 

  71. Castelo-Branco C, Cancelo MJ, Villero J, Nohales F, Julia MD (2005) Management of post- menopausal vaginal atrophy and atrophic vaginitis. Maturitas 52:46–52

    Article  Google Scholar 

  72. Suckling J, Lethaby A, Kennedy R (2003) Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev 4:CD001500

    PubMed  Google Scholar 

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Correspondence to Olaf Ortmann.

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Moegele, M., Buchholz, S., Seitz, S. et al. Vaginal estrogen therapy in postmenopausal breast cancer patients treated with aromatase inhibitors. Arch Gynecol Obstet 285, 1397–1402 (2012). https://doi.org/10.1007/s00404-011-2181-6

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  • DOI: https://doi.org/10.1007/s00404-011-2181-6

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