Vaginal Estrogen Therapy for Patients with Breast Cancer

 

 Permissions and Reprints

Abstract

On account of the good prognosis for patients with breast cancer, improving or maintaining the quality of life in the aftercare period is becoming more and more important. In particular, the increasing usage of aromatase inhibitors in the past few years has led to an increased incidence of vaginal atrophy with symptoms such as vaginal dryness, petechial bleeding, dyspareunia and recurrent cystitis. And just these symptoms have a detrimental impact on the quality of life of breast cancer patients. Application of a topical estrogen therapy represents the most effective means to treat vaginal atrophy. The use of a systemic or, respectively, topical hormone therapy is, however, contraindicated for breast cancer patients. Further clinical trials are needed in order to assess the safety of vaginal estrogen therapy.

Zusammenfassung

Aufgrund der guten Prognose von Mammakarzinompatientinnen nimmt die Verbesserung bzw. Erhaltung der Lebensqualität in der Nachsorge einen zunehmenden Stellenwert ein. Gerade der vermehrte Einsatz von Aromatasehemmern hat in den vergangenen Jahren zu einer Zunahme der vaginalen Atrophie mit Symptomen wie Scheidentrockenheit, petechialen Blutungen, Dyspareunie und rezidivierenden Zystitiden geführt. Gerade diese Symptome beeinflussen in gravierender Weise die Lebensqualität von Mammakarzinompatientinnen. Die Anwendung einer lokalen Östrogentherapie stellt die effektivste Behandlungsform der Vaginalatrophie dar. Die Anwendung einer systemischen bzw. einer lokalen Hormontherapie bei Brustkrebspatientinnen ist jedoch kontraindiziert. Zur Beurteilung der Sicherheit einer vaginalen ET sind weitere klinische Studien erforderlich.

• References

• 1 Levi F, Bosetti C, Lucchini F et al. Monitoring the decrease in breast cancer mortality in Europe. Eur J Cancer Prev 2005; 14: 497-502
  CrossrefPubMedGoogle Scholar
• 2 Couzi RJ, Helzlsouer KJ, Fetting JH. Prevalence of menopausal symptoms among women with a history of breast cancer and attitudes toward estrogen replacement therapy. J Clin Oncol 1995; 13: 2737-2744
  PubMedGoogle Scholar
• 3 Ganz PA, Rowland JH, Desmond K et al. Life after breast cancer: understanding womenʼs health-related quality of life and sexual functioning. J Clin Oncol 1998; 16: 501-514
  PubMedGoogle Scholar
• 4 Baumgart J, Nilsson K, Stavreus-Evers A et al. Urogenital disorders in women with adjuvant endocrine therapy after early breast cancer. Am J Obstet Gynecol 2011; 204: 26.e1-26.e7
  CrossrefPubMedGoogle Scholar
• 5 Chin SN, Trinkaus M, Simmons C et al. Prevalence and severity of urogenital symptoms in postmenopausal women receiving endocrine therapy for breast cancer. Clin Breast Cancer 2009; 9: 108-117
  CrossrefPubMedGoogle Scholar
• 6 Jones SE, Cantrell J, Vukelja S et al. Comparison of menopausal symptoms during the first year of adjuvant therapy with either exemestane or tamoxifen in early breast cancer: report of a Tamoxifen Exemestane Adjuvant Multicenter trial substudy. J Clin Oncol 2007; 25: 4765-4771
  CrossrefPubMedGoogle Scholar
• 7 Eisemann N, Waldmann A, Katalinic A. Epidemiology of breast cancer – current figures and trends. Geburtsh Frauenheilk 2013; 73: 130-135
  Article in Thieme ConnectPubMedGoogle Scholar
• 8 Cella D, Fallowfield LJ. Recognition and management of treatment-related side effects for breast cancer patients receiving adjuvant endocrine therapy. Breast Cancer Res Treat 2008; 107: 167-180
  CrossrefPubMedGoogle Scholar
• 9 North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of the North American Menopause Society. Menopause 2007; 14: 355-369
  CrossrefPubMedGoogle Scholar
• 10 Ortmann O, Dören M, Windler E. Hormone therapy in perimenopause and postmenopause (HT): interdisciplinary S3 guideline, Association of the Scientific Medical Societies in Germany AWMF 015/062-short version. Arch Gynecol Obstet 2011; 284: 343-355
  CrossrefPubMedGoogle Scholar
• 11 Fick E-M, Anzeneder T, Katalinic A et al. Bisphosphonates and their role in therapy for breast cancer – results from the PATH Biobank. Geburtsh Frauenheilk 2013; 73: 412-421
  Article in Thieme ConnectPubMedGoogle Scholar
• 12 Rossouw JE, Anderson GL, Prentice RL et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Womenʼs Health Initiative randomized controlled trial. JAMA 2002; 288: 321-333
  CrossrefPubMedGoogle Scholar
• 13 Chlebowski R, Anderson G, Gass M. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA 2010; 304: 1684-1692
  CrossrefPubMedGoogle Scholar
• 14 Prentice R, Manson J, Langer R et al. Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause. Am J Epidemiol 2009; 170: 12-23
  CrossrefPubMedGoogle Scholar
• 15 LaCroix AZ, Chlebowski RT, Manson JE et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA 2011; 305: 1305-1314
  CrossrefPubMedGoogle Scholar
• 16 Shah NR, Borenstein J, Dubois RW. Postmenopausal hormone therapy and breast cancer: a systematic review and meta-analysis. Menopause 2005; 12: 668-678
  CrossrefPubMedGoogle Scholar
• 17 Greiser CM, Greiser EM, Doren M. Menopausal hormone therapy and risk of breast cancer: a meta-analysis of epidemiological studies and randomized controlled trials. Hum Reprod Update 2005; 11: 561-573
  CrossrefPubMedGoogle Scholar
• 18 Lee SA, Ross RK, Pike MC. An overview of menopausal oestrogen-progestin hormone therapy and breast cancer risk. Br J Cancer 2005; 92: 2049-2058
  CrossrefPubMedGoogle Scholar
• 19 Collins JA, Blake JM, Crosignani PG. Breast cancer risk with postmenopausal hormonal treatment. Hum Reprod Update 2005; 11: 545-560
  CrossrefPubMedGoogle Scholar
• 20 Col NF, Hirota LK, Orr RK et al. Hormone replacement therapy after breast cancer: a systematic review and quantitative assessment of risk. J Clin Oncol 2001; 19: 2357-2363
  PubMedGoogle Scholar
• 21 Holmberg L, Anderson H. HABITS (hormonal replacement therapy after breast cancer – is it safe?), a randomised comparison: trial stopped. Lancet 2004; 363: 453-455
  CrossrefPubMedGoogle Scholar
• 22 von Schoultz E, Rutqvist LE. Stockholm Breast Cancer Study Group. Menopausal hormone therapy after breast cancer: the Stockholm randomized trial. J Natl Cancer Inst 2005; 97: 533-535
  CrossrefPubMedGoogle Scholar
• 23 Kenemans P, Bundred NJ, Foidart JM. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol 2009; 10: 135-146
  CrossrefPubMedGoogle Scholar
• 24 Cardozo L, Bachmann G, McClish D et al. Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital Therapy Committee. Obstet Gynecol 1998; 92: 722-727
  CrossrefPubMedGoogle Scholar
• 25 Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev 2003; (4) CD001500
  PubMedGoogle Scholar
• 26 North American Menopause Society. Estrogen and progestogen use in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause 2010; 17: 242-255
  CrossrefPubMedGoogle Scholar
• 27 Mettler L, Olsen PG. Long-term treatment of atrophic vaginitis with low-dose oestradiol vaginal tablets. Maturitas 1991; 14: 23-31
  CrossrefPubMedGoogle Scholar
• 28 Weisberg E, Ayton R, Darling G. Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet. Climacteric 2005; 8: 83-92
  CrossrefPubMedGoogle Scholar
• 29 Gerbaldo D, Ferraiolo A, Croce S et al. Endometrial morphology after 12 months of vaginal oestriol therapy in postmenopausal women. Maturitas 1991; 13: 269-274
  CrossrefPubMedGoogle Scholar
• 30 Luisi M, Franchi F, Kicovic PM. A group-comparative study of effects of Ovestin® cream versus Premarin cream in postmenopausal women with vaginal atrophy. Maturitas 1980; 2: 311-319
  CrossrefPubMedGoogle Scholar
• 31 Buhling KJ, Eydeler U, Borregaard S et al. Systemic bioavailability of estriol following single and repeated vaginal administration of 0.03 mg estriol containing pessaries. Arzneimittelforschung 2012; 62: 378-383
  Article in Thieme ConnectPubMedGoogle Scholar
• 32 Mazur D, Vens-Cappell B, Lohmann K et al. Fractionated use of a 17β estradiol cream for the treatment of vaginal atrophy in postmenopausal women. Geburtsh Frauenheilk 2005; 65: 584-589
  Article in Thieme ConnectPubMedGoogle Scholar
• 33 Simon JA, Komi J. Vulvovaginal atrophy negatively impacts sexual function, psychosocial wellbeing, and partner relationships. N Am Menopause Assoc 2007; 10: 3-6
  PubMedGoogle Scholar
• 34 Graziottin A. Sexuality in the Menopause. In: Studd J, ed. The Yearbook of Royal College of Obstetrics and Gynecologists. London: RCOG Press; 1997: 201-209
  Google Scholar
• 35 Kendall A, Dowsett M, Folkerd E et al. Caution: vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol 2006; 17: 584-587
  CrossrefPubMedGoogle Scholar
• 36 Wills S, Ravipati A, Venuturumilli P et al. Effects of vaginal estrogens on serum estradiol levels in postmenopausal breast cancer survivors and women at risk of breast cancer taking an aromatase inhibitor or a selective estrogen receptor modulator. J Oncol Pract 2012; 8: 144-148
  CrossrefPubMedGoogle Scholar
• 37 Dew JE, Wren BG, Eden JA. A cohort study of topical vaginal estrogen therapy in women previously treated for breast cancer. Climacteric 2003; 6: 45-52
  CrossrefPubMedGoogle Scholar
• 38 Trevoux R, van der Velden WH, Popović D. Ovestin vaginal cream and suppositories for the treatment of menopausal vaginal atrophy. Reproduccion 1982; 6: 101-106
  PubMedGoogle Scholar
• 39 Griesser H, Skonietzki S, Fischer T et al. Low dose estriol pessaries for the treatment of vaginal atrophy: a double-blind placebo-controlled trial investigating the efficacy of pessaries containing 0.2 mg and 0.03 mg estriol. Maturitas 2012; 71: 360-368
  CrossrefPubMedGoogle Scholar
• 40 Pfeiler G, Glatz C, Königsberg R. Vaginal estriol to overcome side-effects of aromatase inhibitors in breast cancer patients. Climacteric 2011; 14: 339-344
  CrossrefPubMedGoogle Scholar
• 41 Biglia N, Peano E, Sgandurra P et al. Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study. Gynecol Endocrinol 2010; 26: 404-412
  CrossrefPubMedGoogle Scholar
• 42 Mattsson LA, Cullberg G. Vaginal absorption of two estriol preparations. A comparative study in postmenopausal women. Acta Obstet Gynecol Scand 1983; 62: 393-396
  CrossrefPubMedGoogle Scholar
• 43 Neven P, Donders G, Moegele M et al. Ultra-low dose vaginal estriol and Lactobacillus acidophilus (Gynoflor®) in early breast cancer survivors on aromatase inhibitors: pharmacokinetic, efficacy and safety results from a phase I study. San Antonio Breast Cancer Symposium 2012; Poster Presentation
  PubMedGoogle Scholar
• 44 Taylor AH, Guzail M, Al-Azzawi F. Differential expression of oestrogen receptor isoforms and androgen receptor in the normal vulva and vagina compared with vulval lichen sclerosus and chronic vaginitis. Br J Dermatol 2008; 158: 319-328
  PubMedGoogle Scholar
• 45 Witherby S, Johnson J, Demers L et al. Topical testosterone for breast cancer patients with vaginal atrophy related to aromatase inhibitors: a phase I/II study. Oncologist 2011; 16: 424-431
  CrossrefPubMedGoogle Scholar
• 46 Bygdeman M, Swahn ML. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas 1996; 23: 259-263
  CrossrefPubMedGoogle Scholar
• 47 Sturdee DW, Panay N. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010; 13: 509-522
  CrossrefPubMedGoogle Scholar

• Supplementary Material