Skip to main content
SpringerLink
Log in

Effect of hormone replacement therapy on postmenopausal endometrial bleeding

  • Article
  • Published:
Pathology & Oncology Research

Abstract

The aim of the study was to determine the effect of postmenopausal hormone replacement therapy (HRT) (treatment using estrogen only and sequential and continuous combined estrogen-progestogen treatment) on endometrial bleeding and histological changes of the endometrium. In a six-year period (2000–2005), 5893 patients were given care and the incidence of postmenopausal uterine bleeding was detected in groups of patients having and not having received hormonal treatment at the Menopause Out-patient Unit of the authors’ department. In the case of bleeding, fractioned abrasion was performed and the samples were analyzed histologically. Among the postmenopausal patients who had not been given hormonal treatment, the incidence of bleeding episodes was significantly higher as among those having received hormonal treatment. In the samples, findings of proliferative endometrium occurred significantly more often in case of non-treated patients and those treated with sequential combined hormone therapy compared to patients receiving continuous combined hormone therapy. Although it was statistically not significant, hyperplasia simplex and complex together showed a tendency of reduced incidence in patients medicated by continuous combined treatment. These findings suggest that continuous combined hormonal treatment started at the right time (even before the menopause) may reduce the chances of the development of hyperplasia. A significantly higher incidence of hyperplasia was noted in patients using estrogen treatment only. It is possible that unopposed estrogen treatment further engraves an already diagnosed endometrial hyperplasia. In the group having received hormonal treatment, no complex hyperplasia accompanied by atypia occurred, only hyperplasia simplex was diagnosed in these cases. As a result of continuous reliance on combined preparations, the endometrium had become atrophied, therefore the chance of hyperplasia-related changes and of bleeding as a side effect decreased significantly. According to the authors’ experience, hormonal treatment does not pose a risk to the development of endometrial carcinoma; on the contrary, continuous combined preparations appear to reduce the risk of hyperplasia and, indirectly, the chances of the development of adenocarcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Anastasiadis PG, Koutlaki NG, Skaphida PG et al: Endometrial polypus: prevalence, detection, and malignant potential in women with abnormal uterine bleeding. Eur J Gynaecol Oncol 21: 180–183, 2000.

    PubMed  CAS  Google Scholar 

  2. Astrup K, Olivarius N: Frequency of spontaneously occurring postmenopausal bleeding in the general population. Acta Obstet Gynecol Scand 83: 203–205, 2004.

    Article  PubMed  Google Scholar 

  3. Bachmann LM, Riet G, Clark TJ et al: Probability analysis for diagnosis of endometrial hyperplasia and cancer in postmenopausal bleeding: an approach for a rational diagnostic workup. Acta Obstet Gynecol Scand 82: 1–6, 2003.

    Article  Google Scholar 

  4. Bernard JP, Rizk E, Camatte S et al: Saline contrast sonohysterography in the preoperative assessment of benign intrauterine disorders. Ultrasound Obstet Gynecol 17: 145–149, 2001.

    Article  PubMed  CAS  Google Scholar 

  5. Burger HG, Dudley EC, Hopper JL et al: The endocrinology of the menopausal transition: a cross-sectional study of a population-based sample. J Clin Endocrinol Metab 80: 3537–3545, 1995.

    Article  PubMed  CAS  Google Scholar 

  6. Cerin A, Heldaas K, Moeller B: Adverse endometrial effects of long-cycle estrogen and progestagen replacement therapy. The Scandinavian Long-Cycle Study Group. New Engl J Med 334: 668–669, 1996.

    Article  PubMed  CAS  Google Scholar 

  7. Clark TJ, Barton PM, Coomarasamy A et al: Investigating postmenopausal bleeding for endometrial cancer: cost-effectiveness of initial diagnostic strategies. Br J Obstet Gynecol 113: 502–510, 2006.

    CAS  Google Scholar 

  8. Dahmoun M, Ödmark IS, Risberg B et al: Apoptosis, proliferation, and sex steroid receptors in postmenopausal endometrium before and during HRT. Maturitas 49: 114–123, 2004.

    Article  PubMed  CAS  Google Scholar 

  9. Dijkhuizen FP, Mol BW, Brolmann HA et al: The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer 89: 1765–1772, 2000.

    Article  PubMed  CAS  Google Scholar 

  10. Epstein E, Valentin L: Managing women with post-menopausal bleeding. Best Pract Res Clin Obstet Gynaecol 18: 125–143, 2004.

    Article  PubMed  Google Scholar 

  11. Erkkola R, Kumento U, Lehmuskoski S et al: No increased risk of endometrial hyperplasia with fixed long-cycle oestrogen-progestogen therapy after five years. J Br Menopause Soc 10: 9–13, 2004.

    Article  PubMed  Google Scholar 

  12. Farquhar CM, Lethaby A, Sowter M et al: An evaluation of risk factors for endometrial hyperplasia in premenopausal women with abnormal menstrual bleeding. Am J Obstet Gynecol 181: 525–529, 1999.

    Article  PubMed  CAS  Google Scholar 

  13. Ferenczy A: Pathophysiology of endometrial bleeding. Maturitas 45: 1–14, 2003.

    Article  PubMed  CAS  Google Scholar 

  14. Ferenczy A, Gelfand MM: Endometrial histology and bleeding patterns in postmenopausal women taking sequential, combined E2 and dydrogesterone. Maturitas 26: 219–226, 1997.

    Article  PubMed  CAS  Google Scholar 

  15. Goldschmit R, Katz Z, Blickstein I et al: The accuracy of endometrial Pipelle sampling with and without sonographic measurement of endometrial thickness. Obstet Gynecol 82: 727–730, 1993.

    Google Scholar 

  16. Goldstein SR, Zeltser I, Horan CK et al: Ultrasonography-based triage for perimenopausal patients with abnormal uterine bleeding. Am J Obstet Gynecol 177: 102–108, 1997.

    Article  PubMed  CAS  Google Scholar 

  17. Grady D, Ernster VL: Hormone replacement therapy and endometrial cancer: are current regimens safe? J Natl Cancer Inst 89: 1088–1089, 1997.

    Article  PubMed  CAS  Google Scholar 

  18. Grimes DA: Diagnostic dilation and curettage: a reappraisal. Am J Obstet Gynecol 142: 1–6, 1982.

    PubMed  CAS  Google Scholar 

  19. Gusberg SB: Precursors of corpus carcinoma. Estrogens and adenomatous hyperplasia. Am J Obstet Gynecol 54: 905–907, 1947.

    Google Scholar 

  20. Hickey M, Fraser IS: The structure of endometrial microvessels. Hum Reprod 3: 57–66, 2000.

    Google Scholar 

  21. Hickey M, Higham J, Sullivan M et al: Endometrial bleeding in hormone replacement therapy users: preliminary findings regarding the role of matrix metalloproteinase 9 (MMP-9) and tissue inhibitors of MMPs. Fertil Steril 75: 288–296, 2001.

    Article  PubMed  CAS  Google Scholar 

  22. Hickey M, Pillai G, Higham JM et al: Changes in endometrial blood vessels in the endometrium of women with hormone replacement therapy-related irregular bleeding. Hum Reprod 18: 1100–1106, 2003.

    Article  PubMed  CAS  Google Scholar 

  23. Holst T, Lang E, Winkler U et al: Bleeding patterns in peri and postmenopausal women taking a continuous combined regimen of estradiol with norethisterone acetate or a conventional sequential regimen of conjugated equine estrogens with medrogestone. Maturitas 43: 265–275, 2002.

    Article  Google Scholar 

  24. Hulley S, Grady D, Bush T et al: Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women: Heart and Estrogen/Progestin Replacement Study (HERS). JAMA 280: 605–613, 1998.

    Article  PubMed  CAS  Google Scholar 

  25. Kimura T, Kamiura S, Yamamoto T et al: Abnormal uterine bleeding and prognosis of endometrial cancer. Int J Gynecol Obstet 85: 145–150, 2004.

    Article  CAS  Google Scholar 

  26. Klein NA, Soules MR: Endocrine changes of the perimenopause. Clin Obstet Gynecol 41: 912–920, 1998.

    Article  PubMed  CAS  Google Scholar 

  27. March CM: Bleeding problems and treatment. Clin Obstet Gynecol 41: 928–939, 1998.

    Article  PubMed  CAS  Google Scholar 

  28. Mirkin S, Navarro F, Archer DF: Hormone therapy and endometrial angiogenesis. Climact 6: 273–277, 2003.

    Article  Google Scholar 

  29. Mishell DR Jr,Kaunitz AM: Devices for endometrial sampling. A comparison. J Reprod Med 43: 180–184, 1998.

    PubMed  Google Scholar 

  30. Mossa B, Imperato F, Marziani R et al: Hormonal replacement therapy and evaluation of intrauterine pathology in postmenopausal women: a ten-year study. Eur J Gynaecol Oncol 24: 507–512, 2003.

    PubMed  CAS  Google Scholar 

  31. Oehler MK, MacKenzie I, Kehoe S et al: Assessment of abnormal bleeding in menopausal women: an update. J Br Menopause Soc 9: 117–121, 2003.

    Article  PubMed  Google Scholar 

  32. Omodei U, Ferrazzia E, Ruggeri C et al: Endometrial thickness and histological abnormalities in women on hormonal replacement therapy: a transvaginal ultrasound/hysteroscopic study. Ultrasound Obstet Gynecol 15: 317–320, 2000.

    Article  PubMed  CAS  Google Scholar 

  33. Papp Z (ed): A szülészet-nõgyógyászat tankönyve. Semmelweis Kiadó, Budapest, 2002.

    Google Scholar 

  34. Perrone G, DeAngelis C, Critelli C et al: Hysteroscopic findings in postmenopausal abnormal uterine bleeding: a comparison between HRT users and non-users. Maturitas 43: 251–255, 2002.

    Article  PubMed  CAS  Google Scholar 

  35. Pike MC, Peters RK, Cozen W: Estrogen-progestin replacement therapy and endometrial cancer. J Natl Cancer Inst 89: 1110–1116, 1997.

    Article  PubMed  CAS  Google Scholar 

  36. Reslova T, Tosner J, Resl M et al: Endometrial polypus. A clinical study of 245 cases. Arch Gynecol Obstet 262: 133–139, 1999.

    Article  PubMed  CAS  Google Scholar 

  37. Samsioe G.: Hormone replacement therapy: aspects of bleeding problems and compliance. Int J Fertil Menopausal Stud 41: 11–15, 1996.

    PubMed  CAS  Google Scholar 

  38. Schmidt T, Nawroth F, Breidenbach M et al: Differential indication for histological evaluation of endometrial fluid in postmenopause. Maturitas 50: 177–181, 2005.

    Article  PubMed  CAS  Google Scholar 

  39. Seltzer VL, Benjamin F, Deutsch S: Perimenopausal bleeding patterns and pathological findings. J Am Med Womens Assoc 45: 132–134, 1990.

    PubMed  CAS  Google Scholar 

  40. Shapiro S, Kelly JP, Rosenberg L et al: Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens. N Engl J Med 313: 969–972, 1985.

    PubMed  CAS  Google Scholar 

  41. Sivridis E, Giatromanolaki A: Proliferative activity in postmenopausal endometrium: the lurking potential for giving rise to an endometrial adenocarcinoma. J Clin Pathol 57: 840–844, 2004.

    Article  PubMed  CAS  Google Scholar 

  42. Toon VG, Patrick N: Endometrial safety of hormone replacement therapy: review of literature. Maturitas 42: 93–104, 2002.

    Article  Google Scholar 

  43. Valle RF: Office hysteroscopy. Clin Obstet Gynecol 42: 276–289, 1999.

    Article  PubMed  CAS  Google Scholar 

  44. Van de Weijer PHM, Scholten P, van der Mooren MJ: Bleeding patterns and endometrial histology in postmenopausal women taken low dose, sequential combined E2 and dydrogesterone. Climact 2: 1–9, 1999.

    Article  Google Scholar 

  45. Weber AM, Belinson JL, Piedmonte MR: Risk factors for endometrial hyperplasia and cancer among women with abnormal bleeding. Obstet Gynecol 93: 594–598, 1999.

    Article  PubMed  CAS  Google Scholar 

  46. Wildemeersch D, Schacht E, Wildemeersch P: Performance and acceptability of intrauterine release of levonorgestrel with a miniature delivery system for hormonal substitution therapy, contraception and treatment in peri- and postmenopausal women. Maturitas 44: 237–245, 2003.

    Article  PubMed  CAS  Google Scholar 

  47. Woodruff JD, Pickar JH: Incidence of endometrial hyperplasia in postmenopausal women taken conjugated estrogens (Premarin) with medroxyprogesterone acetate versus conjugated estrogens alone. Am J Obstet Gynecol 170: 1213–1223, 1994.

    PubMed  CAS  Google Scholar 

  48. Wren BG, Brown L: Compliance with hormonal replacement therapy. Maturitas 13: 17–21, 1991.

    Article  PubMed  CAS  Google Scholar 

  49. Writing Group for the PEPI Trial. Effects of hormonal replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen-Progestin Interventions (PEPI) Trial. JAMA 275: 370–375 1996.

    Article  Google Scholar 

  50. Zerbe MJ, Zhang J, Bristow RE et al: Retrograde seeding of malignant cells during hysteroscopy in presumed early endometrial cancer. Gynecol Oncol 79: 55–58, 2000.

    Article  PubMed  CAS  Google Scholar 

  51. Zupi E, Sbracia M, Marconi D et al: TNFalpha expression in hyperplastic endometrium. Am J Reprod Immunol 44: 153–159, 2000.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. 1st Department of Obstetrics and Gynecology, Faculty of Medicine, Semmelweis University, Baross u. 27, H-1088, Budapest, Hungary

    Zoltan Magyar MD, Eniko Berkes, Zsolt Csapo & Zoltan Papp

Authors
  1. Zoltan Magyar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eniko Berkes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zsolt Csapo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zoltan Papp
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zoltan Magyar MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Magyar, Z., Berkes, E., Csapo, Z. et al. Effect of hormone replacement therapy on postmenopausal endometrial bleeding. Pathol. Oncol. Res. 13, 351–359 (2007). https://doi.org/10.1007/BF02940316

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02940316

Key words

Search

Navigation