Impact of menopausal hormone therapy on the development and progression of cervical and endometrial cancers

Yakushevskaya O.V., Babaeva N.A., Yureneva S.V., Ashrafyan L.A.

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow, Russia
Antitumor therapy for malignant diseases of the reproductive system is often accompanied by the development of induced menopause. Studying the possibility of safely prescribing menopausal hormone therapy (MHT) in this group of patients is an urgent task, since most patients have to deal with the consequences of estrogen deficiency states after antitumor therapy for many years. The review analyzes the available information on the rate of progression/recurrence of the neoplastic process in cervical cancer/endometrial cancer (CC/EC) survivors during MHT. Articles were sought in accordance with the recommendations of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) presented in PubMed and SCOPUS. The use of MHT was evaluated in two ways: 1) as a risk factor for CC/EC in women without a history of this pathology and 2) as a risk factor for CC/EC recurrence/progression. Analyzing the available publications revealed no reliable evidence for the negative effect of MHT on the outcomes of CC/EC. To prescribe MHT after favorable completion of antitumor therapy in patients with a history of squamous cell CC has long been a routine practice. With hormone-dependent СC/EC in young women with induced menopause, the possibility of using MHT should be resolved in favor of the existing advantages (in reducing the risk of age-associated pathology and in improving the quality of life) and assessing the corresponding risks.
Conclusion: The possibility of prescribing MHT to patients with a history of cancer should be discussed within the framework of a council of physicians, such as a gynecological oncologist, a chemotherapist, and an obstetrician/gynecologist. Further prospective and randomized studies are needed to fully evaluate the impact of MHT on oncological outcomes in CC/EC survivors.


cervical cancer
endometrial cancer
menopausal hormone therapy
iatrogenic menopause


  1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018; 68(6):394-424.
  2. Arbyn M., Weiderpass E., Bruni L., de Sanjosé S., Saraiya M., Ferlay J. et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob. Health. 2020; 8(2): e191-e203.
  3. National Cancer Institute. Surveillance, Epidemiology and End Results Program. Cancer stat facts: cervical cancer. Available at: (Accessed November 11, 2018).
  4. Abu-Rustum N.R., Yashar C.M, Bean S., Bradley K., Campos S.M, Chon H.S. et al. NCCN guidelines insights: cervical cancer, version 1.2020: featured updates to the NCCN guidelines. J. Natl. Compr. Canc. Netw. 2020; 18(6): 660-6.
  5. Шабалова О.В., Юренева С.В., Ермакова Е.И., Хохлова С.В., Гарданова Ж.Р., Якушевская О.В. Хирургическая менопауза как фактор риска раннего развития коморбидных состояний у женщин репродуктивного возраста. Акушерство и гинекология. 2021; 6: 54-9. [Shabalova O.V., Yureneva S.V., Ermakova E.I., Khokhlova S.V., Gardanova Zh.R., Yakushevskaya O.V. Surgical menopause as a risk factor for the early development of comorbid conditions in reproductive-aged women. Obstetrics and Gynecology. 2021; 6: 54-9. (in Russian)].
  6. Якушевская О.В., Юренева С.В., Протасова А.Э., Хабас Г.Н., Думановская М.Р. Менопаузальная гормональная терапия и рак тела матки: допустимость тандема. Гинекология. 2018; 20(6): 42-7. [Yakushevskaya O.V., Yureneva S.V., Protasova A.E., Khabas G.N., Dumanovskaya M.R. Menopausal hormone therapy and uterine cancer: the asseptability of the tandem. Gynecology. 2018; 20(6): 42-7. (in Russian)]. 10.26442/20795696.2018.6.180113.
  7. Zhai Y., Bommer G.T., Feng Y., Wiese A.B., Fearon E.R., Cho K.R. Loss of estrogen receptor 1 enhances cervical cancer invasion. American Journal of Pathology. 2010; 177(2): 884-95.
  8. Rauh L.A., Pannone A.F., Cantrell L.A. Hormone replacement therapy after treatment for cervical cancer: are we adhering to standard of care? Gynecol. Oncol. 2017; 147(3): 597-600.
  9. Якушевская О.В., Юренева С.В., Хабас Г.Н., Протасова А.Э. Менопаузальная гормональная терапия и рак шейки матки: современный взгляд на проблему. Акушерство и гинекология. 2017; 11: 148-53. [Yakushevskaya O.V., Yureneva S.V., Khabas G.N., Protasova A.E. Menopausal hormone therapy and cervical cancer: A current view of the problem. Obstetrics and Gynecology. 2017; 11: 148-53. (in Russian)].
  10. Vargiu V., Amar I.D., Rosati A., Dinoi G., Turco L.C., Capozzi V.A. et al. Hormone replacement therapy and cervical cancer: a systematic review of the literature. Climacteric. 2021; 24(2): 120-7.
  11. Persson I., Yuen J., Bergkvist L., Schairer C. Cancer incidence and mortality in women receiving estrogen and estrogen-progestin replacement therapy–long-term follow-up of a Swedish cohort. Int. J. Cancer. 1996; 67(3): 327-32.<327::AID-IJC4>3.0.CO;2-T.
  12. Schneider C., Jick S.S., Meier C.R. Risk of gynecological cancers in users of estradiol/dydrogesterone or other HRT preparations. Climacteric. 2009; 12(6): 514-24.
  13. Roura E., Travier N., Waterboer T., de Sanjosé S., Bosch F.X., Pawlita M. et al. The influence of hormonal factors on the risk of developing cervical cancer and pre-cancer: results from the EPIC Cohort. PLoS One. 2016; 11(1): e0147029. 10.1371/journal.pone.0147029.
  14. Bristol M.L., James C.D., Wang X., Fontan C.T., Morgan I.M. Estrogen attenuates the growth of human papillomavirus-positive epithelial cells. mSphere. 2020; 5(2): e00049-20.
  15. Ploch E. Hormonal replacement therapy in patients after cervical cancer treatment. Gynecol. Oncol. 1987; 26(2): 169-77.
  16. Gadduccia A., Cosio S., Fuzzetti F. Estro-progestin contraceptives and risk of cervical cancer: a debated issue. Anticancer Res. 2020; 40(11): 5995-6002. anticanres.14620 .
  17. Asthana S., Busa V., Labani S. Oral contraceptives use and risk of cervical cancer - a systematic review and meta-analysis. Eur. J. Obstet. Gynecol. Reprod.Biol. 2020; 247: 163-75.
  18. Frega A., Scardamaglia P., Piazze J., Cerekja A., Pacchiarotti A., Verrico M., Moscarini M. Oral contraceptives and clinical recurrence of human papillomavirus lesions and cervical intraepithelial neoplasia following treatment. Int. J. Gynaecol. Obstet. 2008; 100(2): 175-8.
  19. Lacey J.V. Jr., Brinton L.A., Barnes W.A., Gravitt P.E., Greenberg M.D., Hadjimichael O.C. et al. Use of hormone replacement therapy and adenocarcinomas and squamous cell carcinomas of the uterine cervix. Gynecol. Oncol. 2000; 77(1): 149-54.
  20. Richardson A., Watson L., Persic M., Phillips A. Safety of hormone replacement therapy in women with a history of cervical аdenocarcinoma. Post Reprod. Health. 2021; 27(3): 167-73.
  21. Jaakkola S., Pukkala E., Lyytinen H.K., Ylikorkala O. Рostmenopausal estradiol-progestagen therapy and risk for uterine cervical cancer. Int. J. Cancer. 2012; 131(4): E537-43.
  22. Rodolakis A., Biliatis I., Morice P., Reed N., Mangler M., Kesic V., Denschlag D. European Society of Gynecological Oncology Task Force for Fertility Preservation: clinical recommendations for fertility-sparing management in young endometrial cancer patients. Int. J. Gynecol. Cancer. 2015; 25(7):1258-65.
  23. Deli T., Orosz M., Jacab A. Hormone replacement therapy in cancer survivors - review of the literature. Pathol. Oncol. Res. 2020; 26(1): 63-78.
  24. Barakat R.R., Bundy B.N., Spirtos N.M., Bell J., Mannel R.S.; Gynecologic Oncology Group Study. 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(4): 587-92.
  25. Shim S.H., Lee S.J., Kim S.N. Effects of hormone replacement therapy on the rate of recurrence in endometrial cancer survivors: a meta-analysis. Eur. J. Cancer. 2014; 50(9): 1628-37.
  26. Mitra S., Lami M.S., Ghosh A., Das R., Tallei T.K., Fatimawali et al. Hormonal therapy for gynecological cancers: how far has science progressed toward clinical applications? Cancers (Basel). 2022; 14(3): 759.
  27. Bodner K., Laubichler P., Kimberger O., Czerwenka K., Zeillinger R., Bodner-Adler B. Oestrogen and progesterone receptor expression in patients with adenocarcinoma of the uterine cervix and correlation with various clinicopathological parameters. Anticancer Res. 2010; 30(4): 1341-5.
  28. Martin J.D., Hähnel R., McCartney A.J., De Klerk N. The influence of estrogen and progesterone receptors on survival in patients with carcinoma of the uterine cervix. Gynecol. Oncol. 1986; 23(3): 329-35.
  29. Smith E.M., Levy B.T., Ritchie J.M., Jia J., Wang D., Haugen T.H., Turek L.P. Is use of hormone replacement therapy associated with increased detection of human papillomavirus and potential risk of HPV-related genital cancers? Eur. J. Cancer Prev. 2002; 11(3): 295-305.
  30. Smith E.M., Ritchie J.M., Levy B.T., Zhang W., Wang D., Haugen T.H., Turek L.P. Prevalence and persistence of human papillomavirus in postmenopausal age women. Cancer Detect. Prev. 2003; 27(6): 472-80.

Received 13.05.2022

Accepted 15.07.2022

About the Authors

Oksana V. Yakushevskaya, Ph.D., Researcher at the Department of Gynecological Endocrinology, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, +7(495)531-44-44,,,
117997, Russia, Moscow, Ac. Oparina str., 4.
Nataliya A. Babaeva, Dr. Med. Sci., Oncologist, Oncological Department of Surgical Methods of Treatment, Leading Researcher, Institute of Oncogynecology and Mammology, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia,,,, 117997, Russia, Moscow, Ac. Oparina str., 4.
Svetlana V. Yureneva, Dr. Med. Sci., Leading Researcher of the Department of Gynecological Endocrinology, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia,,, 117997, Russia, Moscow, Ac. Oparina str., 4.
Levon A. Ashrafyan, Academician of the RAS, Dr. Med. Sci., Professor, Director of the Institute of Oncogynecology and Mammology, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia,,,
117997, Russia, Moscow, Akademika Oparina str., 4.

Authors' contributions: Yakushevskaya O.V. – obtaining data for analysis, analysis of the findings, writing the article;
Yureneva S.V. – obtaining data for analysis, analysis of the article written; Babaeva N.A., Ashrafyan L.A. – analysis of the article written.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The article has been written without financial support.
For citation: Yakushevskaya O.V., Babaeva N.A., Yureneva S.V., Ashrafyan L.A.
Impact of menopausal hormone therapy on the development and
progression of cervical and endometrial cancers.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2022; 8: 30-35 (in Russian)

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