RSS-Feed abonnieren
DOI: 10.1055/s-0045-1802985
The Safety of Hormone Replacement Therapy in Gynecological Cancer Survivors

Abstract
Treatment of gynecological cancers often induces a premature menopause. Plus advancing treatments mean more gynecological cancer survivors are living to physiological menopause. Hormone replacement therapy (HRT) has proven substantial long-term benefits in physiological menopause and premature menopause particularly. We aimed to evaluate the current evidence on the safety of HRT in gynecological cancer survivors to help clinicians counsel these patients. HRT is not contraindicated in most gynecological cancer survivors, as evidence available often shows safety or even benefit with HRT use. However, HRT is contraindicated in a few cancers—in low-grade serous ovarian carcinoma, high-risk endometrial carcinoma, and some uterine sarcomas. Caution is advised in high-grade serous, late-stage endometrioid, and granulosa ovarian carcinomas when there is substandard evidence demonstrating safety, but also a theoretical harm present. Due to deficient large randomized controlled trials and methodological biases being present in most studies, HRT use needs to be individualized in most cancers—ovarian carcinomas, endometrial carcinomas, and cervical adenocarcinomas. Justification for HRT use is strong, and HRT is not contraindicated in most gynecological cancers due to largely reassuring evidence. More robust long-term data are needed for further reliable guidance for clinicians and patients.
Publikationsverlauf
Artikel online veröffentlicht:
18. März 2025
© 2025. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1 Cancer Today. International Agency for Research on Cancer. Accessed September 28, 2024 at: https://gco.iarc.who.int/today/
- 2 Morice P, Scambia G, Abu-Rustum NR. et al. Fertility-sparing treatment and follow-up in patients with cervical cancer, ovarian cancer, and borderline ovarian tumours: guidelines from ESGO, ESHRE, and ESGE. Lancet Oncol 2024; 25 (11) e602-e610
- 3 British Gynaecological Cancer Society and, British Menopause Society. Management of Menopausal Symptoms Following Treatment of Gynaecological Cancer. British Gynaecological Cancer Society and British Menopause Society [online]. 2024:1–40. Accessed October 11, 2024 at: https://www.bgcs.org.uk/wp-content/uploads/2024/09/BGCS-BMS-Guidelines-on-Management-of-Menopausal-Symptoms-after-Gynaecological-Cancer-09.09.24.pdf
- 4 Rees M, Angioli R, Coleman RL. et al. European Menopause and Andropause Society (EMAS) and International Gynecologic Cancer Society (IGCS) position statement on managing the menopause after gynecological cancer: focus on menopausal symptoms and osteoporosis. Maturitas 2020; 134: 56-61
- 5 Rodolakis A, Scambia G, Planchamp F. et al. ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma. Int J Gynecol Cancer 2023; 33 (02) 208-222
- 6 Hamoda H, Panay N, Pedder H, Arya R, Savvas M. The British Menopause Society & Women's Health Concern 2020 recommendations on hormone replacement therapy in menopausal women. Post Reprod Health 2020; 26 (04) 181-209
- 7 POI Guideline Development Group. Guideline on the management of premature ovarian insufficiency. ESHRE [online]. 2015. Accessed September 28, 2024 at: https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Management-of-premature-ovarian-insufficiency.aspx
- 8 Saeaib N, Peeyananjarassri K, Liabsuetrakul T, Buhachat R, Myriokefalitaki E. Hormone replacement therapy after surgery for epithelial ovarian cancer. Cochrane Database Syst Rev 2020; 1 (01) CD012559
- 9 Li D, Ding CY, Qiu LH. Postoperative hormone replacement therapy for epithelial ovarian cancer patients: a systematic review and meta-analysis. Gynecol Oncol 2015; 139 (02) 355-362
- 10 von Kartaschew ÅE, Dahm-Kähler P, Rodriguez-Wallberg KA, Holmberg E, Rådestad AF. Hormone replacement in premenopausal women treated with bilateral oophorectomy for ovarian cancer - a nationwide population-based study. Gynecol Oncol 2022; 167 (03) 476-482
- 11 Collaborative Group on Epidemiological Studies of Ovarian Cancer. Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. The Lancet [online]. Accessed October 5, 2024 at: https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)61687-1.pdf2015;385(9980):1835-1842
- 12 Liu Y, Ma L, Yang X. et al. Menopausal hormone replacement therapy and the risk of ovarian cancer: a meta-analysis. Front Endocrinol (Lausanne) 2019; 10: 801
- 13 Vavilis D, Chatzigeorgiou K, Goulis D. et al. Hormonal replacement therapy in ovarian cancer survivors: a survey among Greek gynecologists. Eur J Gynaecol Oncol 2011; 32 (05) 538-541
- 14 Hancke K, Foeldi M, Zahradnik HP, Gitsch G, Gilbert L, Denschlag D. Estrogen replacement therapy after endometrial cancer: a survey of physicians' prescribing practice. Climacteric 2010; 13 (03) 271-277
- 15 Everhov ÅH, Nyberg T, Bergmark K. et al. Hormone therapy after uterine cervical cancer treatment: a Swedish population-based study. Menopause 2015; 22 (06) 633-639
- 16 Rauh LA, Pannone AF, Cantrell LA. Hormone replacement therapy after treatment for cervical cancer: Are we adhering to standard of care?. Gynecol Oncol 2017; 147 (03) 597-600
- 17 van der Hoef C, Bawuah Dsane L, Schuur N. et al. Hormone replacement therapy in women with iatrogenic premature ovarian insufficiency after radiotherapy for cervical cancer: a retrospective cohort and survey study. Maturitas 2024; 185: 108004
- 18 Deli T, Orosz M, Jakab A. Hormone replacement therapy in cancer survivors - review of the literature. Pathol Oncol Res 2020; 26 (01) 63-78
- 19 Achimaș-Cadariu PA, Păun DL, Pașca A. Impact of hormone replacement therapy on the overall survival and progression free survival of ovarian cancer patients: a systematic review and meta-analysis. Cancers (Basel) 2023; 15 (02) 356
- 20 Eeles RA, Morden JP, Gore M. et al. Adjuvant hormone therapy may improve survival in epithelial ovarian cancer: results of the AHT Randomized Trial. J Clin Oncol 2015; 33 (35) 4138-4144
- 21 Guidozzi F, Daponte A. Estrogen replacement therapy for ovarian carcinoma survivors: a randomized controlled trial. Cancer 1999; 86 (06) 1013-1018
- 22 Li L, Pan Z, Gao K. et al. Impact of post-operative hormone replacement therapy on life quality and prognosis in patients with ovarian malignancy. Oncol Lett 2012; 3 (01) 244-249
- 23 Wen Y, Huang H, Huang H, Wu M, Shen K, Pan L. The safety of postoperative hormone replacement therapy in epithelial ovarian cancer patients in China. Climacteric 2013; 16 (06) 673-681
- 24 Mascarenhas C, Lambe M, Bellocco R. et al. Use of hormone replacement therapy before and after ovarian cancer diagnosis and ovarian cancer survival. Int J Cancer 2006; 119 (12) 2907-2915
- 25 Eeles RA, Tan S, Wiltshaw E. et al. Hormone replacement therapy and survival after surgery for ovarian cancer. BMJ 1991; 302 (6771): 259-262
- 26 Ji E, Kim K, Lee B. et al. Postoperative hormone replacement therapy and survival in women with ovarian cancer. Cancers (Basel) 2022; 14 (13) 3090
- 27 Zhang YL, Chen JH, Lu W, Li BL, Zhu QY, Wan XP. Efficacy of postoperative hormone replacement therapy on prognosis of patients with serous ovarian carcinoma. Chin Med J (Engl) 2016; 129 (11) 1316-1321
- 28 Ursic-Vrscaj M, Bebar S, Žakelj MP. Hormone replacement therapy after invasive ovarian serous cystadenocarcinoma treatment: the effect on survival. Menopause 2001; 8 (01) 70-75
- 29 Bešević J, Gunter MJ, Fortner RT. et al. Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study. Br J Cancer 2015; 113 (11) 1622-1631
- 30 Malfetano J, Beecham JB, Bundy BN, Hatch KD. A phase II trial of medroxyprogesterone acetate in epithelial ovarian cancers. A Gynecologic Oncology Group study. Am J Clin Oncol 1993; 16 (02) 149-151
- 31 Sourouni M, Kiesel L. Hormone replacement therapy after gynaecological malignancies: a review article. Geburtshilfe Frauenheilkd 2021; 81 (05) 549-554
- 32 O'Donnell RL, Clement KM, Edmondson RJ. Hormone replacement therapy after treatment for a gynaecological malignancy. Curr Opin Obstet Gynecol 2016; 28 (01) 32-41
- 33 Power L, Lefas G, Lambert P. et al. Hormone use after nonserous epithelial ovarian cancer: overall and disease-free survival. Obstet Gynecol 2016; 127 (05) 837-847
- 34 Londero AP, Parisi N, Tassi A, Bertozzi S, Cagnacci A. Hormone replacement therapy in endometrial cancer survivors: a meta-analysis. J Clin Med 2021; 10 (14) 3165
- 35 Barakat RR, Bundy BN, Spirtos NM, Bell J, Mannel RS. 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 (04) 587-592
- 36 Chapman JA, DiSaia PJ, Osann K, Roth PD, Gillotte DL, Berman ML. Estrogen replacement in surgical stage I and II endometrial cancer survivors. Am J Obstet Gynecol 1996; 175 (05) 1195-1200
- 37 Lim S, Kim YH, Lee KB, Lee JM. The influence of hormone therapy with drospirenone-estradiol on endometrioid type endometrial cancer patients. J Gynecol Oncol 2018; 29 (05) e72
- 38 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 (02) 805-808
- 39 Lee RB, Burke TW, Park RC. Estrogen replacement therapy following treatment for stage I endometrial carcinoma. Gynecol Oncol 1990; 36 (02) 189-191
- 40 Arteaga-Gómez AC, Castellanos-Barroso G, Colín-Valenzuela A, García-Vargas J, Márquez-Acosta G, Reyes-Muñoz E. [Hormone therapy effect in postmenopausal women with history of endometrial cancer]. Ginecol Obstet Mex 2011; 79 (01) 11-17
- 41 Cho HW, Ouh YT, Lee JK, Hong JH. Effects of hormone therapy on recurrence in endometrial cancer survivors: a nationwide study using the Korean Health Insurance Review and Assessment Service database. J Gynecol Oncol 2019; 30 (04) e51
- 42 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 (04) 555-560
- 43 Creasman WT, Henderson D, Hinshaw W, Clarke-Pearson DL. Estrogen replacement therapy in the patient treated for endometrial cancer. Obstet Gynecol 1986; 67 (03) 326-330
- 44 Edey KA, Rundle S, Hickey M. Hormone replacement therapy for women previously treated for endometrial cancer. Cochrane Database Syst Rev 2018; 5 (05) CD008830
- 45 Shim SH, Lee SJ, Kim SN. Effects of hormone replacement therapy on the rate of recurrence in endometrial cancer survivors: a meta-analysis. Eur J Cancer 2014; 50 (09) 1628-1637
- 46 Maxwell GL, Tian C, Risinger JI, Hamilton CA, Barakat RR. Gynecologic Oncology Group Study. Racial disparities in recurrence among patients with early-stage endometrial cancer: is recurrence increased in black patients who receive estrogen replacement therapy?. Cancer 2008; 113 (06) 1431-1437
- 47 Biliatis I, Thomakos N, Rodolakis A, Akrivos N, Zacharakis D, Antsaklis A. Safety of hormone replacement therapy in gynaecological cancer survivors. J Obstet Gynaecol 2012; 32 (04) 321-325
- 48 Chu MC, Mor G, Lim C, Zheng W, Parkash V, Schwartz PE. Low-grade endometrial stromal sarcoma: hormonal aspects. Gynecol Oncol 2003; 90 (01) 170-176
- 49 Pink D, Lindner T, Mrozek A. et al. Harm or benefit of hormonal treatment in metastatic low-grade endometrial stromal sarcoma: single center experience with 10 cases and review of the literature. Gynecol Oncol 2006; 101 (03) 464-469
- 50 Thanopoulou E, Thway K, Khabra K, Judson I. Treatment of hormone positive uterine leiomyosarcoma with aromatase inhibitors. Clin Sarcoma Res 2014; 4: 5
- 51 Thanopoulou E, Aleksic A, Thway K, Khabra K, Judson I. Hormonal treatments in metastatic endometrial stromal sarcomas: the 10-year experience of the sarcoma unit of Royal Marsden Hospital. Clin Sarcoma Res 2015; 5 (01) 8
- 52 Maccaroni E, Lunerti V, Agostinelli V. et al. New insights into hormonal therapies in uterine sarcomas. Cancers (Basel) 2022; 14 (04) 921
- 53 Rizzo A, Pantaleo MA, Saponara M, Nannini M. Current status of the adjuvant therapy in uterine sarcoma: a literature review. World J Clin Cases 2019; 7 (14) 1753-1763
- 54 Thanopoulou E, Judson I. Hormonal therapy in gynecological sarcomas. Expert Rev Anticancer Ther 2012; 12 (07) 885-894
- 55 Akhan SE, Yavuz E, Tecer A. et al. The expression of Ki-67, p53, estrogen and progesterone receptors affecting survival in uterine leiomyosarcomas. A clinicopathologic study. Gynecol Oncol 2005; 99 (01) 36-42
- 56 Kapp DS, Shin JY, Chan JK. Prognostic factors and survival in 1396 patients with uterine leiomyosarcomas: emphasis on impact of lymphadenectomy and oophorectomy. Cancer 2008; 112 (04) 820-830
- 57 Vargiu V, Amar ID, Rosati A. et al. Hormone replacement therapy and cervical cancer: a systematic review of the literature. Climacteric 2021; 24 (02) 120-127
- 58 Ploch E. Hormonal replacement therapy in patients after cervical cancer treatment. Gynecol Oncol 1987; 26 (02) 169-177
- 59 Richardson A, Watson L, Persic M, Phillips A. Safety of hormone replacement therapy in women with a history of cervical adenocarcinoma. Post Reprod Health 2021; 27 (03) 167-173
- 60 Lee SH, Cho YJ, Cho KJ. et al. Effect of tibolone on the survival of early stage cervical adenocarcinoma patients. Obstet Gynecol Sci 2018; 61 (05) 584-589
- 61 Roura E, Travier N, Waterboer T. 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 (01) e0147029
- 62 Lacey Jr JV, Brinton LA, Barnes WA. et al. Use of hormone replacement therapy and adenocarcinomas and squamous cell carcinomas of the uterine cervix. Gynecol Oncol 2000; 77 (01) 149-154
- 63 Jaakkola S, Pukkala E, K Lyytinen H, Ylikorkala O. Postmenopausal estradiol-progestagen therapy and risk for uterine cervical cancer. Int J Cancer 2012; 131 (04) E537-E543
- 64 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 (04) 1341-1345
- 65 Martin JD, Hähnel R, McCartney AJ, De Klerk N. The influence of estrogen and progesterone receptors on survival in patients with carcinoma of the uterine cervix. Gynecol Oncol 1986; 23 (03) 329-335
- 66 Madsen BS, Jensen HL, van den Brule AJC, Wohlfahrt J, Frisch M. Risk factors for invasive squamous cell carcinoma of the vulva and vagina – population-based case-control study in Denmark. Int J Cancer 2008; 122 (12) 2827-2834
- 67 Sherman KJ, Daling JR, McKnight B, Chu J. Hormonal factors in vulvar cancer. A case-control study. J Reprod Med 1994; 39 (11) 857-861
- 68 Somoye GO, Gull S. Adenocarcinoma of the vaginal vault following prolonged unopposed oestrogen hormone replacement therapy. J Obstet Gynaecol 2005; 25 (02) 220-221
- 69 Parazzini F, La Vecchia C, Negri E. et al. Case-control study of oestrogen replacement therapy and risk of cervical cancer. BMJ 1997; 315 (7100): 85-88