{"paper_id":"4801e67e-9e87-43ce-907c-f263e36fbb3d","body_text":"Letter to the Editor\n238\nCopyright© 2025 The Author. Published by Galenos Publishing House on behalf of Turkish-German Gynecological Association. \nThis is an open access article under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 (CC BY-NC-ND) International License.\nDear Editor,\nWe read the article entitled “management of menopause in women \nwith a history of endometriosis” by Akgün et al. (1) with a great \ndeal of interest. The authors discussed the hormone replacement \ntherapy (HRT) options, indications, and contraindications in \npostmenopausal patients with endometriosis. Furthermore, \na recently published prospective cohort study examined the \nrelationship between endometriosis and fibroids and the risk \nof premature mortality, highlighting the importance for primary \ncare providers to consider these gynecological disorders in their \nassessment of women’s health (2). Barnard et al. (3) investigated \nthe relationship between endometriosis typology and ovarian \ncancer risk. Ovarian cancer risk was highest in women with \ndeep infiltrating endometriosis and/or ovarian endometriomas \nfor all ovarian cancers. These authors recommended counseling \nregarding ovarian cancer risk and prevention (3).\nAs mentioned by Akgün et al. (1), endometriosis is a hormone-\ndependent condition and residual or recurrent endometriotic \nlesions might still be found in menopause. In this scenario, \nwe would like to ask whether HRT might increase the risk of \nmalignancy. A recent meta-analysis reported that the risk of \novarian malignancy, especially for serous histological type, \nincreased with prolonged exposure time, especially when \nestrogen replacement therapy (ERT) exceeded 10 years. In \nthe same meta-analysis, it was recommended that long-time \nusers should consider continuous estrogen-progesterone \nreplacement therapy (EPRT) as a safer alternative (4).\nMoreover, Lee et al. (5) analyzed a database of ten cancers \n(cervical, uterine, ovarian, breast, colon, stomach, liver, lung, \npancreas, and thyroid) and showed that HRT was a significant \nrisk factor for uterine cancer, but decreased the risk of liver \nand thyroid cancer while ERT decreased the risks of breast and \nlung cancers significantly. In the same study, tibolone was not \nassociated with the risk of any of the cancers assessed. Finally, \nthe same group of researchers clarified in another meta-analysis \nthat, although the use of ERT was found to be a significant risk \nfactor for ovarian cancer, after adjusting for co-variables, HRT \nuse, duration of HRT, EPRT and tibolone were not found to be \nassociated with increased risk of developing ovarian cancer \n(6). The practical implications for clinical decision-making and \na clearer differentiation of risks associated with ERT, EPRT, and \ntibolone would further enhance its impact. \nChristos Iavazzo1, Ioannis D. Gkegkes2,3\n1Department of Gynaecological Oncology, Metaxa Cancer \nHospital, Piraeus, Greece\n2Athens Colorectal Laboratory, Athens, Greece\n3Department of Colorectal Surgery, Royal Devon and Exeter \nNHS Foundation Trust, Exeter, United Kingdom\nReferences\n1. Akgün N, Sarıdoğan E. Management of menopause in women with \na history of endometriosis. J Turk Ger Gynecol Assoc. 2024; 25: 107-\n1.\n2. Wang YX, Farland LV , Gaskins AJ, Wang S, Terry KL, Rexrode KM, \net al. Endometriosis and uterine fibroids and risk of premature \nmortality: prospective cohort study. BMJ. 2024; 387: e078797.\n3. Barnard ME, Farland LV , Yan B, Wang J, Trabert B, Doherty JA, et al. \nEndometriosis typology and ovarian cancer risk. JAMA. 2024; 332: \n482-89.\n4. Xiang H, Wang L, Sun L, Xu S. The risk of ovarian cancer in hormone \nreplacement therapy users: a systematic review and meta-analysis. \nFront Endocrinol (Lausanne). 2024; 15: 1414968. \n5. Lee HJ, Lee B, Choi H, Lee M, Lee K, Lee TK, et al. Hormone \nreplacement therapy and risks of various cancers in postmenopausal \nwomen with de novo or a history of endometriosis. Cancers \n(Basel). 2024; 16: 809.\n6. Lee HJ, Lee B, Choi H, Kim T, Kim Y, Kim YB. Impact of hormone \nreplacement therapy on risk of ovarian cancer in postmenopausal \nwomen with de novo endometriosis or a history of endometriosis. \nCancers (Basel). 2023; 15: 1708.\nIs HRT a trigger for cancer in postmenopausal patients \nwith a history of endometriosis?\nReceived: 12 August, 2024 Accepted: 04 July, 2025 Publication Date:  03 September, 2025\nAddress for Correspondence: Ioannis D. Gkegkes\ne-mail: ioannisgkegkes@gmail.com ORCID: orcid.org/0000-0001-8637-5679\nDOI: 10.4274/jtgga.galenos.2025.2024-8-4\nCite this article as: Iavazzo C, Gkegkes ID. Is HRT a trigger for cancer in postmenopausal patients with a history of endometriosis? J Turk Ger Gynecol \nAssoc. 2025; 26(3): 238-9\n\nIavazzo and Gkegkes.\nIs HRT a trigger for cancer in postmenopausal patients with history of endometriosis? 239\nJ Turk Ger Gynecol Assoc 2025; 26(3): 238-9\nAuthor’s Response \nDear Editor, \nWe thank Iavazzo and Gkegkes for their interest in our review \non “management of menopause in women with a history of \nendometriosis” and reiterating the messages in it (1). As Iavazzo \nand Gkegkes highlight, the messages in our review have been \nfurther supported by additional epidemiological evidence \nsince the preparation of our review. Wang et al. (2) analysed \nthe risk of premature mortality in women with a history of \nlaparoscopically confirmed endometriosis based on data \nfrom Nurses’ Health Study II and found that laparoscopically \nconfirmed endometriosis was associated with an increased \nrisk of premature deaths (deaths before age 70 years), mainly \ndriven by increased gynaecological malignancies, along with \nnon-malignant mortality caused by respiratory disorders, \nsenility and ill-defined diseases and diseases of the central \nnervous system and sense organs. These findings add a new \ndimension to our messages that women with endometriosis are \nat greater risk of cardiovascular disease, hypercholesterolemia \nand osteoporosis. They support our main conclusion that \nhormone replacement therapy (HRT) should be recommended \nto women who have a history of endometriosis, when they \nbecome menopausal at an early age, at least until the age of \nnatural menopause (1). This approach is likely to improve their \nquality of life and may reduce the increased morbidity and \nmortality that the new data show in this group of women. \nThe article by Xiang et al. (3) is suggestive of increased risk \nof ovarian cancer in users of HRT who have a history of \nendometriosis, although more recent studies indicate the \nrisk is minimal. The article by Lee et al. (4) is suggestive of an \nincrease in the risk of uterine cancer but not ovarian cancer, \nand a decrease in the risks of liver and thyroid cancers in \nestrogen/progesterone users and in the risk of breast cancer \nin estrogen-only users. These studies indicate that there are \nstill methodological challenges in analysing the risk of cancer \nin HRT users and demonstrate that further research is needed \nwith a more robust design. \nWe reiterate our assertion that combined HRT with estrogen \nand progesterone, or tibolone should be used in women with \na history of endometriosis, even after a hysterectomy, as this \napproach may reduce the risk of malignant transformation \nand disease reactivation. Future research may shed some light \non the potential benefits and risks of HRT in the long-term. \nIt is necessary to determine whether HRT contributes to the \nincreased premature mortality due to increased gynaecological \nmalignancies.\nNilüfer Akgün1, Ertan Sarıdoğan2,3\n1Clinic of Obstetrics and Gynecology, University of Health \nSciences Türkiye, Ankara Etlik City Hospital, Ankara, Türkiye \n2Department of Obstetrics and Gynecology, University \nCollege London Hospital, London, United Kingdom \n3Elizabeth Garrett Anderson Institute for Women’s Health, \nUniversity College London, London, United Kingdom\nReferences\n1. Akgün N, Sarıdoğan E. Management of menopause in women with \na history of endometriosis. J Turk Ger Gynecol Assoc. 2024; 25: 107-\n11.\n2. Wang YX, Farland LV , Gaskins AJ, Wang S, Terry KL, Rexrode KM, \net al. Endometriosis and uterine fibroids and risk of premature \nmortality: prospective cohort study. BMJ. 2024; 387: e078797. \n3. Xiang H, Wang L, Sun L, Xu S. The risk of ovarian cancer in hormone \nreplacement therapy users: a systematic review and meta-analysis. \nFront Endocrinol (Lausanne). 2024; 15: 1414968. \n4. Lee HJ, Lee B, Choi H, Lee M, Lee K, Lee TK, et al. Hormone \nreplacement therapy and risks of various cancers in postmenopausal \nwomen with de novo or a history of endometriosis. Cancers \n(Basel). 2024; 16: 809.","source_license":"CC0","license_restricted":false}