Is HRT a trigger for cancer in postmenopausal patients with a history of endometriosis?

Christos Iavazzo, Ioannis D. Gkegkes
Journal of the Turkish German Gynecological Association · 2025 · vol. 26(3) , pp. 238–239 · doi:10.4274/jtgga.galenos.2025.2024-8-4 · PMID:40899438 · PMC12406973 · W4413959933
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This retrospective study investigated whether hormone replacement therapy (HRT) increases cancer risk in postmenopausal patients with a history of endometriosis.

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References

1. Akgün N, Sarıdoğan E. Management of menopause in women with a history of endometriosis. J Turk Ger Gynecol Assoc. 2024; 25: 107- 1. 2. Wang YX, Farland LV , Gaskins AJ, Wang S, Terry KL, Rexrode KM, et al. Endometriosis and uterine fibroids and risk of premature mortality: prospective cohort study. BMJ. 2024; 387: e078797. 3. Barnard ME, Farland LV , Yan B, Wang J, Trabert B, Doherty JA, et al. Endometriosis typology and ovarian cancer risk. JAMA. 2024; 332: 482-89. 4. Xiang H, Wang L, Sun L, Xu S. The risk of ovarian cancer in hormone replacement therapy users: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2024; 15: 1414968. 5. Lee HJ, Lee B, Choi H, Lee M, Lee K, Lee TK, et al. Hormone replacement therapy and risks of various cancers in postmenopausal women with de novo or a history of endometriosis. Cancers (Basel). 2024; 16: 809. 6. Lee HJ, Lee B, Choi H, Kim T, Kim Y, Kim YB. Impact of hormone replacement therapy on risk of ovarian cancer in postmenopausal women with de novo endometriosis or a history of endometriosis. Cancers (Basel). 2023; 15: 1708. Is HRT a trigger for cancer in postmenopausal patients with a history of endometriosis? Received: 12 August, 2024 Accepted: 04 July, 2025 Publication Date: 03 September, 2025 Address for Correspondence: Ioannis D. Gkegkes e-mail: [email protected] ORCID: orcid.org/0000-0001-8637-5679 DOI: 10.4274/jtgga.galenos.2025.2024-8-4 Cite 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 Assoc. 2025; 26(3): 238-9 Iavazzo and Gkegkes. Is HRT a trigger for cancer in postmenopausal patients with history of endometriosis? 239 J Turk Ger Gynecol Assoc 2025; 26(3): 238-9 Author’s Response Dear Editor, We thank Iavazzo and Gkegkes for their interest in our review on “management of menopause in women with a history of endometriosis” and reiterating the messages in it (1). As Iavazzo and Gkegkes highlight, the messages in our review have been further supported by additional epidemiological evidence since the preparation of our review. Wang et al. (2) analysed the risk of premature mortality in women with a history of laparoscopically confirmed endometriosis based on data from Nurses’ Health Study II and found that laparoscopically confirmed endometriosis was associated with an increased risk of premature deaths (deaths before age 70 years), mainly driven by increased gynaecological malignancies, along with non-malignant mortality caused by respiratory disorders, senility and ill-defined diseases and diseases of the central nervous system and sense organs. These findings add a new dimension to our messages that women with endometriosis are at greater risk of cardiovascular disease, hypercholesterolemia and osteoporosis. They support our main conclusion that hormone replacement therapy (HRT) should be recommended to women who have a history of endometriosis, when they become menopausal at an early age, at least until the age of natural menopause (1). This approach is likely to improve their quality of life and may reduce the increased morbidity and mortality that the new data show in this group of women. The article by Xiang et al. (3) is suggestive of increased risk of ovarian cancer in users of HRT who have a history of endometriosis, although more recent studies indicate the risk is minimal. The article by Lee et al. (4) is suggestive of an increase in the risk of uterine cancer but not ovarian cancer, and a decrease in the risks of liver and thyroid cancers in estrogen/progesterone users and in the risk of breast cancer in estrogen-only users. These studies indicate that there are still methodological challenges in analysing the risk of cancer in HRT users and demonstrate that further research is needed with a more robust design. We reiterate our assertion that combined HRT with estrogen and progesterone, or tibolone should be used in women with a history of endometriosis, even after a hysterectomy, as this approach may reduce the risk of malignant transformation and disease reactivation. Future research may shed some light on the potential benefits and risks of HRT in the long-term. It is necessary to determine whether HRT contributes to the increased premature mortality due to increased gynaecological malignancies. Nilüfer Akgün1, Ertan Sarıdoğan2,3 1Clinic of Obstetrics and Gynecology, University of Health Sciences Türkiye, Ankara Etlik City Hospital, Ankara, Türkiye 2Department of Obstetrics and Gynecology, University College London Hospital, London, United Kingdom 3Elizabeth Garrett Anderson Institute for Women’s Health, University College London, London, United Kingdom

References

1. Akgün N, Sarıdoğan E. Management of menopause in women with a history of endometriosis. J Turk Ger Gynecol Assoc. 2024; 25: 107- 11. 2. Wang YX, Farland LV , Gaskins AJ, Wang S, Terry KL, Rexrode KM, et al. Endometriosis and uterine fibroids and risk of premature mortality: prospective cohort study. BMJ. 2024; 387: e078797. 3. Xiang H, Wang L, Sun L, Xu S. The risk of ovarian cancer in hormone replacement therapy users: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2024; 15: 1414968. 4. Lee HJ, Lee B, Choi H, Lee M, Lee K, Lee TK, et al. Hormone replacement therapy and risks of various cancers in postmenopausal women with de novo or a history of endometriosis. Cancers (Basel). 2024; 16: 809.

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