Endometriosis-associated lesions during or after long-term estrogen-only therapy following hysterectomy: 2 cases

Daisuke Sugimoto, Hiroshi Ishikawa, Miyuki Harada, N. Kaneda, Keisuke Matsusaka, Kaori Koga
JCEM case reports · 2026 · vol. 4(12) , pp. luag329 · doi:10.1210/jcemcr/luag329 · PMID:42923654 · W7223176610
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Two case reports describe endometriosis lesions developing during or after long-term estrogen-only therapy following hysterectomy, highlighting that residual disease may persist and warrant histopathologic evaluation despite lacking causal proof.

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Abstract

Estrogen-only menopausal hormone therapy (MHT) is prescribed after hysterectomy; however, occult or residual endometriotic tissue may remain hormonally responsive. We report 2 women in whom endometriotic lesions were identified during or after long-term transdermal estrogen-only MHT after hysterectomy and bilateral salpingo-oophorectomy. The first patient was a 48-year-old woman treated for International Federation of Gynecology and Obstetrics 2009 stage IA, grade 1 endometrioid endometrial carcinoma at 44 years of age. Her estrogen-progestogen MHT for treatment-related premature ovarian insufficiency was changed to transdermal estrogen-only MHT. About 3 years later, she developed a progressively enlarging ileocecal mass, with resection revealing endometriosis. The second patient was a 54-year-old woman who had undergone hysterectomy and bilateral salpingo-oophorectomy for endometriosis at 46 years of age. She received transdermal estrogen-only MHT for approximately 6 years and was diagnosed with atypical endometrial hyperplasia in vaginal cuff endometriosis 1 year after estrogen withdrawal. These observations do not establish a causal relationship between estrogen-only MHT and lesion development. Occult disease, residual disease, or iatrogenic implantation remain plausible explanations. Nevertheless, these cases highlight that new abdominal masses or posthysterectomy vaginal bleeding during or after MHT warrant careful evaluation with histopathologic confirmation. MHT should be individualized according to current clinical guidelines.

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