Endometrial cancer after combined hormone replacement therapy

Objective: It has been suggested that exposure to relatively high levels of unopposed estrogen is a risk factor for endometrial cancer. Combined thera py of estrogen with cyclic progestagen was therefore highly recommended for menopausal women with an intact uterus. Methods: The cases of two postmeno pausal women who developed endometrial cancer after laking continuous seque ntial HRT for lj months are reported. Both were without bleeding for more t han 2 years and presented with a normal vaginal ultrasound, They had severe menopausal symptoms and asked for HRT. Results: After 15 months irregular bleeding occurred and a hysterectomy was performed. The pathohistological f inding in both cases was endometrial cancer. As we measured the serum estra diol levels 4 h after tablet ingestion supraphysiologic values ranging betw een 418 and 442 pg/ml were found. Conclusion: Our report strengthens the ev idence that supraphysiologic estradiol levels despite combination with cycl ic progestagen therapy, increase the risk of endometrial cancer. (C) 1999 E lsevier Science Ireland Ltd. All rights reserved.