Effect of tamoxifen on serum estradiol concentrations and the development of endometrial pathology in postmenopausal women with breast cancer

Objective: Tamoxifen is used widely as adjuvant therapy for breast cancer in postmenopausal women. Our objective was to evaluate the effects of tamoxifen on serum estradiol and the endometrium of postmenopausal patients with breast cancer attending the Oncology Clinic at Belfast City Hospital. Design: A prospective study of 48 selected patients with breast cancer on maintenance tamoxifen therapy were assessed. Serum follicle-stimulating hormone, luteinizing hormone, and estradiol were measured. Vaginal ultrasound and endometrial biopsy were performed. The patients were divided into two groups: group A, those with amenorrhea (n = 34), and group B, those with abnormal vaginal bleeding (n = 14). Both groups were matched for age and duration of tamoxifen therapy. Results: Gonadotrophin levels were comparable between the two groups (p > 0.05). However, the serum estradiol levels were significantly elevated in those with abnormal vaginal bleeding (group B) as compared with the levels in those with amenorrhea (group A; p < 0.01). The mean endometrial thickness as measured using vaginal ultrasound was significantly greater in group B (7.2 mm) than in group A (4.4 mm) (p < 0.01). In group A, all the available endometrial biopsies demonstrated normal basal endometrium. In group B, the majority of endometrial samples (50%) demonstrated a normal endometrial pattern. Endometrial polyps were found in 43% of the samples from group B, and 7% showed cystic hyperplasia without atypia. There were no cases of malignancy in any of the endometrial biopsies. Conclusions: Our findings suggest that the presence of abnormal Vaginal bleeding in a postmenopausal woman on tamoxifen therapy may indicate that the estradiol levels are elevated. It seems reasonable to suggest that these patients should have their estradiol levels measured urgently and, if elevated, the rationale for their tamoxifen therapy reviewed.