RISK OF ENDOMETRIAL HYPERPLASIA AND MALIGNANCY AMONG WOMEN USING TAMOXIFEN: A COMPARATIVE CLINICAL STUDY.

Abstract

: Tamoxifen widely used in estrogen-receptor–positive breast cancer, is associated with estrogen-agonistic effects on the endometrium. Prolonged use may lead to endometrial thickening, hyperplasia, or malignancy, particularly in postmenopausal women. Assessing these risks is essential for timely diagnosis, surveillance planning, and safe therapeutic decision-making among women receiving long-term tamoxifen therapy.

Objectives: To determine the frequency of endometrial hyperplasia and malignancy among tamoxifen users and compare endometrial changes with non-users, assessing their relationship with demographic characteristics and clinical risk factors.

Methodology: This comparative cross-sectional study included women aged 30–70 years attending the gynecology clinic. Participants were categorized into tamoxifen users and non-users. Transvaginal ultrasound assessed endometrial thickness, and biopsy confirmed histopathology. Demographic data, duration of tamoxifen use, and clinical symptoms were recorded. Statistical analysis using SPSS 24 applied chi-square and t-tests, with p < 0.05 considered significant.

Results: A total of 150 women participated in the study, comprising 80 tamoxifen users and 70 non-users. The mean age of the tamoxifen group was 52.4 ± 8.6 years, whereas non-users had a mean age of 49.8 ± 7.9 years, showing a statistically significant age difference (p = 0.04). Endometrial thickness measured by transvaginal ultrasound was significantly higher among tamoxifen users (10.2 ± 3.4 mm) compared to non-users (6.1 ± 2.7 mm) (p < 0.001). Histopathological examination revealed endometrial hyperplasia in 22 (27.5%) tamoxifen users versus 8 (10%) non-users (p = 0.006). Among the hyperplasia cases, atypical hyperplasia was more prevalent in the tamoxifen group. Endometrial carcinoma was diagnosed in 6 (7.5%) tamoxifen users compared with 1 (1.25%) non-user (p = 0.04). The frequency of abnormal findings was significantly associated with endometrial thickness ≥10 mm (p < 0.001) and tamoxifen therapy duration greater than three years (p < 0.05). Postmenopausal women showed a disproportionately higher rate of endometrial abnormalities (p = 0.03). Logistic regression demonstrated that tamoxifen uses independently predicted hyperplasia and malignancy after adjusting for age, BMI, and parity. Overall, long-term tamoxifen therapy substantially increased endometrial pathology risk.

Conclusion: Tamoxifen use is significantly associated with increased endometrial thickness, higher frequency of hyperplasia, and elevated malignancy risk compared to non-users. Longer duration of therapy further increases pathological changes, emphasizing the need for routine surveillance. Early identification through ultrasound and biopsy can improve outcomes and guide individualized management in women receiving long-term tamoxifen therapy.