Endometrial protection from tamoxifen-stimulated changes by a levonorgestrel-releasing intrauterine system: a randomised controlled trial

• Published in: The Lancet (British edition) Vol. 356; no. 9243; pp. 1711 - 1717
• Main Authors: Gardner, FJE, Konje, JC, Abrams, KR, Brown, LJR, Khanna, S, Al-Azzawi, F, Bell, SC, Taylor, DJ
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 18-11-2000; Lancet; Elsevier Limited
• Subjects: Aged; Antineoplastic Agents, Hormonal - adverse effects; Antineoplastic Agents, Hormonal - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Clinical trials; Drug therapy; Endometrium - drug effects; Endometrium - pathology; Female; Follow-Up Studies; Hormones. Endocrine system; Humans; Intrauterine Devices, Medicated; Levonorgestrel - administration & dosage; Medical sciences; Middle Aged; Patient Dropouts; Pharmacology. Drug treatments; Postmenopause; Reproductive system; Tamoxifen - adverse effects; Tamoxifen - therapeutic use; Treatment Outcome; Uterine Hemorrhage - chemically induced; Uterine Hemorrhage - prevention & control; Women; Antineoplastic agent; Human; Carcinoma; Intrauterine administration; Toxicity; Antiestrogen; Levonorgestrel; Antihormone; Malignant tumor; Tamoxifene; Progestagen; Prevention; Mammary gland diseases; Chemotherapy; Randomization; Uterus; Female genital system; Secondary effect; Clinical trial; Female; Contraceptive; Mammary gland; Non steroid compound; Endometrium
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(00)03204-9

Tamoxifen is currently the most commonly used adjuvant treatment for breast cancer, however, it frequently causes episodes of unscheduled uterine bleeding, which could be associated with proliferative changes of the endometrium, or even endometrial cancer. We aimed to assess whether a levonorgestrel intrauterine system could modulate the uterine responses to tamoxifen. We also aimed to assess women's tolerance of the screening procedures, the insertion, removal, and potential side-effects of the device.
We did a randomised controlled trial, in which postmenopausal women who had had at least 1 year of adjuvant tamoxifen treatment and who were undergoing regular follow-up for breast cancer were randomly assigned to either endometrial surveillance alone, or endometrial surveillance before and after insertion of the levonorgestrel intrauterine system for 12 months. We assessed tolerance of the surveillance procedures and the device with visual analogue scales.
Baseline assessment showed only benign uterine changes in all women (n=122). Hysteroscopic assessment indicated a uniform decidual response (confirmed histologically in 40 of 41 cases) in all women fitted with the intrauterine system; there were no new polyps in these women and 13% had fewer fibroids than in controls. Both screening procedures and device were well tolerated. There was an excess of bleeding in the women fitted with intrauterine systems but this resolved to a baseline similar to those receiving surveillance only.
The levonorgestrel-releasing intrauterine system had a protective action against the uterine effects of tamoxifen. The effectiveness of this device in preventing uterine changes in the endometrium needs to be assessed in the context of decreasing the need for repeated investigations of postmenopausal bleeding in women taking tamoxifen.