1. In a prospective cohort study of over 89 000 postmenopausal women, the use of bisphosphonates for osteoporosis was associated with a significant reduction in the risk of endometrial cancer.
Evidence Rating Level: 3 (Average)
Study Rundown: Although oral bisphosphonates are most commonly used for the treatment of osteoporosis among post-menopausal women, previous large prospective studies have demonstrated an associated between the use of bisphosphonates and cancer risk reduction. Previous results from the National Cancer Institute’s Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial suggested an association between bisphosphonate use and endometrial cancer as well. The purpose of this study was to further investigate the potential protective effect of bisphosphonates in endometrial cancer. This study performed a secondary analysis of the Women’s Health Initiative Trial, which included a prospective cohort of over 89 000 post-menopausal women, for bisphosphonate use and follow-up endometrial cancer diagnoses. At the conclusion of this study, a history of ever use of bisphosphonates was associated with a moderate reduction in endometrial cancer risk, consistent with the findings of the PLCO trial. The results of this study support the hypothesis of a protective effect of bisphosphonates in endometrial cancer. The strengths of this study include the large population size. However, the study is limited by its observational design, which makes it difficult to control for important confounders such as low endogenous estrogen level resulting in both high fracture risk and lower risk of endometrial cancer. Additional randomized controlled trials are required to fully elucidate this relationship.
In-Depth [prospective cohort]: This study was a secondary analysis of 89 918 postmenopausal women enrolled in the Women’s Health Initiative (WHI) prospective cohort. WHI collected enrolled over 160 000 women aged 50-79 from over 40 clinical sites across the United States from 1993 to 1998. All women had an intact uterus upon enrollment; exclusion criteria included patients with a history of endometrial or breast cancer, hysterectomy, anti-estrogen use, or hormone therapy for bone fracture. The primary outcomes were bisphosphonate use and incidence of invasive endometrial cancer. Outcomes were determined from a detailed health interview at intake, and determined bisphosphonate use from medication inventories at baseline and at 1, 3, and 6 years follow-up. Patients were considered bisphosphonate ever-users if they had reported use for at least 2 weeks in duration. After a median follow-up was 12.5 years, bisphosphonate use ranged from 2% at the start of the study to 10% by year 6. A total of 1123 women developed endometrial cancer over this time period. Bisphosphonate ever-users were associated with a significantly reduced risk of endometrial cancer (HR: 0.80; 95% CI: 0.64-1.00, p = 0.05). Hazard ratios did not vary significantly with duration of use. There were no significant interactions with patient BMI (p = 0.41), age at the start of the study (p = 0.21) or hip fracture probability score (p = 0.83).
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