Abstract

Abstract Background: Combined oral contraceptive use is associated with a decreased risk of ovarian carcinoma (cancer). However, the relationship between progestin-only contraceptives and ovarian cancer risk is unclear. Two previous studies have suggested a protective effect whereas another reported a non-statistically significant increased risk of ovarian cancer. The current study examined the association between use of depot medroxyprogesterone acetate (DMPA), a progestin-only injectable contraceptive, and ovarian cancer risk, using data from seven case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Methods: A pooled analysis examining the relationship between DMPA use and ovarian cancer risk was conducted using 7,679 invasive ovarian cancer cases and 11,136 controls from six studies from the United States and one from Australia. Combined oral contraceptive use, parity, education level, age, and race/ethnicity were considered important a priori confounders and were included in all statistical models. OCAC study site was also included in all models. The impact of additional exposures, including a personal history of endometriosis, first-degree family history of ovarian cancer, tubal ligation, breastfeeding, body mass index, and menopausal hormonal therapy use on the association between DMPA use and ovarian cancer were considered. None of these variables was found to impact the DMPA use-ovarian cancer association by >10% and thus not included in the final models. Odds ratios (OR) and 95% confidence intervals (CI) were generated from logistic regression models. The association between duration of DMPA use, categorized as never use, <2 years of use, and 2+ years of use, and ovarian cancer risk was examined in the two studies that had this information available. Results: The frequency of DMPA use among controls ranged from 1.25% to 3.53% across the seven studies. DMPA use was more common in controls than in cases in all of the studies. Overall, ever use of DMPA was associated with a 26% decreased risk of ovarian cancer (95% CI 0.58-0.94), after taking into account combined oral contraceptive use, parity, education level, age, race/ethnicity, and OCAC study site. A significant trend with duration of use was observed in the two studies with these data (p=0.02). Conclusions: DMPA use appears to be associated with a decreased risk of ovarian cancer. The finding provides additional evidence that progestins may be protective for ovarian cancer. Further evaluation of the role of DMPA as a potential primary prevention strategy for ovarian cancer, especially in women for whom combined oral contraceptive use is contraindicated due to concerns about estrogen-induced thromboembolic events, is warranted. Citation Format: Minh Tung Phung, Penelope M. Webb, Jennifer Anne Doherty, Holly R. Harris, Pamela J. Thompson, Marc T. Goodman, Kirsten Moysich, Francesmary Modugno, Roberta B. Ness, Joellen M. Schildkraut, Andrew Berchuck, Daniel W. Cramer, Kathryn L. Terry, Linda Titus, Alice W. Lee, Malcolm C. Pike, Anna H. Wu, Celeste Leigh Pearce. Use of progestin-only injectable contraceptive is associated with reduced risk of ovarian cancer in the Ovarian Cancer Association Consortium [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B38.

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