By Rebecca H. Allen, MD, MPH

Associate Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI

Dr. Allen reports she receives grant/research support from Bayer and is a consultant for Merck.

SYNOPSIS: In this systematic review, the odds ratio of ever-use of an intrauterine device and incident ovarian cancer was 0.68 (95% CI 0.62-0.75).

SOURCE: Wheeler LJ, Desanto K, Teal SB, et al. Intrauterine device use and ovarian cancer risk: A systematic review and meta-analysis. Obstet Gynecol 2019; Sep. 10. doi: 10.1097/AOG.0000000000003463. [Epub ahead of print].

This was a systematic review and meta-analysis of existing studies that evaluated both the incidence ovarian cancer and ever-use of an intrauterine device (IUD). IUD use in the setting of menopausal hormone therapy was excluded; both case control and cohort studies were included. Data extracted from the studies included geographic location, years of data collection, year of publication, study size, and characteristics of the study population (age, menopausal status, gravidity, history of oral contraceptive use, body mass index, IUD type, method of ovarian cancer diagnosis, and family history of cancer).

After searching MEDLINE, Embase, Cochrane Library, Web of Science Core Collection, Google Scholar, and ClinicalTrials.gov, and reviewing the results for inclusion, researchers chose 11 trials (nine case-control and two cohort studies) for the analysis. The case-control studies contributed 4,484 cases of ovarian cancer and 9,107 controls, and the cohort studies contributed 649 ovarian cancer patients and 173,928 women without ovarian cancer. All studies took age, parity, and oral contraceptive use into consideration.

In the meta-analysis, the summary odds ratio between ever-use of an IUD and incidence ovarian cancer was 0.68 (95% confidence interval [CI], 0.62-0.75). This inverse association remained even when the meta-analysis was stratified to include studies that evaluated other confounding factors, such as body mass index, history of bilateral tubal ligation, menopausal status, and family history of cancer.

COMMENTARY

The National Cancer Institute estimates there will be 22,530 new cases of ovarian cancer and 13,980 deaths from ovarian cancer in the United States in 2019.¹ The five-year survival rate is 47.6%. Ovarian cancer is the second most common cause of gynecologic cancer in the United States, and the median age of diagnosis is 63 years. To date, attempts to develop screening programs for ovarian cancer have not been successful. Factors that are protective against the development of ovarian cancer are critical to elucidate. Other contraceptive methods known to reduce the risk of ovarian cancer include combined oral contraceptives (50% reduction with 10 or more years of use) and tubal ligation. Recently, the introduction of opportunistic salpingectomy at the time of hysterectomy or for permanent contraception has offered another possibility to reduce ovarian cancer risk.

The authors of this study sought to estimate the effect of IUD use on ovarian cancer incidence. They found that IUD use was protective (32% decreased risk) across multiple large, international, case-control and cohort studies, which increased the generalizability. Unfortunately, the investigators were not able to evaluate the risk by type of IUD; therefore, these data represent different copper, stainless steel, and levonorgestrel IUDs combined. The theoretical mechanism of action for the copper IUD or stainless steel varieties used internationally could include alteration in the pH of the reproductive tract or a localized inflammatory response that would destroy malignant cells.² The levonorgestrel IUD has the additional effects of thickening cervical mucus, inhibition of endometrial proliferation, and also provides occasional ovulation suppression. Both copper and levonorgestrel IUDs are known to reduce the risk of endometrial cancer as well.³

The study is limited by the risk of biases in the individual studies included in the meta-analysis, which may include recall bias, selection bias, and lost-to-follow-up bias. The investigators also could not evaluate whether duration of IUD use affects risk, nor whether one type of IUD worked better than another. Nevertheless, these are promising data that indicate IUD use could have a future effect of reducing ovarian cancer rates as more women opt for this method of contraception. We can inform patients of this important potential non-contraceptive benefit of IUD use during contraceptive counseling.

REFERENCES

1. SEER Cancer Stat Facts: Ovarian Cancer. National Cancer Institute. Bethesda, MD. Available at: https://seer.cancer.gov/statfacts/html/ovary.html. Accessed Oct. 7, 2019.
2. Rivera R, Yacobson I, Grimes D. The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices. Am J Obstet Gynecol 1999;181:1263-1269.
3. Bahamondes L, Valeria Bahamondes M, Schulman LP. Non-contraceptive benefits of hormonal and intrauterine reversible contraceptive methods. Hum Reprod Update 2015;21:640-651.