IUD and risk of ovarian cancer

“The reduced risk of ovarian cancer with the use of oral contraceptives is well established,” said senior author Jacques Balayla, MD, MPH, a clinician-scientist and Osler fellow in the Department of Obstetrics and Gynecology at McGill University in Montreal, Quebec, Canada. “We sought to determine whether other forms of contraception, namely the intrauterine device (IUD), accomplished the same goals.”

Jacques Balayla, MD, MPH

The authors searched the Medline, EMBASE, Google Scholar, Scopus, ISI Web of Science and Cochrane databases, as well as PubMed and the RCT (randomized controlled trials) registry, to conduct a systematic review and meta-analysis comparing ever-use vs. never-use of an IUD and the risk of subsequent ovarian cancer.¹

Of 431 records obtained, 9 met inclusion criteria: 5 case-control studies (a total of 2,232 cancer cases among 4,368 IUD users, with matched control ratios ranging from 1:1 to 1:2) and four cohort studies (a total of 269,045 patients).

Compared to never-use of an IUD, ever-use conferred a lower risk of ovarian cancer: estimated odds ratio (OR) 0.67; 95% confidence interval (CI): 0.60 to 0.74 (P < 0.0001, I 2 = 71%).

Furthermore, this relationship remained significant when results were restricted to studies evaluating the levonorgestrel intrauterine system (LNG-IUD) alone: estimated OR 0.58; 95% CI: 0.47 to 0.71 (P < 0.0001, I 2 = 0%).

The same significant relationship also persisted when the analysis was stratified by study design, with an estimated OR of 0.64 (95% CI: 0.56 to 0.74) for case-control studies and an estimated OR of 0.71 (95% CI: 0.60 to 0.84) for cohort studies (P < 0.0001).

Only one of the nine studies (a cohort study) found an increased risk of ovarian cancer in IUD ever-users.

“An IUD is thought to act locally in the endometrial cavity, with minimal absorption of the hormones secreted into the circulation,” Balayla told Contemporary OB/GYN. “The fact that a locally acting agent can have effects in adjacent organs was a surprising finding.”

The exact reasons why an IUD significantly reduces the risk of ovarian cancer need to be better elucidated, but the authors hypothesized three potential mechanisms: (1) mechanical barrier against potential carcinogenic agents; (2) decreased retrograde menstruation and displacement of endometrial cells; and (3) progesterone-induced benefit amongst hormonal IUDs.

“We already know the benefits of an IUD for contraception, for the treatment of abnormal uterine bleeding, and even for the reduction in rates of endometrial cancer,” Balayla said. “While the use of an IUD is not currently approved for the prevention of ovarian cancer, the findings of our study may point toward yet another benefit of the IUD that could be discussed during the clinical counselling of patients.”

Future studies will need to determine whether the known beneficial effects of an IUD are a function of duration of use, of a particular kind of device or specific tumor types, according to Balayla. “In the meantime, our current findings may serve clinicians to reassure and counsel patients about the added cancer advantage of IUDs,” he said.

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Disclosures

Balayla reports no relevant financial disclosures.

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Reference

1. Balayla J, Gil Y, Lasry A, et al.Ever-use of the intra-uterine device and the risk of ovarian cancer. J Obstet Gynaecol. Published online October 12, 2020. doi:10.1080/01443615.2020.1789960