Meta-Analysis of Intrauterine Device Use and Risk of Endometrial Cancer

https://doi.org/10.1016/j.annepidem.2007.11.011Get rights and content

Purpose

We sought to study the association between intrauterine device (IUD) use and endometrial cancer.

Methods

A comprehensive search of literature published through April 2007 was conducted, studies reviewed, and data abstracted. Data from ten studies were pooled and analyzed using both fixed- and random-effects models to examine the association of ever use of an IUD and endometrial cancer.

Results

Based on the random effects model, a protective crude association between IUD use and endometrial cancer was observed (odds ratio [OR] = 0.39; 95% confidence interval [CI] = 0.29–0.51; heterogeneity p < 0.001) with a pooled adjusted risk of OR = 0.54 (95% CI, 0.47–0.63; heterogeneity p = 0.40). A decreased risk of endometrial cancer also was seen for increased years of IUD use (OR for 5 years of use 0.88; 95% CI = 0.84–0.92; n = 5; heterogeneity p = 0.14), increased years since last IUD use (OR for 5 years of use 0.91; 95% CI, 0.86–0.95; n = 4; heterogeneity p = 0.02), and increased years since first IUD use (OR for 5 years of use 0.89; 95% CI, 0.83–0.95; n = 4; heterogeneity p = 0.04).

Conclusions

Our results suggest that nonhormonal IUD use may be associated with a decreased risk for endometrial cancer; however, the exact mechanism for this association is unclear. Future investigations should address the difference in the proposed association by specific type of IUDs.

Introduction

Endometrial cancer is the most prevalent female genital malignancy in the United States with an estimated 39,080 incident cases and 7,400 associated deaths expected in the United States during 2007 (1). Endometrial cancer primarily affects postmenopausal age women with a mean age at diagnosis of 61 years (2). Factors associated with an increased risk of endometrial cancer are exposure to unopposed estrogen increasing age, elevated body mass index, nulliparity, infertility, polycystic ovary syndrome, amenorrhea, early age at first menarche, delayed onset of menopause, unopposed estrogen therapy, and tamoxifen therapy 2, 3. Previous studies have indicated a protective association between use of combination oral contraceptives and risk of endometrial cancer. Progesterone acts to limit endometrial proliferation, thereby decreasing the overall risk of endometrial cancer (4).

Intrauterine devices (IUDs) are a common method of reversible contraception in many countries, with an estimated 106 million women worldwide who have used an IUD (5). However, the rate of IUD use in North America ranks among the lowest in the world, with an estimated 1.5% of married women in the United States using an IUD, compared with the highest rate, 33.0% in China, and a global rate of 11.9% (5). IUDs were first marketed for use in 1964 (6). The first generation of IUDs was inert devices, followed by a second generation of copper IUDs, first approved by the U.S. Food and Drug Administration (FDA) in 1984 (7), and most recently a third generation of progesterone IUDs, first introduced in 1990 in Finland 7, 8, and later approved by the FDA in December 2000 (7). Currently, two types of IUDs are marketed in the United States, the copper T380A (ParaGard) and the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena) (5).

The overall aims of this study were to quantify the magnitude of the association between IUD use and risk of endometrial cancer, including potential contributing factors: duration of use, time since first use, time since last use, and type of device. A meta-analysis was conducted to evaluate these associations with endometrial cancer.

Section snippets

Literature Review

For this meta-analysis, analytic studies that measured IUD use in relation to endometrial cancer were considered. First, a literature search from 1966 through the end of April 2007 was performed using PubMed. MeSH headings, key words, and text words searched included intrauterine devices, IUD, endometrial cancer, and endometrial neoplasms. The search of PubMed returned 42 articles, of which 11 7, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 were reviewed in detail. The 31 remaining articles were not

Results

Eleven articles reporting on 10 studies were reviewed 6, 10, 11, 12, 13, 14, 15, 16, 17, 18. Study characteristics, including diagnosis years of cases, study location, age range, and number of subjects are described (Table 1). We reported the ORs for the associations between ever versus never IUD use and risk of endometrial cancer, along with the adjustment factors described in each study (Table 1). Only three studies reported on specific types of IUD used; thus the data for types of IUDs used

Discussion

Hormonal (progesterone) IUDs have been marketed since. 1990 7, 8. We assume all of the women included in these studies had used nonhormonal IUDs, since eight of the 10 studies had diagnosis dates of cancer prior to 1993 where participant exposure to IUDs would likely have occurred prior to the 1990s. When the two studies with diagnosis years in the 1990's were excluded, point estimates changed by 0.01 or less, suggesting that these two studies did not differ from the earlier studies.

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