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Intrauterine contraception: Background and device types

Intrauterine contraception: Background and device types
Author:
Tessa Madden, MD, MPH
Section Editor:
Courtney A Schreiber, MD, MPH
Deputy Editor:
Kristen Eckler, MD, FACOG
Literature review current through: Apr 2025. | This topic last updated: Mar 21, 2025.

INTRODUCTION — 

The intrauterine device (IUD) is the most used method of long-acting reversible contraception because of its high efficacy and safety, ease of use, and cost effectiveness. It provides a nonsurgical option for pregnancy prevention that is as effective as surgical sterilization. The most frequently used IUDs have a plastic frame and release either copper or a progestin to enhance the contraceptive action of the device.

Several terms are used to describe IUDs, including IUD and intrauterine contraception; the hormonal IUD or progestin-containing device is also referred to as an intrauterine system. In this topic, we use the term IUD for all types of IUDs.

This topic will discuss types of IUDs and their mechanism of action. Issues related to IUD selection, use in specific populations, removal, side effects, and complications are discussed separately:

●(See "Intrauterine contraception: Candidates and device selection".)

●(See "Intrauterine contraception: Insertion and removal".)

●(See "Intrauterine contraception: Management of side effects and complications".)

In this topic, when discussing study results, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. We encourage the reader to consider the specific counseling and treatment needs of transgender and gender-expansive individuals.

COUNSELING POINTS (ALL IUD TYPES)

Prevalence of use — IUDs are the most commonly used method of reversible contraception globally, with use rates ranging from <1 to >30 percent depending on the country [1,2]. Use of IUDs has increased in the United States: Between 2002 and 2016, IUD use rose from 2 to 14 percent among United States women using contraception [3-8]. Actively informing patients about benefits, risks, and common side effects of IUDs appears to improve consideration and acceptance of the method [9].

Mechanism of action — IUDs primarily prevent conception by inhibiting fertilization, although there are multiple mechanisms (table 1). IUDs are not abortifacients [10-15] as they do not interrupt established pregnancies.

●Mechanisms – Pregnancy appears to be prevented by a foreign body effect induced by the IUD frame and by local changes caused by the released medication.

•Foreign body effect – When the uterus is exposed to a foreign body, a sterile inflammatory reaction occurs, which is toxic to sperm and ova and impairs fertilization [12,14,16-18]. The production of cytotoxic peptides and activation of enzymes lead to inhibition of sperm motility, reduced sperm capacitation and survival, and sperm phagocytosis which also inhibit fertilization [19,20]. These cytotoxic effects are supported by studies in which fallopian tubes of IUD users were flushed but no sperm or fertilized ova were found [12,14].

•Copper – The addition of copper enhances the cytotoxic inflammatory response within the endometrium and prevents fertilization by impacting sperm migration, viability, and acrosomal reaction [11,17,18,21,22].

•Levonorgestrel (LNG) – The addition of LNG thickens cervical mucus, which acts as a barrier to the upper genital tract (ie, reduces sperm access to the upper tract and thereby prevents fertilization), causes endometrial decidualization and glandular atrophy, and may inhibit the binding of the sperm and egg by increasing glycodelin A production, which further impairs fertilization [23-25].

●Minimal impact on ovulation – Copper IUDs do not impact ovulation. For LNG IUD users, most cycles are ovulatory. With initial insertion, ovulation rates may decrease (ie, ovulation is suppressed) and then return to normal as the LNG level drops over time. During the first year of IUD use, LNG 52 mg IUD users ovulated in 45 percent of cycles while users of lower-dose IUDs ovulated in 88 to 97 percent of cycles [26-29].

●Not an abortifacient – There is no evidence that IUDs disrupt an implanted pregnancy [30]. Studies of IUD users were unable to find embryos or detect human chorionic gonadotropin, indicating that transient, or chemical, pregnancies were not occurring [17,31,32]. Despite the evidence that IUDs do not interrupt pregnancy (ie, are not an abortifacient), a 2019 survey of 893 US physicians reported that 17 percent believed that IUDs caused abortion [33].  

Benefits, risks, and patient satisfaction

●Benefits – There are multiple benefits of IUD use, including:

•Highly effective pregnancy prevention (>99 percent) (figure 1).

•Does not require regular adherence from user to maintain high effectiveness.

•Long acting.

•Rapidly reversible. Resumption of fertility after discontinuation is rapid and similar for IUDs [26-29,34], progestin-releasing implants [35,36], and contraceptive pills, rings, and patches [37,38].

•Few medical contraindications for most women. (See "Intrauterine contraception: Candidates and device selection", section on 'Contraindications'.)

•Suitable for teens and nulliparous women.

•Few side effects.

•Private and does not interfere with the spontaneity of sex.

•Avoidance of exogenous estrogen (both IUD types) and hormones (copper IUD only).

•Highly cost-effective with long-term use.

•Reduced risk of cervical, endometrial, and ovarian cancers [39]. Data specific to the LNG IUDs are available below. (See 'Risk of cancer' below.)

-Cervical cancer – A meta-analysis of 16 studies assessing the incidence of cervical cancer in IUD users reported that women with any history of IUD use were approximately 30 percent less likely to develop cervical cancer (summary odds ratio [OR] 0.64, 95% CI 0.53-0.77) [40]. The proposed mechanism is an altered cellular immune response resulting from device insertion and presence [41,42]. These studies primarily collected data about nonhormonal IUD use.

-Endometrial cancer – Both copper and LNG IUDs reduce the risk of endometrial cancer; the LNG IUD suppresses the endometrial growth and the copper IUD creates a local inflammatory response [39].

-Ovarian cancer – Results on the effect of IUDs on ovarian cancer risk are conflicting, although most studies show a reduced risk [39]. A meta-analysis of 11 studies (9 case control, 2 cohort) reported a reduced rate of ovarian cancer with ever-use of an IUD (summary OR 0.68, 95% CI 0.62-0.75) [43]. The mechanisms by which an IUD might reduce cancer risk and the impact of device type on cancer risk are not known.

•Noncontraceptive benefits. (See 'Noncontraceptive benefits' below.)

●Risks – The risk of either complication or pregnancy with IUD use is low overall. Most of the risks associated with IUD use occur at the time of placement and include difficult insertion, bleeding, infection, and perforation of the uterus. Insertion is often associated with cramping and/or pain, which typically resolves quickly. Detailed discussions of complications are presented in related content. (See "Intrauterine contraception: Management of side effects and complications".)

●Patient satisfaction and method continuation – The above factors contribute to high patient satisfaction and method continuation rates [44-46]. A 2015 United States study of over 5300 women ages 14 to 45 years using either the LNG or copper 380 mm2 IUDs reported one-, two-, three-, four-, and five-year continuation rates of 88, 79, 70, 62 and 52 percent for the LNG IUD and 85, 77, 70, 64, and 56 percent for the copper IUD [46-48]. A Finnish study including almost 18,000 women using an LNG IUD reported continuation rates at one, two, three, four, and five years of 93, 87, 81, 75, and 65 percent, respectively [44]. For comparison, United States women using short-acting methods (ie, depot medroxyprogesterone acetate or hormonal contraceptive pills, patch, or ring) reported a 30 percent three-year contraceptive continuation rate in one study.

Cost effectiveness — All IUDs are highly cost-effective; although the initial cost of the device and insertion can be high, the overall cost decreases with each year of use because no additional expenditure is required. At five years of use, the IUD is one of the most cost-effective methods of reversible contraception available [49]. A 2015 United States cost analysis study that compared the cost of long-acting and short-acting reversible contraceptives calculated that long-acting reversible contraception (including the copper and LNG 52 mg IUD) began saving money after 2.1 years of use when compared with short-acting reversible contraception that included pills, patch, ring, or injection [50].

Risk of sexually transmitted infections and pelvic inflammatory disease — While IUDs do not protect against sexually transmitted infections (STIs), presence of an IUD is not associated with an increased risk of pelvic inflammatory disease (PID) should an STI be acquired [51-53]. Data conflict as to whether or not the risk of STI or PID is greater for users of copper or levonorgestrel IUDs [54,55]. Patients at risk for STI are advised to use condoms (internal or external) to reduce STI risk.

•(See "Intrauterine contraception: Management of side effects and complications", section on 'Infection and/or pelvic inflammatory disease'.)

•(See "External (formerly male) condoms".)

•(See "Internal (formerly female) condoms".)

COPPER IUDS

Device types and characteristics — There are two commonly available copper IUDs, each named for the amount of copper in the device.

●Copper dose and device size – Copper-containing IUDs contain either 380 mm2 or 175 mm2 of copper.

•Copper 380 mm2 – The copper 380 mm2 IUD (commercial name ParaGard) is approved for up to 10 years of use [56,57] This device has a T-shaped polyethylene frame with 380 mm2 of exposed surface consisting of fine copper wire wound around a vertical stem and copper collars on each of the horizontal arms [57]. The device size measures 32 mm horizontally and 36 mm vertically; the placement applicator has a 4.4 mm diameter [58]. A 3 mm ball at the base of the stem decreases the risk of cervical perforation (picture 1) [59]. A white or clear polyethylene monofilament string is knotted through this ball. The frame contains barium sulfate to make it radiopaque. The device is latex free.

The copper 380 mm2 IUD can be inserted for emergency contraception for at least five days (120 hours) from unprotected intercourse and has the lowest pregnancy rate (<0.1 percent) [60,61]. The device can then be left in place to provide ongoing contraception [62]. (See "Emergency contraception", section on 'What are the emergency contraception methods?'.)

•Copper 175 mm2 – The copper 175 mm2 device (commercial name Miudella) is approved for three years of use [63]. It has a flexible nitinol (nickel-titanium alloy) frame with 175 mm of exposed copper. The copper sleeves are located on the distal arms and the base. The device measures 32 mm horizontally and 30 mm vertically; the placement applicator has a 3.7 mm diameter [63]. The device comes preloaded in an applicator with a rounded tip and a polypropylene monofilament retrieval thread pre-cut to a length of 7.8 cm. The device does not contain barium sulfate or latex. The devices compatibility with magnetic resonance imaging (MRI) is listed as conditional. The copper 175 mm2 IUD is not to be used for emergency contraception.

●Use for emergency contraception – The copper 380 mm2 is an established method of emergency contraception. The 175 mm2 device is contraindicated for use as emergency contraception. A complete discussion of emergency contraception is available separately. (See "Emergency contraception".)

●Copper serum levels – Serum copper levels are approximately 216 mcg/dL for the 380 mm2 and 63.5 ng/mL for the 175 mm2 device [57,63]. While serum copper levels are higher in copper 380 mm2 users compared with nonusers and above the normal blood copper level range; however, this increase in circulating copper does not have a negative clinical impact unless the patient has a contraindication to copper (eg, Wilson disease) or allergy [64].

●Copper allergy – Clinically relevant allergy to copper is extremely rare [65]. (See "Intrauterine contraception: Candidates and device selection", section on 'Contraindications'.)

Efficacy

●Comparison of copper IUDs

•380 mm2 IUD – With perfect use of the copper 380 mm2 IUD, the probability of pregnancy in the first year is 0.6 percent; with typical use, the first-year pregnancy rate is 0.5 to 0.8 percent (table 2) [16,66-68].

•175 mm2 IUD – In the initial trials, Pear Indices for years 1, 2, and 3 were 0.94, 1.60, and 0.60 percent, respectively [63]. The cumulative three-year Pearl Index was 1.05 percent (95% CI 0.66-1.60). Available data are from two initial trials that included 1601 healthy women aged 17 to 74 years [58,69].

●Comparison of copper and levonorgestrel IUDs – While failure rates for both IUDs are low overall (figure 1), the rates of failure with the copper IUD are slightly higher than with progestin-releasing IUDs, although conflicting data exist [67]. In one study of over 61,000 women, the copper IUD first-year failure rate was 0.52 versus 0.06 pregnancies per 100 woman-years for the LNG 52 mg IUD [67]. This is similar to the one-year pregnancy rate of 0.7 reported in the copper IUD package insert [70]. In addition, the ectopic pregnancy rate was higher for copper IUDs than the LNG 52 mg IUD (0.08 versus 0.02 ectopic pregnancies per 100 woman-years). While the proportion of ectopic pregnancies was higher for women with LNG IUDs compared with copper IUDs (27 versus 15 percent), the overall incidence rate of ectopic pregnancy was higher for copper IUD users because of the somewhat higher overall failure rate. Of note, the copper IUD study group contained more than 30 types of copper IUDs, which may have impacted the results. As an example, IUDs with less than 380 mm2 of copper and inert IUDs are less effective than those containing ≥380 mm2 of copper [71,72].

●Comparison of copper IUDs and tubal ligation – In a study comparing interval laparoscopic tubal ligation with either copper 380 mm2 or levonorgestrel IUDs (all types), unintended pregnancy rates were similar between tubal ligation and the copper 380 mm2 IUD (adjusted incident rate ratio [aIRR] 0.92, 95% CI 0.82-1.05) but lower with the levonorgestrel IUDs (aIRR 0.72, 95% CI 0.64-0.82). Postpartum tubal ligation was not included in this retrospective cohort study of Medicaid insurance claim data from California.

Additional discussion of permanent contraception is available separately. (See "Overview of female permanent contraception".)

●Impact of younger patient age – Women under age 25 experience a slightly higher failure rate, most likely because they are more fertile than older women. These failure rates are comparable to surgical sterilization [73,74]. (See "Female interval permanent contraception: Procedures".)

Routine and extended duration of use

●Routine use – The copper 380 mm2 IUD is approved for 10 years of use; the copper 175 mm2 IUD is approved for three years of use [57,63].

●Extended use of the 380 mm2 IUD – In appropriately counseled patients, who are typically older and have lower fertility, the copper 380 mm2 IUD can be used for more than 10 years before removal and/or replacement. Extended use of the 175 mm2 IUD is not advised as data are not available.

•Supporting data – Several studies support extended use of the copper 380 mm2 beyond 10 years [75-77]. In two studies of 314 women who used the copper 380 mm2 for an additional two years (10 to 12 years from insertion), no pregnancies were reported [75,76]. Additionally, no pregnancies were reported in the subgroup of eight women who used the device for up to 16 years [76].

•Potential benefits – We counsel patients about the advantages of extended use of the copper 380 mm2 (cost savings, prolongation of contraception, and avoidance of an additional intrauterine procedure). However, for patients with strong preferences for replacement at 10 years, we follow the package insert recommendation to remove or replace the copper 380 mm2 at 10 years.

•Impact of patient age and counseling – In addition to patient preference, extended use depends on patient age at insertion because age impacts fertility.

-<25 years – For patients younger than 25 years at the time of copper 380 mm2 IUD placement, we recommend replacing the IUD after 10 years of use because younger women are more fertile.

-25 to 34 years – For patients age 25 to 34 years at the time of copper 380 mm2 IUD placement, the IUD may be left in place for up to 12 years [75,76].

-≥35 years – For patients age 35 years or older at the time of copper 380 mm2 IUD placement, we recommend leaving the IUD in place until menopause if the patient is happy with the method and still requires contraception [78].

Noncontraceptive benefits — Noncontraceptive benefits of the copper IUD include continued menstrual cyclicity (both devices) and reduced risk of endometrial and cervical cancers (data from studies of the copper 380 mm2 IUD) [39,40,79-82].

Avoid radiofrequency treatment — Patients with copper IUDs are advised to avoid medical treatments and/or equipment that use high levels of radiofrequency energy, such as diathermy [57,63]. There is concern that the copper components could become hot and cause injury. LNG IUDs do not contain metal and thus are not contraindicated.

LEVONORGESTREL IUDS

Devices and characteristics — The levonorgestrel (LNG)-releasing IUDs are available in three different formulations in the United States:

●LNG dose, device size, and duration of use – The LNG IUDs are T-shaped devices that release LNG in four different doses [26-29].

•LNG 52 mg IUDs – This IUD has an initial LNG release rate of approximately 20 mcg/day, which declines to an average release of 10 mcg/day at five years [29]. These devices are approved by the US Food and Drug Administration (FDA) for eight years (abbreviated LNG 52 mg, commercial names Mirena and Liletta) [26,29,83-85].

•LNG 19.5 mg IUD – The initial LNG release rate is 17.5 mcg/day, which declines to 7.4 mcg/day at five years and is FDA approved for five years of use (abbreviated LNG 19.5, commercial name Kyleena) [27].

•LNG 13.5 mg IUD – The initial LNG release rate is approximately 14 mcg/day, which declines to 5 mcg/day at three years and is FDA approved for three years of use (abbreviated LNG 13.5, commercial name Skyla) [28].

●Frame and inserter characteristics

•LNG 52 mg devices – Both 52 mg IUDs consist of a T-shaped polyethylene frame measuring 32 by 32 mm, with a collar containing 52 mg of LNG dispersed in polydimethylsiloxane attached to a vertical stem [26,29]. A string is attached to the distal end of the stem. The insertion tube diameter for the 52 mg LNG IUDs ranges from 4.4 to 4.8 mm. Both devices contain barium in the frame to make them detectable by radiograph.

•LNG 19.5 and 13.5 mg devices – The LNG 19.5 and the LNG 13.5 also use the T-shaped design. In contrast with the LNG 52 mg IUDs, the LNG 19.5 mg and LNG 13.5 mg devices have a smaller frame (28 by 30 mm versus 32 by 32 mm) and are smaller in diameter (3.8 mm inserter versus 4.4 mm) [26-29]. The smaller diameter may allow easier insertion for patients with very small uterine cavities or cervical stenosis, but there are no comparative trials. The LNG 19.5 and LNG 13.5 contain a silver ring at the top of the stem to distinguish them on ultrasound and barium in the frame to make them detectable by radiograph [27,28].

●LNG serum and tissue concentrations – The progestin effect of hormone-releasing IUDs is primarily at the level of the endometrium [86]. As an example, the endometrial concentration of LNG is 1000 times higher with the LNG-releasing IUDs compared with the LNG subdermal implant [87]. However, the high endometrial concentration from the IUDs does not result in a high plasma concentration; the absolute plasma LNG levels are much lower. For the 13.5 mg, 19.5 mg, and 52 mg LNG IUDs, the plasma LNG concentration is highest seven days postinsertion with levels between 100 and 250 pg/mL. There is a gradual decline over time with wide individual variation [26-29,88-90]. This level is half that seen with progestin implants (350 pg/mL) and much less than that associated with progestin-only pills (1500 to 2000 pg/mL) [91,92] but high enough to cause systemic side effects in some users. Serum estradiol levels are not affected [89].

●Use for emergency contraception – The LNG 52 mg IUDs can be used for emergency contraception; the LNG 13.5 and 19.5 mg devices should not be used for emergency contraception. (See "Emergency contraception", section on 'What are the emergency contraception methods?'.)

Efficacy — All levonorgestrel IUDs have low (1 percent or less) rates of unintended pregnancy (ie, failure).

●Comparison of levonorgestrel IUDs – With perfect use of the LNG 52 mg, the probability of pregnancy in the first year is 0.1 percent; with typical use, the first-year pregnancy rate is 0.1 to 0.2 percent (table 2) [67,93,94]. With five years of continuous LNG 52 mg use, the cumulative pregnancy rate is 0.7 percent [26,95,96]. The clinical trial for the LNG 52 mg reported cumulative pregnancy rates of 0.14 percent at one year and 0.87 percent at four years [97]. In a phase three trial of the LNG 19.5 and LNG 13.5 devices, the cumulative pregnancy rates were 0.2 and 0.4 percent at one year and 0.9 and 1.0 percent at three years, respectively [98]. These rates are comparable to those of sterilization procedures (figure 1) [73]. (See "Overview of female permanent contraception", section on 'Counseling and informed consent'.)

●Comparison of copper and levonorgestrel IUDs – While failure rates for copper and levonorgestrel IUDs are low overall (figure 1), the rates of failure with the copper IUD are slightly higher than with progestin-releasing IUDs, as discussed in detail above. (See 'Efficacy' above.)

●Comparison with permanent contraception – In a study comparing interval laparoscopic tubal ligation with either copper 380 mm2 or levonorgestrel IUDs (all types), unintended pregnancy rates were lower with the levonorgestrel IUDs (adjusted incident rate ratio [aIRR] 0.72, 95% CI 0.64-0.82) but similar between tubal ligation and the copper 380 mm2 IUD (aIRR 0.92, 95% CI 0.82-1.05) [74].

•(See 'Efficacy' above.)

•(See "Overview of female permanent contraception", section on 'Counseling and informed consent'.)

●Risk of ectopic pregnancy – While the overall risk of pregnancy is low with LNG IUDs, if a pregnancy is conceived, ectopic pregnancy is more common in patients using LNG IUDs compared with copper IUDs. Thus, individuals who conceive while using any IUD should be evaluated for ectopic pregnancy. (See 'Efficacy' above.)

In a study of over 61,000 European women with a newly inserted IUD, the proportion of ectopic pregnancies was higher in LNG users compared with copper IUD users (27 versus 15 percent) [67]. However, as discussed above, the overall incidence risk of ectopic pregnancy was lower with LNG IUDs because of the lower absolute risk of pregnancy. A smaller cohort study reported similar low rates of ectopic pregnancy between LNG and copper IUD users (both 0.5 per 1000 woman-years) [99]. A retrospective cohort study of over 2000 Swedish women diagnosed with an ectopic pregnancy found the overall risk of an ectopic pregnancy was low among LNG IUD users. However, the risk was higher among users of the 13.5 mg (Pearl Index [PI] 0.136, 95% CI 0.106-0.176) and 19.5 mg (PI 0.037, 95% CI 0.021-0.067) LNG IUD compared with the 52 mg LNG IUD (PI 0.009, 95% CI 0.006-0.014) [100].

Extended use of LNG 52 mg IUDs — Both LNG 52 mg IUDs are approved for up to eight years but studies support extended use may be reasonable [26,29,77,84,85,101-103]. The LNG 19.5 and 13.5 have a lower LNG dose, and there is no evidence supporting extended use of these IUDs past the approved duration [78].

In an extension of a trial that initially enrolled participants up to eight years of LNG 52 mg IUD use, no pregnancies were reported by the participants who continued the IUD for 9 (n = 83) or 10 years (n = 77) of total use [104]. In both groups, the majority of patients were younger than 40 years at study completion (64 patients at 9 years [77 percent] and 44 patients at 10 years [57 percent]).

Noncontraceptive benefits — Noncontraceptive benefits of 52 mg LNG IUDs include reduction in heavy menstrual bleeding, anemia, dysmenorrhea, endometriosis-related pain, and endometrial hyperplasia [39,40,105-113]. The use of the LNG 52 mg IUD for treatment of heavy menstrual bleeding is FDA approved [26,29]. LNG use of 52 mg LNG IUDs for these other noncontraceptive indications is off-label but a common practice that is supported by strong medical evidence. For obese individuals with complex atypical hyperplasia, several observational studies have reported improved resolution with LNG IUD treatment compared with systemic progestin therapy [114,115]. There is also a reduction in the risk of endometrial cancer and ovarian cancer with LNG IUDs.

The use of the IUD or surgical procedures to treat heavy menstrual bleeding is reviewed in detail elsewhere.

●(See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management", section on '52 mg levonorgestrel intrauterine device'.)

●(See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management", section on 'Role of surgery'.)

There is minimal information on the noncontraceptive benefits of the LNG 19.5 and 13.5 IUDs, although it is probable that they also reduce heavy menstrual bleeding, anemia, and dysmenorrhea.

Risk of cancer — LNG IUD use is likely associated with a small increased risk of breast cancer but reduced risk of endometrial and ovarian cancers. Limitations of the available studies include observational data, choice of comparator group (eg, users of other hormonal contraceptives or users of nonhormonal contraceptive methods), duration of study follow-up, prior pregnancy and timing, and baseline cancer risk of study participants, among other variables. The small increased risk of breast cancer is balanced against the larger reductions in endometrial and ovarian cancers on an individual patient basis.

●Breast cancer – The body of evidence suggests a small increased absolute risk of breast cancer with LNG IUD use [116-122], although not all studies agree [123]. In an administrative database study that matched first-time LNG IUD users (any dose) with nonusers of hormonal contraception, there were fewer total cases of breast cancer among LNG IUD users (0.92 versus 1.14 percent), but use was associated with a small increase in overall risk of breast cancer (hazard ratio 1.4, 95% CI 1.2-1.5) [119]. This is similar to the risk reported in an earlier publication by the same research group (RR 1.2, 95% CI 1.1 to 1.33) and in other observational studies with LNG IUD use [116-118,120-122]. For comparison, the increased risk of breast cancer conferred by LNG IUD use appears to be similar to the risk conferred by obesity, alcohol use, or estrogen-progestin contraceptive pills, if the range of published increased risk is considered. We find these comparisons useful in counseling patients and helping each patient understand their individual risk.

•(See "Factors that modify breast cancer risk in females", section on 'Weight and body fat in postmenopausal females'.)

•(See "Overview of the risks and benefits of alcohol consumption", section on 'Breast cancer'.)

•(See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Breast cancer'.)

LNG IUD use is not advised for patients with active breast cancer. (See "Intrauterine contraception: Candidates and device selection", section on 'Contraindications'.)

●Other gynecologic cancers – LNG IUD use has been associated with lower risk of endometrial and ovarian cancer (20 to 30 percent risk reduction for endometrial cancer and 13 to 30 percent risk reduction for ovarian cancer) [39,120,122,124,125]. In a study of Swedish register data comparing over 500,000 LNG users with over 1.5 million nonusers, LNG users had reduced risks of endometrial (adjusted hazard ratio [aHR] 0.67, 95% CI 0.56-0.80) and ovarian cancer (aHR 0.86, 95% CI 0.75-0.99). The risk of cervical cancer also appears to be lower, but with a more modest reduction (aHR 0.91, 95% CI 0.84-0.99) [120]. However, one study reported an increase in cervical intraepithelial neoplasia in LNG IUD users compared with copper IUD users; comparison with the general population was unknown [81,83].

•(See "Endometrial carcinoma: Epidemiology, risk factors, and prevention".)

•(See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Incidence and risk factors".)

•(See "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis".)

IMPACT OF IUDS ON BLEEDING PATTERN — 

In general, copper IUDs are associated with heavier menstrual bleeding while levonorgestrel (LNG) IUDs can cause lighter bleeding, amenorrhea, or minimal change, depending on the LNG dose.

Copper IUDs — Individuals considering the copper IUDs are counseled that menses may be heavier, longer, or more painful, particularly in the first several cycles after insertion [57,63]. The initial increases in bleeding and pain generally resolve by six months of use [126]. The amount of baseline menstrual bleeding the patient has prior to copper IUD insertion does not appear to impact the 12-month device continuation rate. Patients with baseline heavy menstrual bleeding are not more likely than those without to remove the device [127]. Nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease heavy menstrual bleeding in copper IUD users, although studies are limited [128].

●Bleeding volume – While the average monthly menstrual blood loss may increase by up to 55 percent throughout the duration of copper IUD use, it rarely leads to anemia. A systematic review reported the hemoglobin concentration decreased by 0.36 to 0.94 g/dL over 12 months in copper 380 mm2 IUD users who were not anemic at baseline [129]. We discuss with patients that typical menstrual blood loss per cycle is 5 to 80 mL based on clinical data, and may increase with copper IUD use [130,131]. Discussions of menstrual volume are available in other content. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis".)  

●Discontinuation rates for bleeding and/or pain – The initial trial data suggest that the lower dose of the copper 175 mm2 IUD results in less bleeding and cramping, as reflected by the discontinuation rates, compared with the copper 380 mm2 IUD. At 1, 2, and 3 years of use, the discontinuation rates for 175 mm2 users were 8.5, 5.1, and 3.2 percent, respectively, while discontinuation rates for copper 380 mm2 users were 11.9, 9.8, and 7.0 percent, respectively [57,63].

●Comparison of copper 380 mm2 and LNG IUDs – In a study of over 3800 women using either the copper 380 mm2 or the LNG 52 mg, at three months the copper IUD users reported more cramping (63 versus 32 percent), increased bleeding volume (71 versus 12 percent), and increased bleeding frequency (41 versus 33 percent) compared with LNG 52 mg users [126]. Importantly, these symptoms improved rapidly, and at six months the copper IUD users reported symptom reduction to levels similar to the LNG 52 mg users (cramping 14 versus 12 percent, increased bleeding volume 19 versus 8 percent, increased bleeding frequency 13 versus 11 percent). (See "Intrauterine contraception: Management of side effects and complications", section on 'Post-insertion bleeding' and "Intrauterine contraception: Management of side effects and complications", section on 'Irregular bleeding and/or cramping'.)

Levonorgestrel-releasing IUDs — For the LNG-releasing IUDs, the most common changes in bleeding patterns include prolonged bleeding (59 percent), unscheduled bleeding (up to 52 percent), amenorrhea (6 to 20 percent), and spotting (23 to 31 percent) at the end of one year of use [26-28,97,132]. Women should be reassured that the changes in bleeding patterns are a side effect of the hormone on the uterine lining and are not dangerous. All women should be counseled that intermenstrual bleeding is common, especially with the onset of use, and improves by six months of use [26,28,97,126]. A study including 3001 LNG 52 mg users who were surveyed at three and six months of IUD use reported that, by six months, 62 percent of reported lighter bleeding and 55 percent reported decreased frequency of bleeding [126]. The management of these and other hormonal side effects, such as breast tenderness, mood changes, and acne, is discussed in detail separately. (See "Intrauterine contraception: Management of side effects and complications".)

While changes in bleeding patterns are common with the 52 mg, 19.5 mg, and 13.5 mg LNG IUDs, the amenorrhea rate differs substantially among the devices. After one year of use, amenorrhea is reported by approximately 20 percent of LNG 52 mg IUD users, 12 percent of LNG 19.5 mg users, and 6 percent of LNG 13.5 mg users [26-28,97,132,133]. At the end of three years of use, 30 to 50 percent of LNG 52 mg IUD users reported amenorrhea compared with 20 and 12 percent of women using the LNG 19.5 mg and LNG 13.5 mg, respectively [26-28,97]. Therefore, women who prefer to avoid menstrual bleeding may benefit from a 52 mg device, and those who prefer the reassurance of monthly menstruation may benefit from the 19.5 mg or 13.5 mg devices. Both groups must be counseled that the desired menstrual change may not occur; some women with the 52 mg devices will continue to have monthly periods, and some with the lower dose devices will become amenorrheic.

Bleeding-related discontinuation rates — With supportive counseling, most patients are able to tolerate the changes in bleeding patterns, and discontinuation rates are low overall for all devices. In a study of over 3800 women using either the copper 380 mm2 or the LNG 52 mg, the overall satisfaction rate for both the copper IUD and the LNG IUD was greater than 90 percent at six months of use [126]. Only 7 percent of LNG IUD users and 8 percent of copper IUD users discontinued by six months [134]. In the six-year LNG 52 mg clinical trial, 2.3 percent of women discontinued the device early because of bleeding complaints compared with a 12 percent overall early discontinuation rate [97]. Similarly, in the three-year LNG 13.5 clinical trial, the early discontinuation rates were 4.6 percent for bleeding complaints and 18 percent overall [28]. For comparison, other reasons for discontinuation of the LNG 13.5 IUD included device expulsion (3.2 percent), acne/seborrhea (2.9 percent), abdominal pain (2.5 percent), dysmenorrhea/uterine spasms (2.0 percent), and pelvic pain (1.8 percent). (See "Intrauterine contraception: Management of side effects and complications", section on 'Irregular bleeding and/or cramping' and "Intrauterine contraception: Management of side effects and complications", section on 'Continued bleeding and cramping'.)

RISK OF EXPULSION — 

The incidence of expulsion is 3 to 10 percent for the copper IUDs and 3 to 6 percent for the levonorgestrel IUD in the first year of use [16,57,63,66,75,135,136]. The symptoms and risk factors of expulsion are discussed separately.

●(See "Intrauterine contraception: Management of side effects and complications", section on 'Expulsion'.)

●(See "Contraception: Postabortion", section on 'Intrauterine device'.)

●(See "Contraception: Postpartum counseling and methods", section on 'Expulsion'.)

OTHER IUD TYPES — 

Multiple other IUD types and shapes have been used globally (picture 2).

Inert IUDs — Unmedicated IUDs are approved for use outside the United States and are popular because they can remain in place for 20 years or more. The devices are composed of inert materials such as plastic or stainless steel. Flexible stainless steel rings visible on radiographs, but with no string, were widely used in China [137]. The pregnancy rates for the Lippes Loop vary by device size and range from 1 to 4.8 per 100 women-years [138,139]. The higher failure rate of the stainless steel ring compared with copper T IUDs (10.6 versus 1.7 percent) led the Chinese State Family Planning Commission to stop production of the ring in 1993 and to encourage the use of copper or levonorgestrel (LNG)-releasing IUDs instead [16,137,140].

As medicated IUDs are more effective, we recommend replacing inert IUDs with LNG-releasing or copper IUDs, especially for women below age 40, as they have higher fertility rates. We also inform women ages 40 and older that LNG and copper IUDs are more effective than inert IUDs but do not encourage switching if the patient is happy with her device.

Frameless IUDs — Frameless IUDs, which are available outside of the United States, contain either copper or LNG that has been attached to a nonresorbable filament. The GyneFix 330 is made up of copper cylinders threaded onto a polypropylene suture instead of the plastic frame common to other IUDs [141,142]. The FibroPlant is a frameless LNG-releasing IUD consisting of a nonresorbable thread attached to a fibrous delivery system that releases 14 or 20 mcg of LNG per day [143]. These devices are anchored to the endometrium using an insertion technique that requires additional training as the technique is different from the other types of IUDs. The intrauterine ball SCu300A is comprised of copper beads strung on a memory alloy wire that curls into a ball shape on insertion into the uterus [144].

Advantages of these systems include small size, high efficacy, and high tolerability. They may be as effective as conventional IUDs and more adaptable to variations in the shape of the uterine cavity [145,146]. However, the risk of expulsion may vary depending on the IUD shape [147].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Contraception".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Intrauterine devices (IUDs) (The Basics)" and "Patient education: Long-acting methods of birth control (The Basics)" and "Patient education: IUD placement (The Basics)" and "Patient education: IUD removal (The Basics)")

●Beyond the Basics topic (see "Patient education: Long-acting methods of birth control (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Device types and prevalence of use – The two common categories of IUDs are copper-containing and levonorgestrel-releasing (LNG) devices. Globally, an average of 23 percent of contraceptive users report having an IUD, which makes these devices the most used reversible contraceptive worldwide. Both the copper and LNG-releasing devices are available in multiple formulations. (See 'Counseling points (all IUD types)' above.)

●Mechanism of action – Multiple mechanisms appear to contribute to the contraceptive action of IUDs (table 1). The primary mechanism is prevention of fertilization due to by a foreign body effect induced by the IUD frame and by local changes caused by the released medication. LNG IUDs also cause thickening of cervical mucus. (See 'Mechanism of action' above.)

●Benefits of use – There are multiple benefits to IUD use, including high effectiveness and little maintenance for the user (figure 1), which result in high user satisfaction rates. The IUD is also cost-effective when used over multiple years. (See 'Benefits, risks, and patient satisfaction' above and 'Cost effectiveness' above.)

●Copper IUDs – The copper 380 mm2 has a T-shaped polyethylene frame with 380 mm2 of exposed surface consisting of fine copper wire wound around a vertical stem and copper collars on each of the horizontal arms; a 3 mm ball at the base of the stem decreases the risk of cervical perforation (picture 1). The copper 380 mm2 can also be used for emergency contraception and left in place for continued contraception. In 2025, the copper 175 mm2 device (commercial name Miudella) is approved for three years of use. The device is anticipated to be available at the end of 2025. (See 'Copper IUDs' above.)

•Efficacy – With perfect use, the probability of pregnancy in the first year is 0.7 percent; with typical use, the first year pregnancy rate is 0.5 to 0.8 percent (table 2). While failure rates for both copper and LNG-releasing IUDs are low overall, the rates of failure with the copper IUD are somewhat higher than with progestin-releasing IUDs. (See 'Efficacy' above.)

•Duration of use – The copper 380 mm2 is approved by the US Food and Drug Administration (FDA) to remain in place for 10 years. However, this may vary elsewhere since the use of the copper 380 mm2 beyond 10 years is supported by several studies. (See 'Routine and extended duration of use' above.)

•Impact on menses – Women considering the copper IUD are counseled that menses may be heavier, longer, or more painful, particularly in the first several cycles after insertion. These changes in menstrual symptoms often improve over time and generally do not cause women to remove the IUD. (See 'Copper IUDs' above.)

●Levonorgestrel IUDs – There are four types of LNG-releasing IUDs available in the United States, with progestin-release rates ranging from 14 to 20 mcg/day (picture 3). The progestin effect of hormone-releasing IUDs is primarily at the level of the endometrium. (See 'Devices and characteristics' above.)

•Efficacy – With perfect use of the LNG 52 mg IUDs, the probability of pregnancy in the first year is 0.1 percent; with typical use, the first-year pregnancy rate is 0.1 to 0.2 percent (table 2). (See 'Efficacy' above.)

-Duration of use – The duration of use varies with the type of LNG IUD. The LNG 52 mg devices are approved for up to eight years of use by the FDA (commercial names Mirena and Liletta). The LNG 19.5 mg and 13.5 mg have lower LNG doses and are approved for five and three years respectively. There is no evidence supporting extended use of the LNG 19.5 mg and 13.5 mg IUDs. (See 'Extended use of LNG 52 mg IUDs' above.)

•Impact on menses and related benefits – Noncontraceptive benefits of 52 mg LNG IUDs include reduction in heavy menstrual bleeding, anemia, dysmenorrhea, endometriosis-related pain, and endometrial hyperplasia. (See 'Noncontraceptive benefits' above.)

●Other IUD types – Multiple types of IUDs are available globally. Popular devices include inert and frameless IUDs (available outside the United States).

•Inert or unmedicated IUD – Inert, or unmedicated, IUDs are popular because they can remain in place for 20 years or more. The devices are composed of inert materials such as plastic or stainless steel. (See 'Inert IUDs' above.)

•Frameless IUD – Frameless IUDs, which are available outside of the United States, contain either copper or LNG that has been attached to a nonresorbable filament. Advantages of these systems include small size, high efficacy, and high tolerability. They may be as effective as conventional IUDs and more adaptable to variations in the shape of the uterine cavity. (See 'Frameless IUDs' above.)

ACKNOWLEDGMENTS — 

The UpToDate editorial staff acknowledges Gillian Dean, MD, MPH, and Alisa Goldberg, MD, MPH, who contributed to an earlier version of this topic review.

  1. World Contraceptive Use 2022. United Nations Population Division. Available at: https://www.un.org/development/desa/pd/data/world-contraceptive-use (Accessed on August 12, 2024).
  2. Buhling KJ, Zite NB, Lotke P, et al. Worldwide use of intrauterine contraception: A review. Contraception 2014; 89:162.
  3. Finer LB, Jerman J, Kavanaugh ML. Changes in use of long-acting contraceptive methods in the United States, 2007-2009. Fertil Steril 2012; 98:893.
  4. Mosher WD, Martinez GM, Chandra A, et al. Use of contraception and use of family planning services in the United States: 1982-2002. Adv Data 2004; :1.
  5. Kavanaugh ML, Jerman J, Finer LB. Changes in use of long-acting reversible contraceptive methods among U.S. women, 2009-2012. Obstet Gynecol 2015; 126:917.
  6. Daniels K, Daugherty J, Jones J, Mosher W. Current Contraceptive Use and Variation by Selected Characteristics Among Women Aged 15-44: United States, 2011-2013. Natl Health Stat Report 2015; :1.
  7. Kavanaugh ML, Jerman J. Contraceptive method use in the United States: trends and characteristics between 2008, 2012 and 2014. Contraception 2018; 97:14.
  8. Kavanaugh ML, Pliskin E. Use of contraception among reproductive-aged women in the United States, 2014 and 2016. F S Rep 2020; 1:83.
  9. Arrowsmith ME, Aicken CR, Saxena S, Majeed A. Strategies for improving the acceptability and acceptance of the copper intrauterine device. Cochrane Database Syst Rev 2012; :CD008896.
  10. Rivera R, Yacobson I, Grimes D. The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices. Am J Obstet Gynecol 1999; 181:1263.
  11. Stanford JB, Mikolajczyk RT. Mechanisms of action of intrauterine devices: Update and estimation of postfertilization effects. Am J Obstet Gynecol 2002; 187:1699.
  12. Alvarez F, Brache V, Fernandez E, et al. New insights on the mode of action of intrauterine contraceptive devices in women. Fertil Steril 1988; 49:768.
  13. Ortiz ME, Croxatto HB. Copper-T intrauterine device and levonorgestrel intrauterine system: Biological bases of their mechanism of action. Contraception 2007; 75:S16.
  14. El-Habashi M, El-Sahwi S, Gawish S, Osman M. Effect of Lippes loop on sperm recovery from human fallopian tubes. Contraception 1980; 22:549.
  15. Clinical guide to contraception, 6th ed, Jenson JT, Creinin MD (Eds), Lippincott Williams & Wilkins, Philadelphia 2019.
  16. Mechanism of action, safety and efficacy of intrauterine devices. Report of a WHO Scientific Group. World Health Organ Tech Rep Ser 1987; 753:1.
  17. Ortiz ME, Croxatto HB, Bardin CW. Mechanisms of action of intrauterine devices. Obstet Gynecol Surv 1996; 51:S42.
  18. Seleem S, Hills FA, Salem HT, et al. Mechanism of action of the intrauterine contraceptive device: Evidence for a specific biochemical deficiency in the endometrium. Hum Reprod 1996; 11:1220.
  19. Sağiroğlu N. Phagocytosis of spermatozoa in the uterine cavity of woman using intrauterine device. Int J Fertil 1971; 16:1.
  20. Ammälä M, Nyman T, Strengell L, Rutanen EM. Effect of intrauterine contraceptive devices on cytokine messenger ribonucleic acid expression in the human endometrium. Fertil Steril 1995; 63:773.
  21. Patai K, Szilagyi G, Noszal B, Szentmariay I. Local tissue effects of copper-containing intrauterine devices. Fertil Steril 2003; 80:1281.
  22. Tetrault AM, Richman SM, Fei X, Taylor HS. Decreased endometrial HOXA10 expression associated with use of the copper intrauterine device. Fertil Steril 2009; 92:1820.
  23. Lewis RA, Taylor D, Natavio MF, et al. Effects of the levonorgestrel-releasing intrauterine system on cervical mucus quality and sperm penetrability. Contraception 2010; 82:491.
  24. Silverberg SG, Haukkamaa M, Arko H, et al. Endometrial morphology during long-term use of levonorgestrel-releasing intrauterine devices. Int J Gynecol Pathol 1986; 5:235.
  25. Natavio MF, Taylor D, Lewis RA, et al. Temporal changes in cervical mucus after insertion of the levonorgestrel-releasing intrauterine system. Contraception 2013; 87:426.
  26. MIRENA- levonorgestrel intrauterine device. US Food and Drug Administration (FDA) approved product information. Revised August, 2021. US National Library of Medicine. https://dailymed.nlm.nih.gov/ (Accessed on September 02, 2021).
  27. KYLEENA- Levonorgestrel intrauterine device. US Food and Drug Administration (FDA) approved product information. Revised July, 2021. US National Library of Medicine. https://dailymed.nlm.nih.gov/ (Accessed on September 02, 2021).
  28. SKYLA- levonorgestrel intrauterine device. US Food and Drug Administration (FDA) approved product information. Revised July, 2021. US National Library of Medicine. https://www.dailymed.nlm.nih.gov (Accessed on September 02, 2021).
  29. LILETTA- levonorgestrel intrauterine device. US Food and Drug Administration (FDA) approved product information. Revised November, 2022. US National Library of Medicine. https://dailymed.nlm.nih.gov/ (Accessed on November 28, 2022).
  30. Videla-Rivero L, Etchepareborda JJ, Kesseru E. Early chorionic activity in women bearing inert IUD, copper IUD and levonorgestrel-releasing IUD. Contraception 1987; 36:217.
  31. Wilcox AJ, Weinberg CR, Armstrong EG, Canfield RE. Urinary human chorionic gonadotropin among intrauterine device users: detection with a highly specific and sensitive assay. Fertil Steril 1987; 47:265.
  32. Segal SJ, Alvarez-Sanchez F, Adejuwon CA, et al. Absence of chorionic gonadotropin in sera of women who use intrauterine devices. Fertil Steril 1985; 44:214.
  33. Swan LET, Cutler AS, Lands M, et al. Physician beliefs about contraceptive methods as abortifacients. Am J Obstet Gynecol 2023; 228:237.
  34. Paragard [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc; 2014.
  35. Davies GC, Feng LX, Newton JR, et al. Release characteristics, ovarian activity and menstrual bleeding pattern with a single contraceptive implant releasing 3-ketodesogestrel. Contraception 1993; 47:251.
  36. Croxatto HB, Mäkäräinen L. The pharmacodynamics and efficacy of Implanon. An overview of the data. Contraception 1998; 58:91S.
  37. Barnhart KT, Schreiber CA. Return to fertility following discontinuation of oral contraceptives. Fertil Steril 2009; 91:659.
  38. Mansour D, Gemzell-Danielsson K, Inki P, Jensen JT. Fertility after discontinuation of contraception: A comprehensive review of the literature. Contraception 2011; 84:465.
  39. Minalt N, Caldwell A, Yedlicka GM, et al. Association between intrauterine device use and endometrial, cervical, and ovarian cancer: an expert review. Am J Obstet Gynecol 2023; 229:93.
  40. Cortessis VK, Barrett M, Brown Wade N, et al. Intrauterine Device Use and Cervical Cancer Risk: A Systematic Review and Meta-analysis. Obstet Gynecol 2017; 130:1226.
  41. Castellsagué X, Díaz M, Vaccarella S, et al. Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: A pooled analysis of 26 epidemiological studies. Lancet Oncol 2011; 12:1023.
  42. Petry KU. Loops in the natural history of cervical cancer. Lancet Oncol 2011; 12:986.
  43. Wheeler LJ, Desanto K, Teal SB, et al. Intrauterine Device Use and Ovarian Cancer Risk: A Systematic Review and Meta-analysis. Obstet Gynecol 2019; 134:791.
  44. Backman T, Huhtala S, Blom T, et al. Length of use and symptoms associated with premature removal of the levonorgestrel intrauterine system: A nation-wide study of 17,360 users. BJOG 2000; 107:335.
  45. Jensen JT, Nelson AL, Costales AC. Subject and clinician experience with the levonorgestrel-releasing intrauterine system. Contraception 2008; 77:22.
  46. Diedrich JT, Zhao Q, Madden T, et al. Three-year continuation of reversible contraception. Am J Obstet Gynecol 2015; 213:662.e1.
  47. O'Neil-Callahan M, Peipert JF, Zhao Q, et al. Twenty-four-month continuation of reversible contraception. Obstet Gynecol 2013; 122:1083.
  48. Diedrich JT, Madden T, Zhao Q, Peipert JF. Long-term utilization and continuation of intrauterine devices. Am J Obstet Gynecol 2015; 213:822.e1.
  49. Chiou CF, Trussell J, Reyes E, et al. Economic analysis of contraceptives for women. Contraception 2003; 68:3.
  50. Trussell J, Hassan F, Lowin J, et al. Achieving cost-neutrality with long-acting reversible contraceptive methods. Contraception 2015; 91:49.
  51. Sufrin CB, Postlethwaite D, Armstrong MA, et al. Neisseria gonorrhea and Chlamydia trachomatis screening at intrauterine device insertion and pelvic inflammatory disease. Obstet Gynecol 2012; 120:1314.
  52. Birgisson NE, Zhao Q, Secura GM, et al. Positive testing for Neisseria gonorrhoeae and Chlamydia trachomatis and the risk of pelvic inflammatory disease in IUD users. J Womens Health (Larchmt) 2015; 24:354.
  53. Farley TM, Rosenberg MJ, Rowe PJ, et al. Intrauterine devices and pelvic inflammatory disease: An international perspective. Lancet 1992; 339:785.
  54. Toivonen J. Intrauterine contraceptive device and pelvic inflammatory disease. Ann Med 1993; 25:171.
  55. Peipert LJ, Collins KE, Zhao Q, Peipert JF. Copper intrauterine device and incident sexually transmitted infections. Am J Obstet Gynecol 2021; 225:579.
  56. Creinin M, Kohn JE, Tang JH, et al. Society of Family Planning Committee statement on IUD nomenclature. Contraception 2022; 106:1.
  57. Paragard T 380A- copper intrauterine device. US Food and Drug Administration (FDA) approved product information. Revised September 1, 2019. US National Library of Medicine. www.dailymed.nlm.nih.gov/dailymed/index.cfm (Accessed on March 04, 2025).
  58. Turok DK, Nelson AL, Dart C, et al. Efficacy, Safety, and Tolerability of a New Low-Dose Copper and Nitinol Intrauterine Device: Phase 2 Data to 36 Months. Obstet Gynecol 2020; 135:840.
  59. Speroff L, Darney P. A Clinical Guide for Contraception, 3rd ed, Lippincott Williams & Wilkins, Philadelphia 2001.
  60. Cleland K, Raymond EG, Westley E, Trussell J. Emergency contraception review: evidence-based recommendations for clinicians. Clin Obstet Gynecol 2014; 57:741.
  61. Cleland K, Zhu H, Goldstuck N, et al. The efficacy of intrauterine devices for emergency contraception: A systematic review of 35 years of experience. Hum Reprod 2012; 27:1994.
  62. Shen J, Che Y, Showell E, et al. Interventions for emergency contraception. Cochrane Database Syst Rev 2019; 1:CD001324.
  63. Miudella copper intrauterine system. US Food and Drug Administration (FDA) approved product information. Revised February 2025. US Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/218201s000lbl.pdf (Accessed on March 04, 2025).
  64. De la Cruz D, Cruz A, Arteaga M, et al. Blood copper levels in Mexican users of the T380A IUD. Contraception 2005; 72:122.
  65. Hostynek JJ, Maibach HI. Copper hypersensitivity: Dermatologic aspects. Dermatol Ther 2004; 17:328.
  66. Sivin I, Schmidt F. Effectiveness of IUDs: A review. Contraception 1987; 36:55.
  67. Heinemann K, Reed S, Moehner S, Minh TD. Comparative contraceptive effectiveness of levonorgestrel-releasing and copper intrauterine devices: The European active surveillance study for intrauterine devices. Contraception 2015; 91:280.
  68. Paragard T 380A- copper intrauterine device. US Food and Drug Administration (FDA) approved product information. Revised September 1, 2019. US National Library of Medicine. www.dailymed.nlm.nih.gov/dailymed/index.cfm (Accessed on October 17, 2024).
  69. Creinin MD, Gawron LM, Roe AH, et al. Three-year efficacy, safety, and tolerability outcomes from a phase 3 study of a low-dose copper intrauterine device. Contraception 2025; 143:110771.
  70. Paragard® Package Insert, Trumbull, CT: CooperSurgical, Inc. January 2024.
  71. O'Brien PA, Kulier R, Helmerhorst FM, et al. Copper-containing, framed intrauterine devices for contraception: A systematic review of randomized controlled trials. Contraception 2008; 77:318.
  72. French R, Van Vliet H, Cowan F, et al. Hormonally impregnated intrauterine systems (IUSs) versus other forms of reversible contraceptives as effective methods of preventing pregnancy. Cochrane Database Syst Rev 2004; :CD001776.
  73. Peterson HB, Xia Z, Hughes JM, et al. The risk of pregnancy after tubal sterilization: Findings from the U.S. Collaborative Review of Sterilization. Am J Obstet Gynecol 1996; 174:1161.
  74. Schwarz EB, Lewis CA, Dove MS, et al. Comparative Effectiveness and Safety of Intrauterine Contraception and Tubal Ligation. J Gen Intern Med 2022; 37:4168.
  75. Long-term reversible contraception. Twelve years of experience with the TCu380A and TCu220C. Contraception 1997; 56:341.
  76. Bahamondes L, Faundes A, Sobreira-Lima B, et al. TCu 380A IUD: A reversible permanent contraceptive method in women over 35 years of age. Contraception 2005; 72:337.
  77. Ti AJ, Roe AH, Whitehouse KC, et al. Effectiveness and safety of extending intrauterine device duration: a systematic review. Am J Obstet Gynecol 2020; 223:24.
  78. Wu JP, Pickle S. Extended use of the intrauterine device: A literature review and recommendations for clinical practice. Contraception 2014; 89:495.
  79. Guleria K, Agarwal N, Mishra K, et al. Evaluation of endometrial steroid receptors and cell mitotic activity in women using copper intrauterine device: Can Cu-T prevent endometrial cancer? J Obstet Gynaecol Res 2004; 30:181.
  80. Curtis KM, Marchbanks PA, Peterson HB. Neoplasia with use of intrauterine devices. Contraception 2007; 75:S60.
  81. Spotnitz ME, Natarajan K, Ryan PB, Westhoff CL. Relative Risk of Cervical Neoplasms Among Copper and Levonorgestrel-Releasing Intrauterine System Users. Obstet Gynecol 2020; 135:319.
  82. Averbach S, Silverberg MJ, Leyden W, et al. Recent intrauterine device use and the risk of precancerous cervical lesions and cervical cancer. Contraception 2018.
  83. Liletta Supplement Approval. Food and Drug Administration. Department of Health and Human Services. October 2018. www.accessdata.fda.gov/drugsatfda_docs/appletter/2018/206229Orig1s007ltr.pdf (Accessed on October 18, 2018).
  84. MIRENA (levonorgestrel-releasing intrauterine device). US FDA approved product information; Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2000. www.accessdata.fda.gov/drugsatfda_docs/label/2022/021225s043lbl.pdf (Accessed on August 23, 2022).
  85. Jensen JT, Lukkari-Lax E, Schulze A, et al. Contraceptive efficacy and safety of the 52-mg levonorgestrel intrauterine system for up to 8 years: findings from the Mirena Extension Trial. Am J Obstet Gynecol 2022; 227:873.e1.
  86. Xiao BL, Zhou LY, Zhang XL, et al. Pharmacokinetic and pharmacodynamic studies of levonorgestrel-releasing intrauterine device. Contraception 1990; 41:353.
  87. Nilsson CG, Haukkamaa M, Vierola H, Luukkainen T. Tissue concentrations of levonorgestrel in women using a levonorgestrel-releasing IUD. Clin Endocrinol (Oxf) 1982; 17:529.
  88. Nilsson CG, Lahteenmaki PL, Luukkainen T, Robertson DN. Sustained intrauterine release of levonorgestrel over five years. Fertil Steril 1986; 45:805.
  89. Luukkainen T, Lähteenmäki P, Toivonen J. Levonorgestrel-releasing intrauterine device. Ann Med 1990; 22:85.
  90. Seeber B, Ziehr SC, Gschlieβer A, et al. Quantitative levonorgestrel plasma level measurements in patients with regular and prolonged use of the levonorgestrel-releasing intrauterine system. Contraception 2012; 86:345.
  91. Orme ML, Back DJ, Breckenridge AM. Clinical pharmacokinetics of oral contraceptive steroids. Clin Pharmacokinet 1983; 8:95.
  92. Sivin I, Lähteenmäki P, Ranta S, et al. Levonorgestrel concentrations during use of levonorgestrel rod (LNG ROD) implants. Contraception 1997; 55:81.
  93. Sivin I, Stern J. Health during prolonged use of levonorgestrel 20 micrograms/d and the copper TCu 380Ag intrauterine contraceptive devices: A multicenter study. International Committee for Contraception Research (ICCR). Fertil Steril 1994; 61:70.
  94. Eisenberg DL, Schreiber CA, Turok DK, et al. Three-year efficacy and safety of a new 52-mg levonorgestrel-releasing intrauterine system. Contraception 2015; 92:10.
  95. Sivin I, el Mahgoub S, McCarthy T, et al. Long-term contraception with the levonorgestrel 20 mcg/day (LNg 20) and the copper T 380Ag intrauterine devices: A five-year randomized study. Contraception 1990; 42:361.
  96. Andersson K, Odlind V, Rybo G. Levonorgestrel-releasing and copper-releasing (Nova T) IUDs during five years of use: A randomized comparative trial. Contraception 1994; 49:56.
  97. Liletta [package insert]. Irvine, CA: Allergan USA, Inc; 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aaf0eb2a-f88a-4f26-a445-0fd30176c326 (Accessed on October 17, 2020).
  98. Nelson A, Apter D, Hauck B, et al. Two low-dose levonorgestrel intrauterine contraceptive systems: a randomized controlled trial. Obstet Gynecol 2013; 122:1205.
  99. Schultheis P, Montoya MN, Zhao Q, et al. Contraception and ectopic pregnancy risk: a prospective observational analysis. Am J Obstet Gynecol 2021; 224:228.
  100. Elgemark K, Graner S, McTaggart J, et al. The 13.5-mg, 19.5-mg, and 52-mg Levonorgestrel-Releasing Intrauterine Systems and Risk of Ectopic Pregnancy. Obstet Gynecol 2022; 140:227.
  101. McNicholas C, Swor E, Wan L, Peipert JF. Prolonged use of the etonogestrel implant and levonorgestrel intrauterine device: 2 years beyond Food and Drug Administration-approved duration. Am J Obstet Gynecol 2017.
  102. Bahamondes L, Fernandes A, Bahamondes MV, et al. Pregnancy outcomes associated with extended use of the 52-mg 20 μg/day levonorgestrel-releasing intrauterine system beyond 60 months: A chart review of 776 women in Brazil. Contraception 2018; 97:205.
  103. Creinin MD, Schreiber CA, Turok DK, et al. Levonorgestrel 52 mg intrauterine system efficacy and safety through 8 years of use. Am J Obstet Gynecol 2022; 227:871.e1.
  104. Chen BA, Kimble T, Harris LH, et al. Levonorgestrel 52-mg Intrauterine Device Efficacy and Safety After More Than 8 Years of Use. Obstet Gynecol 2023; 141:1004.
  105. Abou-Setta AM, Al-Inany HG, Farquhar CM. Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery. Cochrane Database Syst Rev 2006; :CD005072.
  106. Lethaby AE, Cooke I, Rees M. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev 2005; :CD002126.
  107. Cim N, Soysal S, Sayan S, et al. Two Years Follow-Up of Patients with Abnormal Uterine Bleeding after Insertion of the Levonorgestrel-Releasing Intrauterine System. Gynecol Obstet Invest 2018; 83:569.
  108. Kaunitz AM, Bissonnette F, Monteiro I, et al. Levonorgestrel-releasing intrauterine system or medroxyprogesterone for heavy menstrual bleeding: a randomized controlled trial. Obstet Gynecol 2010; 116:625.
  109. Baker WD, Pierce SR, Mills AM, et al. Nonoperative management of atypical endometrial hyperplasia and grade 1 endometrial cancer with the levonorgestrel intrauterine device in medically ill post-menopausal women. Gynecol Oncol 2017; 146:34.
  110. Bofill Rodriguez M, Lethaby A, Jordan V. Progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev 2020; 6:CD002126.
  111. Beelen P, van den Brink MJ, Herman MC, et al. Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding. Am J Obstet Gynecol 2021; 224:187.e1.
  112. Harada T, Ota I, Kitawaki J, et al. Real-world outcomes of the levonorgestrel-releasing intrauterine system for heavy menstrual bleeding or dysmenorrhea in Japanese patients: A prospective observational study (J-MIRAI). Contraception 2022; 116:22.
  113. Creinin MD, Barnhart KT, Gawron LM, et al. Heavy Menstrual Bleeding Treatment With a Levonorgestrel 52-mg Intrauterine Device. Obstet Gynecol 2023; 141:971.
  114. Ciccone MA, Whitman SA, Conturie CL, et al. Effectiveness of progestin-based therapy for morbidly obese women with complex atypical hyperplasia. Arch Gynecol Obstet 2019; 299:801.
  115. Mandelbaum RS, Ciccone MA, Nusbaum DJ, et al. Progestin therapy for obese women with complex atypical hyperplasia: levonorgestrel-releasing intrauterine device vs systemic therapy. Am J Obstet Gynecol 2020; 223:103.e1.
  116. Mørch LS, Skovlund CW, Hannaford PC, et al. Contemporary Hormonal Contraception and the Risk of Breast Cancer. N Engl J Med 2017; 377:2228.
  117. Fitzpatrick D, Pirie K, Reeves G, et al. Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case-control study and meta-analysis. PLoS Med 2023; 20:e1004188.
  118. Soini T, Hurskainen R, Grénman S, et al. Levonorgestrel-releasing intrauterine system and the risk of breast cancer: A nationwide cohort study. Acta Oncol 2016; 55:188.
  119. Mørch LS, Meaidi A, Corn G, et al. Breast Cancer in Users of Levonorgestrel-Releasing Intrauterine Systems. JAMA 2024; 332:1578.
  120. Yi H, Zhang N, Huang J, et al. Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden. Am J Obstet Gynecol 2024; 231:450.e1.
  121. Niemeyer Hultstrand J, Gemzell-Danielsson K, Kallner HK, et al. Hormonal contraception and risk of breast cancer and breast cancer in situ among Swedish women 15-34 years of age: A nationwide register-based study. Lancet Reg Health Eur 2022; 21:100470.
  122. Tuesley KM, Spilsbury K, Pearson SA, et al. Long-acting, progestin-based contraceptives and risk of breast, gynecological, and other cancers. J Natl Cancer Inst 2025.
  123. Dinger J, Bardenheuer K, Minh TD. Levonorgestrel-releasing and copper intrauterine devices and the risk of breast cancer. Contraception 2011; 83:211.
  124. Soini T, Hurskainen R, Grénman S, et al. Cancer risk in women using the levonorgestrel-releasing intrauterine system in Finland. Obstet Gynecol 2014; 124:292.
  125. Balayla J, Gil Y, Lasry A, Mitric C. Ever-use of the intra-uterine device and the risk of ovarian cancer. J Obstet Gynaecol 2021; 41:848.
  126. Diedrich JT, Desai S, Zhao Q, et al. Association of short-term bleeding and cramping patterns with long-acting reversible contraceptive method satisfaction. Am J Obstet Gynecol 2015; 212:50.e1.
  127. Hobby JH, Zhao Q, Peipert JF. Effect of baseline menstrual bleeding pattern on copper intrauterine device continuation. Am J Obstet Gynecol 2018; 219:465.e1.
  128. Christelle K, Norhayati MN, Jaafar SH. Interventions to prevent or treat heavy menstrual bleeding or pain associated with intrauterine-device use. Cochrane Database Syst Rev 2022; 8:CD006034.
  129. Lowe RF, Prata N. Hemoglobin and serum ferritin levels in women using copper-releasing or levonorgestrel-releasing intrauterine devices: A systematic review. Contraception 2013; 87:486.
  130. Higham JM, O'Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol 1990; 97:734.
  131. Magnay JL, Nevatte TM, Dhingra V, O'Brien S. Menstrual blood loss measurement: validation of the alkaline hematin technique for feminine hygiene products containing superabsorbent polymers. Fertil Steril 2010; 94:2742.
  132. Sergison JE, Maldonado LY, Gao X, Hubacher D. Levonorgestrel intrauterine system associated amenorrhea: a systematic review and metaanalysis. Am J Obstet Gynecol 2019; 220:440.
  133. Darney PD, Stuart GS, Thomas MA, et al. Amenorrhea rates and predictors during 1 year of levonorgestrel 52 mg intrauterine system use. Contraception 2018; 97:210.
  134. Grunloh DS, Casner T, Secura GM, et al. Characteristics associated with discontinuation of long-acting reversible contraception within the first 6 months of use. Obstet Gynecol 2013; 122:1214.
  135. Aoun J, Dines VA, Stovall DW, et al. Effects of age, parity, and device type on complications and discontinuation of intrauterine devices. Obstet Gynecol 2014; 123:585.
  136. Rivera R, Chen-Mok M, McMullen S. Analysis of client characteristics that may affect early discontinuation of the TCu-380A IUD. Contraception 1999; 60:155.
  137. Bilian X. Chinese experience with intrauterine devices. Contraception 2007; 75:S31.
  138. Thomsen RJ, Rayl DL. Dr. Lippes and his loop. Four decades in perspective. J Reprod Med 1999; 44:833.
  139. Lippes J. Contraception with intrauterine plastic loops. Am J Obstet Gynecol 1965; 93:1024.
  140. Kaufman J. The cost of IUD failure in China. Stud Fam Plann 1993; 24:194.
  141. Van Kets H, Van der Pas H, Thiery M, et al. The GyneFix implant systems for interval, postabortal and postpartum contraception: A significant advance in long-term reversible contraception. International Study Group on Intrauterine Drug Delivery. Eur J Contracept Reprod Health Care 1997; 2:1.
  142. O'Brien PA, Marfleet C. Frameless versus classical intrauterine device for contraception. Cochrane Database Syst Rev 2001; :CD003282.
  143. Wildemeersch D. New frameless and framed intrauterine devices and systems - an overview. Contraception 2007; 75:S82.
  144. Baram I, Weinstein A, Trussell J. The IUB, a newly invented IUD: a brief report. Contraception 2014; 89:139.
  145. Meirik O, Rowe PJ, Peregoudov A, et al. The frameless copper IUD (GyneFix) and the TCu380A IUD: Results of an 8-year multicenter randomized comparative trial. Contraception 2009; 80:133.
  146. O'Brien PA, Marfleet C. Frameless versus classical intrauterine device for contraception. Cochrane Database Syst Rev 2005; :CD003282.
  147. Boehnke T, Bauerfeind A, Eggebrecht L, et al. TEMPORARILY WITHDRAWN: Does the shape of the copper intrauterine device play a role in expulsion? Results from the ongoing European Active Surveillance Study on LCS12. Contraception 2023; :110111.
Topic 116579 Version 50.0

References

1 : World Contraceptive Use 2022. United Nations Population Division. Available at: https://www.un.org/development/desa/pd/data/world-contraceptive-use (Accessed on August 12, 2024).

2 : Worldwide use of intrauterine contraception: A review.

3 : Changes in use of long-acting contraceptive methods in the United States, 2007-2009.

4 : Use of contraception and use of family planning services in the United States: 1982-2002.

5 : Changes in use of long-acting reversible contraceptive methods among U.S. women, 2009-2012.

6 : Current Contraceptive Use and Variation by Selected Characteristics Among Women Aged 15-44: United States, 2011-2013.

7 : Contraceptive method use in the United States: trends and characteristics between 2008, 2012 and 2014.

8 : Use of contraception among reproductive-aged women in the United States, 2014 and 2016.

9 : Strategies for improving the acceptability and acceptance of the copper intrauterine device.

10 : The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices.

11 : Mechanisms of action of intrauterine devices: Update and estimation of postfertilization effects.

12 : New insights on the mode of action of intrauterine contraceptive devices in women.

13 : Copper-T intrauterine device and levonorgestrel intrauterine system: Biological bases of their mechanism of action.

14 : Effect of Lippes loop on sperm recovery from human fallopian tubes.

15 : Effect of Lippes loop on sperm recovery from human fallopian tubes.

16 : Mechanism of action, safety and efficacy of intrauterine devices. Report of a WHO Scientific Group.

17 : Mechanisms of action of intrauterine devices.

18 : Mechanism of action of the intrauterine contraceptive device: Evidence for a specific biochemical deficiency in the endometrium.

19 : Phagocytosis of spermatozoa in the uterine cavity of woman using intrauterine device.

20 : Effect of intrauterine contraceptive devices on cytokine messenger ribonucleic acid expression in the human endometrium.

21 : Local tissue effects of copper-containing intrauterine devices.

22 : Decreased endometrial HOXA10 expression associated with use of the copper intrauterine device.

23 : Effects of the levonorgestrel-releasing intrauterine system on cervical mucus quality and sperm penetrability.

24 : Endometrial morphology during long-term use of levonorgestrel-releasing intrauterine devices.

25 : Temporal changes in cervical mucus after insertion of the levonorgestrel-releasing intrauterine system.

26 : Temporal changes in cervical mucus after insertion of the levonorgestrel-releasing intrauterine system.

27 : Temporal changes in cervical mucus after insertion of the levonorgestrel-releasing intrauterine system.

28 : Temporal changes in cervical mucus after insertion of the levonorgestrel-releasing intrauterine system.

29 : Temporal changes in cervical mucus after insertion of the levonorgestrel-releasing intrauterine system.

30 : Early chorionic activity in women bearing inert IUD, copper IUD and levonorgestrel-releasing IUD.

31 : Urinary human chorionic gonadotropin among intrauterine device users: detection with a highly specific and sensitive assay.

32 : Absence of chorionic gonadotropin in sera of women who use intrauterine devices.

33 : Physician beliefs about contraceptive methods as abortifacients.

34 : Physician beliefs about contraceptive methods as abortifacients.

35 : Release characteristics, ovarian activity and menstrual bleeding pattern with a single contraceptive implant releasing 3-ketodesogestrel.

36 : The pharmacodynamics and efficacy of Implanon. An overview of the data.

37 : Return to fertility following discontinuation of oral contraceptives.

38 : Fertility after discontinuation of contraception: A comprehensive review of the literature.

39 : Association between intrauterine device use and endometrial, cervical, and ovarian cancer: an expert review.

40 : Intrauterine Device Use and Cervical Cancer Risk: A Systematic Review and Meta-analysis.

41 : Intrauterine device use, cervical infection with human papillomavirus, and risk of cervical cancer: A pooled analysis of 26 epidemiological studies.

42 : Loops in the natural history of cervical cancer.

43 : Intrauterine Device Use and Ovarian Cancer Risk: A Systematic Review and Meta-analysis.

44 : Length of use and symptoms associated with premature removal of the levonorgestrel intrauterine system: A nation-wide study of 17,360 users.

45 : Subject and clinician experience with the levonorgestrel-releasing intrauterine system.

46 : Three-year continuation of reversible contraception.

47 : Twenty-four-month continuation of reversible contraception.

48 : Long-term utilization and continuation of intrauterine devices.

49 : Economic analysis of contraceptives for women.

50 : Achieving cost-neutrality with long-acting reversible contraceptive methods.

51 : Neisseria gonorrhea and Chlamydia trachomatis screening at intrauterine device insertion and pelvic inflammatory disease.

52 : Positive testing for Neisseria gonorrhoeae and Chlamydia trachomatis and the risk of pelvic inflammatory disease in IUD users.

53 : Intrauterine devices and pelvic inflammatory disease: An international perspective.

54 : Intrauterine contraceptive device and pelvic inflammatory disease.

55 : Copper intrauterine device and incident sexually transmitted infections.

56 : Society of Family Planning Committee statement on IUD nomenclature.

57 : Society of Family Planning Committee statement on IUD nomenclature.

58 : Efficacy, Safety, and Tolerability of a New Low-Dose Copper and Nitinol Intrauterine Device: Phase 2 Data to 36 Months.

59 : Efficacy, Safety, and Tolerability of a New Low-Dose Copper and Nitinol Intrauterine Device: Phase 2 Data to 36 Months.

60 : Emergency contraception review: evidence-based recommendations for clinicians.

61 : The efficacy of intrauterine devices for emergency contraception: A systematic review of 35 years of experience.

62 : Interventions for emergency contraception.

63 : Interventions for emergency contraception.

64 : Blood copper levels in Mexican users of the T380A IUD.

65 : Copper hypersensitivity: Dermatologic aspects.

66 : Effectiveness of IUDs: A review.

67 : Comparative contraceptive effectiveness of levonorgestrel-releasing and copper intrauterine devices: The European active surveillance study for intrauterine devices.

68 : Comparative contraceptive effectiveness of levonorgestrel-releasing and copper intrauterine devices: The European active surveillance study for intrauterine devices.

69 : Three-year efficacy, safety, and tolerability outcomes from a phase 3 study of a low-dose copper intrauterine device.

70 : Three-year efficacy, safety, and tolerability outcomes from a phase 3 study of a low-dose copper intrauterine device.

71 : Copper-containing, framed intrauterine devices for contraception: A systematic review of randomized controlled trials.

72 : Hormonally impregnated intrauterine systems (IUSs) versus other forms of reversible contraceptives as effective methods of preventing pregnancy.

73 : The risk of pregnancy after tubal sterilization: Findings from the U.S. Collaborative Review of Sterilization.

74 : Comparative Effectiveness and Safety of Intrauterine Contraception and Tubal Ligation.

75 : Long-term reversible contraception. Twelve years of experience with the TCu380A and TCu220C.

76 : TCu 380A IUD: A reversible permanent contraceptive method in women over 35 years of age.

77 : Effectiveness and safety of extending intrauterine device duration: a systematic review.

78 : Extended use of the intrauterine device: A literature review and recommendations for clinical practice.

79 : Evaluation of endometrial steroid receptors and cell mitotic activity in women using copper intrauterine device: Can Cu-T prevent endometrial cancer?

80 : Neoplasia with use of intrauterine devices.

81 : Relative Risk of Cervical Neoplasms Among Copper and Levonorgestrel-Releasing Intrauterine System Users.

82 : Recent intrauterine device use and the risk of precancerous cervical lesions and cervical cancer.

83 : Recent intrauterine device use and the risk of precancerous cervical lesions and cervical cancer.

84 : Recent intrauterine device use and the risk of precancerous cervical lesions and cervical cancer.

85 : Contraceptive efficacy and safety of the 52-mg levonorgestrel intrauterine system for up to 8 years: findings from the Mirena Extension Trial.

86 : Pharmacokinetic and pharmacodynamic studies of levonorgestrel-releasing intrauterine device.

87 : Tissue concentrations of levonorgestrel in women using a levonorgestrel-releasing IUD.

88 : Sustained intrauterine release of levonorgestrel over five years.

89 : Levonorgestrel-releasing intrauterine device.

90 : Quantitative levonorgestrel plasma level measurements in patients with regular and prolonged use of the levonorgestrel-releasing intrauterine system.

91 : Clinical pharmacokinetics of oral contraceptive steroids.

92 : Levonorgestrel concentrations during use of levonorgestrel rod (LNG ROD) implants.

93 : Health during prolonged use of levonorgestrel 20 micrograms/d and the copper TCu 380Ag intrauterine contraceptive devices: A multicenter study. International Committee for Contraception Research (ICCR).

94 : Three-year efficacy and safety of a new 52-mg levonorgestrel-releasing intrauterine system.

95 : Long-term contraception with the levonorgestrel 20 mcg/day (LNg 20) and the copper T 380Ag intrauterine devices: A five-year randomized study.

96 : Levonorgestrel-releasing and copper-releasing (Nova T) IUDs during five years of use: A randomized comparative trial.

97 : Levonorgestrel-releasing and copper-releasing (Nova T) IUDs during five years of use: A randomized comparative trial.

98 : Two low-dose levonorgestrel intrauterine contraceptive systems: a randomized controlled trial.

99 : Contraception and ectopic pregnancy risk: a prospective observational analysis.

100 : The 13.5-mg, 19.5-mg, and 52-mg Levonorgestrel-Releasing Intrauterine Systems and Risk of Ectopic Pregnancy.

101 : Prolonged use of the etonogestrel implant and levonorgestrel intrauterine device: 2 years beyond Food and Drug Administration-approved duration.

102 : Pregnancy outcomes associated with extended use of the 52-mg 20μg/day levonorgestrel-releasing intrauterine system beyond 60 months: A chart review of 776 women in Brazil.

103 : Levonorgestrel 52 mg intrauterine system efficacy and safety through 8 years of use.

104 : Levonorgestrel 52-mg Intrauterine Device Efficacy and Safety After More Than 8 Years of Use.

105 : Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery.

106 : Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding.

107 : Two Years Follow-Up of Patients with Abnormal Uterine Bleeding after Insertion of the Levonorgestrel-Releasing Intrauterine System.

108 : Levonorgestrel-releasing intrauterine system or medroxyprogesterone for heavy menstrual bleeding: a randomized controlled trial.

109 : Nonoperative management of atypical endometrial hyperplasia and grade 1 endometrial cancer with the levonorgestrel intrauterine device in medically ill post-menopausal women.

110 : Progestogen-releasing intrauterine systems for heavy menstrual bleeding.

111 : Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding.

112 : Real-world outcomes of the levonorgestrel-releasing intrauterine system for heavy menstrual bleeding or dysmenorrhea in Japanese patients: A prospective observational study (J-MIRAI).

113 : Heavy Menstrual Bleeding Treatment With a Levonorgestrel 52-mg Intrauterine Device.

114 : Effectiveness of progestin-based therapy for morbidly obese women with complex atypical hyperplasia.

115 : Progestin therapy for obese women with complex atypical hyperplasia: levonorgestrel-releasing intrauterine device vs systemic therapy.

116 : Contemporary Hormonal Contraception and the Risk of Breast Cancer.

117 : Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case-control study and meta-analysis.

118 : Levonorgestrel-releasing intrauterine system and the risk of breast cancer: A nationwide cohort study.

119 : Breast Cancer in Users of Levonorgestrel-Releasing Intrauterine Systems.

120 : Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden.

121 : Hormonal contraception and risk of breast cancer and breast cancer in situ among Swedish women 15-34 years of age: A nationwide register-based study.

122 : Long-acting, progestin-based contraceptives and risk of breast, gynecological, and other cancers.

123 : Levonorgestrel-releasing and copper intrauterine devices and the risk of breast cancer.

124 : Cancer risk in women using the levonorgestrel-releasing intrauterine system in Finland.

125 : Ever-use of the intra-uterine device and the risk of ovarian cancer.

126 : Association of short-term bleeding and cramping patterns with long-acting reversible contraceptive method satisfaction.

127 : Effect of baseline menstrual bleeding pattern on copper intrauterine device continuation.

128 : Interventions to prevent or treat heavy menstrual bleeding or pain associated with intrauterine-device use.

129 : Hemoglobin and serum ferritin levels in women using copper-releasing or levonorgestrel-releasing intrauterine devices: A systematic review.

130 : Assessment of menstrual blood loss using a pictorial chart.

131 : Menstrual blood loss measurement: validation of the alkaline hematin technique for feminine hygiene products containing superabsorbent polymers.

132 : Levonorgestrel intrauterine system associated amenorrhea: a systematic review and metaanalysis.

133 : Amenorrhea rates and predictors during 1 year of levonorgestrel 52 mg intrauterine system use.

134 : Characteristics associated with discontinuation of long-acting reversible contraception within the first 6 months of use.

135 : Effects of age, parity, and device type on complications and discontinuation of intrauterine devices.

136 : Analysis of client characteristics that may affect early discontinuation of the TCu-380A IUD.

137 : Chinese experience with intrauterine devices.

138 : Dr. Lippes and his loop. Four decades in perspective.

139 : Contraception with intrauterine plastic loops.

140 : The cost of IUD failure in China.

141 : The GyneFix implant systems for interval, postabortal and postpartum contraception: A significant advance in long-term reversible contraception. International Study Group on Intrauterine Drug Delivery.

142 : Frameless versus classical intrauterine device for contraception.

143 : New frameless and framed intrauterine devices and systems - an overview.

144 : The IUB, a newly invented IUD: a brief report.

145 : The frameless copper IUD (GyneFix) and the TCu380A IUD: Results of an 8-year multicenter randomized comparative trial.

146 : Frameless versus classical intrauterine device for contraception.

147 : TEMPORARILY WITHDRAWN: Does the shape of the copper intrauterine device play a role in expulsion? Results from the ongoing European Active Surveillance Study on LCS12.