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

doi:10.1016/0010-7824(94)90109-0

Contraception

Volume 49, Issue 1, January 1994, Pages 56-72

https://doi.org/10.1016/0010-7824(94)90109-0 Get rights and content

Abstract

A 20 micrograms/24 hours levonorgestrel-releasing intrauterine contraceptive device (LNG-IUD) has, in an open randomized multicenter study, been compared to the copper-releasing device Nova T during 5 years of use; 1821 women had the LNG-IUD and 937 women had the Nova T inserted. The 5-year cumulative gross pregnancy rate was 5.9 % for Nova T and 0.5% for the LNG-IUD. The local effect of levonorgestrel in the uterine cavity causes reduction of menstrual blood loss and development of oligo-amenorrhea, and the termination rates because of heavy and/or prolonged menstrual flow were significantly (P < 0.001) lower among LNG-IUD users. However, the gross termination rate because of amenorrhea was 6.0 in this group. Hb increased during use of the LNG-IUD and decreased during Nova T use, and the difference between the devices was statistically significant. The incidence of pelvic inflammatory disease (PID) was low in LNG-IUD users regardless of age, whereas in the Nova T group, the PID rate was increased among the youngest women, which makes the difference between the devices significant (P < 0.01). The gross termination rate for reasons considered to be hormonal was 12.1 in the LNG-IUD group compared to 2.0 in the Nova T group (P < 0.001).

The LNG-IUD is a long-acting reversible contraceptive method for 5 years with a pregnancy rate comparable to female sterilization. The incidence of PID is low even in young women. In addition, the positive health effects such as decreased menstrual blood loss and increased blood haemoglobin concentration make the LNG-IUD a favorable combination of hormonal and intrauterine contraception.

References (23)

BB Pharriss et al.
Progestasertr: A uterine therapeutic system for long-term contraception: Philosophy and clinical efficacy
Fertil Steril
(1974)
A Bergkvist et al.
Treatment of menorrhagia with intrauterine release of progesterone
Br J Obstet Gynaecol
(1983)
I Sivin
Dose- and age-dependent ectopic pregnancy risks with intrauterine contraception
Obstet Gynecol
(1991)
CG Nilsson et al.
Endometrial morphology of women using a d-norgestrel-releasing intrauterine device
Fertil Steril
(1978)
T Luukkainen et al.
Five years' experience with levonorgestrel-releasing IUDs
Contraception
(1986)
I Sivin et al.
Long-term contraception with the levonorgestrel 20 meg/day (LNg 20) and the Copper T 380 Ag intrauterine devices: A five-year randomized study
Contraception
(1990)
SL Wang et al.
Three years' experience with levonorgestrel-releasing intrauterine device and Norplant-2 implants: a randomized comparative study
Adv Contracep
(1992)
Indian Council of Medical Research, Task force on IUD
Randomized clinical trial with intrauterine devices, (levonorgestrel intrauterine device (LNG), CuT 380Ag, CuT 220C and CuT 200B. A 36-month study
Contraception
(1989)
T Luukkainen et al.
Effective contraception with the levonorgestrel-releasing intrauterine device: 12-month report of a European multicenter study
Contraception
(1987)
J Toivonen et al.
Protective effect of intrauterine release of levonorgestrel on pelvic infection: Three years comparative experience of levonorgestrel- and copper-releasing intrauterine devices
Obstet Gynecol
(1991)

T Luukkainen et al.

Five years experience of intrauterine contraception with the Nova-T and the Copper-T-200

Am J Obstet Gynecol

(1983)

Cited by (509)

Health-related quality of life and satisfaction associated with 3-year use of a levonorgestrel 13.5 mg intrauterine device vs Nova T copper 380 mm<sup>2</sup> intrauterine device: Results of a phase 4 randomized controlled trial
2024, Contraception
This study aimed to investigate the impact of levonorgestrel 13.5 mg and Nova T copper 380 mm² intrauterine devices (LNG13.5-IUD and Cu380-IUD, respectively) on health-related quality of life (HRQoL) and the satisfaction with the method throughout 3 years of use.
We conducted a single-center, evaluator-masked, randomized controlled trial to compare the bleeding profile of LNG13.5-IUD and Cu380-IUD users. Secondary objectives included HRQoL and satisfaction throughout the study. We used the validated questionnaire of the Spanish Society of Contraception (SEC-QoL), which evaluates social, sexual/psychological well-being, and menstrual/breast symptoms, to assess HRQoL and a 5-point Likert scale for satisfaction.
These secondary outcomes were assessed in the whole population included in the study: 55 LNG13.5-IUD and 51 Cu380-IUD users. The mean overall SEC-QoL scores were similar at baseline (61.5 and 59.6, respectively; p = 0.570) and greater for LNG13.5-IUD after 3 years (69.2 vs 52.5, respectively; p = 0.002). All SEC-QoL domains scored also higher (p < 0.05 vs Cu380-IUD for all). At month 36, 20/30 (67%) and 8/28 (29%) users, respectively, had reached the MID (a 3.4-point increase) in SEC-QoL score (p = 0.004). At this time, 24/29 (82%) and 9/28 (32%) users, respectively, were “very satisfied” (p < 0.001). Willingness to continue the method was similar (22/28 [79%] vs 17/28 [61%] users, respectively; p = 0.170).
Among the use of LNG13.5-IUD was associated with better HRQoL vs Cu380-IUD throughout the 3 years. Satisfaction with the method was higher with LNG13.5-IUD.
People considering having an LNG13.5-IUD or a Cu380-IUD inserted may now benefit from the information regarding the impact of these devices on HRQoL and satisfaction with the method as reported in our study conducted in Spain.
Bleeding profile and safety of a levonorgestrel 13.5 mg intrauterine device versus Nova T copper 380 mm<sup>2</sup> intrauterine device: Results of a 3-year, single-center, randomized phase 4 study
2023, Contraception
To assess the bleeding profiles of the levonorgestrel 13.5 mg intrauterine device (LNG13.5-IUD) and Nova T copper 380 mm² IUD (Cu380-IUD).
Single-center, evaluator-masked, randomized study conducted in women aged 18–45 years starting these methods. Primary outcomes were number of bleeding days, self-reported bleeding intensity, Pictorial Blood Assessment Chart (PBAC) score, and blood biochemical values at baseline, months 3, 6, 12, 24, and 36 per 90-day reference periods except for PBAC (months). Secondary objectives were presence/duration/intensity of dysmenorrhea and tolerability.
We included 106 women aged 32.5 ± 6.7 years: 55 with LNG13.5-IUD and 51 with Cu380-IUD. Data for LNG13.5-IUD versus Cu380-IUD at baseline and month 36 (both respectively) were as follows: (1) median (25th; 75th percentile) number of bleeding days: 12 (9.0; 15.0) versus 12 (9.0; 15.0), p = 0.82, and 4 (0; 13.7) versus 15 (14.2; 20.0), p < 0.001; (2) mean bleeding intensity: 1.7 for both, p = 0.66, and 0.7 and 2.2, p < 0.001. Forty percent versus 0% presented with amenorrhea at month 36; (3) mean PBAC score (95% Confidence interval (CI): 50.7 (16.6; 84.7) versus 130.4 (95.7; 165.0) at month 1, and 7.9 (−26.7; 42.6) versus 126 (90.7; 161.2), p < 0.001; (4) median (25th; 75th percentile) ferritin levels (Ug/L) 33 (19; 53) versus 30 (19; 45), p = 0.70, and 59 (42; 84) versus 21 (8; 39). We did not observe changes or differences between groups in hemoglobin and hematocrit. The duration and intensity of dysmenorrhea were significantly lower with LNG13.5-IUD versus Cu380-IUD. Adverse events were those expected.
LNG13.5-IUD is associated with a significant reduction in blood loss and dysmenorrhea compared with Cu380-IUD.
Women eligible for a levonorgestrel 13.5 mg intrauterine device (IUD) or a copper 380 mm² IUD should be informed of the differences in bleeding profiles—one of the main causes for IUD discontinuation—so they can compare this information against their bleeding expectations.
The suture fixation of levonorgestrel-releasing intrauterine device in the treatment of adenomyosis: A case report
2023, International Journal of Surgery Case Reports
The report on Levonorgestrel⁃releasing intrauterine system (LNG⁃IUS) suture under hysteroscopy is very rare, and currently only three articles have been reported. We reported a patient with adenomyosis who had previously had LNG-IUS, but the LNG-IUS moved downward. We sutured and fixed the LNG-IUS under hysteroscopy.
A 42-year-old woman presented with a 7-year history of adenomyosis of the uterus and adenomyoma adenomyosis. Half a year ago, due to increased menstrual flow, LNG-IUS was placed in the uterine cavity, and the treatment effect was satisfactory. Nine days ago, vaginal bleeding occurred, and ultrasound showed that LNG-IUS had moved downward. We performed LNG-IUS suturing under hysteroscopy for her, and a half-year follow-up ultrasound showed that the position of LNG-IUS was normal.
For adenomyosis, LNG-IUS is the most promising medical therapy due to its ability to suppress hormones to improve symptoms with a low profile of adverse effects while enabling women to maintain fertility. However, the high excretion rate of LNG-IUS may cause patients with adenomyosis to lose confidence in continuing to use this treatment method.
Our case report demonstrated the feasibility and effectiveness of LNG-IUS suture fixation under hysteroscopy. It provided another reliable treatment option for those patients with adenomyosis for whom the LNG-IUS fell off or fell down.
Long-acting intrauterine systems: Recent advances, current challenges, and future opportunities
2022, Advanced Drug Delivery Reviews
Levonorgestrel intrauterine systems (LNG-IUSs) are complex drug-device combination products designed to release a hormonal contraceptive drug for up to 7 years. These drug delivery systems offers a great promise as a modern method of long-acting reversible contraceptives (LARCs) to improve women’s health. Unfortunately, there are some scientific challenges associated with the development of these products which are among the major reasons contributing to the availability of relatively few IUS products on the market. This review summarizes the formulation considerations (drug and excipient attributes), manufacturing methods, advances in characterization and in vitro drug release testing of IUSs, as well as factors influencing drug release from IUSs. A critical discussion on the major challenges to IUS product development is presented. Specifically, insights on bioequivalence evaluation, in vitro-in vivo correlation (IVIVC) establishment, and regulatory challenges are detailed. Lastly, methodological tools to overcome some of these hurdles to product development are proposed. The knowledge furnished through this review will be helpful towards obtaining better product understanding. Such understanding will facilitate the development of these complex drug products, as well as their regulatory approval process.
Contraceptive efficacy and safety of the 52-mg levonorgestrel intrauterine system for up to 8 years: findings from the Mirena Extension Trial
2022, American Journal of Obstetrics and Gynecology
The 52-mg levonorgestrel-releasing intrauterine system is an established, long-acting contraceptive option with approved use for up to 7 years.
The Mirena Extension Trial evaluated the efficacy and safety of the 52-mg levonorgestrel-releasing intrauterine system during extended use beyond 5 and up to 8 years.
This was a multicenter, single-arm study in the United States, enrolling existing users of the 52-mg levonorgestrel-releasing intrauterine system, aged 18 to 35 years, who have had the system for 4.5 to 5 years. We assessed the contraceptive efficacy (Pearl Index) and cumulative failure rate (using the Kaplan–Meier method) of the 52-mg levonorgestrel-releasing intrauterine system during extended use. We also evaluated bleeding outcomes and adverse events.
Of the 362 participants starting year 6, 243 entered and 223 completed 8 years of 52-mg levonorgestrel-releasing intrauterine system use. Just more than half the participants were parous. The mean (standard deviation) age was 29.2 (±2.9) years, and all participants were aged ≤36 years at the end of year 8. Two pregnancies occurred, both with the device in situ. The year 6 pregnancy was of undetermined location and resolved spontaneously. The pregnancy in year 7 was ectopic and resolved with methotrexate treatment. In both cases, the 52-mg levonorgestrel-releasing intrauterine system was removed and the participants left the trial. For years 6 to 8, the 3-year Pearl Index (95% confidence interval) was 0.28 (0.03–1.00) with a 3-year cumulative failure rate of 0.68% (0.17–2.71). Pearl Indexes for years 6, 7, and 8 were 0.34 (0.01–1.88), 0.40 (0.01–2.25), and 0.00 (0.00–1.90), respectively. The 3-year (years 6–8) ectopic pregnancy Pearl Index was 0.14 (0.00–0.77). We found treatment-emergent adverse events in 249 of 362 participants (68.8%), with 65 (18.0%) events considered to be related to the 52-mg levonorgestrel-releasing intrauterine system. The discontinuation rate was 38.4% (139/362), most commonly because of desire for pregnancy (12.2%, 44/362). During extended use beyond 5 years and up to 8 years, participants reported a decrease in the mean number of bleeding or spotting days with approximately half of the women experiencing amenorrhea or infrequent bleeding. We did not enroll a sufficient number of women using the 52-mg levonorgestrel-releasing intrauterine system for contraception and heavy menstrual bleeding to assess extended use for that indication. At the end of year 8, most (98.7%, 220/223) of the participants who completed the study remained satisfied with the continued use of the 52-mg levonorgestrel-releasing intrauterine system. Of the 31 women who discontinued early because of desire for pregnancy with evaluable data for return-to-fertility analysis, 24 reported a posttreatment pregnancy within 1 year, giving a 12-month return-to-fertility rate of 77.4%.
The 52-mg levonorgestrel-releasing intrauterine system, initially approved for 5 years, maintains high contraceptive efficacy, user satisfaction, and a favorable safety profile through 8 years of use. Participants reported 26 posttreatment pregnancies in total, of which 24 occurred in women who had discontinued the 52-mg levonorgestrel-releasing intrauterine system because of a desire for pregnancy. Of note, among women who elected to continue use through 8 years, bleeding patterns remained highly favorable. These findings support continued 52-mg levonorgestrel-releasing intrauterine system use for up to 8 years in women who wish to continue treatment.
Levonorgestrel 52 mg intrauterine system efficacy and safety through 8 years of use
2022, American Journal of Obstetrics and Gynecology
Extending hormonal intrauterine system duration will allow users to have less need for procedures to provide long-term contraception.
This study aimed to evaluate the efficacy and safety of the levonorgestrel 52 mg intrauterine system during years 7 and 8 of use.
A total of 1751 nulliparous and multiparous participants aged 16 to 45 years enrolled in a phase 3, multicenter trial to evaluate the efficacy and safety of the use of the Liletta levonorgestrel 52 mg intrauterine system for up to 10 years. Participants aged 36 to 45 years at enrollment underwent safety evaluation only. After the first year, we evaluated participants every 6 months for intrauterine system location confirmation and urine pregnancy testing at each visit. We assessed the Pearl Indices in years 7 and 8 and the life-table analysis for cumulative pregnancy rates through 8 years of use. For the primary efficacy analyses, all participants aged 16 to 35 years at enrollment were included through year 6; years 7 and 8 included only users aged ≤39 years at the start of each use year. Safety outcomes were assessed in all participants regardless of duration of use. We assessed amenorrhea rates, defined as no bleeding or spotting in the 90 days before the end of the year.
After intrauterine system placement, we followed 1568 participants aged 16 to 35 years and 146 participants aged 36 to 45 years. The 16- to 35-year-old participants included 986 (57.5%) nulliparous and 433 (25.3%) obese users. Overall, 569 participants started year 7, 478 completed year 7 (380 aged ≤39 years at beginning of year) and 343 completed year 8 (257 aged ≤39 years at beginning of year); 77 completed 10 years of use. Eleven pregnancies occurred over 8 years, 7 (64%) of which were ectopic. Two pregnancies occurred in year 7 (Pearl Index, 0.49; 95% confidence interval, 0.06–1.78), 1 in a participant with implantation 4 days after a desired removal; no pregnancies occurred in year 8. The cumulative life-table pregnancy rate in the primary efficacy population through year 8 was 1.32 (95% confidence interval, 0.69–2.51); without the postremoval pregnancy, the rate was 1.09 (95% confidence interval, 0.56–2.13). Two perforations (0.1%) occurred, none noted after year 1. Expulsion occurred in 71 (4.1%) participants overall, with 3 in year 7 and 2 in year 8. Pelvic infection was diagnosed in 16 (0.9%) participants during intrauterine system use, 1 each in years 7 and 8. Only 44 (2.6%) participants overall discontinued because of bleeding complaints (4 total in years 7 and 8) with rates per year of 0.1% to 0.5% for years 3 to 8. Amenorrhea rates were 39% at both years 7 and 8.
The levonorgestrel 52 mg intrauterine system is highly effective over 8 years of use and has an excellent extended safety profile. This report details the longest period of efficacy and safety data for continuous use of a levonorgestrel 52 mg intrauterine system for contraception.

View all citing articles on Scopus

View full text

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

Abstract

Progestasertr: A uterine therapeutic system for long-term contraception: Philosophy and clinical efficacy

Fertil Steril

Treatment of menorrhagia with intrauterine release of progesterone

Br J Obstet Gynaecol

Dose- and age-dependent ectopic pregnancy risks with intrauterine contraception

Obstet Gynecol

Endometrial morphology of women using a d-norgestrel-releasing intrauterine device

Fertil Steril

Five years' experience with levonorgestrel-releasing IUDs

Contraception

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

Contraception

Three years' experience with levonorgestrel-releasing intrauterine device and Norplant-2 implants: a randomized comparative study

Adv Contracep

Randomized clinical trial with intrauterine devices, (levonorgestrel intrauterine device (LNG), CuT 380Ag, CuT 220C and CuT 200B. A 36-month study

Contraception

Effective contraception with the levonorgestrel-releasing intrauterine device: 12-month report of a European multicenter study

Contraception

Protective effect of intrauterine release of levonorgestrel on pelvic infection: Three years comparative experience of levonorgestrel- and copper-releasing intrauterine devices

Obstet Gynecol

Five years experience of intrauterine contraception with the Nova-T and the Copper-T-200

Am J Obstet Gynecol