New Drug Reviews
Levonorgestrel-Releasing Intrauterine System (Mirena) for Contraception
Am Fam Physician. 2006 May 15;73(10):1799-1806.
The levonorgestrel-releasing intrauterine system (Mirena) is a T-shaped intrauterine device (IUD), 1.3 inches (32 mm) in length and width, that releases levonorgestrel. It is labeled for use as a contraceptive agent for up to five years.1
|Name||Dosage||Dose form||Approximate cost*|
Levonorgestrel-releasing intrauterine system (Mirena)
One intrauterine device inserted every five years; the device initially releases approximately 20 mcg levonorgestrel per day, decreasing progressively to 10 mcg1
$453 for five years
*—Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2005.
The levonorgestrel-releasing intrauterine system is licensed for use in more than 25 countries. It has been available in Finland and Sweden since the early 1990s, and it has been used by more than 2 million European women.2 Long-term use of the device does not increase the risk of pelvic inflammatory disease. However, as with other intrauterine devices, the risk of pelvic inflammatory disease may be increased during the first 20 days following insertion.1,3 Like other hormonal contraceptives, the levonorgestrel-releasing intrauterine system does not protect against sexually transmitted diseases.1
When the device is removed, endometrial changes reverse in two to six months; users may conceive immediately after removal depending on baseline fertility level.4,5 Rates of ectopic pregnancy in women using the device (0.02 per 100 woman-years) are lower than those observed in women using copper devices (0.25 per 100 woman-years) and women not using any form of contraception (0.12 to 0.5 per 100 woman-years).3,4
Uterine perforation is a rare complication of any IUD insertion, occurring in 0.6 to 1.6 of 1,000 insertions.6 To reduce the incidence of perforation and expulsion, the manufacturers recommend that postpartum insertion of the levonorgestrel-releasing intrauterine system be delayed until uterine involution is complete (i.e., approximately six weeks after delivery).1 The device can be inserted immediately after termination of a first-trimester pregnancy.1
Like other progestin-only contraceptives, the levonorgestrel-releasing intrauterine system does not interfere with the quality or quantity of milk supply in lactating women, although lactation has been cited as a risk factor for perforation.1 One study involving 14 women who were breastfeeding found that infant serum levels of levonorgestrel were about 7 percent of maternal serum levels; this amount is considered to be clinically insignificant.1,7
Unlike oral contraceptives, the levonorgestrel-releasing intrauterine system is not contraindicated in women with a history of venous thromboembolic events, those at increased risk of myocardial infarction or stroke, or those who smoke.1
The main tolerability issue with the levonorgestrel intrauterine system is unexpected menstruation-like bleeding during the first three months of use. At one month after insertion, users report bleeding or spotting for an average of 16 days, but this diminishes to about four days at 12 months. Twenty percent of users will develop amenorrhea by one year.1,8 Physicians should counsel women to expect menstrual irregularities, particularly for the first four months after insertion.2
Some users experience pain on insertion. This is more likely if the woman has a uterine cavity shorter than 2.4 inches (6 cm) or if the insertion is performed by a physician who is less experienced with the insertion method. Although the hormonal effects of the levonorgestrel-releasing intra-uterine system primarily are local, in 5 percent of users or more, systemic absorption leads to headaches, acne, breast tenderness, or depression.1 In studies, the incidence of these effects usually peaked at three months after insertion and then declined.3 Weight gain directly attributable to use of the levonorgestrel-releasing intrauterine system has not been observed.8
The five-year cumulative rate of expulsion is 5.8 percent for the levonorgestrel-releasing intrauterine system and 6.7 percent for copper IUDs; expulsion usually occurs within the first months after insertion.4 Women who are nulliparous and those with a previous history of IUD expulsion are at increased risk.
Two long-term studies representing 113,000 woman-years of exposure and an additional 58,000 woman-years of postmarketing data are available.1,2,4 The estimated five-year cumulative pregnancy rate is 0.7 percent, similar to that of female sterilization.1
The actions of the levonorgestrel-releasing intrauterine system primarily are local: levonorgestrel causes thickening of cervical mucus, which reduces sperm motility and penetration and, with time, decreases proliferation of the endometrium. The frame stimulates a local inflammatory response thought to be toxic to sperm.2 Ovulation is not inhibited in many users.4
Although not labeled for these uses, the levonorgestrel-releasing intrauterine system has been shown to be an alternative to gonadotropin-releasing hormone analogues for the control of endometriosis, chronic pelvic pain, and dysmennorhea.9 When compared with hysterectomy for the treatment of menorrhagia, use of the device has a similar effect on quality of life and is much less costly.10 Other uses include management of anemia associated with menorrhagia and relief of menopausal symptoms in place of oral progestins.11,12
The cost of the levonorgestrel-releasing intra-uterine system is approximately $453 for five years, which is less than the cost for five years of oral contraceptives ($1,500 to $1,800).13 Other than those of the insertion and removal, there are no costs associated with the monitoring of the IUD.
The device is supplied sterile in a disposable inserter and the physician prescribing information clearly explains the insertion technique. If strings are visible, gentle traction can be used to remove the device. The manufacturer recommends that users check proper placement by feeling for the threads after each menstrual period.1 The device does not offer protection from sexually transmitted diseases; therefore, condoms should be used in addition to the device if there is a risk of infection.
The levonorgestrel-releasing intrauterine system is a reliable, reversible, low-maintenance method of long-term contraception. Rates of failure are similar to those of female sterilization, and the risk of expulsion is minimal for most users.
1. Mirena (levonorgestrel-releasing intrauterine system). Product information. Montville, N.J.: Berlex, 2004. Accessed online February 28, 2006, at: http://www.berlex.com/html/products/pi/Mirena_PI.pdf.
2. Shulman LP, Nelson AL, Darney PD. Recent developments in hormone delivery systems. Am J Obset Gynecol. 2004;190(4 suppl):S3948.
3. Black A. Intrauterine devices. In: SOGC clinical practice guidelines: Canadian contraception consensus. J Obstet Gynaecol Can. 2004;26:219–96.
4. 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;49:56–72.
5. Andersson K, Batar I, Rybo G. Return to fertility after removal of a levonorgestrel-releasing intrauterine device and Nova-T. Contraception. 1992;46:575–84.
6. Grimes D, Schulz K, van Vliet H, Stanwood N. Immediate post-partum insertion of intrauterine devices. Cochrane Database Syst Rev. 2001;(2):CD003036.
7. Ito S. Drug therapy for breast-feeding women [published correction appears in N Engl J Med 2000;343:1348]. N Engl J Med. 2000;343:118–26.
8. Ronnerdag M, Odlind V. Health effects of long-term use of the intrauterine levonorgestrel-releasing system. A follow-up study over 12 years of continuous use. Acta Obstet Gynecol Scand. 1999;78:716–21.
9. Petta CA, Ferriani RA, Abrao MS, Hassan D, Rosa e Silva JC, Podgaec S, et al. Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Hum Reprod. 2005;20:1993–8.
10. Hurskainen R, Teperi J, Rissanen P, Aalto AM, Grenman S, Kivela A, et al. Clinical outcomes and costs with the levonorgestrel-releasing intrauterine system or hysterectomy for treatment of menorrhagia: randomized trial 5-year follow-up. JAMA. 2004;291:1456–63.
11. Faundes A, Alvarez F, Brache V, Tejada AS. The role of the levonorgestrel intrauterine device in the prevention and treatment of iron deficiency anemia during fertility regulation. Int J Gynaecol Obstet. 1988;26:429–33.
12. Boon J, Scholten PC, Oldenhave A, Heintz AP. Continuous intrauterine compared with cyclic oral progestin administration in perimenopausal HRT. Maturitas. 2003;46:69–77.
13. Dailard C. The cost of contraceptive insurance coverage. Guttmacher Report on Public Policy, March 2003. Accessed online February 28, 2006, at: http://www.guttmacher.org/pubs/ib_4-03.html.
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The series coordinator is Allen F. Shaughnessy, Pharm.D., Tufts University Family Medicine Residency Program, Malden, Mass.
Copyright © 2006 by the American Academy of Family Physicians.
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