The levonorgestrel intrauterine device, which delivers a progestin directly into the uterus, is not only a highly effective contraceptive, but is proving to offer several noncontraceptive benefits. Because it gradually releases levonorgestrel, its developer calls it an intrauterine "system" or IUS instead of intrauterine device (IUD).
Like the Copper T IUD, the IUS has a T-shape and is inserted into the uterus. It releases 20 mcg of levonorgestrel daily, giving it qualities similar to other progestin-only methods. The IUS's distinctive noncontraceptive benefits are due to this hormonal feature.
Among the benefits are a substantial decrease in menstrual blood loss and pain. The IUS also protects against the growth of fibroids, which are noncancerous growths of uterine muscle that can cause painful and heavy menstruation. It can stop the development of endometriosis, which is the formation in the pelvis of tissue similar to the endometrium, or uterine lining.
Ectopic pregnancies are very rare among women using the IUS, even rarer than among women using no contraception or those using a Copper T IUD. While data are conflicting and more research is needed, the IUS may protect against pelvic inflammatory disease (PID). Finally, it can be used with estrogen replacement therapy (ERT) during menopause to protect the endometrium.
The noncontraceptive health benefits of modern methods are of increasing interest to many women, especially since most modern methods are considered to be both safe and effective.
The IUS may be as effective as female sterilization, considered to be the most effective method available. The pregnancy rate at five years is estimated to be from 0.5 to 1.1 per 100 women, according to international studies involving some 3,000 IUS users.1 It is 1.3 per 100 women for female sterilization2 and 1.4 per 100 women for the Copper T 380A IUD.3 Furthermore, this low pregnancy rate does not vary based upon the age of the user. Other contraceptive methods have higher failure rates among women under the age of 30 who tend to be more fertile and have sexual intercourse more frequently than do older women.4
After IUS removal, fertility returns quickly. In two studies of fertility recovery after IUS use, 80 percent of 138 users and 96 percent of 60 users, respectively, became pregnant within the first year after removal.5 Notably, women in these studies had the IUD removed because they wished to become pregnant.
The IUS can be a good alternative to male or female sterilization for couples who wish to have no more children. Although the device is approved in the United Kingdom for five years of use, it may be effective for at least seven years.6 Left in place through menopause, it can be an important addition to ERT, which is used to treat menopausal symptoms.
However, the device is relatively expensive and is not widely available outside of Europe.
Bleeding and fibroids
Like other methods that use a progestin hormone, the IUS prevents pregnancy primarily by thickening cervical mucus, which impedes sperm entry into the uterus. The device suppresses ovulation in some cycles and, like a copper IUD, may inhibit sperm motility and function. Levonorgestrel also affects the endometrium, causing it to remain thin and reducing the rare chance that a fertilized egg would be implanted.
Because endometrial growth is suppressed, users can expect a marked reduction in the amount of menstrual blood loss. Initially, the device tends to increase the number of days of bleeding or spotting. But, after a few months of use, both amount and duration of bleeding decrease. Many women experience little or no bleeding (amenorrhea) within a year.
By reducing menstrual blood loss, the IUS helps maintain the body's iron reserves. This could be particularly important for women in developing countries where high parity, poor nutrition and diseases can easily result in iron deficiency.
In addition, the IUS protected against fibroid development in a six-country study conducted by the Population Council that compared the IUS and Copper T 380A. Over seven years, one of 1,125 women using an IUS developed fibroids, compared with 14 of 1,121 women using the copper IUD.7 Fibroids are the most common tumors found in women, with one in five women (or approximately 225 of 1,125 women) developing them by age 40.
"Whether use of the LNg IUD actually reduces the size of preexisting fibroids has been investigated in only one small pilot study," says Dr. Vera Grigorieva, an obstetrician and gynecologist at the Ott Institute Family Planning Center in St. Petersburg, Russia, and a former FHI fellow. Results of a study that Dr. Grigorieva is conducting of IUS use among women with fibroids may help clarify the issue.
Because the IUS is highly effective at preventing pregnancy in general, its use rarely is associated with ectopic pregnancies (estimated in one study to be one ectopic pregnancy in 5,000 woman-years).8 None occurred in a total of 3,416 woman-years of IUS use in the six-country Population Council study comparing the IUS with the Copper T 380A.9 Similarly, no ectopic pregnancies occurred in 882 woman-years of IUS use in a three-year study by the Indian Council of Medical Research (ICMR).10
However, like IUD users, women who receive the IUS should be told of the possibility of an ectopic pregnancy (implantation of a fertilized egg outside of the uterus, usually in a fallopian tube). A woman receiving an IUS should be counseled to seek medical attention promptly if she experiences signs of pregnancy, since it could be ectopic. Ectopic pregnancies are life-threatening.
PID protection?
Data are conflicting as to whether the IUS provides some protection against PID. This rare inflammation of a woman's upper genital tract can lead to chronic pelvic pain, ectopic pregnancy and even death.
One group of investigators found in a five-year study that PID rates were lower among 1,800 women with IUSs than among 900 women with copper Nova T IUDs.11 The five-year removal rates for PID were 0.8 per 100 users in the IUS group, compared with 2.2 per 100 users in the Copper T IUD group. The difference between groups was significant for women younger than 25 years old. In general, young, sexually active women are at greater risk of PID than older women who are sexually active. A lower risk of PID associated in this study with the IUS, compared with copper IUDs, is likely to be important to many young women who are interested in protecting their future fertility.
Researchers have speculated that if the IUS protects against PID, the protection may be due to thickened cervical mucus (blocking the passage of pathogens into the uterus); endometrial suppression (reducing the area that pathogens can infect); or reduced bleeding (decreasing the chance that menstrual blood will flow backwards, carrying pathogens into the fallopian tubes).
However, the six-country Population Council study comparing the IUS with the Copper T 380A found no difference between five-year removal rates attributable to PID and endometriosis (0.7 per 100 woman-years) among 1,125 women using the IUS and 1,121 women using copper IUDs.12 Another study conducted by the ICMR in India did not find significant differences after three years in PID-related removal rates between IUS users and women who used various copper IUDs.13 Thus, further research is needed to clarify this issue.
In terms of cancer risk, no differences in the incidence of breast or cervical cancer were found at five years among IUS and Copper T 380A users in the six-country study comparing the two devices.14 The incidence of cervical cancer was less than 0.1 per 100 women-years for both devices. Breast cancer incidence was less than 0.1 per 100 woman-years for IUS users; no cases occurred among copper IUD users.
Several studies in India have shown that use of the IUS by breastfeeding women for more than three months had no adverse effect on the reproductive hormones, growth, or physical and mental well-being of the women's infants.15
The IUS may be especially well suited for postabortion contraception. A study of the menstrual diaries of some 300 Finnish women showed that, among IUS users, postabortion insertion was associated with better bleeding patterns (for example, fewer days of bleeding during the first two months postinsertion) than postmenstrual insertion.16
Like other estrogen-free methods, the IUS may be a good contraceptive choice for women with high blood pressure; diabetes with vascular disease or diabetes for more than 20 years; epilepsy, or severe, recurrent headaches with focal neurological symptoms; and women with a history of, or currently experiencing, deep venous thrombosis or pulmonary embolism.17
For HIV-positive women also, the IUS may be a good contraceptive choice, although it offers no protection against HIV transmission or any other sexually transmitted disease. Its use by infected women is not restricted by World Health Organization (WHO) guidelines. It should not be inserted in an HIV-positive woman with an AIDS-defining illness who is infected with a sexually transmitted disease, such as chlamydia or gonorrhea, since her suppressed immune system may make her particularly vulnerable to PID.
Amenorrhea counseling
The IUS has a few known disadvantages. Progestin-related side effects -- such as headache, nausea, acne, abnormal hairiness, depression and other mood changes, and breast tenderness -- are uncommon and gradually decrease over time. Persistent unruptured ovarian follicles (also known as functional ovarian cysts) are slightly more common in the users of progestin-only contraceptive methods (such as progestin-only pills and subdermal implants), and can also occur with use of the device. They can cause lower-abdominal discomfort, but are not harmful and generally disappear without treatment a few weeks after IUS discontinuation.
Some women view IUS-related amenorrhea as an advantage. Other women, however, may not tolerate the intermenstrual bleeding that often occurs in the first months of use, or amenorrhea later. A multicenter WHO study that involved some 3,400 women and compared the IUS with the Copper T 380A found, at three years of use, a 27 percent removal rate due to amenorrhea for the IUS, compared with a 0.2 percent removal rate for the Copper T 380A. Removal rates for pain or bleeding were 17 percent for the IUS versus 11 percent for the Copper T 380A.18
A review of three other multicenter, international studies indicated lower rates of discontinuation for IUS-related amenorrhea, ranging from 6 percent to 20 percent at five years among some 4,000 women.19 These differences in rates may reflect the design and execution of the studies. Investigators in two of the studies, for example, knew which device women were using and might have prepared some of the women for the possibility of bleeding disturbances. Also, women in different cultures react differently to menstrual changes.
That counseling can boost IUS continuation rates was demonstrated in a study involving 381 women receiving the device in a clinic in Campinas, Brazil, and 200 IUS users in Santo Domingo, Dominican Republic. Brazilian researchers concluded that special emphasis placed on good counseling in the Campinas clinic was one reason for a significantly lower one-year IUS discontinuation rate in Campinas (18 per 100 IUS users) than in Santo Domingo (33 per 100 users).20
Key counseling messages are that the IUS is not harmful to health, that menstrual blood loss serves no useful purpose, and -- given the IUS's high efficacy -- that amenorrhea almost certainly is not a sign of an unintended pregnancy.
-- Kim Best
References
Sivin I, Stern J, Coutinho E, et al. Prolonged intrauterine contraception: a seven-year randomized study of the levonorgestrel 20 mcg/day (LNg 20) and the Copper T380 Ag IUDs. Contraception 1991;44(5):473-80; 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(1):56-72; Allonen H. The levonorgestrel IUD. In Bardin CW, Mishell DR Jr., eds. Proceedings from the Fourth International Conference on IUDs. (Newton, MA: Butterworth-Heinemann, 1994)287.
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(4):1161-70.
Sivin, Stern, Coutinho; Allonen.
Peterson; Luukkainen T, Toivonen J. Levonorgestrel-releasing IUD as a method of contraception with therapeutic properties. Contraception 1995;52(5):269-76.
Andersson K, Batar I, Rybo G. Return to fertility after removal of a levonorgestrel-releasing intrauterine device and Nova T. Contraception 1992;46(6):575-84; Belhadj H, Sivin I, Díaz S, et al. Recovery of fertility after use of the levonorgestrel 20 mcg/d or Copper T 380 Ag intrauterine device. Contraception 1986;34(3):261-67.
Luukkainen T, Allonen H, Haukkamaa M, et al. Five years' experience with levonorgestrel-releasing IUDs. Contraception 1986;33(2):139-48.
Sivin I, Stern J. Health during prolonged use of levonorgestrel 20 µg/d and the Copper TCu 380Ag intrauterine contraceptive devices: a multicenter study. Fertil Steril 1994;61(1):74.
Ojutiku D, Cutner A, Rymer J. Ectopic pregnancy with levonorgestrel releasing intrauterine system. Br J Fam Plann 1998;24(2):85-86.
Sivin, Stern.
Indian Council of Medical Research, Task Force on IUDs. Randomized clinical trials with intrauterine devices (levonorgestrel intrauterine device, (LNg), CuT 380Ag, CuT 220C, CuT 200B). A 36-month study. Contraception 1989;39(1):37-52.
Andersson, Odlind, Rybo.
Sivin, Stern.
Indian Council of Medical Research.
Sivin, Stern.
Toddywalla VS, Patel SB, Betrabet SS, et al. Low-dose progestogen contraception and the nursing mother. Adv Contracept 1995;11(4):285-94.
Suvisaari J, Lähteenmäki P. Detailed analysis of menstrual bleeding patterns after postmenstrual and postabortal insertion of a copper IUD or a levonorgestrel-releasing intrauterine system. Contraception 1996;54(4):201-8.
World Health Organization. Improving Access to Quality Care in Family Planning: Medical Eligibility Criteria for Contraceptive Use. Geneva: World Health Organization, 1996.
D'Arcanques C, Griffin PD, von Hertzen, et al. Technology development and assessment. In Van Look PFA, ed. Annual Technical Report 1997. (Geneva: World Health Organization, 1998)79.
Chi I-c, Farr G. The non-contraceptive effects of the levonorgestrel-releasing intrauterine device. Adv Contracept 1994;10(4):271-85.
Faúndes A, Alvarez F, Díaz J. A Latin American experience with levonorgestrel IUD. Ann Med 1993;25(2):149-53.
The intrauterine system (IUS) can be used to supplement estrogen replacement therapy (ERT), in which estrogen is used to relieve such menopausal symptoms as hot flashes, sweating, sleep disturbances and vaginal dryness. ERT also helps prevent osteoporosis and cardiovascular disease.
However, ERT also stimulates the endometrium. Adding a progestin at menopause, such as the levonorgestrel in the IUS, counteracts endometrial stimulation and helps protect against overgrowth of endometrial tissue, precancerous endometrial changes and endometrial cancer.1
The sustained release of low-dose levonorgestrel directly into the uterus via the IUS may result in more endometrial protection, less irregular bleeding, and fewer systemic side effects than the release of progestins via pills or implants.2
Dr. Helen Roberts, 48, senior lecturer in women's health at the School of Medicine, University of Auckland, New Zealand, uses an IUS as a contraceptive and as an addition to ERT. "About four years ago I began to get night sweats," a common menopausal symptom, she says. "I started using oral estrogen every day and oral progestogen for half of each month. The night sweats disappeared after about a week, but when I was taking the progestogen pills, I felt bloated and moody.
"At that stage, the IUS began to look like a good option. ... Most of the hormone in the IUS stays inside the uterus and only a small dose is in the systemic circulation -- about one-third of the dose of the progestogen-only pill. This meant that my side effects really improved. I had spotting and some bloating for the first few months, but now -- a year later -- I have no periods at all and no progestogen-related side effects. In terms of contraception and hormone replacement, it has been the perfect solution for me."
-- Kim Best
References
Wollter-Svensson LO, Stadberg E, Andersson K, et al. Intrauterine administration of levonorgestrel 5 and 10 microg/24 hours in perimenopausal hormone replacement therapy, a randomized clinical study during one year. Acta Obstet Gynecol Scand 1997;76(5):449-54;Taddei GL, Bargelli G, Scarselli B, et al. Precancerous lesions of the endometrium and medical treatment. Eur J Contracept Reprod Health Care 1997;2(4):239-41.
Suhonen SP, Holmström T, Allonen HO, et al. Intrauterine and subdermal progestin administration in postmenopausal hormone replacement therapy. Fertil Steril 1995;63(2):336-42; Suhonen SP, Allonen HO, Lähteenmäki P. Sustained-release estradiol implants and a levonorgestrel-releasing intrauterine device in hormone replacement therapy. Am J Obstet Gynecol 1995;172(2 Pt 1):562-67.
The levonorgestrel intrauterine device (IUS) is expected to be submitted soon to the U.S. Food and Drug Administration (FDA) to be considered for use in the United States, a process that typically takes about a year. If approved, the device would be eligible for distribution to developing countries through the United States' foreign aid program.
The device has recently been approved for marketing in China and Brazil, and is currently used by 1 million women in more than a dozen countries, according to the manufacturer, Schering AG of Germany. It is available in most European countries including Russia, and in Singapore, New Zealand and several French overseas territories, such as Martinique, Guadeloupe, New Caledonia and Guyana. It is marketed under the brand name Mirena, except in Nordic countries, where the brand name is Levonova.
Its price for use by foreign aid programs, however, will determine its availability in developing countries. Some observers believe its use in developing countries would be limited even if foreign assistance programs can negotiate an acceptable price, since it could still be relatively expensive compared with other options.
"It is likely that international development agencies in European countries such as Sweden, Germany or Finland will make the first purchases of the device for distribution in the developing world," says Dr. Elof Johansson, biomedical research director of the Population Council, which owns rights to the device. "In large part, this is because they will have had longer experience [than the United States] using the device in their own countries. And, in Europe, its popularity has been strong and stable."
The U.S. Agency for International Development (USAID) would need to negotiate an acceptable low price from the device's manufacturer before the IUS could be considered for USAID distribution, says Jeff Spieler, chief of research at USAID's Center for Population, Health and Nutrition.
The IUS is expensive on the retail market, from approximately U.S. $120 to U.S. $220, depending on the country involved. However, lower prices have been negotiated for other expensive contraceptives for use in foreign aid programs. For example, the Copper T 380A IUD has a retail cost of U.S. $350 in the United States, yet USAID pays only about U.S. $1.45. The Norplant subdermal implant has a retail cost of U.S. $393 in the United States, but costs USAID about U.S. $24.
-- Kim Best
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